PHENYLKETONURIA 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., 1960Phenylketonuria: 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: 0-597-84164-0 1. Phenylketonuria-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.
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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 phenylketonuria. 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 PHENYLKETONURIA ................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Phenylketonuria ............................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 23 The National Library of Medicine: PubMed ................................................................................ 24 CHAPTER 2. NUTRITION AND PHENYLKETONURIA........................................................................ 69 Overview...................................................................................................................................... 69 Finding Nutrition Studies on Phenylketonuria........................................................................... 69 Federal Resources on Nutrition ................................................................................................... 79 Additional Web Resources ........................................................................................................... 79 CHAPTER 3. ALTERNATIVE MEDICINE AND PHENYLKETONURIA ................................................. 81 Overview...................................................................................................................................... 81 National Center for Complementary and Alternative Medicine.................................................. 81 Additional Web Resources ........................................................................................................... 88 General References ....................................................................................................................... 89 CHAPTER 4. DISSERTATIONS ON PHENYLKETONURIA ................................................................... 91 Overview...................................................................................................................................... 91 Dissertations on Phenylketonuria................................................................................................ 91 Keeping Current .......................................................................................................................... 92 CHAPTER 5. CLINICAL TRIALS AND PHENYLKETONURIA .............................................................. 93 Overview...................................................................................................................................... 93 Recent Trials on Phenylketonuria................................................................................................ 93 Keeping Current on Clinical Trials ............................................................................................. 94 CHAPTER 6. PATENTS ON PHENYLKETONURIA .............................................................................. 97 Overview...................................................................................................................................... 97 Patents on Phenylketonuria ......................................................................................................... 97 Patent Applications on Phenylketonuria ................................................................................... 104 Keeping Current ........................................................................................................................ 106 CHAPTER 7. BOOKS ON PHENYLKETONURIA ................................................................................ 107 Overview.................................................................................................................................... 107 Book Summaries: Federal Agencies............................................................................................ 107 Book Summaries: Online Booksellers......................................................................................... 108 The National Library of Medicine Book Index ........................................................................... 109 Chapters on Phenylketonuria..................................................................................................... 110 CHAPTER 8. MULTIMEDIA ON PHENYLKETONURIA ..................................................................... 115 Overview.................................................................................................................................... 115 Bibliography: Multimedia on Phenylketonuria.......................................................................... 115 CHAPTER 9. PERIODICALS AND NEWS ON PHENYLKETONURIA .................................................. 117 Overview.................................................................................................................................... 117 News Services and Press Releases.............................................................................................. 117 Newsletters on Phenylketonuria ................................................................................................ 119 Academic Periodicals covering Phenylketonuria ....................................................................... 119 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 121 Overview.................................................................................................................................... 121 U.S. Pharmacopeia..................................................................................................................... 121 Commercial Databases ............................................................................................................... 122 Researching Orphan Drugs ....................................................................................................... 122 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 127 Overview.................................................................................................................................... 127
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NIH Guidelines.......................................................................................................................... 127 NIH Databases........................................................................................................................... 129 Other Commercial Databases..................................................................................................... 132 The Genome Project and Phenylketonuria................................................................................. 132 APPENDIX B. PATIENT RESOURCES ............................................................................................... 137 Overview.................................................................................................................................... 137 Patient Guideline Sources.......................................................................................................... 137 Finding Associations.................................................................................................................. 142 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 145 Overview.................................................................................................................................... 145 Preparation................................................................................................................................. 145 Finding a Local Medical Library................................................................................................ 145 Medical Libraries in the U.S. and Canada ................................................................................. 145 ONLINE GLOSSARIES................................................................................................................ 151 Online Dictionary Directories ................................................................................................... 152 PHENYLKETONURIA DICTIONARY ..................................................................................... 155 INDEX .............................................................................................................................................. 207
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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 phenylketonuria 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 phenylketonuria, 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 phenylketonuria, 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 phenylketonuria. 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 phenylketonuria, 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 phenylketonuria. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON PHENYLKETONURIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on phenylketonuria.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and phenylketonuria, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “phenylketonuria” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Implications of Phenylketonuria on Oral Health Source: Pediatric Dentistry. 21(7): 433-437. November-December 1999. Contact: Available from American Academy of Pediatric Dentistry. Publications Department, 211 East Chicago Avenue, Suite 700, Chicago, IL 60611-2663. Website: www.aapd.org. Summary: This article reports on a study performed to evaluate the oral health of children with phenylketonuia (PKU) and to assess, in vitro, the erosive potential of 5 amino acid supplements commonly prescribed in the management of these children. Forty children with PKU underwent a full dental examination and were compared with an age and sex matched control group. The erosive potential of the supplements was assessed by comparing their pH and titratable acidity to those of Coca Cola and orange
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Phenylketonuria
juice. There was no significant difference between the affected groups and the control groups in the level of dental caries, with over 75 percent of the children examined being caries free. However, significantly more (33 percent) children with PKU exhibited signs of tooth wear compared with 24 percent of the controls. While Coca Cola had the lowest pH (2.46), the titratable acidity of the flavored supplements was significantly higher than both their unflavored counterparts and Coca Cola. The authors also note that, despite the potentially damaging nature of their diet, significantly less children with PKU had ever seen a dentist. Health professionals involved in the care of these patients should be aware of the implications of management and provide appropriate dental advice and referral. 1 figure. 3 tables. 22 references.
Federally Funded Research on Phenylketonuria The U.S. Government supports a variety of research studies relating to phenylketonuria. 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 phenylketonuria. 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 phenylketonuria. The following is typical of the type of information found when searching the CRISP database for phenylketonuria: •
Project Title: AROMATIC AMINO ACID HYDROXYLASES AS THERAPEUTICS Principal Investigator & Institution: Bouyer, James H.; Florida Agricultural and Mechanical Univ Tallahassee, Fl 32307 Timing: Fiscal Year 2001; Project Start 05-JUN-2000; Project End 30-APR-2005 Summary: Development of Aromatic Amino Acid Hydroxylases as Therapeutics The long-term goal of the research is to develop mammalian aromatic amino acid hydroxylases as therapeutics in the treatment of metabolic disorders such as Parkinson's disease (tyrosine (tyrosine hydroxylase), Segawa's syndrome (tyrosine hydroxylase) and phenylketonuria (phenylalanine hydroxylase). The research design is to develop a high throughput screen that will detect mutant hydroxylases with increased activity and/or stability. The mutant enzymes that possess the desired characteristics of increased activity and/or stability will be targeted as candidates for gene therapy in the treatment of Parkinson's, Segawa's syndrome and phenylketonuria. The high-throughput screen will be based on a co-expression system that produces the hydroxylase and a second enzyme that converts the product of the hydroxylase into a colored compound that can be easily detected and assay. The proposed research provides the first step in achieving
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
the long-term goal, because it supports the development of co-expression systems that will serve as the starting material for the mutagenesis and screening process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGICAL OXIDATION OF PHENYLALANINE BY NONHEME IRON Principal Investigator & Institution: Caradonna, John P.; Associate Professor; Chemistry; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2004 Summary: The major objective of this research is to elucidate the chemical and physical properties of the mononuclear non-heme iron dependent metalloenzyme, phenylalanine hydroxylase (PAH, phenylalanine 4-monooxygenase, E.C. 1.14.16.1). PAH is a mixedfunction oxidase whose active site ferrous iron center catalyzes the hydroxylation of Lphenylalanine (L-phe) to L-tyrosine (L-tyr) in the presence of dioxygen and the reduced cofactor, tetrahydropterin. Genetic defects in the PAH gene that induce a significant decrease in PAH activity lead to the autosomal recessive human genetic disorder, classic phenylketonuria (PKU). This disorder is characterized by an increase in serum L-phe concentrations and the abnormal accumulation of phenylalanine-based metabolic products that are thought to cause defective myelination of the central nervous system, leading to postnatal brain damage and severe mental retardation. PKU is the most common inborn error in amino acid metabolism that is of clinical importance; approximately 1 in 50 individuals carry the disease trait with an average incidence of about 1 in 10,000 for Caucasians. Early detection and strict dietary management have significantly reduced the neurological defects and mental retardation characteristics of untreated PKU. Among the specific aims of this project is to identify and interpret, in terms of their structural and chemical implications, changes in the active site iron environment as a function of the requisite allosteric activation process, and the binding of substrate(s) and cofactor. Advanced methodologies, including MCD, XAS, M ssbauer, ESEEM, and ENDOR spectroscopies, will be utilized to probe the active site structures of multiple physiologically relevant enzyme states, all of which can be generated in homogeneous forms. A comparison of the active site characteristics of native, homotetrameric PAH with dimeric/monomeric forms of the enzyme will be performed; truncated dimeric forms of PAH support promiscuous oxidation chemistry in terms of which substrates can be oxidized versus wildtype full length PAH, which only efficiently accepts L-phe as substrate. Additional objectives are to compare wildtype PAH with selected PKU inducing missense mutations as a further probe of PAH mechanism and to initiate studies designed to defining the chemical basis for hyperphenylalaninemic disorders. Finally, the use of double mixing stopped-flow UV/vis and florescence experiments will be utilized to probe the compulsory reduction of the ferric active site prior to catalytic oxidation of substrate. Kinetic and mechanistic experiments will be performed to identify the factors that control and regulate iron reduction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CLINICAL STUDIES OF INBORN ERRORS OF METABOLISM Principal Investigator & Institution: Semenza, Gregg L.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001
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Phenylketonuria
Summary: Inborn errors of amino acid metabolism are individually rare but collectively represent significant causes of mortality and morbidity in the Pediatric population. The most comprehensive information source for these disorders list over 100 known disorders of amino acid metabolism. Hoever, the rarity of each individual disorder has hempered our understanding of these diseases. Indeed, many of the disorders are defined by fewer than 100 published cases. Their very rarity means that each patient should be evaluated in such a way that we not only meet the medical needs of the patient, but also further delineate and understand the natural history of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--DEVELOPMENTAL NEUROPSYCHOLOGY Principal Investigator & Institution: Pennington, Bruce; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CRYSTAL HYDROXYLASE
STRUCTURE
DETERMINATION
OF
TYROSINE
Principal Investigator & Institution: Goodwill, Kenneth E.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001 Summary: The crystal structure of the catalytic domain of tyrosine hydroxylase (TyrOH) to 2.3 E resolution has recently been completed in our laboratory by the MIRAS method. Structural studies are in progress of TyrOH with substrates, inhibitors, and the required biopterin cofactor bound. Using molecular replacement with TyrOH, structural studies have begun for the closely related enzyme phenylalanine hydroxylase. These high resolution structures will provide new knowledge about the function of this family of enzymes as well as the role of single amino acid mutations that cause human diseases such as L-DOPA responsive parkinsonism and phenylketonuria (PKU). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF COGNITIVE FUNCTIONS: FRONTAL LOBE Principal Investigator & Institution: Diamond, Adele D.; Director; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2001; Project Start 10-JUN-1997; Project End 31-MAY-2003 Summary: The goals of the proposed research are three:(1) to test children with brain damage localized to frontal cortex on tests (a) which have been linked specifically to frontal cortex function through neuroanatomical and behavioral studies with infant and adult monkeys and (b) on which we know the normal developmental progression in children. Important aspects of this work will be to look for converging evidence from diverse tests all linked to the same subregion of frontal cortex, and to attempt to dissociate performance on these tests from performance on tests linked to other neural circuits. The goal is to develop non-invasive tests capable of detecting frontal cortex damage in infants and young children. Presently such damage often goes undetected for many years because of the lack of such tests. (2) to investigate the relationship of dopamine levels to performance on these tasks, and to begin to investigate the
Studies
7
hypothesis that the fundamental maturational change which underlies the emergence of cognitive abilities dependent on frontal cortex during infancy is increasing levels of frontal cortex dopamine. To do this, children with early-treated PKU, who have no known structural brain damage but who are vulnerable to reduced levels of dopamine will be tested. Because their general cognitive functioning is good, if deficits are found they are likely to be selective. If they are selectively impaired on tests of frontal cortex function, this will be the first demonstration in humans of a cognitive deficit on frontal cortex tasks from dopamine depletion alone. Because L-dopa and the dopamine precursor, tyrosine, can be taken orally, there is an excellent chance that if deficits are found, therapeutic interventions will be possible to alleviate any impairments. (3) to better understand the abilities required for success on tasks that depend on frontal cortex function. Hypotheses will be considered that suggest that memory for space, and/or time, or for relational information in general is dissociable from memory for other information and dependent upon frontal cortex function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVICE FOR RAPID SCREENING OF PLASMA HOMOCYSTEINE Principal Investigator & Institution: Davies, Malonne I.; Bioanalytical Systems, Inc. (Basi) 2701 Kent Ave West Lafayette, in 479061389 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-MAY-2003 Summary: (Applicant's abstract) The objective of the proposed work is fast, sensitive integrated clinical analyzers for the diagnosis of two metabolism disorders, homocysteinuria and phenylketonuria (PKU). The assays are based on microchip capillary electrophoresis with electrochemical detection. This format has several advantages, including small sample requirements, fast analysis times, and inexpensive manufacture of multiple chips. Electrochemical detectors are ideally suited to microchip CE because they can be easily miniaturized and integrated into the analysis system. Monitoring phenylanlanine concentration in plasma samples of newborns is required by law. The current assay has a relatively high rate of failure (1:70) and requires instrumentation frequently not found in-house, especially in small hospitals. High levels of homocysteine in plasma has been associated with cerebrovascular, peripheral vascular, and coronary heart diseases. The assay for homocysteine involves online reduction of the protein-bound homocysteine with tris-(2-carboxyethyl)phosphine, separation by electrophoresis, and electrochemical detection at a gold/mercury electrode. Phenylalanine will be determined in plasma in a similar manner using a copper electrode. The chips will be used with a portable analysis system based on a battery-powered high voltage power supply, miniaturized potentiostat, and integrated data analysis system. The chips we develop will generate a foundation for other clinical assays based on electrochemical detection. PROPOSED COMMERCIAL APPLICATION: The current trend in clinical analysis is away form large centralized labs and toward point of care testing. Thus, a compact device for performance of assays for homocysteine and other clinically relevant animo acids in the clinic or physician's office has large commercial potential. Recently, the American Heart Association recommended homocysteine screening for patients at risk for cardiovascular disease. This should lead to a large demand for accurate and cost-effective assays for homocysteine similar to the current cholesterol screening assays. The development of a small, fast and reliable assay for phenylalanine in blood will make it possible to test infants quickly and accurately for PKU. The electrochemical based clinical analyzers developed here will provide a format that can be used for the development of a number of other assays for clinically
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important analytes. What is demonstrated with homocysteine and phenylalanine is just the beginning of a large array of clinical analyzers based on microchip CEEC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIET PHENYLKETONURIA
INTERVENTION
AND
CLINICAL
OUTCOMES
IN
Principal Investigator & Institution: Rouse, Bobbye M.; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001 Summary: Phenylketonuria (PKU) is a disorder usually diagnosed by newborn screening. Persons with PKU cannot properly process phyenylalanine (phe), an amino acid found in food. The only known treatment for PKU is a diet consisting of a protein source without Phe called a Medical Food (formula) plus limited amounts of low protein foods. The diet is started immediately after PKU is diagnosed to prevent mental retardation in newborns. In the past, many persons with PKU were taken off the diet around school age. Some of them stopped the diet on their own. Researchers found that the children off diet began losing IQ points. The current recommendation is for all persons with PKU to remain on the Medical Food and protein restricted diet throughout life. Of special concern is the effect of PKU on pregnancy. Women with PKU who were not on the diet before and during pregnancy delivered babies with serious birth defects. The Maternal PKU Study began collecting information from women with PKU in 1984 to determine the effects of the phe-restricted diet and Medical Food before and during pregnancy. The purpose of the study is to determine the proper blood phe levels needed for the woman to have the best chance of having a healthy baby. The study checks the dietary intake of the women and their blood phe levels and other nutrients in the blood such as, iron and protein. The children born to women in the study receive a thorough physical at birth and yearly thereafter. Developmental testing is done on each child at 1, 2, 4, 7 and 10 years of age. The mother's blood phe levels and diet before and during pregnancy are compared to the child's growth and development. From this information the study aims to develop guidelines for clinics caring for women with PKU. The project has significant implications for preventing birth defects in the babies born to women with PKU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIETARY CONDITIONS
ADHERENCE
IN
CHILDREN
WITH
CHRONIC
Principal Investigator & Institution: Ievers-Landis, Carolyn E.; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 11-JUN-2001; Project End 31-MAY-2006 Summary: (Adapted from applicant's description): The candidate is a research associate in pediatric psychology who is advancing to a junior faculty position. This award is expected to help transition the focus of the candidate's research and provide additional training in measurement of dietary adherence, particularly of barriers associated with following prescribed diets for children with various chronic conditions. The candidate's career goals are to develop an independent research career related to elucidation of barriers and family interaction patterns that interfere with dietary adherence and development of intervention programs to promote adherence. Specific objectives are: 1) learn specialized methods of measurement to identify the challenges related to the dietary management of chronic conditions of childhood, including in-depth interviews
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9
and behavioral analyses of family interactions at mealtimes, and 2) use data from these methods to develop family-based interventions to promote adherence to dietary regimens. The candidate proposes a five-year training program with faculty mentors from a strong pediatric research department and medical school. Her sponsor is a very experienced pediatric psychology researcher whose work has focused on identifying factors that enhance or disrupt the psychosocial adaptation of children with chronic illness. Mentors represent subspecialty divisions that are directly relevant to the research and career development plan. The career development plan describes activities focused on enhancing knowledge of research-related approaches to the identification of barriers to dietary adherence and design of intervention programs through clinical observation, course work, and independent studies with mentors. Other activities include research training in statistical methods and supervised experience in preparation of grant proposals for individual research support. The candidate's proposed research involves two studies. Study 1 is a two-phase assessment of barriers to dietary adherence in children with hyperlipidemia, insulin-dependent diabetes mellitus, phenylketonuria, and Prader-Willi syndrome. Study 2 is a pilot study to develop and evaluate family-based intervention programs to improve dietary adherence for children in the target populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOES PKU PROTECT AGAINST CANCER? Principal Investigator & Institution: Sidell, Neil; Professor; Gynecology and Obstetrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): The disease phenylketonuria (PKU) is caused by mutations in the gene coding for phenylalanine hydroxylase (PAH) which results in hyperphenylalaninemia and elevated levels of abnormal phenylalanine metabolites. Among these metabolites is phenylacetic acid, or the ionized form of the molecule phenylacetate (PA). Recently, PA has come under intense investigation due to its demonstrated anticancer activity against a variety of malignancies, including breast and prostate cancers. These findings suggest the possibility that PKU may offer protection against cancer through chronically elevated blood levels of PA. The investigator's overall objective is to test this hypothesis. This will be accomplished by studies involving two in vivo mouse models. Specific Aim 1 will assess the ability of therapeutic intervention with a PA analogue to inhibit estrogen-dependent carcinogenesis using the investigator's existing aromatase transgenic mouse colony. In these experiments, the PA derivative 4-chloro-PA will be chronically administered to the mice in their drinking water and its chemopreventative activity on the development of preneoplastic / neoplastic lesions assessed. Specific Aim 2 will test the hypothesis that PKU can protect against breast cancer using "PKU mice". These studies will utilize an established PKU mouse model (ENU2/2), which has a mutation in the gene coding for PAH and display a range of phenotypic characteristics comparable to those of affected human individuals. The ENU2/2 mice will be treated with the chemical carcinogen DMBA under different protocols and the resulting induction of mammary tumors compared with control mice of the same genetic background. Taken together, the information gained from these in vivo studies will determine whether the genetic disorder that results in PKU can protect against breast cancer whose etiology may involve hormonal and/or environmental factors (carcinogens). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Phenylketonuria
Project Title: DROSOPHILA PATTERNS FOR TWO PTERIN COFACTOR DEFECTS Principal Investigator & Institution: Primus, Jann P.; Spelman College 350 Spelman Ln Sw Atlanta, Ga 30314 Timing: Fiscal Year 2001 Summary: In born errors in the biosynthesis of the pterin cofactors tetrahydrobiopterin (H4B) and molybdopterin (MoCo) are associated with serious human diseases. Genetic variations in the synthesis of H4B have been associated with serious human diseases. Genetic variations in the synthesis of H4B have been associated with diseases such as atypical phenylketonuria, Parkinson's disease, and dystonias. The importance of H4B to these processes is found in its role as an essential cofactor for phenylalanine, tyrosine and tryptophan hydroxylases, enzymes that are involved in amino acid degradation and the biosynthesis of catecholamines and serotonin. The MoCo functions as an essential enzymatic cofactor for molybdenum hydroxylase enzymes such as sulfite oxidase and xanthine dehydrogenase. Genetic deficiencies in the biosynthesis of the MoCo ar3e associated with a severely debilitating neurological disorder, molybdenum cofactor deficiency, and with xanthinuria, a malady of purine metabolism. The proposed studies utilize Drosophila melanogaster, the only model system in which changes in pterin synthesis are reflected in a visible phenotype (eye color), as a genetic model system for pterin cofactor biosynthesis. The studies center on two Drosophila proteins, aldose reductase and the maroon-like+ (ma- 1+) protein, which are involved, respectively, in the synthesis of H4B and MoCo. Expressed sequence tags (ESTSs) identified from partial amino acid analysis will be used to obtain molecular clones encoding the aldose reductase. Aldose reductase clones will be used as probes to determine the cytogenetic locus of the aldose reductase gene(s). Knowledge of the cytogenetic locus of the aldose reductase will allow mutant analysis to assess the protein's involvement in the H4B pathway. Polyclonal antisera raised to maroon-like (ma-1) peptides will be used to follow the standard purification of the maroon-like protein, a putative cysteine transulfurase, and the first eukaryotic member of the nif-S-like gene family to be described. Such antibodies will also be used to localized the ma-1 protein in situ and to analyze existing ma-1 mutants. These studies will lead to a better understanding of the terminal steps of BH4 and MoCo biosynthesis in higher organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENZYMES OF NEUROTRANSMITTER BIOSYNTHESIS Principal Investigator & Institution: Fitzpatrick, Paul F.; Professor; Biochemistry and Biophysics; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2001; Project Start 01-MAY-1992; Project End 20-APR-2003 Summary: The eukaryotic pterin-dependent hydroxylases each catalyze physiologically critical reactions. Phenylanine hydroxylase catalyzes the hydroxylation of phenylalanine to tyrosine during catabolism. Mutations in phenylalanine hydroxylase result in phenylketonuria. Tyrosine hydroxylase catalyzes the formation of dihydroxyphenylalanine from tyrosine, the first step in biosynthesis of the catecholamine neurotransmitters. Imbalances in catecholamine levels have been implicated in a number of disease states, including hypertension. Tryptophan hydroxylase catalyze the hydroxylation of tryptophan, the first step in the biosynthesis of serotonin. Imbalances in serotonin levels have been implicated in several neurological and psychiatric disorders, including depression. Thus, these enzymes have central roles in the health of an individual. Despite their importance, little is known about them at a molecular level. The long term goals of the research proposed here are to determine the
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catalytic mechanisms of the pterin dependent hydroxylases and to determine at a molecular level the effects of phosphorylation on tyrosine hydroxylase. The specific aims of the present proposal are to examine the mechanisms using alternative substrates, probe the role of the active site iron in oxygen activation, determine the role of active site residues using site-directed mutagenesis and the recently determined structures, and further characterize the effects of phosphorylation on tyrosine hydroxylase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR METABOLIC DISORDERS Principal Investigator & Institution: Whitley, Chester B.; Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 10-JAN-1995; Project End 31-DEC-2002 Summary: The central theme of this program is to exploit recent advances in basic science for t he development of innovative gene therapy strategies, especially for metabolic disorders causing mental retardation. The program is highly focused on identifying and resolving the barriers to clinical gene therapy. In this period, five projects aim to exploit recent innovations t hat would enhance gene delivery and expression or actually correct genomic mutations in vivo. These projects are: Therapy for Hyperammonemia with Genetically-Engineered Bacteria (Tuchman). AdenoAssociated Virus Vector Treatment of Spinocerebellar Ataxia (McIvor) Chimeraplasty for Mutations Associated with Mental Retardation (Kren) Sleeping Beauty Transposon for Gene Therapy (Hackett) Lentiviral Ex Vivo Hematopoietic Stem Cell Gene Therapy for Mucopolysaccharidosis Type 1 (Whitley) The projects utilize a number of models of human metabolic disorders causing brain disease, notably, murine models of mucopolysaccharidosis, hyperammonemia, phenylketonuria and spinocerebellar ataxia. The program share core facilities for administration, microchemicals, quantitative PCR, hematopoietic cell processing, animal resources and viral vector production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY FOR PHENYLKETONURIA Principal Investigator & Institution: Laipis, Philip J.; Professor; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001 Summary: Phenylketonuria (PKU) is one of the most common genetic disorders affecting children in North America and Europe, with an incidence of about 1 in 10,000 births. Mutations in the enzyme phenylalanine hydroxylase (PAH) are the major cause of PKU. PAH deficiency results in elevated serum phenylalanine (Phe) levels, leading to abnormal brain development and mental retardation. PKU's frequency, coupled with the ability of early dietary modification to greatly reduce the severe neurological problems associated with the disorder, has led to neonatal testing programs in all states. Unfortunately, there is a widespread impression that dietary control effects a "cure" for this disease. In reality, strict adherence to the diet is exceedingly difficult and lapses can cause serious long-term neuro-development sequelae, particularly in offspring of PAHdeficient women. Given the well-understood single gene defect, gene therapy for PKU is both technically feasible and therapeutically desirable. Recent important advances in gene therapy have come from the use of AAV-based vectors to provide effective, stable, and safe correction of metabolic. It is hypothesized that AAV vectors will be useful in PKU. To this hypothesis, the ability of AAV vectors to: 1) Provide effective rescue of
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Phenylketonuria
defective Phe metabolism in the Pah/enu2 mouse will be examined. Serum Phe levels will be related to the number of vector genomes and transfected cells as well as to the degree of reduction of PKU symptoms. 2) Give safe PAH delivery to liver with non germ-line transmission of vector sequences in either adult and neonatal Pah/enu2 mice will be tested. The potential for liver toxicity and immune responses to vector will also be examined. 3) Optimize PAH expression and hepatocyte delivery by using alternative control elements and tissue-specific targeting. These experiments provide a rational approach to examining the potential of AAV-driven gene therapy to truly cure PKU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR TREATMENT OF HEMOPHILIA A Principal Investigator & Institution: Herweijer, Hans; Director of Preclinical Research; Mirus Corporation 505 S Rosa Rd, #104 Madison, Wi 53711 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 30-SEP-2002 Summary: (provided by applicant): Gene therapy promises to be a singular advance in the treatment of both acquired and genetic diseases at the most fundamental levels of pathology. Hemophilia A patients express insufficient levels of factor VIII. This protein is primarily expressed in the liver. A novel method of intravascular injection of plasmid DNA expression vectors results in highly efficient transfection of hepatocytes. This project will use this simple and innovative gene transfer approach to develop a gene therapy protocol for the treatment of hemophilia A. Despite the promise of this nonviral gene therapy approach, there are two problems that have to be solved for it to be clinically-viable: 1) current plasmid DNA expression vectors do not result in long term expression; 2) gene transfer is often accompanied by hepatocyte damage. In this Phase I application, experiments are proposed to developed plasmid DNA expression vectors that will enable long-term expression of human factor VIII (hF8). We will generate vectors with liver specific promoters and hF8 genomic sequences. Recently, a similar plasmid DNA expression vector was described that expressed human factor IX for more than 6 months. Phase II will focus on developing the surgical approaches for delivering the naked pDNA to the liver with minimal liver toxicity, using catheter-based techniques frequently used in clinical practice. These experiments will generate the preclinical data required for a human trial application. These gene delivery techniques can also be used for the development of gene therapy protocols for applications such as other clotting factor abnormalities, phenylketonuria, alpha 1 -antitrypsin deficiency, complement factor deficiencies, and other hematologic or metabolic disorders. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY TREATMENT FOR SEVERE ANEMIA Principal Investigator & Institution: Lewis, David L.; Senior Scientist; Mirus Corporation 505 S Rosa Rd, #104 Madison, Wi 53711 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 30-SEP-2002 Summary: (provided by the applicant): Gene therapy holds a promise for the treatment of both acquired and genetic diseases. Patients with diseases including end-stage kidney disease, acquired immunodeficiency syndrome and patients who are treated for cancer with high dose chemotherapy and bone marrow transplantation often develop anemia that can be treated or prevented by injection of recombinant EPO protein. EPO delivery via gene therapy would provide a significant treatment benefit. EPO is normally expressed in the kidney, which is a poor target for gene therapy in most patients
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because of severe organ failure. Yet, serum proteins such as EPO can be produced at ectopic sites and secreted to the serum. A novel method of intra-vascular injection of plasmid DNA expression vector results in highly efficient tranfection of skeletal muscle. This project will use this simple and innovative approach to develop a gene therapy protocol for the treatment of severe anemia. In this Phase 1 application, experiments are proposed to optimize EPO expression following intra-vascular delivery of plasmid DNA expression vectors and test this gene therapy protocol in a severe anemia model. During the Phase II studies, intra-vascular delivery techniques will be optimized to target small, defined muscle groups in a safe clinically applicable protocol. PROPOSED COMMERCIAL APPLICATION: The intravascular delivery methodology will be used in Phase III for the internal development of gene therapy protocols for severe anemia and applications such as clotting factor abnormalities, phenylketonuria, a1-antitrypsin deficiency, complement factor deficiencies, and other hematologic or metabolic disorders within Mirus and licensed to other companies for use within their ene therapy applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC RECONSTITUTION FOR PHENYLKETONURIA Principal Investigator & Institution: Woo, Savio L.; Professor and Director; Center for Gene Therapy & Molecular Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Classical Phenylketonuria (PKU) is a recessive monogenic disorder in amino acid metabolism that results from a deficiency of hepatic phenylalanine hydroxylase (PAH), and it predisposes affected individuals to severe and permanent mental retardation. While the disease phenotype in PKU patients can be prevented by dietary restriction, the treatment suffers from the need of life-long patient management and poor patient compliance. Discontinuation of dietary restriction during pregnancy in female PKU patients has also caused various birth defects in the offspring regardless of the PAH genotypes. This syndrome, known as maternal PKU, has become a public health concern since most treated female PKU patients of child-bearing age have been off diet restriction. We have therefore begun the development of complementary treatment modalities for PKU and maternal PKU by genetic reconstitution in vivo. To achieve persistent and high level transgene expression in the liver, recombinant adeno-associated virus (AAV) vectors deleted of all viral genes will be used for in vivo delivery of the murine PAH ene to the livers of the PAH-deficient Pah anu2 mice, an extraordinarily faithful animal model of PKU and maternal PKU in humans. Recombinant AAV vectors have recently been shown to effectively transduce hepatocytes in vivo, which resulted in the persistent expression of transgene products without apparent toxicity or eliciting a cellular immune response against the virally transduced cells. Its application in treatment of metabolic disorders however, is limited by the fact that only a small fraction of vector-transduced hepatocytes in vivo resulted in persistent expression of the transgenes, thus requiring high levels of transgene expression per cell for the treatment to be effective. In addition, there still remains the difficulty in large-scale production of purified rAAV vectors for effective transgene delivery into large animals including humans. To overcome or circumvent these obstacles, we propose the following molecular strategies: 1) develop and use of hybrid rAAV vectors with capsids from alternative serotypes to enhance hepatocyte transduction efficiency in vivo; 2) incorporate cis-acting genetic elements into the promoter-enhancer region of transgene expression cassettes that will lead to elevated
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Phenylketonuria
gene transcription; and 3) insert cis-acting elements into the 3'-untranslated region of mRNAs that will increase their stability in vector-transduced cells. We envision that these molecular strategies for hepatic gene transfer and expression will be synergistic in elevating the level of mPAH activity in the livers of PKU mice, which will restore blood phenylalanine levels to normal. This beneficial outcome might also be accomplished at reduced vector doses so that the need for large-scale production of the purified vectors can be minimized. Successful conduct of these studies will provide the scientific foundation for future applications in the genetic treatment of PKU as well as other metabolic disorders secondary to hepatic enzyme deficiencies in patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF A PKU/MSUD METABOLIC CAMP ON SELF MANAGEMENT SKILLS Principal Investigator & Institution: Singh, Rani H.; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001 Summary: The study is designed to evaluate the effectiveness of comprehensive nutrition education and a disease curriculum in a one-week supportive camp environment for young girls (age 10 yrs or >) with phenylketonuria (PKU) and maple syrup urine disease (MSUD). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: METABOLIC ENGINEERING AS THERAPY FOR MURINE PKU Principal Investigator & Institution: Harding, Cary; Pediatrics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2003 Summary: adapted from applicant's abstract): The overall objective of this project is to investigate the efficacy of liver or muscle-directed gene therapy using recombinant adeno-associated virus (rAAV) vectors in the treatment of phenylketonuria (PKU) using, as a model, the phenylalanine hydroxylase (PAH) deficient Pahenu2 mouse. Recombinant adeno-associated virus has in recent studies shown promise as a gene delivery vector for both liver and muscle. We propose to compare the effects of muscledirected vs. liver-directed rAAV-mediated gene therapy upon hyperphenylalaninemia in the Pahenu2 mouse. Restoration of liver enzyme activity is the most obvious approach for gene therapy of PKU. However, the disease pathophysiology associated with PKU is caused by circulating toxins, namely phenylalanine and its metabolites; PAH deficiency has no direct pathologic effect upon the liver. Therefore, any treatment approach that can effectively remove the toxic metabolites from the body could prevent disease-associated pathology. We have shown previously that PAH expression in muscle can lower serum phenylalanine levels if the enzyme is supplied with sufficient tetrahydrobiopterin (BH4), a required cofactor for PAH activity. However, attaining a sufficient continuous supply through exogenous administration of BH4 is very difficult and expensive. We propose two potential methods for avoiding this complication: engineering of skeletal muscle to express, along with PAH, components of the BH4 synthetic pathway or alternatively to induce muscle expression of phenylalanine ammonia lyase (PAL), an enzyme from yeast that requires no exogenous cofactors. In this project, we will first compare the ability of rAAV vectors to produce stable PAH expression in liver and muscle and assess the effect upon hyperphenyl-alaninemia in Pabenu2 mice. Secondly, we will develop germline modified mice that carry a muscle-
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specific transgene containing the PAH cDNA and elements of the BH4 synthetic pathway (GTP cyclohydrolase I (GTPCH) or GTPCH and pyruvoyltetrahydropterin synthase (PTPS)) in an attempt to induce both constitutive PAH expression and BH4 synthesis. We will breed these animals to Pahenu2 mice to determine whether muscle PAH expression together with BH4 synthesis can correct hyperphenylalaninemia in PKU. Finally, we will investigate PAL expression induced either by germline modification or rAAV-mediated gene transfer in Pahenu2 mouse muscle, as a possible treatment of hyperphenylalaninemia. The ultimate goal of our research is the development of effective and safe gene therapy for phenylketonuria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MONOCARBOXYLIC ACIDS AND AMINO ACIDS IN BRAIN METABOLISM AND TRAFFICKING Principal Investigator & Institution: Mckenna, Mary C.; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001 Summary: Studies in Project II address the hypothesis that it is crucial for the brain to maintain the proper balance of production and utilization of lactate since this monocarboxylic acid is a key substrate in both developing brain and mature brain. Impairment in transport of lactate or ketone bodies into brain may limit the use of these key substrates for energy and neurotransmitter biosynthesis in developing brain in Phenylketonuria (PKU) and Maple Syrup Urine Disease. Conversely, an elevated concentration of lactate in cerebrospinal fluid and/or brain tissue is a prominent feature in Leigh's disease, a condition associated with mental retardation. There is evidence that amino acid and monocarboxylic acid metabolism are intimately and dynamically interconnected. A substantial portion of lactate, particularly in the cerebellum, is formed from glutamate and glutamine metabolized via the TCA cycle an converted to pyruvate via malic enzyme. Specifically, labeled precursors and 13/C-NMR will be used to determine the relative importance of the amino acids glutamate and glutamine as precursors for lactate production in astrocytes and neurons. The relative contribution of lactate and ketone bodies to neurotransmitter biosynthesis in cortical neurons, cerebellar granule cells, and in the PAHenu2 mouse (which has the same mutation of humans with PKU) will be determine. Glial/neuronal trafficking of substrates in the PKU mouse brain will be evaluated using [1- 13C]glucose and [2-/13C]acetate. Inhibition of TCA cycle activity with fluorocitrate will be used as a model for Leigh's disease. If a significant portion of the lactate in conditions with cerebral lactic acidosis is synthesize from amino acids, modulating lactate production by this biosynthetic pathway would require different therapeutic strategies than if it was produced via glycolysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NON-INVASIVE BLOOD PHENYLALANINE MONITOR Principal Investigator & Institution: Ghanem, Abdel-Halim; Aciont, Inc. 350 West 800 North, Ste 250 Salt Lake City, Ut 84103 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Phenylketonuria (PKU) is a genetic deficiency of phenylalanine hydroxylase (PAH). Without PAH, the patient with PKU cannot metabolize phenylalanine (PHE) to tyrosine. The resulting accumulation of PHE and the accumulation of phenylpyruvate by a secondary metabolic pathway in the patient's blood produce neuropathies including severe mental retardation, behavioral problems,
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schizophrenia, and tremors. PKU treatment is tailored to keep plasma PHE concentrations between 2 and 6 mg/dl through a low-PHE diet and frequent blood monitoring. The invasiveness of this monitoring exposes the patient to infection risk, hypodermophobia (especially in children), plus the inconvenience and expense of performing invasive procedures and mailing or delivering the sample to the treatment center. We propose developing and commercializing a novel non-invasive, in-home monitoring device that can sample PHE through the patient's skin and correlate extracted PHE to blood concentrations with a high degree of accuracy and reproducibility using ACiont's proprietary reverse iontophoretic process. During development, we will team up with a bioengineering firm to develop a PHE biosensor for real-time, quantitative analysis. When complete, our device will allow patients to: easily perform the test and obtain results in a home setting, reduce clinic visit frequency by allowing result communications with clinicians over the internet, get real-time data with which to tailor treatment, decrease overall treatment costs through increased efficiency and elimination of third party laboratories, and drastically improve their control over PKU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUTRIENTS AND GROWTH IN PHENYLKETONURIA Principal Investigator & Institution: Elsas, Louis J.; Professor of Pediatrics and Biochemistry; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This proposal is designed to test the hypothesis that different types of formulas commercially available for children with PKU have different capacities to support their growth. The investigators will measure growth and nutritional parameters in children aged 2-12 years on one of three different formulas: Phenex-2, Periflex and Phenyl-Free. Children to be studied are already receiving one of these therapies. They will be followed for one year. Enrollment is ongoing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOPHYSIOLOGY OF PKU Principal Investigator & Institution: Dyer, Charissa A.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: (Adapted from the applicant's Description) The focus of this revised application is to determine if a correlation exists between myelination and neurotransmitter production in phenylketonuria. The investigator's preliminary data show that myelination, demyelination, and remyelination take place in PKU mice as they are cycled on rounds of low Phenylalanine diet and regular diet. Since blood Phe levels change rapidly compared to changes in myelination, she proposed to examine the relationship between gain and loss of myelin and neurotransmitter production. The investigator will employ histochemical, immunohistochemical, molecular, and biochemical techniques to better understand the pathophysiology of PKU, and ultimately lead to the development of additional therapies for PKU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOPHYSIOLOGY/OUTCOME PHENYLKETONURIA
OF
EARLY
17
TREATED
Principal Investigator & Institution: Wasserstein, Melissa; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHENYLALANINE HYDROXYLASE DEFICIENCY: RESPONSE TO BH4 Principal Investigator & Institution: Matalon, Reuben; Head, Section of Genetics & Metabolism; Pediatrics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Phenylketonuria (PKU), due to phenylalanine hydroxylase (PAH) deficiency, is treated by dietary restriction of phenylalanine (Phe). Treatment of PKU with Phe-restricted diet has been difficult and often not possible to achieve the desired level of blood Phe for many patients. Reports indicate poor school performance, loss of IQ, and white matter deterioration in the brain when diet is relaxed. Furthermore, there is no agreed upon criteria for follow up and what blood Phe levels need to be pursued in older children and adults. Another complicating factor is pregnancy with PKU, which is at risk for offspring with neurological deficits and congenital heart defects. Recently, some patients with PAH deficiency have been found to respond to high doses of tetrahydrobiopterin (BH4). Tetrahydrobiopterin is a cofactor required for PAH activity. The reports of PAH deficiency responding to BH4 suggest Km mutations of PAH while the metabolism of BH4 is normal. Analysis of PAH in these patients showed various mutations, suggesting that there may be a wide range of PAH mutations that should respond to BH4. This pilot study is intended to investigate, over a period of two years, patients with PKU and their response to BH4 loading. The metabolism of BH4 will be studied, mutations of PAH will be determined, and the response to BH4 will be studied by monitoring blood Phe levels, in situ directed mutagenesis, enzyme expression, and enzyme kinetics in the presence of varying levels of BH4. Earlier studies of in vitro expression of PKU mutations were not aimed to identify mutations that respond to BH4, so such data are not available on approximately 400 mutations of PAH. Success of these studies will lead to new research on the treatment for many patients with PKU, and for a systematic new study of the mutations of PAH in order to identify which mutations respond to BH4. Treatment with BH4 should lead to a better outcome for PKU patients and for maternal PKU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREFRONTALLY-MEDIATED MEMORY IN PHENYLKETONURIA Principal Investigator & Institution: White, Desiree A.; Associate Professor; Psychology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2008 Summary: (provided by investigator): Recent work from our research group shows that school-age children with phenylketonuria (PKU) exhibit impairments in two prefrontally-mediated cognitive abilities of crucial importance to early learning: working memory and strategic processing in long-term memory. These impairments are
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more evident in older than younger children, suggesting that the impairments are not stable across development but instead may emerge with age. In the proposed research, the developmental trajectory of working memory and strategic memory processing will be charted longitudinally to determine if impairments emerge in individual children. Two neuropathological mechanisms that may underlie impairments in prefrontallymediated aspects of memory also will be examined. This research has implications for the development of rehabilitation strategies designed to improve learning and memory in children with PKU and other developmental disorders affecting prefrontal function. The aims and the methods for addressing the aims of this study are as follows: (1) To test the hypothesis that children with PKU exhibit impairments in prefrontally-mediated aspects of memory. To achieve this aim, working memory and strategic memory processing tasks will be administered to children with PKU who range from 7 to 18 years of age. Comparisons will be made with demographically matched, typically developing children. (2) To test the hypothesis that impairments in prefrontallymediated aspects of memory emerge as children with PKU age. To achieve this aim, working memory and strategic memory processing will be evaluated on a longitudinal basis. By doing so, the developmental trajectory of prefrontally-mediated aspects of memory will be defined at the level of individual children. (3) To test the hypothesis that white matter abnormalities contribute to impairments in prefrontally-mediated aspects of memory in children with early-treated PKU. This aim will be achieved through the use of diffusion tensor imaging (DTI), a neuroimaging technique permitting refined examination of white matter integrity. Dopamine deficiency also will be examined by assessing blood phenylalanine (a dopamine precursor) levels. Findings from DTI and phenylalanine levels will be examined in relation to findings from the memory tasks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QUALITY CONTROL TOOL FOR NEWBORN SCREENING BLOOD SAMPLES Principal Investigator & Institution: Craine, Brian L.; Western Research Company, Inc. 2127 E Speedway, Ste 209 Tucson, Az 85719 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 31-AUG-2004 Summary: (provided by applicant): Essentially all newborns in the United States (about 4 million per year) and at least 30 other countries have blood samples obtained on filter paper cards for the purpose of screening for a number of metabolic and genetic diseases. To prevent morbidity, such as brain damage, from metabolic diseases such as phenylketonuria or congenital hypothyroidism, it is critical that the screening results be obtained in a timely fashion. A persistent and well-documented problem for the newborn screening programs has been the arrival of inadequate blood card samples at the testing laboratories. These result in expensive recall testing and introduce a dangerous delay in the diagnosis of disease. This project will develop an imaging based system for the evaluation of blood cards to determine if they are adequate. Use of such a system at a birthing center will allow for the immediate correction of the problem, saving health care dollars and preventing any unnecessary delay in the diagnosis of important metabolic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RECOMBINANT ABNORMALITIES
AAV
FOR
CORRECTION
OF
GENETIC
Principal Investigator & Institution: Flotte, Terence R.; Professor; Pediatrics; University of Florida Gainesville, Fl 32611
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Timing: Fiscal Year 2001; Project Start 25-SEP-2000; Project End 31-JUL-2005 Summary: The liver plays a pivotal role in numerous biochemical processes, including intermediary metabolism, synthesis and secretion of serum proteins, energy metabolism, and detoxification of drugs and other xenobiotics. Hepatocytes are, therefore, an important target for gene therapy, and important target for gene therapy in many genetic diseases that disrupt these processes. In the current application, our group is seeking to optimize the conditions for gene transfer into hepatocytes using recombinant adeno-associated virus (rAAV) vectors, which possess the inherent advantages of long-term stability, safety, and low immunogenicity. rAAV-mediated gene transfer is very efficient in myofibers and some other cell types, but previous reports have indicated that long-term rAAV transduction of the liver may be limited to maximum of approximately 5% of hepatocytes using current methods. This may not be sufficient for many genetic/metabolic disorders. The primary goal of the current application is to identify and circumvent the rate-limiting steps in rAAV-mediated transduction of hepatocytes and thereby increase the efficiency of rAAV-mediated transduction of hepatocytes to a point where it is sufficient for widespread clinical use. The optimization of hepatocyte gene transfer will be accomplished in the context of three gene therapy projects, each of which typifies a defect in one of the major hepatic functions: Project 1: gene therapy for phenylketonuria (a disorder of amino acid metabolism), Project 2: gene therapy for alpha 1-anti-trypsin deficiency (a defect in hepatic synthesis and secretion), and Project 3: gene therapy for glycogen storage (that affect a key process in energy metabolism, the release of free glucose from glycogen). In addition, a pilot study will investigate the feasibility of gene therapy in the murine mdr2 knock-out mouse (a model defect in bile salt secretion analogous to progressive familial Intrahepatic cholestasis), in a paradigm whereby corrected cells could selectively repopulate the liver due to their survival advantage. In order to fully develop rAAV transduction of the liver, it may be necessary to enhance delivery to the hepatocyte, increase attachment to the cell membrane, improve internalization, nuclear entry and uncoating, maximize the transcriptional activity of vector genomes, and optimize conditions for therapeutic protein secretion. Since these disorders may ultimately require therapy in the newborn period or during child-bearing years, biological safety issues related to long-term genetic stability and biodistribution of rAAV genomes will also be addressed. These studies will be supported by the UF Vector Core Facility, for the production of high-titer, highly purified rAAV stocks, and the UF Immunology/Pathology Core. It is anticipated that by the end of this grant period, these basic improvements in rAAV-mediated delivery of genes to the liver will have improved the changes for successful gene therapy in one or more of these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEROTONIN RECEPTORS IN PHENYLKETONURIC RATS Principal Investigator & Institution: Ike, Justus O.; Biology; Fisk University Nashville, Tn 372083051 Timing: Fiscal Year 2000; Project Start 08-AUG-2000; Project End 31-JUL-2004 Summary: (adapted from applicant's abstract) Phenylketonuria (PKU) causes mental retardation in children. The underlying cause of PKU is not well understood. The critical biochemical parameters and reaction in the development of PKU is plasma phenylalanine elevation whereas tyrosine is maintained at a relatively low level. The serotonergic system has consistently been implicated in the pathogenesis of PKU. The goal of this research is to determine if changes in serotonin receptors (5-HT2C)
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contribute to the conditions associated with PKU by inducing the primary characteristics of PKU beginnings in 9-day-old rats. To achieve this goal, animal models of PKU will be used to examine a number of pharmacological parameters, including quantitation of serotonin levels by means of high performance liquid chromatography (HPLC), and radioligand binding assays that are coupled with determinations of blood phenylalanine levels. The findings of this work may contribute toward an understanding of the mechanisms involved in this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SFT FUNCTION AND REGULATION IN HEMOCHROMATOSIS Principal Investigator & Institution: Wessling-Resnick, Marianne; Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 15-SEP-1999; Project End 31-AUG-2004 Summary: Hereditary hemochromatosis is a genetic disorder that promotes increased intestinal absorption and progressive tissue deposition of iron resulting in cirrhosis of the liver, hepatic carcinoma, congestive heart failure, endocrinopathies and premature death. It is estimated that 1 in 200-to-400 people in the US are homozygous for this disease which is the most common defective genetic trait known in humans, more prevalent than cystic fibrosis, phenylketonuria and muscular dystrophy combined. Iron assimilation is a tightly regulated process that is limited to prevent harmful effects due to overload of this toxic metal and therefore a reciprocal relationship exists between body iron stores and dietary iron absorption, although the molecular basis for ion homeostasis remains unknown. Many studies of the molecular basis for hemochromatosis have evaluated the expression of factors involved in iron metabolism , including transferrin, transferrin receptor, ferritin and IRPs, but strong evidence to support their abnormal regulation in this disease is lacking. We recently identified SFT (Stimulator of Fe Transport) as a facilitator of non-transferrin-bound iron uptake. Our preliminary results demonstrate that SFT expression is down- regulated at both the mRNA and protein level in response to iron-loading. However, in the course of these studies, we made the significant discovery that SFT mRNA is 5-fold higher in liver from hemochromatosis patients despite the deposition of iron that occurs in this tissue. Thus, our working hypothesis is that malregulated expression of SFT contributes to the etiology of hemochromatosis. The proposed research will specifically evaluate our hypothesis through the following goals: 1) determination of SFT activity in iron transport by hepatocytes and intestinal enterocytes; 2) examination of interactions of interactions with the hemochromatosis protein Hfe that may modulate SFT expression and function in these cells; and 3) characterization of the mechanism that regulates SFT expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SKIN MONITORING
BIOENGINEERING:
NONINVASIVE
TRANSDERMAL
Principal Investigator & Institution: Guy, Richard H.; Adjunct Professor; University of Geneva 3 Place De L'universite Geneva, Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term objective is to develop and optimize a novel, noninvasive, iontophoretic approach for clinical monitoring via the skin. The lowlevel current density drives both charged and highly polar (yet neutral) compounds across the skin at rates much greater than passive diffusion. As the skin offers a
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uniquely accessible body surface across which information can be extracted, we hypothesize that truly noninvasive and highly sensitive devices, which exploit uniquely paired flows of at least two substances, can be developed for iontophoretic monitoring applications. The research strategy will optimize iontophoretic and sensing technology to satisfy three key criteria for success: (a) fundamental understanding of electrotransport across the skin; (b) reproducible enhancement of transdermal permeability to identify clinical monitoring opportunities via the skin; and (c) characterization and validation of simple, user-friendly devices for sample collection coupled with sensitive and specific analytical tools. The specific aims of the project are:[1] To refine understanding of electrotransport across the skin; to exploit the interactions (and independence) of solute and ion flows in the presence of an applied electric field. [2] To demonstrate that the simultaneous, 'reverse iontophoretic' extraction of a target analyte, together with an endogenous substance of essentially constant concentration within the body, can offer truly noninvasive, clinical monitoring. [3] To engineer simple, elegant, prototypical devices, of small volume (100 mu-L or less), into which reverse iontophoretically extracted samples may be efficiently collected. [4] To couple these systems to highly sensitive and specific chromatographic and electrochemical analytical tools both off-line and, eventually, on-line, in situ. Proof-of-principle targets three analytes of significant interest: glucose, phenylalanine and lithium. Furthermore, the bioengineering and analytical chemistry advances envisaged will allow broad, 'massscreening' of the substances extracted (and extractable) by reverse iontophoresis revealing additional opportunities for the approach. In summary, this project aims to evaluate iontophoretic bioengineering technology in vivo in man; specifically, applications with respect to clinical chemistry and therapeutic drug monitoring are foreseen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECTROSCOPIC STUDIES OF MONONUCLEAR NON-HEME FE ENZYMES Principal Investigator & Institution: Solomon, Edward I.; Professor; Chemistry; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-JUL-1988; Project End 30-JUN-2007 Summary: (provided by applicant): Mononuclear non-heme iron enzymes are involved in a wide range of reactions with oxygen including dioxygenation, hydroxylation, desaturation, 4-electron oxidation and H-atom abstraction. These enzymes are involved in the biosynthesis of antibiotics (penicillins, cephalosporins, vancomycin) and lactamase inhibitors (clavulanic acid), associated with genetic diseases (phenylketonuria, alkaptonuria, tyrosinemia, Refsum's disease), involved in the biosynthesis of lekotrienes and lipoxins (lipoxygenase (LO)), important in the bioremediation of pollutants including PCBs, and in the treatment of certain cancers (Bleomycin). These enzymes have been much more difficult to study than heme systems as they do not have the dominant spectroscopic features of the porphyrin and mostly activate dioxygen from a high-spin ferrous site which is a non-Kramers ion and generally not EPR active. New methods have been developed for the study of this wide class of enzymes including variable-temperature variable-field magnetic circular dichroism (VTVH MCD) of non-Kramers ions, VTVH MCD/zero field splitting/density functional theory of Kramers ions to define electronic structure of oxygen intermediates, and L-edge X-ray absorption spectroscopy (XAS) to define the covalencies of the metal orbitals. Application of these methods has thus far determined a general mechanistic strategy utilized by many members of this class of enzymes, defined the nature of the
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Phenylketonuria
highly covalent Tyr-Fe III bond in the intradiol dioxygenases, and steps in the mechanism of H-atom abstraction by LO, determined the electronic structure of activated bleomycin (involved in H-atom abstraction from DNA) and shown its reactivity to be fundamentally different from that of heme systems, and developed insight into its reaction coordinate. These studies are now focused on: 1) Extending the VTVH MCD studies to define structure/function correlations for a wide range of members of this class of enzymes and their mutants related to genetic diseases; 2) understanding O2 reaction coordinates of the ferrous sites with different co-factors to generate reactive oxygen intermediates; 3) trapping and determining the geometric and electronic structures of these oxygen intermediates and their differences in reactivity (hydroxylation, desaturation, etc.); and 4) utilizing the L-edge XAS method to define electronic structure differences between heme and non-heme iron sites which correlate with differences in O2 activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL UNDERSTANDING OF PHENYLKETONURIA (PKU) Principal Investigator & Institution: Stevens, Raymond C.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: The three-dimensional structure of the enzymes phenylalanine hydroxylase and tryptophan hydroxylase will be studied using crystallographic methods. The structures of the catalytic domain of human phenylalanine hydroxylase, catalytic domain plus tetramerization domain, catalytic domain plus regulatory domain, and catalytic domain with catecholamine inhibitors have previously been determined in my lab at various resolutions (1.9 Angstroms to 3.0 Angstroms). The family of aromatic amino acid hydroxylases are known to be involved in inherited metabolic disorders. The enzyme phenylalanine hydroxylase is the known cause of the disease known as PKU (phenylketonuria). The enzyme normally converts the essential amino acid phenylalanine to tyrosine. Failure of the conversion results in a buildup of phenylalanine. Excessive amounts of phenylalanine are toxic to the central nervous system and causes severe problems associated with PKU. Based on the threedimensional structure of the modeled full-length enzyme, the mutations will be mapped and site- specific mutagenesis will be conducted to understand the structural basis of PKU. As a complement to the studies on phenylalanine hydroxylase, tryptophan hydroxylase will be studied as comparisons of it and phenylalanine hydroxylase may provide important insights into the mechanisms of PKU. A second goal of the research is to understand the structural basis of pterin-dependent hydroxylase catalysis. The three-dimensional structure of both enzymes will be determined in the presence of cofactors, substrates, and inhibitors in order to understand the mechanism of catalysis and role of inhibitors. The last goal is to crystallize and determine the three-dimensional structure of the intact holoenzyme. By combining the structures of the isolated domains with adequate overlap, a proposed full-length enzyme model can be assembled. However it is important to determine the three dimensional structure of the full-length enzyme in order to fully understand the complex regulatory, catalytic, and stability issues associated with this family of enzymes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE/FUNCTION OF FEEDBACK REGULATOR PROTEIN Principal Investigator & Institution: Hatakeyama, Kazuyuki; Surgery; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
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Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 30-NOV-2001 Summary: Tetrahydrobiopterin (BH4) regulates the production of nitric oxide, serotonin, dopamine and tyrosine by serving as an essential cofactor for the enzymes that produce these molecules. The long-range objectives of this research are to understand the mechanisms which regulate GTP cyclohydrolase I (GC), the first and rate-limiting enzyme in the biosynthetic pathway for BH4. Dr. Hatakeyama has focused on investigating the role of a newly identified feedback regulator protein (Frp) in the regulation of GC activity. Frp mediates feedback inhibition of GC activity by BH4. Furthermore, Frp changes the kinetic behavior of GC from sigmoidal to hyperbolic in the presence of phenylalanine, which is the substrate for the BH4-dependent enzyme phenylalanine hydroxylase. GC is a decamer showing a positive cooperativity against GTP. The current working hypothesis is that the catalytic function of GC is determined by different conformational states of the complexes between two Frp molecules (pentamer of 9.5 kDa subunit) and one GC (decamer of 25-kDa subunit) which are formed by the binding of respective effectors. The goal of the proposed research is to define the relationship among the kinetic behavior of GC activity, the effector binding to protein and the protein conformation. The P.I. has established bacterial overexpression systems for both Frp and GC and the purification procedures for each protein. The specific aims are: 1) to characterize the effects of BH4 and phenylalanine on kinetic parameters of GC and to determine the effectors which modulate the system; 2) to determine the subunit composition of the complexes by gel filtration, to examine the effector binding to the complexes by gel filtration, and to examine the effector binding to the complexes and individual proteins by equilibrium dialysis to determine the affinity, stoichiometry, and specificity of the effectors; 3) to define the gross conformational states of Frp, GC and the complexes in association with the binding of effectors by sedimentation and protease sensitivity; and 4) to determine the three-dimensional structure of Frp by crystallography. Crystals of Frp that diffract to 2.0 Angstroms have been obtained. These studies are fundamental for understanding the molecular mechanisms of allosteric regulation of GS by Frp and will provide insights into the regulation of the biosynthesis of BH4. A better understanding of the regulation of BH4 biosynthesis is expected to yield insight into the altered metabolism of BH4 reported in some types of phenylketonuria, Parkinson s disease, familial dystonia and infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “phenylketonuria” (or synonyms) into the search box. This search gives you access
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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to full-text articles. The following is a sample of items found for phenylketonuria in the PubMed Central database: •
A different approach to treatment of phenylketonuria: Phenylalanine degradation with recombinant phenylalanine ammonia lyase. by Sarkissian CN, Shao Z, Blain F, Peevers R, Su H, Heft R, Chang TM, Scriver CR.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26785
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Cerebral protein synthesis in a genetic mouse model of phenylketonuria. by Smith CB, Kang J.; 2000 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27140
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Founder Effect of a Prevalent Phenylketonuria Mutation in the Oriental Population. by Wang T, Okano Y, Eisensmith RC, Harvey ML, Lo WH, Huang S, Zeng Y, Yuan L, Furuyama J, Oura T, Sommer SS, Woo SL.; 1991 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51186
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Phenylketonuria: Old disease, new approach to treatment. by Levy HL.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33523
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with phenylketonuria, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “phenylketonuria” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for phenylketonuria (hyperlinks lead to article summaries): •
A case of co-incident phenylketonuria, pemphigus foliaceus, and tinea amiantacea treated with tetracycline and nicotinamide. Author(s): Scheinfeld N. Source: J Drugs Dermatol. 2003 April; 2(2): 202-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852375&dopt=Abstract
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A clinical investigation of 228 patients with phenylketonuria in mainland China. Author(s): Yanling Y, Qiang G, Zhixiang Z, Chunlan M, Lide W, Xiru W. Source: Southeast Asian J Trop Med Public Health. 1999; 30 Suppl 2: 58-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400786&dopt=Abstract
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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•
A different approach to breast-feeding of the infant with phenylketonuria. Author(s): van Rijn M, Bekhof J, Dijkstra T, Smit PG, Moddermam P, van Spronsen FJ. Source: European Journal of Pediatrics. 2003 May; 162(5): 323-6. Epub 2003 March 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692713&dopt=Abstract
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A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase. Author(s): Sarkissian CN, Shao Z, Blain F, Peevers R, Su H, Heft R, Chang TM, Scriver CR. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 March 2; 96(5): 2339-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10051643&dopt=Abstract
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A longitudinal study of phenylketonuria based on the data of the Budapest Screening Center. Author(s): Schuler A, Somogyi C, Toros I, Pataki L, Mete M, Kiss E, Nagy A. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S50-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828609&dopt=Abstract
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A prefrontal dysfunction model of early-treated phenylketonuria. Author(s): Welsh MC. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S87-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828618&dopt=Abstract
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A role for overdominant selection in phenylketonuria? Evidence from molecular data. Author(s): Krawczak M, Zschocke J. Source: Human Mutation. 2003 April; 21(4): 394-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655549&dopt=Abstract
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A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. Author(s): Chao HK, Hsiao KJ, Su TS. Source: Human Genetics. 2001 January; 108(1): 14-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214902&dopt=Abstract
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A structural hypothesis for BH4 responsiveness in patients with mild forms of hyperphenylalaninaemia and phenylketonuria. Author(s): Erlandsen H, Stevens RC. Source: Journal of Inherited Metabolic Disease. 2001 April; 24(2): 213-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405341&dopt=Abstract
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Acceptability of a new modular protein substitute for the dietary treatment of phenylketonuria. Author(s): Rohr FJ, Munier AW, Levy HL. Source: Journal of Inherited Metabolic Disease. 2001 November; 24(6): 623-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768582&dopt=Abstract
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Acetylcholinesterase activity and biogenic amines in phenylketonuria. Author(s): Schulpis KH, Karikas GA, Tjamouranis J, Michelakakis H, Tsakiris S. Source: Clinical Chemistry. 2002 October; 48(10): 1794-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324501&dopt=Abstract
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ACOG committee opinion. Maternal phenylketonuria. Committee on Genetics. Author(s): Committee on Genetics, American College of Obstetricians and Gynecologists, Washington, DC 20090-6920, USA. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 January; 72(1): 83-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203688&dopt=Abstract
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Adjustment and intelligence among children with phenylketonuria in Sweden. Author(s): Lundstedt G, Johansson A, Melin L, Alm J. Source: Acta Paediatrica (Oslo, Norway : 1992). 2001 October; 90(10): 1147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697426&dopt=Abstract
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Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria. Author(s): White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Source: Journal of the International Neuropsychological Society : Jins. 2002 January; 8(1): 1-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843066&dopt=Abstract
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American Academy of Pediatrics: Maternal phenylketonuria. Author(s): American Academy of Pediatrics. Committee on Genetics. Source: Pediatrics. 2001 February; 107(2): 427-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158484&dopt=Abstract
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An automated enzymatic method on the Roche COBAS MIRA S for monitoring phenylalanine in dried blood spots of patients with phenylketonuria. Author(s): Randell EW, Lehotay DC. Source: Clinical Biochemistry. 1996 April; 29(2): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8601321&dopt=Abstract
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Are tablets a practical source of protein substitute in phenylketonuria? Author(s): MacDonald A, Ferguson C, Rylance G, Morris AA, Asplin D, Hall SK, Booth IW. Source: Archives of Disease in Childhood. 2003 April; 88(4): 327-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651759&dopt=Abstract
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Asbjorn Folling and the discovery of phenylketonuria. Author(s): Christ SE. Source: Journal of the History of the Neurosciences. 2003 March; 12(1): 44-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785112&dopt=Abstract
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Assessment of adult phenylketonuria. Author(s): Cleary M, Walter JH. Source: Annals of Clinical Biochemistry. 2001 September; 38(Pt 5): 450-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587123&dopt=Abstract
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Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria. Author(s): Luciana M, Sullivan J, Nelson CA. Source: Child Development. 2001 November-December; 72(6): 1637-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768137&dopt=Abstract
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Barriers to successful dietary control among pregnant women with phenylketonuria. Author(s): Brown AS, Fernhoff PM, Waisbren SE, Frazier DM, Singh R, Rohr F, Morris JM, Kenneson A, MacDonald P, Gwinn M, Honein M, Rasmussen SA. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2002 March-April; 4(2): 84-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882785&dopt=Abstract
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Biochemical control, genetic analysis and magnetic resonance imaging in patients with phenylketonuria. Author(s): Walter JH, Tyfield LA, Holton JB, Johnson C. Source: European Journal of Pediatrics. 1993 October; 152(10): 822-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7901023&dopt=Abstract
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Biotinidase activity in patients with phenylketonuria. Author(s): Schulpis KH, Papakonstantinou E, Kalogirou S. Source: Journal of Inherited Metabolic Disease. 1995; 18(6): 750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8750615&dopt=Abstract
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Birth distribution in cystic fibrosis and phenylketonuria. Author(s): Machill G, Gedschold J, Kropf S. Source: European Journal of Pediatrics. 1990 March; 149(6): 406-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2332009&dopt=Abstract
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Birth weight and pathogenesis in phenylketonuria. Author(s): Crockett DJ, Woolf LI, McBean MS, Woolf FM, Cahalane SF. Source: The International Journal of Neuroscience. 1990 October; 54(3-4): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2265974&dopt=Abstract
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Birth weight in phenylketonuria. Author(s): Woolf LI, Crockett DJ. Source: Archives of Disease in Childhood. 1995 September; 73(3): 276. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7492180&dopt=Abstract
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Blood-brain barrier phenylalanine transport and individual vulnerability in phenylketonuria. Author(s): Moller HE, Weglage J, Wiedermann D, Ullrich K. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 1998 November; 18(11): 1184-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809507&dopt=Abstract
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Blood-brain barrier transport of amino acids in healthy controls and in patients with phenylketonuria. Author(s): Knudsen GM, Hasselbalch S, Toft PB, Christensen E, Paulson OB, Lou H. Source: Journal of Inherited Metabolic Disease. 1995; 18(6): 653-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8750601&dopt=Abstract
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Body protein in prepubertal children with phenylketonuria. Author(s): Allen JR, Baur LA, Waters DL, Humphries IR, Allen BJ, Roberts DC, Gaskin KJ. Source: European Journal of Clinical Nutrition. 1996 March; 50(3): 178-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8654332&dopt=Abstract
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Bone mineral status in children with phenylketonuria under treatment. Author(s): Al-Qadreh A, Schulpis KH, Athanasopoulou H, Mengreli C, Skarpalezou A, Voskaki I. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 November; 87(11): 1162-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9846918&dopt=Abstract
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Bone mineral status in children with phenylketonuria--relationship to nutritional intake and phenylalanine control. Author(s): McMurry MP, Chan GM, Leonard CO, Ernst SL. Source: The American Journal of Clinical Nutrition. 1992 May; 55(5): 997-1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1570811&dopt=Abstract
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Brain CT and MR findings in hyperphenylalaninemia due to dihydropteridine reductase deficiency (variant of phenylketonuria). Author(s): Sugita R, Takahashi S, Ishii K, Matsumoto K, Ishibashi T, Sakamoto K, Narisawa K. Source: Journal of Computer Assisted Tomography. 1990 September-October; 14(5): 699703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2398144&dopt=Abstract
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Brain MRI changes in phenylketonuria. Associations with dietary status. Author(s): Thompson AJ, Tillotson S, Smith I, Kendall B, Moore SG, Brenton DP. Source: Brain; a Journal of Neurology. 1993 August; 116 ( Pt 4): 811-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8353710&dopt=Abstract
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Breast-feeding in the management of the newborn with phenylketonuria: a practical approach to dietary therapy. Author(s): Greve LC, Wheeler MD, Green-Burgeson DK, Zorn EM. Source: Journal of the American Dietetic Association. 1994 March; 94(3): 305-9. Erratum In: J Am Diet Assoc 1994 July; 94(7): 716. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8120296&dopt=Abstract
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Cardiovascular defects among the progeny of mouse phenylketonuria females. Author(s): McDonald JD, Dyer CA, Gailis L, Kirby ML. Source: Pediatric Research. 1997 July; 42(1): 103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9212044&dopt=Abstract
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Care of the adult with phenylketonuria. Author(s): Koch R, Azen C, Friedman EG, Fishler K, Baumann-Frischling C, Lin T. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S90-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828619&dopt=Abstract
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Cerebral energy metabolism in phenylketonuria: findings by quantitative In vivo 31P MR spectroscopy. Author(s): Pietz J, Rupp A, Ebinger F, Rating D, Mayatepek E, Boesch C, Kreis R. Source: Pediatric Research. 2003 April; 53(4): 654-62. Epub 2003 February 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612190&dopt=Abstract
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Characterization of phenylalanine hydroxylase alleles in untreated phenylketonuria patients from Victoria, Australia: origin of alleles and haplotypes. Author(s): Ramus SJ, Treacy EP, Cotton RG. Source: American Journal of Human Genetics. 1995 May; 56(5): 1034-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7726156&dopt=Abstract
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Characterization of phenylketonuria alleles in the Italian population. Author(s): Dianzani I, Giannattasio S, de Sanctis L, Alliaudi C, Lattanzio P, Vici CD, Burlina A, Burroni M, Sebastio G, Carnevale F, et al. Source: European Journal of Human Genetics : Ejhg. 1995; 3(5): 294-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8556304&dopt=Abstract
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Clinical analysis of West syndrome associated with phenylketonuria. Author(s): Zhongshu Z, Weiming Y, Yukio F, Cheng-LNing Z, Zhixing W. Source: Brain & Development. 2001 November; 23(7): 552-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11701254&dopt=Abstract
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Cognitive development related to metabolic phenotype and mutation genotype in 25 Hungarian patients with phenylketonuria. Author(s): Schuler A, Somogyi C, Mate M, Pataki L, Toros I, Woo SL, Eisensmith RC, Fekete G. Source: Journal of Inherited Metabolic Disease. 1994; 17(3): 372. Erratum In: J Inherit Metab Dis 1994; 17(6): 651. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807958&dopt=Abstract
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Comments on behavior in early treated phenylketonuria. Author(s): Weglage J. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221748&dopt=Abstract
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Comments on diet and compliance in phenylketonuria. Author(s): Fisch RO. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S142-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221742&dopt=Abstract
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Comments on final intelligence in late treated patients with phenylketonuria. Author(s): Levy HL. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S149. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221743&dopt=Abstract
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Comments on in vivo proton magnetic resonance spectroscopy in phenylketonuria. Author(s): Kreis R. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S126-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221741&dopt=Abstract
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Comments on neuropsychological approaches to treatment policy issues in phenylketonuria. Author(s): Stemerdink NB. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S87-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221747&dopt=Abstract
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Comments on patterns of academic achievement among early treated patients with phenylketonuria. Author(s): Tiefenthaler M. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S100-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221740&dopt=Abstract
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Comments on the International Collaborative Study of Maternal Phenylketonuria: status report 1998. Author(s): Lee PJ. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S161-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221744&dopt=Abstract
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Comparison of different indices of dietary control in phenylketonuria. Author(s): Rupp A, Burgard P. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 May; 84(5): 521-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7633147&dopt=Abstract
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Comparison of epidermal keratinocytes and dermal fibroblasts as potential target cells for somatic gene therapy of phenylketonuria. Author(s): Christensen R, Guttler F, Jensen TG. Source: Molecular Genetics and Metabolism. 2002 August; 76(4): 313-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208136&dopt=Abstract
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Complete reversal of moderate/severe brain MRI abnormalities in a patient with classical phenylketonuria. Author(s): Walter JH, White F, Wraith JE, Jenkins JP, Wilson BP. Source: Journal of Inherited Metabolic Disease. 1997 July; 20(3): 367-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266357&dopt=Abstract
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Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. Author(s): Levy HL, Guldberg P, Guttler F, Hanley WB, Matalon R, Rouse BM, Trefz F, Azen C, Allred EN, de la Cruz F, Koch R. Source: Pediatric Research. 2001 May; 49(5): 636-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328945&dopt=Abstract
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Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Author(s): Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC. Source: Nature Structural Biology. 1997 December; 4(12): 995-1000. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9406548&dopt=Abstract
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Cutaneous findings in a 51-year-old man with phenylketonuria. Author(s): Belloso LM, Lowitt MH. Source: Journal of the American Academy of Dermatology. 2003 August; 49(2 Suppl Case Reports): S190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894120&dopt=Abstract
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Decreased bone mineralization in children with phenylketonuria under treatment. Author(s): Hillman L, Schlotzhauer C, Lee D, Grasela J, Witter S, Allen S, Hillman R. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S148-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828633&dopt=Abstract
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Decreased trabecular bone mineral density in patients with phenylketonuria measured by peripheral quantitative computed tomography. Author(s): Schwahn B, Mokov E, Scheidhauer K, Lettgen B, Schonau E. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 January; 87(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9510449&dopt=Abstract
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Decreasing choline signal--a marker of phenylketonuria? Author(s): Dezortova M, Hejcmanova L, Hajek M. Source: Magma (New York, N.Y.). 1996 September-December; 4(3-4): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220406&dopt=Abstract
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Deficits in memory strategy use related to prefrontal dysfunction during early development: evidence from children with phenylketonuria. Author(s): White DA, Nortz MJ, Mandernach T, Huntington K, Steiner RD. Source: Neuropsychology. 2001 April; 15(2): 221-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11324865&dopt=Abstract
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Deficits in selective and sustained attention processes in early treated children with phenylketonuria--result of impaired frontal lobe functions? Author(s): Weglage J, Pietsch M, Funders B, Koch HG, Ullrich K. Source: European Journal of Pediatrics. 1996 March; 155(3): 200-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8929728&dopt=Abstract
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Delayed onset of phenylketonuria. Author(s): Weglage J, van Teefelen-Heithoff A, Zschocke J, Zass R, Marquardt T, Koch HG. Source: European Journal of Pediatrics. 1998 February; 157(2): 171. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9504799&dopt=Abstract
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Delusional disorder in a boy with phenylketonuria and amine metabolites in the cerebrospinal fluid after treatment with neuroleptics. Author(s): Shiwach RS, Sheikha S. Source: The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine. 1998 March; 22(3): 244-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9502013&dopt=Abstract
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Dental disease indices and caries related oral microflora in children with phenylketonuria. Author(s): Lucas VS, Contreras A, Loukissa M, Roberts GJ. Source: Asdc J Dent Child. 2001 July-August; 68(4): 263-7, 229. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11862879&dopt=Abstract
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Development of corn starch-gum bread for phenylketonuria patients. Author(s): Ozboy O. Source: Die Nahrung. 2002 April; 46(2): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017998&dopt=Abstract
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Development of the phenylketonuria screening programme in Estonia. Author(s): Ounap K, Lillevali H, Metspalu A, Lipping-Sitska M. Source: Journal of Medical Screening. 1998; 5(1): 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9575455&dopt=Abstract
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Developmental neurotoxicity: do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria. Author(s): Costa LG, Guizzetti M, Burry M, Oberdoerster J. Source: Toxicology Letters. 2002 February 28; 127(1-3): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052659&dopt=Abstract
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Diet in phenylketonuria: how long? Policies under discussion. Author(s): Endres W. Source: Annals of Nutrition & Metabolism. 1998; 42(2): 63-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9625276&dopt=Abstract
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Dietary control of phenylketonuria. Author(s): Mundy H, Lilburn M, Cousins A, Lee P. Source: Lancet. 2002 December 21-28; 360(9350): 2076. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504429&dopt=Abstract
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Dietary control of phenylketonuria. Author(s): Meli C, Bianca S. Source: Lancet. 2002 December 21-28; 360(9350): 2075-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504428&dopt=Abstract
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Different phenotypic manifestations associated with identical phenylketonuria genotypes in two Spanish families. Author(s): Perez B, Desviat LR, Garcia MJ, Ugarte M. Source: Journal of Inherited Metabolic Disease. 1994; 17(3): 377-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807962&dopt=Abstract
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Different presentations of late-detected phenylketonuria in two brothers with the same R408W/R111X genotype in the PAH gene. Author(s): Gizewska M, Cabalska B, Cyrytowski L, Nowacki P, Zekanowski C, Walczak M, Jozwiak I, Koziarska D. Source: Journal of Intellectual Disability Research : Jidr. 2003 February; 47(Pt 2): 146-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542580&dopt=Abstract
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Diffusion-weighted imaging of white matter abnormalities in patients with phenylketonuria. Author(s): Phillips MD, McGraw P, Lowe MJ, Mathews VP, Hainline BE. Source: Ajnr. American Journal of Neuroradiology. 2001 September; 22(8): 1583-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559511&dopt=Abstract
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Direct detection of a major mutation responsible for phenylketonuria in the population of the Federal Republic of Germany. Author(s): Lichter-Konecki U, Schlotter M, Trefz FK, Konecki DS. Source: European Journal of Pediatrics. 1989 November; 149(2): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2591403&dopt=Abstract
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Discordant phenylketonuria phenotypes in one family: the relationship between genotype and clinical outcome is a function of multiple effects. Author(s): Tyfield LA, Zschocke J, Stephenson A, Cockburn F, Harvie A, Bidwell JL, Wood NA, Hunt LP. Source: Journal of Medical Genetics. 1995 November; 32(11): 867-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8592329&dopt=Abstract
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Does a single plasma phenylalanine predict quality of control in phenylketonuria? Author(s): MacDonald A, Rylance GW, Asplin D, Hall SK, Booth IW. Source: Archives of Disease in Childhood. 1998 February; 78(2): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579152&dopt=Abstract
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Early-treated phenylketonuria: adult neuropsychologic outcome. Author(s): Ris MD, Williams SE, Hunt MM, Berry HK, Leslie N. Source: The Journal of Pediatrics. 1994 March; 124(3): 388-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8120707&dopt=Abstract
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Editorial comment on phenylketonuria. Author(s): Zetterstrom R. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 July; 84(7): 716-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549285&dopt=Abstract
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Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria. Author(s): Pietz J, Landwehr R, Kutscha A, Schmidt H, de Sonneville L, Trefz FK. Source: The Journal of Pediatrics. 1995 December; 127(6): 936-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8523192&dopt=Abstract
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Effect of high-protein meal plus aspartame ingestion on plasma phenylalanine concentrations in obligate heterozygotes for phenylketonuria. Author(s): Curtius HC, Endres W, Blau N. Source: Metabolism: Clinical and Experimental. 1994 April; 43(4): 413-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8159095&dopt=Abstract
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Effect of L-dopa on pattern visual evoked potentials (P-100) and neuropsychological tests in untreated adult patients with phenylketonuria. Author(s): Ullrich K, Weglage J, Oberwittler C, Pietsch M, Funders B, van Eckhardstein H, Colombo JP. Source: Journal of Inherited Metabolic Disease. 1994; 17(3): 349-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807950&dopt=Abstract
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Effect of L-dopa on visual evoked potentials and neuropsychological tests in adult phenylketonuria patients. Author(s): Ullrich K, Weglage J, Oberwittler C, Pietsch M, Funders B, von Eckardstein H, Colombo JP. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S74-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828615&dopt=Abstract
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Effect of maternal blood phenylalanine level on mouse maternal phenylketonuria offspring. Author(s): Cho S, McDonald JD. Source: Molecular Genetics and Metabolism. 2001 December; 74(4): 420-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11749047&dopt=Abstract
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Effects of a low selenium state in patients with phenylketonuria. Author(s): Jochum F, Terwolbeck K, Meinhold H, Behne D, Menzel H, Lombeck I. Source: Acta Paediatrica (Oslo, Norway : 1992). 1997 July; 86(7): 775-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9240892&dopt=Abstract
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Effects of concurrent phenylalanine levels on sustained attention and calculation speed in patients treated early for phenylketonuria. Author(s): Schmidt E, Burgard P, Rupp A. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S82-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828617&dopt=Abstract
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Effects of selenium supplementation on thyroid hormone metabolism in phenylketonuria subjects on a phenylalanine restricted diet. Author(s): Calomme M, Vanderpas J, Francois B, Van Caillie-Bertrand M, Vanovervelt N, Van Hoorebeke C, Vanden Berghe D. Source: Biological Trace Element Research. 1995 January-March; 47(1-3): 349-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7779569&dopt=Abstract
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Emotional outcome of adolescents and young adults with early and continuously treated phenylketonuria. Author(s): Sullivan JE. Source: Journal of Pediatric Psychology. 2001 December; 26(8): 477-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700332&dopt=Abstract
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Evaluation of 6-year application of the enzymatic colorimetric phenylalanine assay in the setting of neonatal screening for phenylketonuria. Author(s): Schulze A, Mayatepek E, Hoffmann GF. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 March; 317(1-2): 27-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814455&dopt=Abstract
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Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria. Author(s): Silva LC, Pires RF, Coelho JC, Jardim LB, Giugliani R. Source: Clinical Genetics. 1997 April; 51(4): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9184243&dopt=Abstract
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Evidence for central nervous system glial cell plasticity in phenylketonuria. Author(s): Dyer CA, Kendler A, Philibotte T, Gardiner P, Cruz J, Levy HL. Source: Journal of Neuropathology and Experimental Neurology. 1996 July; 55(7): 795814. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965095&dopt=Abstract
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Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity. Author(s): Desviat LR, Perez B, De Lucca M, Cornejo V, Schmidt B, Ugarte M. Source: American Journal of Human Genetics. 1995 August; 57(2): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7668259&dopt=Abstract
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Examination of infants for phenylketonuria. Author(s): Indiana. Source: Indiana Code Indiana. 1979; Sections 16.8.6.1 to 16.8.6.7: Unknown. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043676&dopt=Abstract
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Executive function and psychosocial adjustment in children with early treated phenylketonuria: correlation with historical and concurrent phenylalanine levels. Author(s): Griffiths P, Tarrini M, Robinson P. Source: Journal of Intellectual Disability Research : Jidr. 1997 August; 41 ( Pt 4): 317-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9297609&dopt=Abstract
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Executive function in treated phenylketonuria as measured by the one-back and twoback versions of the continuous performance test. Author(s): Griffiths P, Campbell R, Robinson P. Source: Journal of Inherited Metabolic Disease. 1998 April; 21(2): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9584263&dopt=Abstract
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Expression of human phenylalanine hydroxylase activity in T lymphocytes of classical phenylketonuria children by retroviral-mediated gene transfer. Author(s): Lin CM, Tan Y, Lee YM, Chang CC, Hsiao KJ. Source: Journal of Inherited Metabolic Disease. 1997 November; 20(6): 742-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9427141&dopt=Abstract
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Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria. Author(s): Lidsky AS, Ledley FD, DiLella AG, Kwok SC, Daiger SP, Robson KJ, Woo SL. Source: American Journal of Human Genetics. 1985 July; 37(4): 619-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556654&dopt=Abstract
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Factors affecting cognitive, motor, behavioral and executive functioning in children with phenylketonuria. Author(s): Arnold GL, Kramer BM, Kirby RS, Plumeau PB, Blakely EM, Sanger Cregan LS, Davidson PW. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 May; 87(5): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9641741&dopt=Abstract
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Factors affecting the variation in plasma phenylalanine in patients with phenylketonuria on diet. Author(s): MacDonald A, Rylance G, Hall SK, Asplin D, Booth IW. Source: Archives of Disease in Childhood. 1996 May; 74(5): 412-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8669956&dopt=Abstract
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Failure to detect phenylketonuria. Author(s): Verkerk PH, van der Meer SB. Source: European Journal of Pediatrics. 1995 February; 154(2): 163. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7720748&dopt=Abstract
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False positive result of Guthrie inhibition assay for histidinaemia in a patient with phenylketonuria. Author(s): Sakura N, Kawahara N, Tanabe M, Miura T, Kanamori K, Yoshino A, Ohtake H. Source: Journal of Inherited Metabolic Disease. 1990; 13(2): 234-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2116557&dopt=Abstract
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Fatty acid metabolism in phenylketonuria. Author(s): Giovannini M, Agostoni C, Biasucci G, Rottoli A, Luotti D, Trojan S, Riva E. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S132-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828629&dopt=Abstract
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Fatty acid supplementation in a case of maternal phenylketonuria. Author(s): Giovannini M, Biasucci G, Agostoni C, Bellu R, Riva E. Source: Journal of Inherited Metabolic Disease. 1994; 17(5): 630-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7837774&dopt=Abstract
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Fetal damage due to maternal phenylketonuria: effects of dietary treatment and maternal phenylalanine concentrations around the time of conception (an interim report from the UK Phenylketonuria Register). Author(s): Smith I, Glossop J, Beasley M. Source: Journal of Inherited Metabolic Disease. 1990; 13(4): 651-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2122128&dopt=Abstract
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Fish oil supplementation improves visual evoked potentials in children with phenylketonuria. Author(s): Beblo S, Reinhardt H, Muntau AC, Mueller-Felber W, Roscher AA, Koletzko B. Source: Neurology. 2001 October 23; 57(8): 1488-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673596&dopt=Abstract
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Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria. Author(s): Benit P, Rey F, Melle D, Munnich A, Rey J. Source: Human Mutation. 1994; 4(3): 229-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7833954&dopt=Abstract
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Fluorometric method for phenylalanine microplate assay adapted for phenylketonuria screening. Author(s): Gerasimova NS, Steklova IV, Tuuminen T. Source: Clinical Chemistry. 1989 October; 35(10): 2112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2791280&dopt=Abstract
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Focus on the molecular genetics of phenylketonuria. Author(s): Zschocke J. Source: Human Mutation. 2003 April; 21(4): 331-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655542&dopt=Abstract
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Follow up of fetal outcome in cases of maternal phenylketonuria in Northern Ireland. Author(s): Magee AC, Ryan K, Moore A, Trimble ER. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 September; 87(2): F141-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193524&dopt=Abstract
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Founder effect of a prevalent phenylketonuria mutation in the Oriental population. Author(s): Wang T, Okano Y, Eisensmith RC, Harvey ML, Lo WH, Huang SZ, Zeng YT, Yuan LF, Furuyama JI, Oura T, et al. Source: Proceedings of the National Academy of Sciences of the United States of America. 1991 March 15; 88(6): 2146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2006152&dopt=Abstract
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Fractures and phenylketonuria. Author(s): Greeves LG, Carson DJ, Magee A, Patterson CC. Source: Acta Paediatrica (Oslo, Norway : 1992). 1997 March; 86(3): 242-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9099311&dopt=Abstract
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Frequencies of the most common mutations responsible for phenylketonuria in Poland. Author(s): Zekanowski C, Nowacka M, Zgulska M, Horst J, Cabalska B, Mazurczak T. Source: Molecular and Cellular Probes. 1994 August; 8(4): 323-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7870074&dopt=Abstract
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Frequency of 12 mutations in 114 children with phenylketonuria in the Midwest region of the USA. Author(s): Kaul R, Matalon R, Allen R, Fisch RO, Michals K, Petrosky A, Sullivan D. Source: Journal of Inherited Metabolic Disease. 1994; 17(3): 356-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807952&dopt=Abstract
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Frequency of the IVS-10nt546 mutation in 44 Turkish phenylketonuria patients. Author(s): Ozguc M, Ozalp I, Coskun T, Yilmaz E, Erdem H, Ayter S. Source: Turk J Pediatr. 1993 January-March; 35(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7901929&dopt=Abstract
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Gene therapy for phenylketonuria. Author(s): Eisensmith RC, Woo SL. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S16-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828602&dopt=Abstract
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Gene therapy for phenylketonuria. Author(s): Eisensmith RC, Woo SL. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. 1994 December; 407: 124-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7766948&dopt=Abstract
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Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer. Author(s): Fang B, Eisensmith RC, Li XH, Finegold MJ, Shedlovsky A, Dove W, Woo SL. Source: Gene Therapy. 1994 July; 1(4): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7584088&dopt=Abstract
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Genetic analysis of treated and untreated phenylketonuria in one family. Author(s): Tyfield LA, Meredith AL, Osborn MJ, Primavesi R, Chambers TL, Holton JB, Harper PS. Source: Journal of Medical Genetics. 1990 September; 27(9): 564-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1977916&dopt=Abstract
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Genetic and neurological evaluation of untreated and late-treated patients with phenylketonuria. Author(s): Ozalp I, Coskun T, Ozguc M, Tokatli A, Yalaz K, Vanli L, Yilmaz E, Erbay A. Source: Journal of Inherited Metabolic Disease. 1994; 17(3): 371. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807957&dopt=Abstract
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Genetic background of clinical homogeneity of phenylketonuria in Poland. Author(s): Jaruzelska J, Matuszak R, Lyonnet S, Rey F, Rey J, Filipowicz J, Borski K, Munnich A. Source: Journal of Medical Genetics. 1993 March; 30(3): 232-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8097262&dopt=Abstract
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Genetic diversity within the R408W phenylketonuria mutation lineages in Europe. Author(s): Tighe O, Dunican D, O'Neill C, Bertorelle G, Beattie D, Graham C, Zschocke J, Cali F, Romano V, Hrabincova E, Kozak L, Nechyporenko M, Livshits L, Guldberg P, Jurkowska M, Zekanowski C, Perez B, Desviat LR, Ugarte M, Kucinskas V, Knappskog P, Treacy E, Naughten E, Tyfield L, Byck S, Scriver CR, Mayne PD, Croke DT. Source: Human Mutation. 2003 April; 21(4): 387-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655548&dopt=Abstract
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Genetic history of phenylketonuria mutations in Italy. Author(s): Dianzani I, Giannattasio S, de Sanctis L, Marra E, Ponzone A, Camaschella C, Piazza A. Source: American Journal of Human Genetics. 1994 October; 55(4): 851-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7942862&dopt=Abstract
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Genetic implications for newborn screening for phenylketonuria. Author(s): de la Cruz F, Koch R. Source: Clin Perinatol. 2001 June; 28(2): 419-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499062&dopt=Abstract
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Genetic study of phenylketonuria. Author(s): Hashishe MM. Source: J Egypt Public Health Assoc. 1992; 67(3-4): 443-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1296972&dopt=Abstract
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Genotype-phenotype correlations in phenylketonuria. Author(s): Trefz FK, Burgard P, Konig T, Goebel-Schreiner B, Lichter-Konecki U, Konecki D, Schmidt E, Schmidt H, Bickel H. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1993 July 30; 217(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8222278&dopt=Abstract
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German Maternal Phenylketonuria Study. Author(s): Cipcic-Schmidt S, Trefz FK, Funders B, Seidlitz G, Ullrich K. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S173-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828639&dopt=Abstract
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Gestational carrier--a reproductive haven for offspring of mothers with phenylketonuria (PKU): an alternative therapy for maternal PKU. Author(s): Fisch RO, Tagatz G, Stassart JP. Source: Journal of Inherited Metabolic Disease. 1993; 16(6): 957-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8127071&dopt=Abstract
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Gliotic, nodular lesions in phenylketonuria: MR imaging findings. Author(s): Sener RN. Source: Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. 1996 September-October; 20(5): 399-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9007368&dopt=Abstract
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Golgi-Kopsch silver study of the brain of a patient with untreated phenylketonuria, seizures, and cortical blindness. Author(s): Kornguth S, Gilbert-Barness E, Langer E, Hegstrand L. Source: American Journal of Medical Genetics. 1992 November 1; 44(4): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1442885&dopt=Abstract
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Growth and skeletal maturation in children with phenylketonuria. Author(s): Schaefer F, Burgard P, Batzler U, Rupp A, Schmidt H, Gilli G, Bickel H, Bremer HJ. Source: Acta Paediatrica (Oslo, Norway : 1992). 1994 May; 83(5): 534-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8086734&dopt=Abstract
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Growth in patients with phenylketonuria. Author(s): Weglage J, Bramswig JH, Koch HG, Karassalidou S, Ullrich K. Source: European Journal of Pediatrics. 1994 July; 153(7): 537-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7957375&dopt=Abstract
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Gypsy phenylketonuria: a point mutation of the phenylalanine hydroxylase gene in Gypsy families from Slovakia. Author(s): Kalanin J, Takarada Y, Kagawa S, Yamashita K, Ohtsuka N, Matsuoka A. Source: American Journal of Medical Genetics. 1994 January 15; 49(2): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8116675&dopt=Abstract
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Haplotype analysis of phenylalanine hydroxylase alleles in polish families with phenylketonuria. Author(s): Jaruzelska J, Borski K, Riess O, Blin N, Slomski R. Source: Acta Biochimica Polonica. 1989; 36(3-4): 323-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2577230&dopt=Abstract
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Haplotype analysis of the phenylalanine hydroxylase gene in Turkish phenylketonuria families. Author(s): Stuhrmann M, Riess O, Monch E, Kurdoglu G. Source: Clinical Genetics. 1989 August; 36(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2569949&dopt=Abstract
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Hereditary fructose intolerance in a patient with phenylketonuria. Author(s): Coskun T, Ozalp I, Tekinalp G. Source: Turk J Pediatr. 1991 July-September; 33(3): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1792698&dopt=Abstract
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Heterogeneity of mutations in Bulgarian phenylketonuria haplotype 1 and 4 alleles. Author(s): Kalaydjieva L, Dworniczak B, Kremensky I, Koprivarova K, Radeva B, Milusheva R, Aulehla-Scholz C, Horst J. Source: Clinical Genetics. 1992 March; 41(3): 123-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1563085&dopt=Abstract
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Heterogeneity of phenylketonuria at the clinical, protein and DNA levels. Author(s): Cotton RG. Source: Journal of Inherited Metabolic Disease. 1990; 13(5): 739-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2246858&dopt=Abstract
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Heterogeneity of phenylketonuria in Belgium at the genotype-phenotype level. Author(s): Francois B, Vandevyver C, Verelst P, Phillippaert L, Raus J. Source: Journal of Inherited Metabolic Disease. 1994; 17(3): 369-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807956&dopt=Abstract
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Heterozygous carriers of classical phenylketonuria in a sample of the Turkish population: detection by a spectrofluorimetric method. Author(s): Guneral F, Ozalp I, Tatlidil H. Source: Journal of Inherited Metabolic Disease. 1991; 14(5): 741-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1843186&dopt=Abstract
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Historical perspective: tyrosine and maternal phenylketonuria, welcome news. Author(s): Bessman SP. Source: The American Journal of Clinical Nutrition. 1998 March; 67(3): 357-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9497176&dopt=Abstract
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Homocysteine and other vascular risk factors in patients with phenylketonuria on a diet. Author(s): Schulpis KH, Karikas GA, Papakonstantinou E. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(8): 905-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222713&dopt=Abstract
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How practical are recommendations for dietary control in phenylketonuria? Author(s): Walter JH, White FJ, Hall SK, MacDonald A, Rylance G, Boneh A, Francis DE, Shortland GJ, Schmidt M, Vail A. Source: Lancet. 2002 July 6; 360(9326): 55-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114043&dopt=Abstract
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Immune function in children with classical phenylketonuria and tetrahydrobiopterin deficiencies. Author(s): Karagoz T, Coskun T, Ozalp I, Ozkaya E, Ersoy F. Source: Indian Pediatrics. 2003 September; 40(9): 822-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530542&dopt=Abstract
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Immune status of children with phenylketonuria. Author(s): Gropper SS, Chaung HC, Bernstein LE, Trahms C, Rarback S, Weese SJ. Source: Journal of the American College of Nutrition. 1995 June; 14(3): 264-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8586776&dopt=Abstract
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Impact of medical genetics concerning phenylketonuria: accomplishments, status and practical future possibilities. Author(s): Guttler F. Source: Clinical Genetics. 1989 November; 36(5): 333-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2598484&dopt=Abstract
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Impaired arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acid synthesis by phenylalanine metabolites as etiological factors in the neuropathology of phenylketonuria. Author(s): Infante JP, Huszagh VA. Source: Molecular Genetics and Metabolism. 2001 March; 72(3): 185-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243724&dopt=Abstract
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Impaired sensitivity to visual contrast in children treated early and continuously for phenylketonuria. Author(s): Diamond A, Herzberg C. Source: Brain; a Journal of Neurology. 1996 April; 119 ( Pt 2): 523-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8800946&dopt=Abstract
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Impairment of callosal and corticospinal system function in adolescents with earlytreated phenylketonuria: a transcranial magnetic stimulation study. Author(s): Roricht S, Meyer BU, Irlbacher K, Ludolph AC. Source: Journal of Neurology. 1999 January; 246(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9987710&dopt=Abstract
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In vivo disposal of phenylalanine in phenylketonuria: a study of two siblings. Author(s): Treacy E, Pitt JJ, Seller K, Thompson GN, Ramus S, Cotton RG. Source: Journal of Inherited Metabolic Disease. 1996; 19(5): 595-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8892014&dopt=Abstract
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In vivo effects of high phenylalanine blood levels on Na+,K+-ATPase, Mg2+-ATPase activities and biogenic amine concentrations in phenylketonuria. Author(s): Schulpis KH, Tjamouranis J, Karikas GA, Michelakakis H, Tsakiris S. Source: Clinical Biochemistry. 2002 June; 35(4): 281-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135689&dopt=Abstract
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Incidence of phenylketonuria in Iran estimated from consanguineous marriages. Author(s): Koochmeshgi J, Bagheri A, Hosseini-Mazinani SM. Source: Journal of Inherited Metabolic Disease. 2002 February; 25(1): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999985&dopt=Abstract
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Incidence of phenylketonuria in Israel. Author(s): Merrick J, Schwarz G, Sela BA. Source: Isr Med Assoc J. 2000 October; 2(10): 801-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344743&dopt=Abstract
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Individual blood-brain barrier phenylalanine transport determines clinical outcome in phenylketonuria. Author(s): Weglage J, Wiedermann D, Denecke J, Feldmann R, Koch HG, Ullrich K, Harms E, Moller HE. Source: Annals of Neurology. 2001 October; 50(4): 463-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601498&dopt=Abstract
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Individual blood-brain barrier phenylalanine transport in siblings with classical phenylketonuria. Author(s): Weglage J, Wiedermann D, Denecke J, Feldmann R, Koch HG, Ullrich K, Moller HE. Source: Journal of Inherited Metabolic Disease. 2002 October; 25(6): 431-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555936&dopt=Abstract
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Influence of knowledge of the disease on metabolic control in phenylketonuria. Author(s): Bekhof J, van Spronsen FJ, Crone MR, van Rijn M, Oudshoorn CG, Verkerk PH. Source: European Journal of Pediatrics. 2003 June; 162(6): 440-2. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684903&dopt=Abstract
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Inhibition of prepotent responding and attentional flexibility in treated phenylketonuria. Author(s): Huijbregts S, de Sonneville L, Licht R, Sergeant J, van Spronsen F. Source: Developmental Neuropsychology. 2002; 22(2): 481-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537335&dopt=Abstract
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Intake and blood levels of fatty acids in treated patients with phenylketonuria. Author(s): Acosta PB, Yannicelli S, Singh R, Eisas LJ 2nd, Kennedy MJ, Bernstein L, Rohr F, Trahms C, Koch R, Breck J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 September; 33(3): 2539. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593118&dopt=Abstract
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Intake of major nutrients by women in the Maternal Phenylketonuria (MPKU) Study and effects on plasma phenylalanine concentrations. Author(s): Acosta PB, Matalon K, Castiglioni L, Rohr FJ, Wenz E, Austin V, Azen C. Source: The American Journal of Clinical Nutrition. 2001 April; 73(4): 792-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11273855&dopt=Abstract
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Intellectual and school performance in adolescents with phenylketonuria according to their dietary compliance. The Czech-Slovak Collaborative Study. Author(s): Zeman J, Pijackova A, Behulova J, Urge O, Saligova, Hyanek J. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S56-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828611&dopt=Abstract
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Intellectual development of the patients of the German Collaborative Study of children treated for phenylketonuria. Author(s): Burgard P, Schmidt E, Rupp A, Schneider W, Bremer HJ. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S33-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828606&dopt=Abstract
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Intelligence and professional career in young adults treated early for phenylketonuria. Author(s): Schmidt H, Burgard P, Pietz J, Rupp A. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S97-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828621&dopt=Abstract
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Iron and protein sufficiency and red cell indices in phenylketonuria. Author(s): Arnold GL, Kirby R, Preston C, Blakely E. Source: Journal of the American College of Nutrition. 2001 February; 20(1): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293470&dopt=Abstract
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Keeping phenylketonuria under control. Author(s): Gibbings B. Source: Mod Midwife. 1994 October; 4(10): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7874527&dopt=Abstract
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Large daily fluctuations in plasma tyrosine in treated patients with phenylketonuria. Author(s): van Spronsen FJ, van Dijk T, Smit GP, van Rijn M, Reijngoud DJ, Berger R, Heymans HS. Source: The American Journal of Clinical Nutrition. 1996 December; 64(6): 916-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8942417&dopt=Abstract
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Large deletions in the phenylalanine hydroxylase gene as a cause of phenylketonuria in India. Author(s): Guldberg P, Henriksen KF, Mammen KC, Levy HL, Guttler F. Source: Journal of Inherited Metabolic Disease. 1997 November; 20(6): 845-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9427161&dopt=Abstract
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Late diagnosis of phenylketonuria in a Bedouin mother. Author(s): Usha R, Uma R, Farag TI, Girish Y, al-Ghanim MM, al-Najdi K, al-Awadi SA, el-Badramany MH. Source: American Journal of Medical Genetics. 1992 December 1; 44(6): 713-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1481837&dopt=Abstract
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Late effects of phenylketonuria. Author(s): Walter JH. Source: Archives of Disease in Childhood. 1995 December; 73(6): 485-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8546499&dopt=Abstract
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Late-treated phenylketonuria mimicking Angelman syndrome. Author(s): Dan B, Christiaens F, Mewasingh LD, De Laet C, Goyens P. Source: American Journal of Medical Genetics. 2001 December 15; 104(4): 345-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754074&dopt=Abstract
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Life-long treatment for phenylketonuria. Author(s): Oura T. Source: Southeast Asian J Trop Med Public Health. 1999; 30 Suppl 2: 61-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400787&dopt=Abstract
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Linkage disequilibrium between phenylketonuria and RFLP haplotype 1 at the phenylalanine hydroxylase locus in Portugal. Author(s): Caillaud C, Vilarinho L, Vilarinho A, Rey F, Berthelon M, Santos R, Lyonnet S, Briard ML, Osorio RV, Rey J, et al. Source: Human Genetics. 1992 April; 89(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1349566&dopt=Abstract
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Lipid status and fatty acid metabolism in phenylketonuria. Author(s): Giovannini M, Biasucci G, Agostoni C, Luotti D, Riva E. Source: Journal of Inherited Metabolic Disease. 1995; 18(3): 265-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7474891&dopt=Abstract
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Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet. Author(s): Moseley K, Koch R, Moser AB. Source: Journal of Inherited Metabolic Disease. 2002 February; 25(1): 56-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999981&dopt=Abstract
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Lipophilic antioxidants in patients with phenylketonuria. Author(s): Colome C, Artuch R, Vilaseca MA, Sierra C, Brandi N, Lambruschini N, Cambra FJ, Campistol J. Source: The American Journal of Clinical Nutrition. 2003 January; 77(1): 185-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499340&dopt=Abstract
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Localized brain proton NMR spectroscopy in young adult phenylketonuria patients. Author(s): Johannik K, Van Hecke P, Francois B, Marchal G, Smet MH, Jaeken J, Breysem L, Wilms G, Baert AL. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 1994 January; 31(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8121269&dopt=Abstract
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Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. Author(s): Poge AP, Baumann K, Muller E, Leichsenring M, Schmidt H, Bremer HJ. Source: Journal of Inherited Metabolic Disease. 1998 June; 21(4): 373-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700594&dopt=Abstract
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Longitudinal study on early diagnosis and treatment of phenylketonuria in Poland. Author(s): Cabalska MB, Nowaczewska I, Sendecka E, Zorska K. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828610&dopt=Abstract
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Long-term follow up of patients with classical phenylketonuria after diet relaxation at 5 years of age. The Paris Study. Author(s): Rey F, Abadie V, Plainguet F, Rey J. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828607&dopt=Abstract
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Long-term follow-up of children with classical phenylketonuria after diet discontinuation: a review. Author(s): Potocnik U, Widhalm K. Source: Journal of the American College of Nutrition. 1994 June; 13(3): 232-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8077570&dopt=Abstract
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Long-term follow-up of patients treated for phenylketonuria (PKU). Results from the Prague PKU Center. Author(s): Cechak P, Hejcmanova L, Rupp A. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828612&dopt=Abstract
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Low iron stores in infants and children with treated phenylketonuria: a population at risk for iron-deficiency anaemia and associated cognitive deficits. Author(s): Bodley JL, Austin VJ, Hanley WB, Clarke JT, Zlotkin S. Source: European Journal of Pediatrics. 1993 February; 152(2): 140-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8444222&dopt=Abstract
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L-tryptophan in maternal phenylketonuria. Author(s): Wapnir RA. Source: The American Journal of Clinical Nutrition. 1998 December; 68(6): 1306-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9846865&dopt=Abstract
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Magnetic resonance imaging of the brain in adolescents with phenylketonuria and in one case of 6-pyruvoyl tetrahydropteridine synthase deficiency. Author(s): Pietz J, Meyding-Lamade UK, Schmidt H. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828614&dopt=Abstract
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Maternal phenylketonuria and hyperphenylalaninemia: implications for medical practice in the United States. Author(s): Luder AS, Greene CL. Source: American Journal of Obstetrics and Gynecology. 1989 November; 161(5): 1102-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2686439&dopt=Abstract
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Maternal phenylketonuria in two Sicilian families identified by maternal blood phenylalanine level screening and identification of a new phenylalanine hydroxylase gene mutation (P407L) Author(s): Corsello G, Bosco P, Cali F, Greco D, Cammarata M, Ciaccio M, Piccione M, Romano V. Source: European Journal of Pediatrics. 1999 January; 158(1): 83-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9950317&dopt=Abstract
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Maternal phenylketonuria pregnancy outcome: a preliminary report of facial dysmorphology and major malformations. Author(s): Rouse B, Lockhart L, Matalon R, Azen C, Koch R, Hanley W, Levy H, dela Cruz F, Friedman E. Source: Journal of Inherited Metabolic Disease. 1990; 13(3): 289-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2122088&dopt=Abstract
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Maternal phenylketonuria: a metabolic teratogen. Author(s): Levy HL, Ghavami M. Source: Teratology. 1996 March; 53(3): 176-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8761885&dopt=Abstract
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Maternal phenylketonuria: magnetic resonance imaging of the brain in offspring. Author(s): Levy HL, Lobbregt D, Barnes PD, Poussaint TY. Source: The Journal of Pediatrics. 1996 June; 128(6): 770-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8648535&dopt=Abstract
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Maternal phenylketonuria--the Irish experience. Author(s): Naughten E, Saul IP. Source: Journal of Inherited Metabolic Disease. 1990; 13(4): 658-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2122129&dopt=Abstract
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Modelling the phenylalanine blood level response during treatment of phenylketonuria. Author(s): Langenbeck U, Zschocke J, Wendel U, Honig V. Source: Journal of Inherited Metabolic Disease. 2001 December; 24(8): 805-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916313&dopt=Abstract
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Molecular analysis of phenylketonuria (PKU) in newborns from Texas. Author(s): Yang Y, Drummond-Borg M, Garcia-Heras J. Source: Human Mutation. 2001 June; 17(6): 523. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385716&dopt=Abstract
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Molecular basis of phenylketonuria and a correlation between genotype and phenotype in a heterogeneous southeastern US population. Author(s): Eisensmith RC, Martinez DR, Kuzmin AI, Goltsov AA, Brown A, Singh R, Elsas LJ II, Woo SL. Source: Pediatrics. 1996 April; 97(4): 512-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8632937&dopt=Abstract
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Molecular basis of phenylketonuria in Cuba. Author(s): Desviat LR, Perez B, Gutierrez E, Sanchez A, Barrios B, Ugarte M. Source: Human Mutation. 2001 September; 18(3): 252. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11524738&dopt=Abstract
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Molecular characterization of phenylketonuria in Japanese patients. Author(s): Okano Y, Asada M, Kang Y, Nishi Y, Hase Y, Oura T, Isshiki G. Source: Human Genetics. 1998 November; 103(5): 613-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9860305&dopt=Abstract
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Molecular genetics of phenylketonuria in Orientals: linkage disequilibrium between a termination mutation and haplotype 4 of the phenylalanine hydroxylase gene. Author(s): Wang T, Okano Y, Eisensmith R, Huang SZ, Zeng YT, Lo WH, Woo SL. Source: American Journal of Human Genetics. 1989 November; 45(5): 675-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2816939&dopt=Abstract
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Molecular genetics of phenylketonuria: from molecular anthropology to gene therapy. Author(s): Eisensmith RC, Woo SL. Source: Adv Genet. 1995; 32: 199-271. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7741023&dopt=Abstract
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Molecular studies and prenatal diagnosis of phenylketonuria in Chinese patients. Author(s): Fan GX, Qing LX, Jun Y, Mei Z. Source: Southeast Asian J Trop Med Public Health. 1999; 30 Suppl 2: 63-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400788&dopt=Abstract
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Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria. Author(s): Huijbregts SC, De Sonneville LM, Van Spronsen FJ, Berends IE, Licht R, Verkerk PH, Sergeant JA. Source: Neuropsychology. 2003 July; 17(3): 369-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959503&dopt=Abstract
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MR in phenylketonuria-related brain lesions. Author(s): Dezortova M, Hajek M, Tintera J, Hejcmanova L, Sykova E. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2001 September; 42(5): 459-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552882&dopt=Abstract
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Mutation analysis of phenylketonuria in Yamagata prefecture, Japan. Author(s): Kimura T, Ikeda H, Akaba K, Guldberg P, Guttler F, Maki K, Aikawa S, Hayasaka K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 February; 43(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207989&dopt=Abstract
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Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia. Author(s): Kibayashi M, Nagao M, Chiba S. Source: Journal of Human Genetics. 1998; 43(4): 231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9852673&dopt=Abstract
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Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria. Author(s): Acosta A, Silva W Jr, Carvalho T, Gomes M, Zago M. Source: Human Mutation. 2001 February; 17(2): 122-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180595&dopt=Abstract
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Nasomaxillary hypoplasia and severe orofacial clefting in a child of a mother with phenylketonuria. Author(s): Sweeney E, Fryer A. Source: Journal of Inherited Metabolic Disease. 2002 February; 25(1): 77-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999984&dopt=Abstract
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National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management, October 16-18, 2000. Author(s): National Institutes of Health Consensus Development Panel. Source: Pediatrics. 2001 October; 108(4): 972-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11581453&dopt=Abstract
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Neonatal neurological assessment of offspring in maternal phenylketonuria. Author(s): Waisbren SE, Chang P, Levy HL, Shifrin H, Allred E, Azen C, de la Cruz F, Hanley W, Koch R, Matalon R, Rouse B. Source: Journal of Inherited Metabolic Disease. 1998 February; 21(1): 39-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9501268&dopt=Abstract
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Neonatal screening and long-term follow-up of phenylketonuria: the French database. Author(s): Abadie V, Berthelot J, Feillet F, Maurin N, Mercier A, de Baulny HO, de Parscau L. Source: Early Human Development. 2001 December; 65(2): 149-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11641035&dopt=Abstract
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Neonatal screening for congenital hypothyroidism and phenylketonuria at Siriraj Hospital, Mahidol University, Bangkok, Thailand--a pilot study. Author(s): Wasant P, Liammongkolkul S, Srisawat C. Source: Southeast Asian J Trop Med Public Health. 1999; 30 Suppl 2: 33-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400774&dopt=Abstract
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Neonatal screening of phenylketonuria and congenital hypothyroidism in China. Author(s): Fan GX, Jun Y, Rui-guan C. Source: Southeast Asian J Trop Med Public Health. 1999; 30 Suppl 2: 17-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400761&dopt=Abstract
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Neurological aspects of adult phenylketonuria. Author(s): Pietz J. Source: Current Opinion in Neurology. 1998 December; 11(6): 679-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870137&dopt=Abstract
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Neurological findings in early treated phenylketonuria. Author(s): Weglage J, Pietsch M, Funders B, Koch HG, Ullrich K. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 April; 84(4): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7795351&dopt=Abstract
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Neurological outcome in adult patients with early-treated phenylketonuria. Author(s): Pietz J, Dunckelmann R, Rupp A, Rating D, Meinck HM, Schmidt H, Bremer HJ. Source: European Journal of Pediatrics. 1998 October; 157(10): 824-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9809823&dopt=Abstract
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Neuropsychological outcome of experimental manipulation of phenylalanine intake in treated phenylketonuria. Author(s): Griffiths P, Ward N, Harvie A, Cockburn F. Source: Journal of Inherited Metabolic Disease. 1998 February; 21(1): 29-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9501267&dopt=Abstract
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Neurotransmitter positron emission tomographic-studies in adults with phenylketonuria, a pilot study. Author(s): Paans AM, Pruim J, Smit GP, Visser G, Willemsen AT, Ullrich K. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S78-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828616&dopt=Abstract
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Newborn mass screening and molecular genetics of phenylketonuria in east Asia. Author(s): Okano Y, Isshiki G. Source: Southeast Asian J Trop Med Public Health. 1995; 26 Suppl 1: 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8629090&dopt=Abstract
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NIH consensus statement on phenylketonuria. Author(s): Hellekson KL; National Institutes of Health. Source: American Family Physician. 2001 April 1; 63(7): 1430-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310654&dopt=Abstract
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No evidence for individual blood-brain barrier phenylalanine transport to influence clinical outcome in typical phenylketonuria patients. Author(s): Pietz J, Rupp A, Burgard P, Boesch C, Kreis R. Source: Annals of Neurology. 2002 September; 52(3): 382-3; Author Reply 383-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205657&dopt=Abstract
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No fine motor deficits in patients with untreated non-phenylketonuria hyperphenylalaninaemia. Author(s): Weglage J, Ullrich K, Pietsch M, Funders B, Zass R, Koch HG. Source: Acta Paediatrica (Oslo, Norway : 1992). 1996 March; 85(3): 320-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8695989&dopt=Abstract
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Novel mutation in exon 7 of phenylalanine hydroxylase gene in a Chinese patient with phenylketonuria. Author(s): Takarada Y, Yamashita K, Ohtsuka N, Kagawa S, Matsuoka A. Source: Clinical Chemistry. 1993 November; 39(11 Pt 1): 2357. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8222247&dopt=Abstract
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Nutrient intake and congenital heart defects in maternal phenylketonuria. Author(s): Michals-Matalon K, Platt LD, Acosta P P, Azen C, Walla CA. Source: American Journal of Obstetrics and Gynecology. 2002 August; 187(2): 441-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193940&dopt=Abstract
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Nutrient intake and growth of infants with phenylketonuria undergoing therapy. Author(s): Acosta PB, Yannicelli S, Marriage B, Mantia C, Gaffield B, Porterfield M, Hunt M, McMaster N, Bernstein L, Parton P, Kuehn M, Lewis V. Source: Journal of Pediatric Gastroenterology and Nutrition. 1998 September; 27(3): 28791. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9740198&dopt=Abstract
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Nutrient intakes and physical growth of children with phenylketonuria undergoing nutrition therapy. Author(s): Acosta PB, Yannicelli S, Singh R, Mofidi S, Steiner R, DeVincentis E, Jurecki E, Bernstein L, Gleason S, Chetty M, Rouse B. Source: Journal of the American Dietetic Association. 2003 September; 103(9): 1167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963945&dopt=Abstract
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Nutrition support of maternal phenylketonuria. Author(s): Acosta PB. Source: Semin Perinatol. 1995 June; 19(3): 182-90. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7570070&dopt=Abstract
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Osteopenia and phenylketonuria. Author(s): Carson DJ, Greeves LG, Sweeney LE, Crone MD. Source: Pediatric Radiology. 1990; 20(8): 598-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2251005&dopt=Abstract
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Outcome implications of the International Maternal Phenylketonuria Collaborative Study (MPKUCS): 1994. Author(s): Koch R, Levy H, Hanley W, Matalon R, Rouse B, Trefz F, de la Cruz F. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S162-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828636&dopt=Abstract
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Outcome of early detected and early treated phenylketonuria patients. Author(s): Rylance G. Source: Postgraduate Medical Journal. 1989; 65 Suppl 2: S7-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2622815&dopt=Abstract
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Outcome of treatment in young adults with phenylketonuria detected by routine neonatal screening between 1964 and 1971. Author(s): Beasley MG, Costello PM, Smith I. Source: The Quarterly Journal of Medicine. 1994 March; 87(3): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8208903&dopt=Abstract
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Oxidative stress induced by phenylketonuria in the rat: Prevention by melatonin, vitamin E, and vitamin C. Author(s): Martinez-Cruz F, Pozo D, Osuna C, Espinar A, Marchante C, Guerrero JM. Source: Journal of Neuroscience Research. 2002 August 15; 69(4): 550-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210848&dopt=Abstract
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Partial characterization and three-dimensional-structural localization of eight mutations in exon 7 of the human phenylalanine hydroxylase gene associated with phenylketonuria. Author(s): Bjorgo E, Knappskog PM, Martinez A, Stevens RC, Flatmark T. Source: European Journal of Biochemistry / Febs. 1998 October 1; 257(1): 1-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799096&dopt=Abstract
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Phenylalanine-restricted diet should be life long. A case report on long-term followup of an adolescent with untreated phenylketonuria. Author(s): Merrick J, Aspler S, Schwarz G. Source: Int J Adolesc Med Health. 2003 April-June; 15(2): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955819&dopt=Abstract
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Phenylketonuria and glycogen storage disease type III in sibs of one family. Author(s): Yilmazer T, van Gennip AH, Abeling NG, Ozalp I, Coskun T, Bakker HD. Source: Turk J Pediatr. 2002 January-March; 44(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859869&dopt=Abstract
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Phenylketonuria and maternal phenylketonuria. Author(s): Purnell H. Source: Breastfeed Rev. 2001 July; 9(2): 19-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550601&dopt=Abstract
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Phenylketonuria in Iranian population: a study in institutions for mentally retarded in Isfahan. Author(s): Vallian S, Barahimi E, Moeini H. Source: Mutation Research. 2003 May 15; 526(1-2): 45-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714182&dopt=Abstract
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Phenylketonuria tests. Author(s): New Mexico. Source: N M Statut 1978 Annot N M. 1975; Section 24-1-6 As Amended 1975: Unknown. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041495&dopt=Abstract
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Phenylketonuria. Author(s): Illinois. Source: Smith-Hurd Ill Annot Statut Ill. 1982; Chapter 111 1-2 Sections 4901 to 4905: Unknown. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041423&dopt=Abstract
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Phenylketonuria: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy. Author(s): Sener RN. Source: Journal of Computer Assisted Tomography. 2003 July-August; 27(4): 541-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886140&dopt=Abstract
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Phenylketonuria: evidence-based clinical practice. Summary of the roundtable discussion. Author(s): Burgard P, Link R, Schweitzer-Krantz S. Source: European Journal of Pediatrics. 2000 October; 159 Suppl 2: S163-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11221745&dopt=Abstract
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Phenylketonuria: no specific frontal lobe-dependent neuropsychological deficits of early-treated patients in comparison with diabetics. Author(s): Feldmann R, Denecke J, Pietsch M, Grenzebach M, Weglage J. Source: Pediatric Research. 2002 June; 51(6): 761-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032274&dopt=Abstract
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Phenylketonuria: old disease, new approach to treatment. Author(s): Levy HL. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 March 2; 96(5): 1811-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10051548&dopt=Abstract
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Phenylketonuria: tyrosine beyond the phenylalanine-restricted diet. Author(s): van Spronsen FJ, Smit PG, Koch R. Source: Journal of Inherited Metabolic Disease. 2001 February; 24(1): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11286377&dopt=Abstract
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Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Author(s): van Spronsen FJ, van Rijn M, Bekhof J, Koch R, Smit PG. Source: The American Journal of Clinical Nutrition. 2001 February; 73(2): 153-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157309&dopt=Abstract
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Phenylketonuria; congenital hypothyroidism; meniscocytosis. Author(s): Louisiana. Source: Revis Statut La. 1978; Sections 40.1299.40.1299.4: Ons 40: 1299-40: 1299.4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043680&dopt=Abstract
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Phenylketonuria--a problem in eugenics. Author(s): Penrose LS. Source: Annals of Human Genetics. 1998 May; 62 ( Pt 3): 193-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803263&dopt=Abstract
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Plasma micronutrient concentrations in infants undergoing therapy for phenylketonuria. Author(s): Acosta PB, Yannicelli S. Source: Biological Trace Element Research. 1999 January; 67(1): 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10065600&dopt=Abstract
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Plasma phenylalanine is associated with decreased serum ubiquinone-10 concentrations in phenylketonuria. Author(s): Artuch R, Colome C, Vilaseca MA, Sierra C, Cambra FJ, Lambruschini N, Campistol J. Source: Journal of Inherited Metabolic Disease. 2001 June; 24(3): 359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486901&dopt=Abstract
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Preimplantation testing for phenylketonuria. Author(s): Verlinsky Y, Rechitsky S, Verlinsky O, Strom C, Kuliev A. Source: Fertility and Sterility. 2001 August; 76(2): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476784&dopt=Abstract
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Prolactin, a marker for cerebral dopamine deficiency in patients suffering from phenylketonuria (PKU)? Author(s): Denecke J, Schlegel W, Koch GH, Feldmann R, Harms E, Weglage J. Source: Journal of Inherited Metabolic Disease. 2000 December; 23(8): 849-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11196114&dopt=Abstract
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Protein insufficiency and linear growth restriction in phenylketonuria. Author(s): Arnold GL, Vladutiu CJ, Kirby RS, Blakely EM, Deluca JM. Source: The Journal of Pediatrics. 2002 August; 141(2): 243-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183721&dopt=Abstract
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Quality of life and psychologic adjustment in children and adolescents with early treated phenylketonuria can be normal. Author(s): Landolt MA, Nuoffer JM, Steinmann B, Superti-Furga A. Source: The Journal of Pediatrics. 2002 May; 140(5): 516-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032515&dopt=Abstract
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Radiological assessment of the hand and wrist in phenylketonuria and hyperphenylalaninaemia. Author(s): Greeves LG, Thomas PS, Carson DJ. Source: Pediatric Radiology. 1995; 25(5): 353-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7567262&dopt=Abstract
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Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria. Author(s): Smith ML, Hanley WB, Clarke JT, Klim P, Schoonheyt W, Austin V, Lehotay DC. Source: Archives of Disease in Childhood. 1998 February; 78(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579151&dopt=Abstract
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Rapid and efficient PCR/StyI test for identification of common mutation R408W in phenylketonuria patients. Author(s): Ivaschenko T, Baranov VS. Source: Journal of Medical Genetics. 1993 February; 30(2): 153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8445621&dopt=Abstract
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Rapid classification of phenylketonuria genotypes by analysis of heteroduplexes generated by PCR-amplifiable synthetic DNA. Author(s): Wood N, Tyfield L, Bidwell J. Source: Human Mutation. 1993; 2(2): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8318990&dopt=Abstract
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Rapid detection of phenylketonuria mutations by non-radioactive single-strand conformation polymorphism analysis. Author(s): Yao Y, Matsubara Y, Narisawa K. Source: Acta Paediatr Jpn. 1994 June; 36(3): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8091967&dopt=Abstract
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Rapid detection of the R408W and I65T mutations in phenylketonuria by glycosylase mediated polymorphism detection. Author(s): O'Donnell KA, Tighe O, O'Neill C, Naughten E, Mayne PD, McCarthy TV, Vaughan P, Croke DT. Source: Human Mutation. 2001 May; 17(5): 432. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11317360&dopt=Abstract
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Rapid diagnosis of phenylketonuria and other aminoacidemias by quantitative analysis of amino acids in neonatal blood spots by gas chromatography-mass spectrometry. Author(s): Deng C, Shang C, Hu Y, Zhang X. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 July 25; 775(1): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12101068&dopt=Abstract
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Rapid diagnosis of phenylketonuria by quantitative analysis for phenylalanine and tyrosine in neonatal blood spots by tandem mass spectrometry. Author(s): Chace DH, Millington DS, Terada N, Kahler SG, Roe CR, Hofman LF. Source: Clinical Chemistry. 1993 January; 39(1): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8419060&dopt=Abstract
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Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997. Author(s): Burgard P, Bremer HJ, Buhrdel P, Clemens PC, Monch E, Przyrembel H, Trefz FK, Ullrich K. Source: European Journal of Pediatrics. 1999 January; 158(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9950308&dopt=Abstract
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Receiver operating characteristic plots to evaluate Guthrie, Wallac, and Isolab phenylalanine kit performance for newborn phenylketonuria screening. Author(s): Wang ST, Pizzolato S, Demshar HP. Source: Clinical Chemistry. 1997 October; 43(10): 1838-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9342001&dopt=Abstract
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Recommendations for protein and amino acid intake in phenylketonuria patients. Author(s): Przyrembel H. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828628&dopt=Abstract
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Recommendations for protein and energy intakes by patients with phenylketonuria. Author(s): Acosta PB. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828626&dopt=Abstract
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Reduced acetylcholinesterase activity in erythrocyte membranes from patients with phenylketonuria. Author(s): Tsakiris S, Schulpis KH, Tjamouranis J, Michelakakis H, Karikas GA. Source: Clinical Biochemistry. 2002 November; 35(8): 615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498995&dopt=Abstract
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Reduced Na(+), K(+)-ATPase activity in erythrocyte membranes from patients with phenylketonuria. Author(s): Bedin M, Estrella CH, Ponzi D, Duarte DV, Dutra-Filho CS, Wyse AT, Wajner M, Wannmacher CM. Source: Pediatric Research. 2001 July; 50(1): 56-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420419&dopt=Abstract
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Reduction in birth weight in phenylketonuria. Author(s): Woolf LI, Crockett DJ. Source: European Journal of Pediatrics. 1997 February; 156(2): 157. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9039525&dopt=Abstract
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Relation between genotype and phenotype in Swedish phenylketonuria and hyperphenylalaninemia patients. Author(s): Svensson E, von Dobeln U, Eisensmith RC, Hagenfeldt L, Woo SL. Source: European Journal of Pediatrics. 1993 February; 152(2): 132-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8444221&dopt=Abstract
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Relationship between mutation genotype and biochemical phenotype in a heterogeneous Spanish phenylketonuria population. Author(s): Desviat LR, Perez B, Garcia MJ, Martinez-Pardo M, Baldellou A, Arena J, Sanjurjo P, Campistol J, Couce ML, Fernandez A, Cardesa J, Ugarte M. Source: European Journal of Human Genetics : Ejhg. 1997 July-August; 5(4): 196-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9359039&dopt=Abstract
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Resting energy expenditure in children with phenylketonuria. Author(s): Allen JR, McCauley JC, Waters DL, O'Connor J, Roberts DC, Gaskin KJ. Source: The American Journal of Clinical Nutrition. 1995 October; 62(4): 797-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7572712&dopt=Abstract
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Review of neuropsychological functioning in treated phenylketonuria: an information processing approach. Author(s): Waisbren SE, Brown MJ, de Sonneville LM, Levy HL. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. 1994 December; 407: 98103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7766971&dopt=Abstract
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RFLP haplotyping and mutation analysis of the phenylalanine hydroxylase gene in Dutch phenylketonuria families. Author(s): Meijer H, Jongbloed RJ, Hekking M, Spaapen LJ, Geraedts JP. Source: Human Genetics. 1993 December; 92(6): 588-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7903270&dopt=Abstract
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Screening for neonatal hyperbilirubinaemia and ABO alloimmunization at the time of testing for phenylketonuria and congenital hypothyreosis. Author(s): Meberg A, Johansen KB. Source: Acta Paediatrica (Oslo, Norway : 1992). 1998 December; 87(12): 1269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9894828&dopt=Abstract
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Selenium status in infants and children with phenylketonuria and in maternal phenylketonuria. Author(s): Lombeck I, Jochum F, Terwolbeck K. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S140-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828631&dopt=Abstract
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Severity of mutation in the phenylalanine hydroxylase gene influences phenylalanine metabolism in phenylketonuria and hyperphenylalaninaemia heterozygotes. Author(s): Svensson E, Iselius L, Hagenfeldt L. Source: Journal of Inherited Metabolic Disease. 1994; 17(2): 215-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967476&dopt=Abstract
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Short tandem repeat polymorphisms in Japanese families with phenylketonuria. Author(s): Kang Y, Okano Y, Hase Y, Oura T, Isshiki G. Source: Journal of Inherited Metabolic Disease. 1996; 19(3): 375-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8803787&dopt=Abstract
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Short-term dietary interventions in children and adolescents with treated phenylketonuria: effects on neuropsychological outcome of a well-controlled population. Author(s): Huijbregts SC, de Sonneville LM, Licht R, van Spronsen FJ, Sergeant JA. Source: Journal of Inherited Metabolic Disease. 2002 October; 25(6): 419-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12555935&dopt=Abstract
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Should adults with phenylketonuria have diet treatment? Author(s): Merrick J, Aspler S, Schwarz G. Source: Mental Retardation. 2001 June; 39(3): 215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420000&dopt=Abstract
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Social factors and the meaning of food in adherence to medical diets: results of a maternal phenylketonuria summer camp. Author(s): Waisbren SE, Rokni H, Bailey I, Rohr F, Brown T, Warner-Rogers J. Source: Journal of Inherited Metabolic Disease. 1997 March; 20(1): 21-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9061563&dopt=Abstract
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Somatic gene therapy for phenylketonuria and other hepatic deficiencies. Author(s): Eisensmith RC, Woo SL. Source: Journal of Inherited Metabolic Disease. 1996; 19(4): 412-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8884565&dopt=Abstract
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Spectrum and origin of phenylketonuria mutations in Spain. Author(s): Perez B, Desviat LR, De Lucca M, Ugarte M. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. 1994 December; 407: 34-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7766951&dopt=Abstract
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Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. Author(s): Fusetti F, Erlandsen H, Flatmark T, Stevens RC. Source: The Journal of Biological Chemistry. 1998 July 3; 273(27): 16962-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9642259&dopt=Abstract
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Studies of multimodal evoked potentials in treated phenylketonuria: the pattern of vulnerability. Author(s): Ludolph AC, Vetter U, Ullrich K. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S64-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828613&dopt=Abstract
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Subclinical visual impairment in phenylketonuria. A neurophysiological study (VEPP) with clinical, biochemical, and neuroradiological (MRI) correlations. Author(s): Leuzzi V, Rinalduzzi S, Chiarotti F, Garzia P, Trasimeni G, Accornero N. Source: Journal of Inherited Metabolic Disease. 1998 June; 21(4): 351-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700592&dopt=Abstract
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Successful treatment of phenylketonuria with tetrahydrobiopterin. Author(s): Trefz FK, Aulela-Scholz C, Blau N. Source: European Journal of Pediatrics. 2001 May; 160(5): 315. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388602&dopt=Abstract
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Summary of findings from the United States Collaborative Study of children treated for phenylketonuria. Author(s): Azen C, Koch R, Friedman E, Wenz E, Fishler K. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828605&dopt=Abstract
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Sustained attention and inhibition of cognitive interference in treated phenylketonuria: associations with concurrent and lifetime phenylalanine concentrations. Author(s): Huijbregts SC, de Sonneville LM, Licht R, van Spronsen FJ, Verkerk PH, Sergeant JA. Source: Neuropsychologia. 2002; 40(1): 7-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11595258&dopt=Abstract
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Tetrahydrobiopterin and mild phenylketonuria. Author(s): Hanley WB. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1722-4; Author Reply 1722-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715774&dopt=Abstract
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Tetrahydrobiopterin and mild phenylketonuria. Author(s): D'agostino RD. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1722-4; Author Reply 1722-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715773&dopt=Abstract
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Tetrahydrobiopterin and mild phenylketonuria. Author(s): Ponzone A, Peduto A, Spada M. Source: The New England Journal of Medicine. 2003 April 24; 348(17): 1722-4; Author Reply 1722-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711753&dopt=Abstract
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Tetrahydrobiopterin monotherapy for phenylketonuria patients with common mild mutations. Author(s): Steinfeld R, Kohlschutter A, Zschocke J, Lindner M, Ullrich K, Lukacs Z. Source: European Journal of Pediatrics. 2002 July; 161(7): 403-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174822&dopt=Abstract
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Tetrahydrobiopterin responsiveness in phenylketonuria. Two new cases and a review of molecular genetic findings. Author(s): Lassker U, Zschocke J, Blau N, Santer R. Source: Journal of Inherited Metabolic Disease. 2002 February; 25(1): 65-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999982&dopt=Abstract
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The behavioral profile of severe mental retardation in a genetic mouse model of phenylketonuria. Author(s): Cabib S, Pascucci T, Ventura R, Romano V, Puglisi-Allegra S. Source: Behavior Genetics. 2003 May; 33(3): 301-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837019&dopt=Abstract
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The demands of biochemical genetic disorders: a survey of mothers of children with mitochondrial disease or phenylketonuria. Author(s): Read CY. Source: Journal of Pediatric Nursing. 2003 June; 18(3): 181-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796860&dopt=Abstract
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The impact of phenylketonuria on folate metabolism. Author(s): Lucock M, Yates Z, Hall K, Leeming R, Rylance G, MacDonald A, Green A. Source: Molecular Genetics and Metabolism. 2002 August; 76(4): 305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208135&dopt=Abstract
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Treatable neurotransmitter deficiency in mild phenylketonuria. Author(s): Bonafe L, Blau N, Burlina AP, Romstad A, Guttler F, Burlina AB. Source: Neurology. 2001 September 11; 57(5): 908-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552030&dopt=Abstract
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Tyrosine supplementation in phenylketonuria: diurnal blood tyrosine levels and presumptive brain influx of tyrosine and other large neutral amino acids. Author(s): Kalsner LR, Rohr FJ, Strauss KA, Korson MS, Levy HL. Source: The Journal of Pediatrics. 2001 September; 139(3): 421-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562623&dopt=Abstract
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Undiagnosed phenylketonuria in adult women: a hidden public health problem. Author(s): Hanley WB, Clarke JT, Schoonheyt WE. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1990 September 15; 143(6): 513-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2207906&dopt=Abstract
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Use of phenylalanine-to-tyrosine ratio determined by tandem mass spectrometry to improve newborn screening for phenylketonuria of early discharge specimens collected in the first 24 hours. Author(s): Chace DH, Sherwin JE, Hillman SL, Lorey F, Cunningham GC. Source: Clinical Chemistry. 1998 December; 44(12): 2405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9836704&dopt=Abstract
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Utilisation of amino acid mixtures in adolescents with phenylketonuria. Author(s): Monch E, Herrmann ME, Brosicke H, Schoffer A, Keller M. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828625&dopt=Abstract
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Validation of the phenylalanine/tyrosine ratio determined by tandem mass spectrometry: sensitive newborn screening for phenylketonuria. Author(s): Ceglarek U, Muller P, Stach B, Buhrdel P, Thiery J, Kiess W. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 July; 40(7): 693-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241016&dopt=Abstract
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Valine, isoleucine, and leucine. A new treatment for phenylketonuria. Author(s): Berry HK, Brunner RL, Hunt MM, White PP. Source: Am J Dis Child. 1990 May; 144(5): 539-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2184659&dopt=Abstract
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Variability of blood-brain ratios of phenylalanine in typical patients with phenylketonuria. Author(s): Rupp A, Kreis R, Zschocke J, Slotboom J, Boesch C, Rating D, Pietz J. Source: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. 2001 March; 21(3): 276-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295882&dopt=Abstract
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Visual evoked potentials in phenylketonuria: association with brain MRI, dietary state, and IQ. Author(s): Jones SJ, Turano G, Kriss A, Shawkat F, Kendall B, Thompson AJ. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1995 September; 59(3): 260-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7673953&dopt=Abstract
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Visual, auditory, and somatosensorial evoked potentials in early and late treated adolescents with phenylketonuria. Author(s): Leuzzi V, Cardona F, Antonozzi I, Loizzo A. Source: Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. 1994 November; 11(6): 602-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7860722&dopt=Abstract
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Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Author(s): Hanley WB, Feigenbaum AS, Clarke JT, Schoonheyt WE, Austin VJ. Source: European Journal of Pediatrics. 1996 July; 155 Suppl 1: S145-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8828632&dopt=Abstract
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Vitamin B12 deficiency in adolescents and young adults with phenylketonuria. Author(s): Hanley WB, Feigenbaum A, Clarke JT, Schoonheyt W, Austin V. Source: Lancet. 1993 October 16; 342(8877): 997. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8105251&dopt=Abstract
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Vitamin B-6 status of school-aged patients with phenylketonuria. Author(s): Prince AP, Leklem JE. Source: The American Journal of Clinical Nutrition. 1994 August; 60(2): 262-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8030605&dopt=Abstract
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CHAPTER 2. NUTRITION AND PHENYLKETONURIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and phenylketonuria.
Finding Nutrition Studies on Phenylketonuria The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “phenylketonuria” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on phenylketonuria: •
Should dietary treatment of phenylketonuria be continued after infancy? Source: Nutrition-reviews (USA). (June 1985). volume 43(6) page 176-177.
Additional consumer oriented references include: •
Importance of diet in maternal phenylketonuria. Author(s): Department of Nutrition & Food Sciences, University of Vermont, Burlington 05405, USA. Source: Sheard, N F Nutr-Revolume 2000 August; 58(8): 236-9 0029-6643
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New approaches to the treatment of phenylketonuria. Author(s): Departamento de Ciencias Farmaceuticas, Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Brazil. Source: de Freitas, O Izumi, C Lara, M G Greene, L J Nutr-Revolume 1999 March; 57(3): 65-70 0029-6643
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Phenylketonuria--a genetic intrauterine nutritional deficiency. Source: Nutr-M-D. Van Nuys, Calif. : PM, Inc. January 1992. volume 18 (1) page 5. 07320167
The following information is typical of that found when using the “Full IBIDS Database” to search for “phenylketonuria” (or a synonym): •
A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria. Author(s): Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030. Source: Goltsov, A A Eisensmith, R C Naughton, E R Jin, L Chakraborty, R Woo, S L Hum-Mol-Genet. 1993 May; 2(5): 577-81 0964-6906
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Acceptability of a new modular protein substitute for the dietary treatment of phenylketonuria. Author(s): Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
[email protected] Source: Rohr, F J Munier, A W Levy, H L J-Inherit-Metab-Dis. 2001 November; 24(6): 623-30 0141-8955
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Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria. Author(s): Department of Psychology, Washington University, St Louis, Missouri 63130, USA.
[email protected] Source: White, Desiree A Nortz, Marsha J Mandernach, Tammy Huntington, Kathleen Steiner, Robert D J-Int-Neuropsychol-Soc. 2002 January; 8(1): 1-11 1355-6177
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Alanine prevents the reduction of pyruvate kinase activity in brain cortex of rats subjected to chemically induced hyperphenylalaninemia. Author(s): Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, UFRGS, Porto Alegre, RS, Brazil. Source: Feksa, L R Cornelio, A R Rech, V C Dutra Filho, C S Wyse, A T Wajner, M Wannmacher, C M Neurochem-Res. 2002 September; 27(9): 947-52 0364-3190
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An enzyme/brain-barrier theory of psychiatric pathogenesis: unifying observations on phenylketonuria, autism, schizophrenia and postpartum psychosis. Author(s): Department of General Practice, University of Oslo, Blindern, Norway. Source: Seim, A R Reichelt, K L Med-Hypotheses. 1995 November; 45(5): 498-502 03069877
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Assessment of adult phenylketonuria. Author(s): Willink Biochemical Genetics Unit, Manchester Children's Hospital, Pendlebury, UK.
[email protected] Source: Cleary, M Walter, J H Ann-Clin-Biochem. 2001 September; 38(Pt 5): 450-8 00045632
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Associations between phenylalanine-to-tyrosine ratios and performance on tests of neuropsychological function in adolescents treated early and continuously for phenylketonuria. Author(s): Department of Psychology, University of Minnesota, Minneapolis 55455, USA.
[email protected] Source: Luciana, M Sullivan, J Nelson, C A Child-Devolume 2001 Nov-December; 72(6): 1637-52 0009-3920
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Barriers to dietary control among pregnant women with phenylketonuria--United States, 1998-2000. Source: Anonymous MMWR-Morb-Mortal-Wkly-Repage 2002 February 15; 51(6): 117-20 0149-2195
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Barriers to successful dietary control among pregnant women with phenylketonuria. Author(s): Division of Applied Public Health Training, Epidemiology Program Office, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA. Source: Brown, Amanda Savage Fernhoff, Paul M Waisbren, Susan E Frazier, Dianne M Singh, Rani Rohr, Fran Morris, Jill M Kenneson, Aileen MacDonald, Pia Gwinn, Marta Honein, Margaret Rasmussen, Sonja A Genet-Med. 2002 Mar-April; 4(2): 84-9 1098-3600
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Brain MRI changes in phenylketonuria. Associations with dietary status. Author(s): Institute of Neurology, University College, London, UK. Source: Thompson, A J Tillotson, S Smith, I Kendall, B Moore, S G Brenton, D P Brain. 1993 August; 116 ( Pt 4)811-21 0006-8950
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Children with phenylketonuria: the interface of family and child functioning. Author(s): School of Education, Tel-Aviv University, Ramat Aviv Israel. Source: Shulman, S Fisch, R O Zempel, C E Gadish, O Chang, P N J-Dev-Behav-Pediatr. 1991 October; 12(5): 315-21 0196-206X
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Classical phenylketonuria and its variants caused by defects in biopterin metabolism. Source: Kaufman, S. UCLA-Sym-Mol-Cell-Biol. New York : Alan R. Liss. 1987. volume 55 page 517-538. ill.
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Coexistence of cystic fibrosis and phenylketonuria. Author(s): Royal Belfast Hospital for Sick Children. Source: Greeves, L G McCarthy, H L Redmond, A Carson, D J Ulster-Med-J. 1997 May; 66(1): 59-61 0041-6193
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Comparison of eating attitudes and behaviors among adolescent and young women with type 1 diabetes mellitus and phenylketonuria. Author(s): Joslin Diabetes Center, Section of Behavioral and Mental Health Research, Boston, Massachusetts, USA. Source: Antisdel, J E Chrisler, J C J-Dev-Behav-Pediatr. 2000 April; 21(2): 81-6 0196-206X
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Cranial CT and MRI in malignant phenylketonuria. Author(s): Department of Radiology, CHUV, Lausanne, Switzerland. Source: Gudinchet, F Maeder, P Meuli, R A Deonna, T Mathieu, J M Pediatr-Radiol. 1992; 22(3): 223-4 0301-0449
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Development of corn starch-gum bread for phenylketonuria patients. Author(s): Hacettepe University, Faculty of Engineering, Food Engineering Department, 06532 Beytepe, Ankara, Turkey.
[email protected] Source: Ozboy, O Nahrung. 2002 April; 46(2): 87-91 0027-769X
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Developmental neurotoxicity: do similar phenotypes indicate a common mode of action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal phenylketonuria. Author(s): Toxicology Program, University of Washington, 4225 Roosevelt Way NE, #100, Seattle 98105-6099, USA.
[email protected] Source: Costa, L G Guizzetti, M Burry, M Oberdoerster, J Toxicol-Lett. 2002 February 28; 127(1-3): 197-205 0378-4274
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Developments in phenylketonuria. Source: Matalon, K.M. Topics-clin-nutr. Frederick, Md. : Aspen Publishers Inc. Sept 2001. volume 16 (4) page 41-50. 0883-5691
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Dietary interventions for phenylketonuria. Author(s): Evidence Based Child Health Unit, Institute of Child Health, Royal Liverpool Children's Hospital NHS Trust, Alder Hey, Eaton Road, Liverpool, Merseyside, UK, L12 2AP.
[email protected] Source: Poustie, V J Rutherford, P Cochrane-Database-Syst-Revolume 2000; (2): CD001304 1469-493X
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Effect of phenylalanine and its metabolites on the proliferation and viability of neuronal and astroglial cells: possible relevance in maternal phenylketonuria. Author(s): Department of Environmental Health, University of Washington, Seattle, Washington, USA. Source: Oberdoerster, J Guizzetti, M Costa, L G J-Pharmacol-Exp-Ther. 2000 October; 295(1): 295-301 0022-3565
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Evoked potentials and electroencephalography in adolescents with phenylketonuria. Author(s): Pediatric University Hospital Mannheim. Source: Korinthenberg, R Ullrich, K Fullenkemper, F Neuropediatrics. 1988 November; 19(4): 175-8 0174-304X
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Experimental hyperphenylalaninemia provokes oxidative stress in rat brain. Author(s): Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo) 90035-003, Porto Alegre, RS, Brazil. Source: Kienzle Hagen, Martine E Pederzolli, Carolina D Sgaravatti, Angela M Bridi, Raquel Wajner, Moacir Wannmacher, Clovis M D Wyse, Angela T S Dutra Filho, Carlos S Biochim-Biophys-Acta. 2002 April 24; 1586(3): 344-52 0006-3002
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Follow up of fetal outcome in cases of maternal phenylketonuria in Northern Ireland. Author(s): Regional Genetics Service, Belfast City Hospital Trust, Lisburn Road, Belfast BT9 7AB, Northern Ireland, UK. Source: Magee, A C Ryan, K Moore, A Trimble, E R Arch-Dis-Child-Fetal-Neonatal-Ed. 2002 September; 87(2): F141-3 1359-2998
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Future developments in phenylketonuria. Author(s): Murdoch Institute for Research into Birth Defects, Royal Children's Hospital, Melbourne, Australia. Source: Danks, D M Cotton, R G Enzyme. 1987; 38(1-4): 296-301 0013-9432
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Genetic implications for newborn screening for phenylketonuria. Author(s): Mental Retardation and Developmental Disabilities Branch, National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
[email protected] Source: de la Cruz, F Koch, R Clin-Perinatol. 2001 June; 28(2): 419-24 0095-5108
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How practical are recommendations for dietary control in phenylketonuria? Author(s): Willink Biochemical Genetic Unit, Royal Manchester Children's Hospital, Manchester M27 4HA, UK.
[email protected] Source: Walter, J H White, F J Hall, S K MacDonald, A Rylance, G Boneh, A Francis, D E Shortland, G J Schmidt, M Vail, A Lancet. 2002 July 6; 360(9326): 55-7 0140-6736
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Impaired sensitivity to visual contrast in children treated early and continuously for phenylketonuria. Author(s): Department of Psychology, University of Pennsylvania, Philadelphia, USA. Source: Diamond, A Herzberg, C Brain. 1996 April; 119 ( Pt 2)523-38 0006-8950
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Inadequate iron availability as a possible cause of low serum carnitine concentrations in patients with phenylketonuria. Author(s): University Children's Hospital, Frankfurt/Main, Federal Republic of Germany. Source: Bohles, H Ullrich, K Endres, W Behbehani, A W Wendel, U Eur-J-Pediatr. 1991 April; 150(6): 425-8 0340-6199
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Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine. Author(s): John F. Kennedy Institute, Glostrup, Denmark. Source: Lykkelund, C Nielsen, J B Lou, H C Rasmussen, V Gerdes, A M Christensen, E Guttler, F Eur-J-Pediatr. 1988 December; 148(3): 238-45 0340-6199
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Interhemispheric interaction during childhood: II. Children with early-treated phenylketonuria. Author(s): Beckman Institute, Department of Psychology, University of Illinois at Urbana-Champaign, USA.
[email protected] Source: Banich, M T Passarotti, A M White, D A Nortz, M J Steiner, R D DevNeuropsychol. 2000; 18(1): 53-71 8756-5641
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Interhemispheric transfer in children with early-treated phenylketonuria. Author(s): Washington University, Department of Pediatrics, St. Louis, MO 63130. Source: Gourovitch, M L Craft, S Dowton, S B Ambrose, P Sparta, S J-Clin-ExpNeuropsychol. 1994 June; 16(3): 393-404 0168-8634
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In-vivo NMR spectroscopy in patients with phenylketonuria: changes of cerebral phenylalanine levels under dietary treatment. Author(s): Institut fur Klinische Radiologie, Westfalische Wilhelms-Universitat, Munster, Germany. Source: Moller, H E Vermathen, P Ullrich, K Weglage, J Koch, H G Peters, P E Neuropediatrics. 1995 August; 26(4): 199-202 0174-304X
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Keeping phenylketonuria under control. Source: Gibbings, B Mod-Midwife. 1994 October; 4(10): 23-6 0963-276X
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Large neutral amino acids auto exchange when infused by microdialysis into the rat brain: implication for maple syrup urine disease and phenylketonuria. Author(s): Department of Pediatrics, University of Maryland, Pediatric Research, 10-035 BRB, 655 W Baltimore Street, Baltimore, MD 21201, USA.
[email protected] Source: Zielke, H Ronald Zielke, Carol L Baab, Peter J Collins, Roger M Neurochem-Int. 2002 April; 40(4): 347-54 0197-0186
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Life-long treatment for phenylketonuria. Author(s): Osaka City Rehabilitation Training Center. Source: Oura, T Southeast-Asian-J-Trop-Med-Public-Health. 1999; 30 Suppl 2: 61-2 00383619
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Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet. Author(s): Children's Hospital of Los Angeles, Division of Medical Genetics, University of Southern California School of Medicine, Los Angeles 90027, USA.
[email protected] Source: Moseley, K Koch, R Moser, A B J-Inherit-Metab-Dis. 2002 February; 25(1): 56-64 0141-8955
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Long-term development of intelligence (IQ) and EEG in 34 children with phenylketonuria treated early. Author(s): Universitats-Kinderklinik, Neuropadiatrische Abteilung, Heidelberg, Federal Republic of Germany. Source: Pietz, J Benninger, C Schmidt, H Scheffner, D Bickel, H Eur-J-Pediatr. 1988 May; 147(4): 361-7 0340-6199
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Maternal phenylketonuria and hyperphenylalanemia: a problem born of success. Source: Lenke, R.R. J-Pediatr-Perinat-Nutr. New York, N.Y. : Haworth Press. Spring/Summer 1987. volume 1 (1) page 67-74. charts. 8756-6206
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Modelling the phenylalanine blood level response during treatment of phenylketonuria. Author(s): Institute of Human Genetics, University Hospital, Frankfurt/Main, Germany.
[email protected] Source: Langenbeck, U Zschocke, J Wendel, U Honig, V J-Inherit-Metab-Dis. 2001 December; 24(8): 805-14 0141-8955
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Molecular studies and prenatal diagnosis of phenylketonuria in Chinese patients. Author(s): Xin Hua Hospital, Shanghai Second Medical University, Shanghai Institute for Pediatric Research, China.
[email protected] Source: Fan, G X Qing, L X June, Y Mei, Z Southeast-Asian-J-Trop-Med-Public-Health. 1999; 30 Suppl 2: 63-5 0038-3619
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Mouse models of human phenylketonuria. Author(s): McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706. Source: Shedlovsky, A McDonald, J D Symula, D Dove, W F Genetics. 1993 August; 134(4): 1205-10 0016-6731
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MR imaging of phenylketonuria. Author(s): Department of Radiology, University of Washington School of Medicine, Seattle 98195. Source: Shaw, D W Maravilla, K R Weinberger, E Garretson, J Trahms, C M Scott, C R AJNR-Am-J-Neuroradiol. 1991 May-June; 12(3): 403-6 0195-6108
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Mutational spectrum of phenylalanine hydroxylase deficiency in the population resident in Catalonia: genotype-phenotype correlation. Author(s): Laboratorio de Genetica, Servei Genetica, Hospital Clinic, Barcelona, Spain. Source: Mallolas, J Vilaseca, M A Campistol, J Lambruschini, N Cambra, F J Estivill, X Mila, M Hum-Genet. 1999 November; 105(5): 468-73 0340-6717
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Neurological aspects of adult phenylketonuria. Author(s): Department of Pediatric Neurology, University of Heidelberg, Germany.
[email protected] Source: Pietz, J Curr-Opin-Neurol. 1998 December; 11(6): 679-88 1350-7540
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Neurological outcome in adult patients with early-treated phenylketonuria. Author(s): Department of Paediatric Neurology, University of Heidelberg, Germany. Source: Pietz, J Dunckelmann, R Rupp, A Rating, D Meinck, H M Schmidt, H Bremer, H J Eur-J-Pediatr. 1998 October; 157(10): 824-30 0340-6199
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Newborn mass screening and molecular genetics of phenylketonuria in east Asia. Author(s): Department of Pediatrics, Osaka City University Medical School, Japan. Source: Okano, Y Isshiki, G Southeast-Asian-J-Trop-Med-Public-Health. 1995; 26 Suppl 1123-9 0038-3619
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Nurses' role in preventing birth defects in offspring of women with phenylketonuria. Author(s): Ross Laboratories, Columbus, Ohio. Source: Acosta, P B Wright, L J-Obstet-Gynecol-Neonatal-Nurs. 1992 Jul-August; 21(4): 270-6 0884-2175
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Nutrient intake and congenital heart defects in maternal phenylketonuria. Author(s): University of Houston, Texas, USA. Source: Michals Matalon, K Platt, L D Acosta P, P Azen, C Walla, C A Am-J-ObstetGynecol. 2002 August; 187(2): 441-4 0002-9378
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Nutrition support of maternal phenylketonuria. Author(s): Ross Products Division, Abbott Laboratories, Columbus, OH 43215, USA. Source: Acosta, P B Semin-Perinatol. 1995 June; 19(3): 182-90 0146-0005
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Nutritional evaluation of children with phenylketonuria. Author(s): Department of Nutrition, Public Health School, University of Sao Paulo, Brasil.
[email protected] Source: Fisberg, R M da Silva Fernandes, M E Schmidt, B J Fisberg, M Sao-Paulo-Med-J. 1999 September 2; 117(5): 185-91 1516-3180
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Osteopenia and phenylketonuria. Author(s): Department of Child Health, Queens University, Belfast, Northern Ireland. Source: Carson, D J Greeves, L G Sweeney, L E Crone, M D Pediatr-Radiol. 1990; 20(8): 598-9 0301-0449
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Outcome of treatment in young adults with phenylketonuria detected by routine neonatal screening between 1964 and 1971. Author(s): DH Phenylketonuria Register, Institute of Child Health, London, UK. Source: Beasley, M G Costello, P M Smith, I Q-J-Med. 1994 March; 87(3): 155-60 00335622
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Oxidative stress induced by phenylketonuria in the rat: Prevention by melatonin, vitamin E, and vitamin C. Author(s): Department of Medical Biochemistry and Molecular Biology, University of Seville School of Medicine and Virgen Macarena Hospital, Spain.
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Source: Martinez Cruz, F Pozo, D Osuna, C Espinar, A Marchante, C Guerrero, J M JNeurosci-Res. 2002 August 15; 69(4): 550-8 0360-4012 •
Phenylalanine control and family functioning in early-treated phenylketonuria. Author(s): Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129. Source: Reber, M Kazak, A E Himmelberg, P J-Dev-Behav-Pediatr. 1987 December; 8(6): 311-7 0196-206X
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Phenylalanine hydroxylase gene mutation R408W is present on 84% of Estonian phenylketonuria chromosomes. Author(s): Tartu University Institute of Molecular and Cell Biology, Estonian Biocentre, Estonia. Source: Lillevali, H Ounap, K Metspalu, A Eur-J-Hum-Genet. 1996; 4(5): 296-300 10184813
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Phenylketonuria and maternal phenylketonuria. Author(s): Early Childhood Centre, Westmead Hospital and Community Health Services, 39 Bridge St Epping, NSW 2121. Source: Purnell, H Breastfeed-Revolume 2001 July; 9(2): 19-21 0729-2759
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Phenylketonuria--impact of nutrition support on reproductive outcomes. Source: Thompson, T. Dwyer, J.T. Palmer, C.A. Nutr-Today. Baltimore, Md. : Williams & Wilkins. Jan/February 1991. volume 26 (1) page 43-47. charts. 0029-666X
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Physical growth of children treated for phenylketonuria. Author(s): Department of Biostatistics, University of Washington, Seattle. Source: McBurnie, M A Kronmal, R A Schuett, V E Koch, R Azeng, C G Ann-Hum-Biol. 1991 Jul-August; 18(4): 357-68 0301-4460
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Postnatal growth in a mouse genetic model of classical phenylketonuria. Author(s): Department of Biological Sciences, Wichita State University, 1845 Fairmount, Box 26, Wichita, KS 67260-0026, USA. Source: McDonald, J D Contemp-Top-Lab-Anim-Sci. 2000 November; 39(6): 54-6 10600558
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Prospects for somatic gene therapy of phenylketonuria. Source: Ledley, F.D. Woo, S.L.C. UCLA-Sym-Mol-Cell-Biol. New York : Alan R. Liss. 1987. volume 55 page 565-579. ill.
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Psychoeducational findings among children treated for phenylketonuria. Source: Fishler, K Azen, C G Henderson, R Friedman, E G Koch, R Am-J-Ment-Defic. 1987 July; 92(1): 65-73 0002-9351
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Psychological and social findings in adolescents with phenylketonuria. Author(s): Department of Paediatrics, University of Munster, Federal Republic of Germany. Source: Weglage, J Funders, B Wilken, B Schubert, D Schmidt, E Burgard, P Ullrich, K Eur-J-Pediatr. 1992 July; 151(7): 522-5 0340-6199
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Quality of life and psychologic adjustment in children and adolescents with early treated phenylketonuria can be normal. Author(s): Division of Psychosomatics and Psychiatry, University Children's Hospital, Zurich, Switzerland. Source: Landolt, Markus A Nuoffer, Jean Marc Steinmann, Beat Superti Furga, Andrea JPediatr. 2002 May; 140(5): 516-21 0022-3476
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Radiological assessment of the hand and wrist in phenylketonuria and hyperphenylalaninaemia. Author(s): Royal Belfast Hospital for Sick Children, Queens University, Northern Ireland. Source: Greeves, L G Thomas, P S Carson, D J Pediatr-Radiol. 1995; 25(5): 353-5 03010449
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Rapid mutation screening of phenylketonuria by polymerase chain reaction-linked restriction enzyme assay and direct sequence of the phenylalanine hydroxylase gene: clinical application in northern Japan and northern China. Author(s): Department of Pediatrics, National Otaru Hospital, Japan. Source: Sueoka, H Nagao, M Chiba, S Genet-Test. 2000; 4(3): 249-56 1090-6576
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Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997. Author(s): Fachrichtung Psychologie, Universitat des Saarlandes, Im Stadtwald, Saarbrucken, Germany.
[email protected] Source: Burgard, P Bremer, H J Buhrdel, P Clemens, P C Monch, E Przyrembel, H Trefz, F K Ullrich, K Eur-J-Pediatr. 1999 January; 158(1): 46-54 0340-6199
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Red blood cell glutathione peroxidase activity as a function of selenium supplementation in dietary treated children with phenylketonuria. Source: Zachara, B A Wasowicz, W Gromadzinska, J Sklodowska, M Cabalska, B Biomed-Biochim-Acta. 1987; 46(2-3): S209-13 0232-766X
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Regulation of the free amino acid pool of the developing brain: a lesson learned from expreimental phenylketonuria. Source: Huether, G. UCLA-Sym-Mol-Cell-Biol. New York : Alan R. Liss. 1987. volume 55 page 107-122. ill.
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Role of membrane transport in interorgan amino acid flows: where do the depleted amino acids go in phenylketonuria. Source: Christensen, H.N. UCLA-Sym-Mol-Cell-Biol. New York : Alan R. Liss. 1987. volume 55 page 1-17. ill.
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Scleroderma-like skin lesions in two patients with phenylketonuria. Author(s): Division of Metabolism, Hacettepe University, Ankara, Turkey. Source: Coskun, T Ozalp, I Kale, G Gogus, S Eur-J-Pediatr. 1990 December; 150(2): 10910 0340-6199
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Should adults with phenylketonuria have diet treatment? Author(s): Division for the Mentally Retarded, Ministry of Labour and Social Affairs, Box 1260, Il-91012 Jerusalem, Israel.
[email protected] Source: Merrick, J Aspler, S Schwarz, G Ment-Retard. 2001 June; 39(3): 215-7 0047-6765
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Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria. Author(s): Department of Anesthesiology, University of Florida, Gainsville, FL 326100254, USA. Source: Glushakov, A V Dennis, D M Morey, T E Sumners, C Cucchiara, R F Seubert, C N Martynyuk, A E Mol-Psychiatry. 2002; 7(4): 359-67 1359-4184
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Sustained attention and inhibition of cognitive interference in treated phenylketonuria: associations with concurrent and lifetime phenylalanine concentrations. Author(s): Department of Clinical Neuropsychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.
[email protected] 78
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Source: Huijbregts, S C J de Sonneville, L M J Licht, R van Spronsen, F J Verkerk, P H Sergeant, J A Neuropsychologia. 2002; 40(1): 7-15 0028-3932 •
Tetrahydrobiopterin monotherapy for phenylketonuria patients with common mild mutations. Author(s): Department of Pediatrics, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. Source: Steinfeld, R Kohlschutter, A Zschocke, J Lindner, M Ullrich, K Lukacs, Z Eur-JPediatr. 2002 July; 161(7): 403-5 0340-6199
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The impact of phenylketonuria on folate metabolism. Source: Lucock, M. Yates, Z. Hall, K. Leeming, R. Rylance, G. MacDonald, A. Green, A. Mol-genet-metab. Orlando, FL : Academic Press, c1998-. August 2002. volume 76 (4) page 305-312. 1096-7192
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The incidence of phenylketonuria in Thailand. Source: Kietduriyakul, V Komkris, V Tongkittikul, K Leangphibul, P J-Med-Assoc-Thai. 1989 September; 72(9): 516-9 0125-2208
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The management of phenylketonuria (PKU). Author(s): Department of Metabolic Medicine, Royal Children's Hospital, Brisbane, Queensland, Australia. Source: McGill, J J Southeast-Asian-J-Trop-Med-Public-Health. 1999; 30 Suppl 2: 55-7 0038-3619
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The molecular genetics of phenylketonuria. Source: DiLella, A.G. Marvit, J. Woo, S.L.C. UCLA-Sym-Mol-Cell-Biol. New York : Alan R. Liss. 1987. volume 55 page 553-564. ill.
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Treating phenylketonuria by a phenylalanine-free diet. Source: Start, K Prof-Care-Mother-Child. 1998; 8(4): 109-10 0964-4156
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Treatment of phenylketonuria with a formula consisting of low-phenylalanine peptide. A collaborative study. Author(s): Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan. Source: Kitagawa, T Owada, M Aoki, K Arai, S Oura, T Matsuda, I Igarashi, Y Tada, K Katayama, S Hashida, W Enzyme. 1987; 38(1-4): 321-7 0013-9432
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True precocious puberty associated with phenylketonuria. Author(s): Department of Pediatric Nutrition, Metabolism and Gastroenterology, Medical Faculty of Dokuz Eylul University, Izmir, Turkey. Source: Buyukgebiz, B Eroglu, Y Buy ukgebiz, A J-Pediatr-Endocrinol. 1994 OctDecember; 7(4): 361-3 0334-018X
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Tyrosine supplementation for phenylketonuria. Author(s): Evidence Based Child Health Unit, Institute of Child Health, Royal Liverpool Children's Hospital NHS Trust, Alder Hey, Eaton Road, Liverpool, Merseyside, UK, L12 2AP.
[email protected] Source: Poustie, V J Rutherford, P Cochrane-Database-Syst-Revolume 2000; (2): CD001507 1469-493X
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Visual, auditory, and somatosensorial evoked potentials in early and late treated adolescents with phenylketonuria. Author(s): Istituto di Neuropsichiatria Infantile, Universita La Sapienza, Roma, Italy. Source: Leuzzi, V Cardona, F Antonozzi, I Loizzo, A J-Clin-Neurophysiol. 1994 November; 11(6): 602-6 0736-0258
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to phenylketonuria; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin K Source: Healthnotes, Inc.; www.healthnotes.com
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Minerals Selenium Source: Healthnotes, Inc.; www.healthnotes.com
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Food and Diet Non-Nutritive and Artificial Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE PHENYLKETONURIA
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to phenylketonuria. 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 phenylketonuria 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 “phenylketonuria” (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 phenylketonuria: •
A conference for the education of families who have a member with phenylketonuria. Author(s): Kolb SE, Aguilar MC, Kaye C. Source: Journal of Pediatric Nursing. 1999 August; 14(4): 270-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467806&dopt=Abstract
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A yeast-leavened, low-protein, low-electrolyte bread. Author(s): Sorensen MK. Source: Journal of the American Dietetic Association. 1970 June; 56(6): 521-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5463291&dopt=Abstract
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Are tablets a practical source of protein substitute in phenylketonuria? Author(s): MacDonald A, Ferguson C, Rylance G, Morris AA, Asplin D, Hall SK, Booth IW.
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Source: Archives of Disease in Childhood. 2003 April; 88(4): 327-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651759&dopt=Abstract •
Assessment of adult phenylketonuria. Author(s): Cleary M, Walter JH. Source: Annals of Clinical Biochemistry. 2001 September; 38(Pt 5): 450-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587123&dopt=Abstract
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Biochemical effects of supplemented long-chain polyunsaturated fatty acids in hyperphenylalaninemia. Author(s): Agostoni C, Scaglioni S, Bonvissuto M, Bruzzese MG, Giovannini M, Riva E. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2001 February; 64(2): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237478&dopt=Abstract
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Cognition and tyrosine supplementation among school-aged children with phenylketonuria. Author(s): Mazzocco MM, Yannicelli S, Nord AM, van Doorninck W, Davidson-Mundt AJ, Greene CL. Source: Am J Dis Child. 1992 November; 146(11): 1261-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1415060&dopt=Abstract
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Comparative psychological studies of Negroes and whites in the United States: 19591965. Author(s): Dreger RM, Miller KS. Source: Psychological Bulletin. 1968 September; 70(3): Suppl: 1-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4878850&dopt=Abstract
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Dietary threonine reduces plasma phenylalanine levels in patients with hyperphenylalaninemia. Author(s): Sanjurjo P, Aldamiz L, Georgi G, Jelinek J, Ruiz JI, Boehm G. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 January; 36(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499992&dopt=Abstract
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Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria. Author(s): Pietz J, Landwehr R, Kutscha A, Schmidt H, de Sonneville L, Trefz FK. Source: The Journal of Pediatrics. 1995 December; 127(6): 936-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8523192&dopt=Abstract
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Effects of selenium supplementation on thyroid hormone phenylketonuria subjects on a phenylalanine restricted diet.
metabolism
in
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Author(s): Calomme M, Vanderpas J, Francois B, Van Caillie-Bertrand M, Vanovervelt N, Van Hoorebeke C, Vanden Berghe D. Source: Biological Trace Element Research. 1995 January-March; 47(1-3): 349-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7779569&dopt=Abstract •
Experimentally induced phenylketonuria. 3. Inhibitors of phenylalanine hydroxylase related to esculetin. Author(s): DeGraw JI, Cory M, Skinner WA, Theisen MC, Mitoma C. Source: Journal of Medicinal Chemistry. 1968 March; 11(2): 375-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5690961&dopt=Abstract
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Fatty acid supplementation in a case of maternal phenylketonuria. Author(s): Giovannini M, Biasucci G, Agostoni C, Bellu R, Riva E. Source: Journal of Inherited Metabolic Disease. 1994; 17(5): 630-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7837774&dopt=Abstract
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Fish oil supplementation improves visual evoked potentials in children with phenylketonuria. Author(s): Beblo S, Reinhardt H, Muntau AC, Mueller-Felber W, Roscher AA, Koletzko B. Source: Neurology. 2001 October 23; 57(8): 1488-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673596&dopt=Abstract
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Impaired arachidonic (20:4n-6) and docosahexaenoic (22:6n-3) acid synthesis by phenylalanine metabolites as etiological factors in the neuropathology of phenylketonuria. Author(s): Infante JP, Huszagh VA. Source: Molecular Genetics and Metabolism. 2001 March; 72(3): 185-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243724&dopt=Abstract
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In vivo inhibition of rat liver phenylalanine hydroxylase by p-chlorophenylalanine and Esculin. Experimental model of phenylketonuria. Author(s): Valdivieso F, Gimenez C, Mayor F. Source: Biochem Med. 1975 January; 12(1): 72-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=124571&dopt=Abstract
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Increased neurotransmitter biosynthesis in phenylketonuria induced by phenylalanine restriction or by supplementation of unrestricted diet with large amounts of tyrosine. Author(s): Lykkelund C, Nielsen JB, Lou HC, Rasmussen V, Gerdes AM, Christensen E, Guttler F.
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Source: European Journal of Pediatrics. 1988 December; 148(3): 238-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2463918&dopt=Abstract •
Intake and blood levels of fatty acids in treated patients with phenylketonuria. Author(s): Acosta PB, Yannicelli S, Singh R, Eisas LJ 2nd, Kennedy MJ, Bernstein L, Rohr F, Trahms C, Koch R, Breck J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 September; 33(3): 2539. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593118&dopt=Abstract
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Iron status and iron supplementation in children with classical phenylketonuria. Author(s): Miranda da Cruz BD, Seidler H, Widhalm K. Source: Journal of the American College of Nutrition. 1993 October; 12(5): 531-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8263269&dopt=Abstract
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Know your organizations: the National Society for Phenylketonuria and Allied Disorders. Author(s): Thorne C. Source: Health Visit. 1982 January; 55(1): 26. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6915915&dopt=Abstract
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Lipid status and long-chain polyunsaturated fatty acid concentrations in adults and adolescents with phenylketonuria on phenylalanine-restricted diet. Author(s): Moseley K, Koch R, Moser AB. Source: Journal of Inherited Metabolic Disease. 2002 February; 25(1): 56-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999981&dopt=Abstract
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Long-chain polyunsaturated fatty acids in plasma and erythrocyte membrane lipids of children with phenylketonuria after controlled linoleic acid intake. Author(s): Poge AP, Baumann K, Muller E, Leichsenring M, Schmidt H, Bremer HJ. Source: Journal of Inherited Metabolic Disease. 1998 June; 21(4): 373-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9700594&dopt=Abstract
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Molybdenum supplementation in phenylketonuria diets: adequate in early infancy? Author(s): Sievers E, Arpe T, Schleyerbach U, Schaub J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 July; 31(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896072&dopt=Abstract
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National Institutes of Health Consensus Development Conference Statement: phenylketonuria: screening and management, October 16-18, 2000. Author(s): National Institutes of Health Consensus Development Panel.
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Source: Pediatrics. 2001 October; 108(4): 972-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11581453&dopt=Abstract •
Nutritional management of the female with phenylketonuria during pregnancy. Author(s): Pueschel SM, Hum C, Andrews M. Source: The American Journal of Clinical Nutrition. 1977 July; 30(7): 1153-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=879079&dopt=Abstract
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Phenylalanine-restricted diet should be life long. A case report on long-term followup of an adolescent with untreated phenylketonuria. Author(s): Merrick J, Aspler S, Schwarz G. Source: Int J Adolesc Med Health. 2003 April-June; 15(2): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955819&dopt=Abstract
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Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Author(s): van Spronsen FJ, van Rijn M, Bekhof J, Koch R, Smit PG. Source: The American Journal of Clinical Nutrition. 2001 February; 73(2): 153-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157309&dopt=Abstract
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Plasma phenylalanine and tyrosine responses to different nutritional conditions (fasting/postprandial) in patients with phenylketonuria: effect of sample timing. Author(s): van Spronsen FJ, van Rijn M, van Dijk T, Smit GP, Reijngoud DJ, Berger R, Heymans HS. Source: Pediatrics. 1993 October; 92(4): 570-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8414829&dopt=Abstract
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Polyunsaturated fatty acid status in patients with phenylketonuria. Author(s): Sanjurjo P, Perteagudo L, Rodriguez Soriano J, Vilaseca A, Campistol J. Source: Journal of Inherited Metabolic Disease. 1994; 17(6): 704-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7707693&dopt=Abstract
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Problems related to diet management of maternal phenylketonuria. Author(s): Acosta PB, Stepnick-Gropper S. Source: Journal of Inherited Metabolic Disease. 1986; 9 Suppl 2: 183-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2877116&dopt=Abstract
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Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria. Author(s): Smith ML, Hanley WB, Clarke JT, Klim P, Schoonheyt W, Austin V, Lehotay DC.
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Source: Archives of Disease in Childhood. 1998 February; 78(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9579151&dopt=Abstract •
Rationale for the German recommendations for phenylalanine level control in phenylketonuria 1997. Author(s): Burgard P, Bremer HJ, Buhrdel P, Clemens PC, Monch E, Przyrembel H, Trefz FK, Ullrich K. Source: European Journal of Pediatrics. 1999 January; 158(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9950308&dopt=Abstract
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Red blood cell glutathione peroxidase activity as a function of selenium supplementation in dietary treated children with phenylketonuria. Author(s): Zachara BA, Wasowicz W, Gromadzinska J, Sklodowska M, Cabalska B. Source: Biomed Biochim Acta. 1987; 46(2-3): S209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3593299&dopt=Abstract
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Sensory restriction and isolation experiences in children with phenylketonuria. Author(s): Friedman CJ, Sibinga MSMS, Steisel IM, Sinnamon HM. Source: Journal of Abnormal Psychology. 1968 August; 73(4): 294-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5672220&dopt=Abstract
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Serum lipids in children with phenylketonuria (PKU). Author(s): Acosta PB, Alfin-Slater RB, Koch R. Source: Journal of the American Dietetic Association. 1973 December; 63(6): 631-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4752061&dopt=Abstract
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The effect of immobilization and sensory restriction on children with phenylketonuria. Author(s): Sibinga MS, Friedman CJ, Steisel IM, Sinnamon HM. Source: Pediatric Research. 1968 September; 2(5): 371-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5672698&dopt=Abstract
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The management of phenylketonuria (PKU). Author(s): McGill JJ. Source: Southeast Asian J Trop Med Public Health. 1999; 30 Suppl 2: 55-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400785&dopt=Abstract
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The selenium status of children with phenylketonuria: results of selenium supplementation. Author(s): Lipson A, Masters H, O'Halloran M, Thompson S, Coveney J, Yu J.
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Source: Aust Paediatr J. 1988 April; 24(2): 128-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3395305&dopt=Abstract •
The use of a low phenylalanine diet with amino acid supplement in the treatment of behavioural problems in a severely mentally retarded adult female with phenylketonuria. Author(s): Hoskin RG, Sasitharan T, Howard R. Source: Journal of Intellectual Disability Research : Jidr. 1992 April; 36 ( Pt 2): 183-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1591502&dopt=Abstract
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Tyrosine supplementation during pregnancy in a woman with classical phenylketonuria. A case report. Author(s): Lenke RR, Koch R, Fishler K, Platt LD. Source: J Reprod Med. 1983 June; 28(6): 411-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6887149&dopt=Abstract
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Tyrosine supplementation for phenylketonuria treatment. Author(s): Koch R. Source: The American Journal of Clinical Nutrition. 1996 December; 64(6): 974-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8942426&dopt=Abstract
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Tyrosine supplementation for phenylketonuria. Author(s): Poustie VJ, Rutherford P. Source: Cochrane Database Syst Rev. 2000; (2): Cd001507. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796799&dopt=Abstract
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Tyrosine supplementation in phenylketonuria. Author(s): Lines D, Magarey A, Raymond J, Robertson E. Source: Journal of Paediatrics and Child Health. 1997 April; 33(2): 177. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9145371&dopt=Abstract
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Tyrosine supplementation in phenylketonuria: diurnal blood tyrosine levels and presumptive brain influx of tyrosine and other large neutral amino acids. Author(s): Kalsner LR, Rohr FJ, Strauss KA, Korson MS, Levy HL. Source: The Journal of Pediatrics. 2001 September; 139(3): 421-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562623&dopt=Abstract
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Tyrosine supplementation in the treatment of maternal phenylketonuria. Author(s): Rohr FJ, Lobbregt D, Levy HL. Source: The American Journal of Clinical Nutrition. 1998 March; 67(3): 473-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9497192&dopt=Abstract
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Vitamin B6 and mental deficiency; the effects of large doses of B6 (pyridoxine) in phenylketonuria. Author(s): McGEER EG, TISCHLER B. Source: Can J Med Sci. 1959 March; 37(3): 485-91. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13638867&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: 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 phenylketonuria; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Allergies and Sensitivities Source: Healthnotes, Inc.; www.healthnotes.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Phenylketonuria Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Branched-Chain Amino Acids Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com L-tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Tyrosine Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON PHENYLKETONURIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to phenylketonuria. 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 “phenylketonuria” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on phenylketonuria, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Phenylketonuria 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 phenylketonuria. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Profile of Learning Abilities and Behavioral Characteristics of Elementary SchoolAge Children with Phenylketonuria by Falk, Libby Janet, EDD from Temple University, 1971, 214 pages http://wwwlib.umi.com/dissertations/fullcit/7126510
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Cognitive Functioning of Children with Phenylketonuria (Learning Disabilities) by Mollen, Eileen, PhD from The University of Michigan, 1984, 151 pages http://wwwlib.umi.com/dissertations/fullcit/8412212
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Learning Patterns in Children with Phenylketonuria by Hagovsky, Mathias Ralph, PhD from Fordham University, 1977, 96 pages http://wwwlib.umi.com/dissertations/fullcit/7714868
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Parental Adaptation to Phenylketonuria by Schild, Sylvia, DSW from University of Southern California, 1968, 208 pages http://wwwlib.umi.com/dissertations/fullcit/6812061
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Sensory Motor Integration, School Achievement, and Behavior of Children with Phenylketonuria by Skarin, Susan Marne, PhD from University of Southern California, 1981 http://wwwlib.umi.com/dissertations/fullcit/f460246
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Variant Hyperphenylalaninemia: Psychoeducational Outcome of Treated and Untreated Individuals by Lang, Mary Joann, PhD from University of Southern California, 1988 http://wwwlib.umi.com/dissertations/fullcit/f44933
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 PHENYLKETONURIA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning phenylketonuria.
Recent Trials on Phenylketonuria The following is a list of recent trials dedicated to phenylketonuria.8 Further information on a trial is available at the Web site indicated. •
Low Phenylalanine Diet for Mothers with Phenylketonuria (PKU) Condition(s): Phenylketonuria Study Status: This study is completed. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Phenylketonuria (PKU) is a rare genetic condition. If not treated, PKU can cause severe mental retardation. Women with PKU are advised to eat a special diet when pregnant to prevent mental retardation in their children. This study will evaluate the effects of that diet on the children of mothers with PKU. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065299
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Study of a Phenylalanine Restricted Diet During Pregnancy to Prevent Symptoms in Offspring of Patients With Phenylketonuria Condition(s): Phenylketonuria Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Texas
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: Objectives: I. Assess the impact of a phenylalanine restricted diet during pregnancy on symptoms in offspring of patients with phenylketonuria. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006142
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 “phenylketonuria” (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 PHENYLKETONURIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “phenylketonuria” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on phenylketonuria, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Phenylketonuria By performing a patent search focusing on phenylketonuria, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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Phenylketonuria
The following is an example of the type of information that you can expect to obtain from a patent search on phenylketonuria: •
1',2'-Diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin and process for preparing the same Inventor(s): Viscontini; Max (Zurich, CH) Assignee(s): Kanegafuchi Kagaku Kogyo Kabushiki Kaisha (Osaka, JP) Patent Number: 4,540,783 Date filed: November 15, 1982 Abstract: A novel compound, 1',2'-diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin which is prepared by catalytical hydrogenation of a 1',2'-diacyl-L-biopterin in a solvent in the presence of a catalyst. The 1',2'-diacyl-L-biopterin is prepared from a 1,1-dialkylsulfonylL-rhamnose through an acyl derivative of 5-deoxy-L-arabinose and a hydrazine derivative of tetrahydro-L-biopterin without isolating the intermediate products. The 1', 2'-diacyl-(6R,S)-5,6,7,8-tetrahydro-L-biopterin can be used for treatment of atypical phenylketonuria or dihydropterin-reductase deficiency and can readily cross the blood brain barrier without neurotransmitter precursors. Excerpt(s): The present invention relates to a novel compound, 1',2'-diacyl-(6R,S)-5,6,7,8tetrahydro-L-biopterin and a novel compound, 1',2'-diacyl-L-biopterin, and processes for preparing them. It has been found recently that (6R,S)-5,6,7,8-tetrahydro-L-biopterin and 7,8-dihydro-L-biopterin can be successfully used for a treatment of patients with atypical phenylketonuria (hereinafter referred to as PKU) or with dihydropterinreductase deficiency [A. B. Schircks, M. Viscontini and J. Schaub, Lancet, 1979, 131; H.Ch. Curtius, A. Niederwieser, M. Viscontini, A. Otten, J. Schaub, S. Scheibenreiter and H. Schmidt, Clin. Chim. Acta, 93, 251 (1979)]. Though both compounds can conduct an enzymatic hydroxylation of L-tryptophane and L-tyrosine to 5-hydroxytryptophane and DOPA, respectively, in the brain, they have difficulties to cross the blood brain barrier. Therefore neurotransmitter precursors must be given with those compounds during the treatment of both deficiency-diseases. Web site: http://www.delphion.com/details?pn=US04540783__
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Diagnostic and phenylketonuria
diagnosis
method
for
central
nervous
abnormality
and
Inventor(s): Hirose; Tsuyoshi (Tokushima, JP), Ikei; Nobuhiro (Tokushima, JP), Kajiwara; Masahiro (Saitama, JP) Assignee(s): Otsuka Pharmaceutical Co., Ltd. (Tokyo, JP) Patent Number: 5,916,537 Date filed: April 1, 1997 Abstract: There is provided a diagnostic for central nervous abnormality, comprising a labeled transmitter substance of central nervous system or a labeled precursor of the transmitter substance, whose at least one of carbon atoms is substituted for a carbon isotope wherein the diagnostic is useful for diagnosing a central nervous abnormality (e.g. depression, Alzheimer's disease, schizophrenia, etc.) by applying it to a living body by oral administration or injection and examining a change in an amount of the carbon isotope in a breath of the living body.
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Excerpt(s): The present invention relates to a diagnostic comprising a labeled transmitter substance of a central nervous system or a labeled precursor of the transmitter substance, whose a specific carbon atom is replaced by a carbon isotope, which is used for diagnosing a central nervous abnormality and phenylketonuria by measuring an amount of the carbon isotope in a breath of the living body to which the diagnosis has been administered, and a diagnosis method using the above diagnostic. Heretofore, various morbidities with respect to a central nerve, such as depression, Alzheimer's disease, schizophrenia, etc. have been generally referred to as a "central nervous abnormality". Various pharmacological and biological studies on this central nervous abnormality have been made, and the study on a novel drug for treating these diseases by normalizing a metabolic change has also been made. Phenylketonuria is a morbidity caused by dysbolism of phenylalanine. Web site: http://www.delphion.com/details?pn=US05916537__ •
Method for removing phenylalanine from proteinaceous compositions, a product so obtained and use thereof Inventor(s): Harju; Matti (Nummela, FI), Linko; Pekka (Espoo, FI), Outinen; Marko T. (Espoo, FI), Tossavainen; Olli (Helsinki, FI) Assignee(s): Valio Oy (Helsinki, FI) Patent Number: 5,547,687 Date filed: September 12, 1994 Abstract: A method for removing phenylalanine from proteinaceous compositions is disclosed wherein the protein contained in the proteinaceous composition is degraded enzymatically with a proteolytic enzyme into a protein hydrolysate. The protein hydrolysate thus obtained is treated with adsorption resin in a column that is eluted with water, the fraction wherefrom phenylalanine has been removed is recovered and salts are removed from the fraction thus recovered. Finally the recovered fraction is concentrated and dried. A palatable proteinaceous composition from which phenylalanine has been removed is also disclosed. This proteinaceous composition is used as a special nutrient preparation or a component of such in the diet of patients suffering from phenylketonuria. Excerpt(s): The present invention relates to a method for removing phenylalanine from proteinaceous compositions, yielding palatable, at least nearly phenylalanine-free protein hydrolysate compositions, a proteinaceous composition thus obtained wherefrom phenylalanine has been removed either totally or at least for the most part, and the use of such a substantially phenylalanine-free proteinaceous composition as a special nutrient product or a component of such, specifically in the diet of patients suffering from phenylketonuria (PKU). The intake of phenylalanine from food cannot be diminished by selection of the protein source, since phenylalanine is present in all animal and vegetable proteins in an amount of about 4-6%. Thus the PKU patient is well advised to avoid foodstuffs rich in protein, such as egg, fish, meat and cheese. To satisfy the need for other essential amino acids, the patient should use clinical protein products wherefrom phenylalanine has been removed either totally or in part. Phenylketonuria is a congenital disease that, if untreated, causes serious brain damage and often death within a few weeks from birth. The patient lacks the ability to produce phenylalanine hydroxylase (EC 1. 14.16.1) converting phenylalanine, an amino acid derived from food, to tyrosine. The accumulation of phenylalanine and its pyruvate, lactate and acetate derivatives in the blood and the spinal fluid causes compulsive movements, anaemia,
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skin roughening and finally brain damage. The disease can also be detected as an increased phenylacetylglutamine content in the patient's urine, wherefrom the disease has derived its name. Web site: http://www.delphion.com/details?pn=US05547687__ •
Method for treating phenylketonuria Inventor(s): Berry; Helen K. (Cincinnati, OH) Assignee(s): Children's Hospital Medical Center (Cincinnati, OH) Patent Number: 4,209,531 Date filed: September 13, 1978 Abstract: A method for improving motor and cognitive functions in mammalian subjects affected with phenylketonuria by administering a mixture of valine, isoleucine and leucine as a supplement to the restriction of phenylalanine content of their diets. The invention described herein was made in the course of work under a grant from the Department of Health, Education and Welfare. Excerpt(s): In spite of numerous efforts directed toward the study of phenylketonuria (PKU) over four decades, the exact mechanism whereby the enzymatic defect in metabolism of phenylalanine leads to abnormal development of the central nervous system remains obscure. Once the mechanism is understood, therapeutic attempts could be directed toward correcting the basic defect. At present, a restriction of phenylalanine content of the diet, thereby reducing concentration of phenylalanine and/or its metabolites in blood and tissues, including the brain, is the only empirical treatment used. Treatment of children with phenylketonuria by use of phenylalanine restriction in the diet was initiated in this country in about 1955. However, there have been no significant improvements in this highly restrictive treatment since its inception. It has heretofore been reported that high concentrations of phenylalanine, either administered chronically in the diet or acutely by parental injection, produced significant reductions of cerebral concentrations of a number of proteins (Boggs et al, Fed. Proc., 23, 146, 1964). Other reports have suggested that no depletions in such amino acids occur under similar conditions (Carver, J. Neurochem., 12, 45, 1965). More recently it has been confirmed that a significant depletion of cerebral pools of amino acids occurred by injection or feeding with phenylalanine. However, the pattern of cerebral amino acid depletion in experimental animals takes place in the presence of increased levels of serum amino acids. This phenomenon seems at variance with the traditional concept that cerebral amino acid levels are regulated by internal "blood-brain barriers" of a structural nature which are present in the adult, but poorly developed in the immature brain. Other literature publications in this area include McKean et al, J. of Neurochemistry, 15, pp 235-241, 1968 and Anderson et al, Arch. Neurol., 33, pp 634-636, October, 1976. It has been suggested that perhaps some method may be devised whereby phenylalanine could be excluded from the brain and the cerebral deficiencies of amino acids could also be corrected. It is apparent that the present empirical treatment for the restriction of phenylalanine in diet is not completely satisfactory. Moreover, continuance of the treatment diet becomes increasingly difficult as the patient grows older. Phenylalanine requirements steadily decrease while the desire for a more normal life, particularly regarding food habits, becomes urgent as the treatment is successful in producing normal physical and intellectual development. Therefore, there is a need for new methods in the treatment of phenylketonuria to control levels of phenylalanine and to inhibit its deleterious effects on the central nervous system.
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Web site: http://www.delphion.com/details?pn=US04209531__ •
Nutritional formula for phenylketonuria patients Inventor(s): Ballevre; Olivier (Lausanne, CH), Masson; Gerard (Cully, CH), Monti; Julio Cesar (Jongny, CH) Assignee(s): Nestec S.A. (Vevey, CH) Patent Number: 6,506,422 Date filed: February 22, 1999 Abstract: A nutritional formula for PKU patients. The nutritional formula has, as a protein source, a mixture of caseino-glyco-macropeptide and complementary essential amino acids other than Phe to provide a balanced amino acid profile. Vitamins and minerals sufficient to meet daily requirements are also included. When used as a complete diet, the nutritional formula includes a carbohydrate source and a fat source. However the nutrutional formula may also be used as a protein supplement in which case the carbohydrate source and the fat source may be omitted. The nutritional formula has a pleasant taste. Excerpt(s): This invention relates to a nutritional formula having a balanced amino acid profile which is suitable for patients suffering from phenylketonuria. Phenylketonuria (PKU) is an inherited defect of amino acid metabolism which results in an excess of phenylalanine (Phe) in the brain and plasma. If it is not detected and treated early in the life of an infant, the condition leads to irreversible damage of the nervous system, severe mental retardation and poor brain development. Once detected, the condition is treated by providing the infant, and later the child, with a low or Phe-free diet. Also, pregnant women who suffer from the condition are recommended a diet which is free from or low in Phe to avoid the risk of impairment of the development of the foetus and congenital malformation. However a diet which is composed of natural foods and which is free from or low in Phe, eliminates many source of essential amino acids, vitamins and minerals. Consequently, without supplementation, such a diet would provide inadequate protein, energy, vitamins and minerals to support normal growth and development. Therefore it is common to use nutritional formulas to supplement the diets of PKU patients. Also, for babies, it is common to use infant formulas which have a low Phe content as the sole or primary food source. Web site: http://www.delphion.com/details?pn=US06506422__
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Phenylalanine free protein Inventor(s): Hainline; Bryan E. (1622 Nottingham Dr., Indianapolis, IN 46240) Assignee(s): none reported Patent Number: 6,004,930 Date filed: July 3, 1996 Abstract: The present invention is directed to dietary compositions for treating patients having phenylketonuria and methods for making the dietary compositions. The compositions comprise a natural protein modified to eliminate phenylalanine from the protein's amino acid sequence. These modified proteins are synthesized from genes modified to eliminate phenylalanine codons from the reading frame of the native genes.
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Excerpt(s): The present invention relates to dietary therapies for minimizing the physiological symptoms of phenylketonuria in patients having phenylketonuria. More particularly, this invention is directed to a composition comprising a natural protein modified to eliminate phenylalanine from the protein's amino acid sequence, and methods for making the same. Phenylketonuria (PKU) is an inherited metabolic disease of humans caused by the deficiency of, or low activity of, the enzyme phenylalanine hydroxylase. Phenylalanine hydroxylase normally functions in the human body to convert the amino acid phenylalanine to tyrosine. When this enzyme is deficient, phenylalanine and its abnormal breakdown products accumulate in the bloodstream. These breakdown products are harmful to developing cells of central nervous system, resulting in symptoms of mental retardation, developmental delay, and seizures. PKU is caused by recessive mutations in a single allele in the homozygous state. About 1 in every 15,000 infants born in the United States is homozygous for this allele. Dietary therapies have been used to effectively treat infants with PKU and prevent PKU symptoms from appearing. All states require routine tests of all newborn babies to detect PKU homozygotes. Those identified at birth are put on a special diet containing low amounts of phenylalanine. These diets provide enough phenylalanine (an essential amino acid) to supply dietary needs but not enough to permit toxic accumulations. Web site: http://www.delphion.com/details?pn=US06004930__ •
Process for preparing a phenylalanine-free dietary product in dragee or tablet form Inventor(s): Schweikhardt; Friedrich (Friedrichsdorf/Ts.-2, DE), Tesmer; Erhard (Offenburg/Baden, DE), Wachtel; Ursula (Bad Homburg vd.H., DE) Assignee(s): Milupa Aktiengesellschaft (Friedrichsdorf/Ts., DE) Patent Number: 5,393,532 Date filed: June 25, 1993 Abstract: The invention pertains to a process for preparing a phenylalanine-free dietetic product comprising L-amino acids, and optionally comprising carbohydrates, minerals, trace elements and/or vitamins, for persons afflicted with phenylketonuria particularly adults, juveniles and pregnant women. The process comprises preparing a wet batch by dispersing in water the L-amino acids, some or all of the optional components, and at least one fatty material as an emulsifier, after which the wet batch is spray-dried. The spray-dried wet batch is then mixed with additional vitamins and/or carbohydrates and at least one fatty material as a separation agent to produce a mass. The mass thus produced is processed into cores for dragees or tablets, and the dragee or tablet cores are provided with coatings or dragee covers. The dietetic product is used as a nutrition supplement. Excerpt(s): The invention concerns a phenylalanine-free dietetic product based on amino acids, which is intended for persons, in particular children, adults and pregnant women who suffer from phenylketonuria, as well as to a process for preparing this phenylalanine-free dietetic product and a carrier to be used therewith. Phenylketonuria belongs to genetically determined diseases representing disorders in which altered coding sequences of deoxyribonucleic acid determine the state of the disease. Because of genetic mutation, anomalous proteins are expressed. For example, the pathogenesis of enzymopathies (those diseases caused by reduced or absent enzyme activity) is based on the accumulation of the substrates left unmetabolized and their metabolites. Presently eleven different mutations are known in the phenylalanine hydroxylase gene. When such mutation results in a complete lack of activity by such enzyme, then there will be a
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so-called phenylketonuria (hereafter PKU). If the enzyme effects only a reduced activity, then this condition leads to the so-called hyperphenylalanine anemias which must also be treated in part. Web site: http://www.delphion.com/details?pn=US05393532__ •
Test strip for phenylketone bodies Inventor(s): Ogawa; Yasunao (Ikeda, JA), Yonetani; Yukio (Nara, JA) Assignee(s): Shionogi & Co., Ltd. (Osaka, JA) Patent Number: 3,954,412 Date filed: June 17, 1974 Abstract: A test strip for the detection of phenylketone bodies in the body fluids, especially in the urine, comprising an absorbing material, a ferric salt and an ironchelating agent. The test strip is useful in early diagnosis of phenylketonuria, inborn disorder of phenylalanine metabolism. Excerpt(s): This invention relates to a test strip for the detection of phenylketone bodies in the body fluids and to a composition therefor. More particularly, the present invention relates to a test strip for the detection of phenylketone bodies in the body fluids, especially in the urine, comprising an absorbing material, a ferric salt and an iron-chelating agent and to a composition therefor comprising a ferric salt and an ironchelating agent. The presence of phenylketone bodies such as phenylpyruvic acid in the body fluids, especially in the urine, is indicative of phenylketonuria which is an inborn disorder of phenylalanine metabolism in the living bodies. Such serious metabolic disease is causal for mental disorders, mental decline, decreased pigmentation, skin diseases, etc. Normal metabolism of phenylalanine to tyrosine is observed in normal newly-born infants. However, since patients with phenylketonueia lack phenylalanine hydroxylase, phenylketone bodies are accumulated in the living bodies, and excreted in the urine in a large amount. Thus, detection of phenylketone bodies such as phenylpyruvic acid in the body fluids (e.g. urine, serum, plasma) provide a diagnosis of phenylketonuria. Since phenylketonuria can be recovered by limiting the uptake of phenylalanine in a diet, early diagnosis of such disease is required. It is known that a test strip containing as an active component ferric chloride alone or ferric ammonium sulfate alone can be used for the diagnosis of phenylketonuria, but such test strip is unstable and its sensitivity to phenylketone bodies is not high. Japanese Pat. publication No. 14246/1970 discloses a diagnostic composition for phenylketonuria, comprising a ferric salt, an organic acid and a phosphate complexing agent. Also, as a commercially available test paper used for such detection are exemplified a test paper comprising ferric ammonium sulfate and sodium cyclamate, and a test paper comprising ferric ammonium sulfate, magnesium sulfate and boric acid. However, when these test papers are contacted with a diaper moist with urine, the diaper becomes colored and dirty with the reagent contained in the test paper, and the formed color of the test paper is not uniform and prone to fade rapidly. To the contrary, the test strips of the invention for phenylketonuria do not possess such drawbacks mentioned above, and they show various advantageous features as following: (1) the result of the test is reliable, (2) semiquantitative analysis is possible, (3) the test strip can detect phenylketone bodies in the urine at a concentration of more than 10 mg/100 ml, (4) distinct, stable, and uniform color [yellow (normal)--blueish green (abnormal)] appears immediately, and the determination can be quickly made, (5) the color formed by the test does not fade
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rapidly, ( 6) the detection of phenylketone bodies is even possible on a diaper moist with urine without making it dirty. Web site: http://www.delphion.com/details?pn=US03954412__
Patent Applications on Phenylketonuria As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to phenylketonuria: •
Method of treating amino acid metabolic disorders using recombinant adenoassociated virus virions Inventor(s): Kume, Akihiro; (Utsunomiya, JP), Mizukami, Hiroaki; (Kawachi-gun, JP), Ozawa, Keiya; (Kawachi-gun, JP) Correspondence: Stoel Rives Llp; 201 South Main Street, Suite 1100; Salt Lake City; UT; 84111; US Patent Application Number: 20030198620 Date filed: April 16, 2002 Abstract: Methods for delivering a heterologous gene to a mammalian subject using recombinant adeno-associated virus (rAAV) virions are described. Recombinant AAV virions containing a heterologous gene encoding a metabolic protein are delivered to a mammalian subject having a metabolic disorder. The rAAV virion-delivered heterologous gene is expressed at a therapeutic level thereby ameliorating a sign or symptom of the metabolic disease. Exemplary examples of metabolic diseases are those caused by defects in aromatic amino acid metabolism. Exemplary examples of heterologous genes include those encoding an aromatic amino acid hydroxylase, aromatic amino acid decarboxylase, and enzymes involved in tetrahydrobiopterin synthesis. Methods for treating phenylketonuria are also described. Excerpt(s): The present invention relates to methods of delivering genes to patients with metabolic disorders. More particularly, the present invention relates to delivering genes using recombinant adeno-associated virus (rAAV) virions for treating amino acid metabolic disorders. Living organisms are not in a state of chemical and physical equilibrium. Rather, they require a continuous influx of free energy to maintain order against an environment oriented toward disorder. Metabolism is the overall process through which living systems acquire and utilize the free energy they require to maintain this order (i.e., to carry out the functions necessary to sustain life). They achieve this by coupling the exergonic reactions of nutrient oxidation to the endergonic processes required to maintain the living state (e.g., the performance of mechanical work, the active transport of molecules against concentration gradients, and the biosynthesis of complex macromolecules). Animals obtain this free energy by oxidizing organic compounds (carbohydrates, lipids, and proteins) obtained from other organisms. The liberated free energy from oxidation reactions is most often coupled to endergonic reactions through the intermediate synthesis of adenosine triphosphate and other high-energy phosphate compounds. In addition to being completely oxidized,
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This has been a common practice outside the United States prior to December 2000.
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nutrients are broken down to common intermediates that are used as precursors in the synthesis of other biological molecules. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
PHENYLALANINE-FREE PROTEIN AND DNA CODING THEREFOR Inventor(s): CARR, NOEL G.; (WARWICKSHIRE, GB), MANN, NICHOLAS H.; (WARWICKSHIRE, GB) Correspondence: Townwsend & Townsend And Crew, Llp; Two Embarcadero Center; 8th Floor; San Francisco; CA; 941113834 Patent Application Number: 20020192744 Date filed: January 16, 1996 Abstract: A DNA molecule coding for a food protein, such as ovalbumin or casein, modified so that the codons for phenylalanine have been omitted or replaced by codons for one or more other metabolisable amino acids. Also a modified edible protein coded for by such a DNA molecule. Such modified proteins are useful in the nutrition of patients suffering from phenylketonuria. Excerpt(s): This invention relates to an edible protein which has been modified so that it is phenylalanine free, to DNA coding for it, and to a method of producing it. Such a protein is a useful nutrient in the treatment of diseases which are associated with difficulty in metabolising phenylalanine. A particular example of such a disease is phenylketonuria (PKU). PKU is a genetically acquired disease that occurs in a relatively fixed proportion of new births in a human population. A defect in the enzyme carrying out the pterin-dependent hydroxylation of phenylalanine to tyrosine prevents the body from metabolizing the amino acid phenylalanine. This amino acid occurs in varying proportions in all proteins in foodstuffs and is, in the correct amount, essential for human protein synthesis, and therefore for the growth and maintenance of the body. Patients with PKU cannot remove excess phenylalanine from the blood and tissues and the failure to achieve this control over phenylalanine levels leads to grave neurological damage, especially in the growing child. PKU patients are at present fed with a synthetic diet which contains a metabolically-correct amount of phenylalanine along with a mixture of the other amino acids needed for growth. Such a diet is unpalatable and is presented in liquid form only and therefore has difficulty in achieving patient compliance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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USE OF THREONINE FOR THE TREATMENT OF PHENYLKETONURIA Inventor(s): GEORGI, GILDA; (FRIEDRICHSDORF, DE), SAWATZKI, GUNTHER; (MUNZENBERG, DE) Correspondence: Bacon & Thomas; 625 Slaters Lane 4th Floor; Alexandria; VA; 22314 Patent Application Number: 20010011070 Date filed: March 2, 1998 Abstract: The invention relates to the use of threonine for the treatment of phenylketonuria. The invention is based on the surprising discovery that the concentration of phenylalanine in the plasma of PKU patients can be reduced by
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additional doses of threonine. The object of the invention is therefore an composition for dietetic or pharmaceutical use in phenylketonuria, which composition contains at least 8 g threonine per 100 g amino acids. This composition may consist of foods, in particular formula foods and PKU dietetic products. Excerpt(s): The invention relates to a composition for the dietetic or pharmaceutical treatment of phenyl-ketonuria and the use of threonine for the treatment of phenylketonuria. Phenylketonuria (referred to below as PKU) is among the genetically determined diseases and is a metabolic disorder which if untreated usually leads to severe impairment of physical and mental development. Under normal nutritional conditions, phenylalanine is absorbed with all proteins of animal and plant origin. In persons with the disease, phenylalanine accumulates in the blood and tissues because of the metabolic disorder. The consequences of the sometimes excessively high phenylalanine level are metabolic imbalances, which can lead via various symptoms to irreversible, progressive mental disability. PKU is not curable, but can be treated by appropriate diets, which are low in phenylalanine, so that the amount of phenylalanine introduced via the diet is only such that the synthesis of endogenous proteins for growth and regeneration is optimally ensured and at the same time the phenylalanine blood level lies in the normal range. 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 phenylketonuria, 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 “phenylketonuria” (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 phenylketonuria. You can also use this procedure to view pending patent applications concerning phenylketonuria. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON PHENYLKETONURIA Overview This chapter provides bibliographic book references relating to phenylketonuria. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on phenylketonuria include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “phenylketonuria” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on phenylketonuria: •
Genetic Disorders and Birth Defects: A Compendium of AAP Guidelines and Resources for the Primary Care Practitioner Source: Elk Grove Village, IL: American Academy of Pediatrics (AAP). 1997. 130 p. Contact: Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. PRICE: $24.95 each (members); $29.95 each (nonmembers); plus shipping and handling. Order Number BMA0097. Summary: This volume provides a compendium of the American Academy of Pediatrics (AAP) guidelines and resources for health care providers who are working with patients who have genetic disorders and birth defects. The compendium serves as a diagnostic and management resource guide for pediatricians and primary care physicians.
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Although some of the disorders covered are relatively uncommon, it is likely that most pediatricians will encounter and care for a few such patients in their practice panel. The authors emphasize that early intervention services, multidisciplinary care, and developmental assessment and management form a major part of continuing care for many children with genetic conditions. The AAP Policy Statements are provided on folic acid for the prevention of neural tube defects, issues in newborn screening, maternal phenylketonuria, maternal serum alpha-fetoprotein screening, newborn screening for congenital hypothyroidism, newborn screening fact sheets, and prenatal genetic diagnosis for pediatricians. In addition, policy statements are provided for the health supervision of children born with the following conditions: achondroplasia, Down syndrome, fragile X syndrome, Marfan syndrome, neurofibromatosis, sickle cell disease, and Turner syndrome. Each Policy Statement includes references. The compendium includes extensive appendices, covering topics including fetal alcohol syndrome, general principles of care for children and adolescents with genetic and other chronic health conditions, hospital stays, medical homes, preventive pediatric health care, and transition of care provided for adolescents with special health care needs. The compendium also lists the references where the policy statements were first published, the contact information for national and regional genetic organizations, and the members of the AAP Section on Genetics and Birth Defects.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “phenylketonuria” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “phenylketonuria” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “phenylketonuria” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Parents's Guide to Newborn Screening for Phenylketonuria, Congenital Hypothryroidism and Cystic Fibrosis (2002); ISBN: 1902030729; http://www.amazon.com/exec/obidos/ASIN/1902030729/icongroupinterna
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Advances in Phenylketonuria Research by V. Romano (Editor) (1993); ISBN: 3805557590; http://www.amazon.com/exec/obidos/ASIN/3805557590/icongroupinterna
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Carbohydrate and Glycoprotein Metabolism; Maternal Phenylketonuria by R. Angus Harkness (Editor), et al (1991); ISBN: 0792389476; http://www.amazon.com/exec/obidos/ASIN/0792389476/icongroupinterna
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Low Protein Cookery for Phenylketonuria by Virginia E. Schuett; ISBN: 0299153843; http://www.amazon.com/exec/obidos/ASIN/0299153843/icongroupinterna
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Phenylketonuria (PKU) screening and management : January 1980 through July 2000, plus selected earlier citations : 3,394 citations (SuDoc HE 20.3516/2:2000-4) by Karen Patrias; ISBN: B000113NKM; http://www.amazon.com/exec/obidos/ASIN/B000113NKM/icongroupinterna
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Phenylketonuria and some other inborn errors of amino acid metabolism: biochemistry, genetics, diagnosis, therapy; ISBN: 3134669013; http://www.amazon.com/exec/obidos/ASIN/3134669013/icongroupinterna
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Practical Developments in Inherited Metabolic Disease: DNA Analysis, Phenylketonuria and Screening for Congenital Adrenal Hyperplasia by G.M. Addison, et al (1987); ISBN: 085200690X; http://www.amazon.com/exec/obidos/ASIN/085200690X/icongroupinterna
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Report of the NIH Consensus Development Conference on Phenylketonuria (PKU) (SuDoc HE 20.3352:P 52) by U.S. Dept of Health and Human Services; ISBN: B000115O7W; http://www.amazon.com/exec/obidos/ASIN/B000115O7W/icongroupinterna
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The child with phenylketonuria by J. B. Holton; ISBN: 0855370211; http://www.amazon.com/exec/obidos/ASIN/0855370211/icongroupinterna
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The Official Parent's Sourcebook on Phenylketonuria by James N. Parker, Icon Health Publications (2002); ISBN: 0597832048; http://www.amazon.com/exec/obidos/ASIN/0597832048/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “phenylketonuria” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Cost and availability of dietary treatment of phenylketonuria (PKU): report of a national survey Author: California. Dept. of Health Services. Genetic Disease Branch.; Year: 1999; Berkeley, Calif.: The Branch, 1997
•
Dental health in children with Phenylketonuria, PKU: and other inborn errors of metabolism managed by diet Author: Casamassimo, Paul S.; Year: 1986; Rockville, Md.: U.S. Dept. of Health; Human Services, Public Health Service, Health Resources and Services Administration, Bureau of Health Care Delivery and Assistance, Division of Maternal and Child Health, 1984
•
Diet and nutrition sourcebook: basic consumer health information about dietary guidelines, recommended daily intake values, vitamins, minerals, fiber, fat, weight control, dietary supplements, and food additives: along with special sections on nutrition needs throughout life and nutrition for people with such specific medical concerns as allergies, high blood cholesterol, hypertension, diabetes, celiac disease, seizure disorders, phenylketonuria (PKU), cancer, and eating disorders: and including reports on current nutrition research and source listings for additional help and
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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information Author: Bellenir, Karen.; Year: 2000; Detroit, MI: Omnigraphics, c1999; ISBN: 0780802284 http://www.amazon.com/exec/obidos/ASIN/0780802284/icongroupinterna •
Dietary management of inherited metabolic disease: phenylketonuria, galactosemia, tyrosinemia, homocystinuria, maple syrup urine disease Author: Acosta, Phyllis B.; Year: 1978; Atlanta: ACELMU publishers, c1976
•
Management of newborn infants with phenylketonuria Author: Collaborative Study of Children Treated for Phenylketonuria.; Year: 1965; [Rockville, Md.]: U. S. Dept. of Health, Education, and Welfare, Public Health Service, Health Services Administration, Bureau of Community Health Services, 1978
•
Phenylketonuria (PKU) [electronic resource]: screening and management: January 1980 through July 2000, plus selected earlier citations: 3,394 citations Author: Patrias, Karen.; Year: 1965; Bethesda, Md. (8600 Rockville Pike): U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of Medicine, Reference Section, [2000]
•
Phenylketonuria and other inborn errors of metabolism: the Oregon program Author: Ashley, Carl G. (Carl George),; Year: 1984; [Portland, Ore.: Maternal and Child Health Section, Preventive Medical Services Division, Oregon State Board of Health, 1965?]
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Phenylketonuria. Author: Lyman, Frank Lewis,; Year: 1963; Springfield, Ill., Thomas [c1963]
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Phenylketonuria; a selected bibliography. [Listing prepared by Gladys M. Krueger. Author: United States. Children's Bureau.; Year: 1963; Washington] 1963
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Phenylketonuria; an inherited metabolic disorder associated with mental retardation [by] Willard R. Centerwall [and] Siegried A. Centerwall. Author: Centerwall, Willard R.,; Year: 1972; [Bethesda, Md.] U. S. Maternal and Child Health Service; [for sale by the Supt. of Docs., U. S. Govt. Print. Off., Washington] 1972
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PKU; a diet guide for parents of children with phenylketonuria. Author: California. Bureau of Public Health Nutrition.; Year: 1962; [Berkeley, 1962]
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Report of the NIH Consensus Development Conference on Phenylketonuria (PKU): screening and management Author: National Institutes of Health (U.S.); Year: 1976; Bethesda, Md.: The Institutes, 2001
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State laws pertaining to phenylketonuria as of November 1970. Author: United States. Maternal and Child Health Service.; Year: 1971; Rockville, Md., 1971
Chapters on Phenylketonuria In order to find chapters that specifically relate to phenylketonuria, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and phenylketonuria using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “phenylketonuria” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on phenylketonuria:
Books
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Genetic Disorders Source: in Roe, S.N., ed. Dietitian's Patient Education Manual. Frederick, MD: Aspen Publishers, Inc. 1991. p. 11: 1-11: 30. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21701-9782. (800) 638-8437 or (301) 417-7500. PRICE: $255; plus shipping and handling. ISBN: 0834201968. Summary: This book chapter, from a dietitian's patient education manual, discusses four genetic disorders: phenylketonuria (PKU), galactosemia, maple syrup urine disease, and homocystinuria. For each disorder covered, the author presents a definition and rationale for treatment, considerations for diet counseling, and details of food intake. Specific topics include requirements for infants and children with various inherited disorders of amino acid metabolism, the use of food exchange lists, snacks, a meal plan for maternal PKU, foods to avoid, reading food labels, strategies for enhancing patient compliance, teaching children to use a scale, special considerations for the teenager with PKU, and common questions and answers about each disorder. Also included are numerous suggestions for games to play with children as part of their patient education. This manual contains numerous charts and short sidebars for easy photocopying and incorporation into any patient education program. The chapter concludes with recipes and a list of related publications and resource organizations.
•
Differential Diagnosis of Scleroderma-like Disorders Source: in Clements, P.J.; Furst, D.E., Eds. Systemic Sclerosis. Baltimore, MD: Williams and Wilkins. 1996. p. 99-120. Contact: Available from Williams and Wilkins, Special Sales Department. (800) 358-3583. Summary: This chapter for health professionals focuses on the differential diagnosis of scleroderma-like disorders. These disorders include scleredema, scleredema associated with paraproteinemia or myeloma, scleromyxedema, scleroderma-like lesions in endocrine disorders, Werner's syndrome, progeria, sclerodermiform neonatal progeria, restrictive dermopathy, sclerodermiform chronic graft-versus-host disease, and scleroderma-like changes of porphyria cutanea tarda. Other disorders include scleroderma-like lesions in phenylketonuria, congenital fascial dystrophy, sclerodermalike changes induced by bleomycin, scleroderma-like plaques after vitamin K injection, progressive facial hemiatrophy, fibroblastic rheumatism, localized lipoatrophies, lichen sclerosus et atrophicus, sclerodermiform variety of acrodermatitis chronica atrophicans, and atrophoderma Pasini- pierini. Most of these disorders are discussed in terms of their clinical features, pathology and pathophysiology, differential diagnosis, and treatment. 115 references and 10 figures.
•
Nutrition and Disorders of the Liver Source: in Whitney, E.N., Cataldo, C.B., and Rolfes, S.R. Understanding Normal and Clinical Nutrition. 4th ed. St. Paul, MN: West Publishing Company. 1994. p. 822-841. Contact: Available from West Publishing. 620 Opperman Drive, St. Paul, MN 55164. (800) 340-9378 or (612) 687-7000. PRICE: $67.00. ISBN: 0314041788. Summary: This chapter on nutrition and disorders of the liver is from an introductory medical textbook on nutrition. Topics include fatty liver, hepatitis, cirrhosis, liver transplantation, and nutrition assessment. The authors focus on the appropriate diet therapy for each of these liver disorders. The chapter concludes with study questions,
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clinical application questions, and a 'highlight' section describing inborn errors of metabolism, most notably phenylketonuria and galactosemia. 8 figures. 1 table. 19 references. (AA-M). •
Food Intolerance Source: in Gerber, J.M. Handbook of Preventive and Therapeutic Nutrition. Frederick, MD: Aspen Publishers, Inc. 1993. p. 42-45. Contact: Available from Aspen Publishers, Inc. 7201 McKinney Circle, Frederick, MD 21701-9782. (800) 638-8437 or (301) 417-7500. PRICE: $34. ISBN: 0834203189. Summary: This chapter, from a handbook of preventive and therapeutic nutrition, provides an overview about food intolerance. Sections include maldigestion disorders; gastrointestinal disease, including celiac sprue, cystic fibrosis, and cholecystitis; metabolic defects, including phenylketonuria, and galactosemia; psychologic reactions; natural substances causing food intolerance, including phenylethylamine, tyramine, histamine, and histamine-releasing agents; food additives causing food intolerance, including tartrazine (yellow No. 5), benzoic acid, sulfites, and monosodium glutamate (MSG); and microorganism contamination causing food intolerance, including proteus and gonyaulax catenella. In each section, brief information is presented on the type of reaction common to the agent described.
•
Inborn Errors of Metabolism Source: in Thoene, J.G., ed. Physicians' Guide to Rare Diseases. 2nd ed. Montvale, NJ: Dowden Publishing Company. 1995. p. 167-248. Contact: Available from Dowden Publishing Company, Inc. 110 Summit Avenue, Montvale, NJ 07645. (201) 391-9100. Fax (201) 391-2778. PRICE: $97.50 plus shipping and handling. ISBN: 0962871613. Summary: This chapter, from a physicians' guidebook to rare diseases, discusses inborn errors of metabolism. The book's intent is to help doctors and their patients identify rare disorders and find treatments and support groups. After an introductory section, this chapter covers more than ninety disorders, including the following, which relate to the digestive system: Andersen disease; Fabry disease; Forbes disease; fructose intolerance; galactosemia; Gaucher disease; Menkes disease; phenylketonuria; porphyria; Refsum syndrome; Sandhoff disease; Tangier disease; vitamin E deficiency; von Gierke disease; Wilson disease; and Zellwinger syndrome. For each disorder, the author includes a description, synonyms, and information about signs and symptoms, etiology, epidemiology, related disorders, standard and investigational treatments, and support groups and additional resources. A brief reference list for each disorder is also included.
•
Metabolic and Endocrine Disorders Source: in Grundy, M.C.; Shaw, L.; and Hamilton, D.V. Illustrated Guide to Dental Care for the Medically Compromised Patient. St. Louis, MO: Mosby-Year Book, Inc. 1993. p. 51-59. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-9934. (800) 426-4545 or (314) 872-8370; Fax (800) 535-9935 or (314) 4321380; E-mail:
[email protected]; http://www.mosby.com. PRICE: $24.95 plus shipping and handling. ISBN: 0815140223.
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Summary: This chapter, from an illustrated guide to dental care for medically compromised patients, discusses metabolic and endocrine disorders. The chapter's topics include diabetes mellitus (insulin-dependent and noninsulin-dependent), including hypoglycemia and hyperglycemia; phenylketonuria; adrenocortical diseases; Addison's disease, including secondary adrenal insufficiency and Cushing's syndrome; thyroid disorders, including hyperthyroidism and hypothyroidism; and parathyroid disorders. For each condition, the authors provide a brief description, the components of medical management, and suggestions for dental care. Illustrations, including photographs, are included. 5 figures.
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CHAPTER 8. MULTIMEDIA ON PHENYLKETONURIA Overview In this chapter, we show you how to keep current on multimedia sources of information on phenylketonuria. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Bibliography: Multimedia on Phenylketonuria The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in phenylketonuria (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on phenylketonuria: •
Phenylketonuria (PKU) [electronic resource]: screening and management: January 1980 through July 2000, plus selected earlier citations: 3,394 citations Source: prepared by Karen Patrias, Felix F. de la Cruz; Year: 2000; Format: Electronic resource; Bethesda, Md. (8600 Rockville Pike): U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, National Library of Medicine, Reference Section, [2000]
•
Phenylketonuria [videorecording] Source: a presentation of Films for the Humanities & Sciences; a Leeds University Television production for Shotlist; Year: 2001; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c2001
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CHAPTER 9. PERIODICALS PHENYLKETONURIA
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover phenylketonuria.
News Services and Press Releases One of the simplest ways of tracking press releases on phenylketonuria is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “phenylketonuria” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to phenylketonuria. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “phenylketonuria” (or synonyms). The following was recently listed in this archive for phenylketonuria: •
Drug may help patients with mild phenylketonuria Source: Reuters Health eLine Date: December 27, 2002
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Link between low protein intake and congenital heart defects in maternal phenylketonuria Source: Reuters Medical News Date: September 05, 2002
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Adherence to dietary control of phenylketonuria poor in older children Source: Reuters Medical News Date: July 08, 2002
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Women with phenylketonuria should restrict diet before and during pregnancy Source: Reuters Medical News Date: January 12, 2000
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Recombinant enzyme may improve therapy for phenylketonuria Source: Reuters Medical News Date: March 04, 1999
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Psychiatric Symptoms In Adults With Phenylketonuria Of Psychologic Origin Source: Reuters Medical News Date: March 11, 1997 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “phenylketonuria” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.
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Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “phenylketonuria” (or synonyms). If you know the name of a company that is relevant to phenylketonuria, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “phenylketonuria” (or synonyms).
Newsletters on Phenylketonuria Find newsletters on phenylketonuria using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “phenylketonuria.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “phenylketonuria” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
PKU CORPS bulletin Source: Boston, MA: PKU Community Outreach Resource Programs, Children's Hospital. 1995-. irregular. Contact: Available from Ildiko Szabo, Children's Hospital, PKU Community Outreach Resource Programs, 300 Longwood Avenue, Boston, MA 02115. Telephone: (617) 3557346 / fax: (617) 730-0461 / e-mail:
[email protected]. Summary: This newsletter contains articles on topics of interest to families affected by phenylketonuria (PKU) who live in the New England region. Among other topics, it includes news from the readers, notices from state agencies regarding services, news about future social events, and dietary suggestions. [Funded by the Maternal and Child Health Bureau].
Academic Periodicals covering Phenylketonuria Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to phenylketonuria. In addition to these sources, you can search for articles covering phenylketonuria that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.”
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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for phenylketonuria. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).
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Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to phenylketonuria by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “phenylketonuria” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for
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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for phenylketonuria: •
Phenylalanine ammonia-lyase (trade name: Phenylase) http://www.rarediseases.org/nord/search/nodd_full?code=366
•
Valine, isoleucine and leucine (trade name: VIL) http://www.rarediseases.org/nord/search/nodd_full?code=270
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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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
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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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
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “phenylketonuria” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “phenylketonuria” (or synonyms) into the “For these words:” box. The following is a sample result: •
Cost and availability of dietary treatment of phenylketonuria (PKU): Report of a national survey Source: Berkeley, CA: Genetic Disease Branch, California Department of Health Services. 1997. ca. 200 pp. Contact: Available from National Maternal and Child Health Clearinghouse, 2070 Chain Bridge Road, Suite 450, Vienna, VA 22182-2536. Telephone: (703) 356-1964 or (888) 4344MCH / fax: (703) 821-2098 / e-mail:
[email protected] / Web site: http://www.nmchc.org. Available at no charge. Summary: This survey discusses the costs of treating children with phenylketonuria (PKU), who need low protein formula and food products. A questionnaire was sent to parents of children with PKU, information about reimbursement was collected from private insurance companies, state health agencies were surveyed on their diet provision policies and applicable state laws, data on available dietary products was collected from manufacturers, and the costs of feeding a child with PKU were calculated using data on food costs from the U.S. Department of Agriculture. The survey ends with four appendices providing the parents' questionnaire, correspondence with the Health Insurance Association of America, state laws relating to a PKU diet, and an American Academy of Pediatrics statement. [Funded by the Maternal and Child Health Bureau].
The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 15 16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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Type “phenylketonuria” (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 5432 139 641 5 1 6218
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “phenylketonuria” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for
17
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
18
The HSTAT URL is http://hstat.nlm.nih.gov/.
19
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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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/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Phenylketonuria In the following section, we will discuss databases and references which relate to the Genome Project and phenylketonuria. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “phenylketonuria” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for phenylketonuria: •
Phenylketonuria Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?261600
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Phenylketonuria II Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?261630
23
Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html
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Entrez Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “phenylketonuria” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually 24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.
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limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “phenylketonuria” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
25
Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 phenylketonuria 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 phenylketonuria. 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 phenylketonuria. 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 “phenylketonuria”:
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Other guides Alpha-1 Antitrypsin Deficiency http://www.nlm.nih.gov/medlineplus/alpha1antitrypsindeficiency.html Chiropractic http://www.nlm.nih.gov/medlineplus/chiropractic.html Down Syndrome http://www.nlm.nih.gov/medlineplus/downsyndrome.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Phenylketonuria http://www.nlm.nih.gov/medlineplus/phenylketonuria.html Prader-Willi Syndrome http://www.nlm.nih.gov/medlineplus/praderwillisyndrome.html Turner's Syndrome http://www.nlm.nih.gov/medlineplus/turnerssyndrome.html
Within the health topic page dedicated to phenylketonuria, the following was listed: •
General/Overviews PKU Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1219.asp
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Diagnosis/Symptoms How Is Phenylketonuria Diagnosed? Source: Dolan DNA Learning Center http://www.yourgenesyourhealth.org/pku/diagnosis.htm
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Nutrition Is Aspartame Safe for My Child? Source: Nemours Foundation http://kidshealth.org/parent/growth/feeding/aspartame.html Look-Alike Foods: A Solution or a Pandora's Box? http://depts.washington.edu/pku/pdfs/lookalike.pdf What is the Diet for PKU? Source: University of Washington PKU Clinic http://depts.washington.edu/pku/diet.html
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Coping What Is It Like to Have Phenylketonuria (PKU)? Source: Dolan DNA Learning Center http://www.yourgenesyourhealth.org/pku/have.htm
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Specific Conditions/Aspects Aspartame Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/aspartame.htm Babysitter's Guide to PKU http://depts.washington.edu/pku/pdfs/babysitter.pdf How Is Phenylketonuria Inherited? Source: Dolan DNA Learning Center http://www.yourgenesyourhealth.org/pku/inherited.htm Introduction to Drug Products Containing Phenylalanine Source: National PKU News http://www.pkunews.org/diet/aspartame.htm What Causes Phenylketonuria? Source: Dolan DNA Learning Center http://www.yourgenesyourhealth.org/pku/cause.htm
•
Prevention/Screening Extending the Successful Prevention of Mental Retardation Through Newborn Screening Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r020215b.htm Newborn Screening Tests Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/298_834.asp
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on phenylketonuria. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search
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options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Newborn screening fact sheets. (Rev. ed.) Source: [Evanston, IL]: American Academy of Pediatrics. 1996. 29 pp. Contact: Available from Librarian, National Center for Education in Maternal and Child Health, 2000 15th Street, North, Suite 701, Arlington, VA 22201-2617. Telephone: (703) 524-7802 / fax: (703) 524- 9335 / e-mail:
[email protected] / Web site: http://www.ncemch.org. Available for loan. Summary: These fact sheets were developed to assist pediatricians in understanding the individual genetic screening tests, their characteristics, and their strengths and weaknesses. The fact sheets do not advocate specific newborn screening tests but assist pediatricians in evaluating policies and procedures and in developing appropriate positions based on the needs of their patients and their geographic regions. Testing facts are provided regarding biotinidase deficiency, branched-chain keoaciduria (maple syrup urine disease), congenital adrenal hyperplasia, congenital hypothyroidism, cystic fibrosis, galactosemia, homocystinuria, phenylketonuria, sickle cell diseases, toxoplasmosis, and tyrosinemia.
•
NutraSweet Use During Pregnancy Source: Deerfield, IL: NutraSweet Company. 1990. 4 p. Contact: Available from NutraSweet Consumer Center. P.O. Box 830, Deerfield, IL 60015. (800) 321-7254 or (708) 405-7679. PRICE: Single copy free. Summary: This brief brochure describes NutraSweet brand sweetener: what it is and why it is safe for use during pregnancy and breast feeding. The brochure presents evidence to show that NutraSweet is safe for the general population, including children and pregnant and breast-feeding women. Two figures compare the components of NutraSweet with those found in common dietary items including milk, tomato juice, and hamburger. A brief sidebar presents information about phenylketonuria.
•
NutraSweet Use During Pregnancy: Information for the Health Care Provider Source: Deerfield, IL: NutraSweet Company. 1990. 8 P. Contact: NutraSweet Company. The NutraSweet Center, Box 830, 01751 Lake Cook Road, Deerfield, IL 60015. (800)321-7254. PRICE: Single copy free. Summary: This brochure presents information for health care providers on the safety of aspartame (NutraSweet) during pregnancy. Topics covered include the chemical composition of aspartame, a summary of preclinical studies of aspartame, clinical studies of aspartame and its effects, information about phenylketonuria, phenylalanine blood levels, acute and chronic clinical studies conducted with aspartame, aspartame use in normal pregnant women, and the safety of aspartame use for pregnant women. A contact address and toll-free telephone number for NutraSweet is included.
•
Facts About Aspartame Source: Journal of American Dietetic Association. 93(10): 959-960. October 1993. Contact: Available from American Dietetic Association. 216 West Jackson Boulevard, Chicago, IL 60606. (800) 366-1655.
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Summary: This fact sheet acquaints readers with aspartame (NutraSweet brand), a nutritive sweetener. Written in a question-and-answer format, the fact sheet discusses the role of aspartame-sweetened foods in a healthful eating plan; the safety of aspartame; problems caused by aspartame in people with a rare genetic disease called phenylketonuria (PKU); the uses of aspartame; and product labeling information. The fact sheet includes the American Dietetic Association's Consumer Nutrition Hotline (800-366-1655) and encourages readers to use this number for further information about aspartame. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “phenylketonuria” (or synonyms). The following was recently posted: •
Maternal phenylketonuria Source: American Academy of Pediatrics - Medical Specialty Society; 2001 February; 2 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2777&nbr=2003&a mp;string=phenylketonuria
•
Phenylketonuria: screening and management Source: National Institute of Child Health and Human Development - Federal Government Agency [U.S.]; 2000 October 18; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2716&nbr=1942&a mp;string=phenylketonuria Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Phenylketonuria (PKU) Source: March of Dimes Birth Defects Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3268
•
Phenylketonuria (PKU): Screening and Management Summary: This NIH consensus statement covers the incidence and prevalence of phenylketonuria (PKU), screening strategies, strategy effectiveness, and treatment regimens. Source: National Institutes of Health, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6336
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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 phenylketonuria. 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. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on phenylketonuria can be purchased from NORD for a nominal fee. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: 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 phenylketonuria. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with phenylketonuria.
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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 phenylketonuria. 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 “phenylketonuria” (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 “phenylketonuria”. 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 “phenylketonuria” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “phenylketonuria” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.26
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)27: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
27
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on phenylketonuria: •
Basic Guidelines for Phenylketonuria Phenylketonuria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001166.htm PKU Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001166.htm
•
Signs & Symptoms for Phenylketonuria Athetosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003197.htm Hyperactivity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003256.htm Microcephaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003272.htm
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Rashes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Skin rashes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003297.htm •
Diagnostics and Tests for Phenylketonuria Enzyme assay Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003332.htm Phenylalanine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003362.htm PK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003357.htm
•
Nutrition for Phenylketonuria Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm
•
Background Topics for Phenylketonuria Amino acids Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002222.htm Central nervous system Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm Enzyme Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002353.htm Melanin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002256.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
Online Glossaries 153
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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PHENYLKETONURIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Hydroxytryptophan: Precursor of serotonin used as antiepileptic and antidepressant. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] 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] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrodermatitis: Inflammation involving the skin of the extremities, especially the hands and feet. Several forms are known, some idiopathic and some hereditary. The infantile form is called Gianotti-Crosti syndrome. [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
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enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Hyperplasia, Congenital: A group of inherited disorders of adrenal steroidogenesis, the physical expression of which varies with the sex of the patient, the severity of the congenital enzyme defect, and the age at which the defect makes its presence felt. The most common form, the simple virilizing form, is due to a 21-hydroxylase deficiency. There is also a salt-losing form (a more complete 21-hydroxylase deficiency), a hypertensive form (11-hydroxylase deficiency), a 17-hydroxylase deficiency form, a desmolase deficiency form, and a 3-beta-hydroxysteroid deficiency form. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] 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
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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 substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaptonuria: An inborn error of amino acid metabolism resulting from a defect in the enzyme homogentisate 1,2-dioxygenase and causing an accumulation of homogentisic acid in the urine. The condition is characterized by ochronosis in various tissues and arthritis. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from
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which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Sulfate: Sulfuric acid diammonium salt. It is used in fractionation of proteins. [NIH]
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] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
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] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of
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hemoglobin. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anthropology: The science devoted to the comparative study of man. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid
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to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Aspartame: Flavoring agent sweeter than sugar, metabolized as phenylalanine and aspartic acid. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH]
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Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH]
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Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]
Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal
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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] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchial: Pertaining to one or more bronchi. [EU] 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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH]
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Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] 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 Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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]
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Chiropractic: A system of treating bodily disorders by manipulation of the spine and other parts, based on the belief that the cause is the abnormal functioning of a nerve. [NIH] Cholecystitis: Inflammation of the gallbladder. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the
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action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] 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] Complement 3: The fourth component to attach in the complement reaction sequence. It is a beta-globulin with a sedimentation coefficient of 5.5, a molecular weight of 185,000 and a serum concentration of 1.3 micrograms/ml. Its fragments have anaphylatoxic, chemotactic, and histaminic action and affect smooth muscle. [NIH] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complement Factor D: A serum protein which during the alternate pathway of complement activation converts the inactive factor B to complement 3 convertase. EC 3.4.21.46. [NIH] 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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD
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results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortical Blindness: The inability to understand or interpret what is seen due to a disturbance in the cerebral associational areas, the retina, the sensory pathways, and the striate area being intact. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Curative: Tending to overcome disease and promote recovery. [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] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [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 is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH]
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Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [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] Dermal: Pertaining to or coming from the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dietary Proteins: Proteins obtained from foods. They are the main source of the essential amino acids. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [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
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movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydropteridine Reductase: An enzyme that catalyzes the dihydropteridine to 5,6,7,8-tetrahydropteridine. EC 1.6.99.7. [NIH]
reduction
of
6,7-
Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diurnal: Occurring during the day. [EU] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Duodenum: The first part of the small intestine. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is
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based on the results of a randomized control trial. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]
Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH]
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Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [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]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH]
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Estrogen: One of the two female sex hormones. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Color: Color of the iris. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Hemiatrophy: A syndrome characterized by slowly progressive unilateral atrophy of facial subcutaneous fat, muscle tissue, skin, cartilage, and bone. The condition typically progresses over a period of 2-10 years and then stabilizes. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH]
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Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flatus: Gas passed through the rectum. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]
Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]
Food Exchange: See: Exchange lists. [NIH] Food Habits: Acquired or learned food preferences. [NIH] Food Preferences: The selection of one food over another. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH]
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Fructose Intolerance: An autosomal recessive fructose metabolism disorder due to deficient fructose-1-phosphate aldolase (EC 2.1.2.13) activity, resulting in accumulation of fructose-1phosphate. The accumulated fructose-1-phosphate inhibits glycogenolysis and gluconeogenesis, causing severe hypoglycemia following ingestion of fructose. Prolonged fructose ingestion in infants leads ultimately to hepatic failure and death. Patients develop a strong distaste for sweet food, and avoid a chronic course of the disease by remaining on a fructose- and sucrose-free diet. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] 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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single
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cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]
Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver
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involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels
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of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] High blood cholesterol: Cholesterol is the most abundant steroid in animal tissues, especially in bile and gallstones. The relationship between the intake of cholesterol and its manufacture by the body to its utilization, sequestration, or excretion from the body is called the cholesterol balance. When cholesterol accumulates, the balance is positive; when it declines, the balance is negative. In 1993, the NHLBI National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults issued an updated set of recommendations for monitoring and treatment of blood cholesterol levels. The NCEP guidelines recommended that total cholesterol levels and subfractions of high-density lipoprotein (HDL) cholesterol be measured beginning at age 20 in all adults, with subsequent periodic screenings as needed. Even in the group of patients at lowest risk for coronary heart disease (total cholesterol 200 mg/dL and HDL 35 mg/dL), the NCEP recommended that rescreening take place at least once every 5 years or upon physical examination. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is
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required for the production of histamine. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperammonemia: Metabolic disorder characterized by elevated level of ammonia in blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to
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cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [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
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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH]
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Ingestion: Taking into the body by mouth [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intravascular: Within a vessel or vessels. [EU] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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 is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] 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] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the
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posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Ketonuria: Having ketone bodies in the urine; a warning sign of diabetic ketoacidosis (DKA). [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] 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] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH]
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Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] 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] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different
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degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Maple Syrup Urine Disease: A genetic disorder involving deficiency of an enzyme necessary in the metabolism of branched-chain amino acids, and named for the characteristic odor of the urine. [NIH] Mass Screening: Organized periodic procedures performed on large groups of people for the purpose of detecting disease. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH]
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Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted,
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usually because of a missing enzyme. [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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] 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] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] 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] Monogenic: A human disease caused by a mutation in a single gene. [NIH]
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Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [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] Neonatal Screening: The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] 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]
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Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
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Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutrition Assessment: Evaluation and measurement of nutritional variables in order to assess the level of nutrition or the nutritional status of the individual. Nutrition surveys may be used in making the assessment. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Ochronosis: Deposition of polymerized homogentisic acid as a brown-black pigment in the connective tissue. It occurs in alkaptonuria, but has also been observed in connection with exposure to certain chemicals (e.g., phenol, trinitrophenol, benzene derivatives). [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is
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comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary
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in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylalanine Hydroxylase: An enzyme of the oxidoreductase class that catalyzes the formation of L-tyrosine, dihydrobiopterin, and water from L-phenylalanine, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause phenylketonurias and phenylketonuria, maternal. EC 1.14.16.1. [NIH] Phenylketonurias: A group of autosomal recessive disorders marked by a deficiency of the hepatic enzyme phenylalanine hydroxylase or less frequently by reduced activity of dihydropteridine reductase (i.e., atypical phenylketonuria). Classical phenylketonuria is caused by a severe deficiency of phenylalanine hydroxylase and presents in infancy with developmental delay; seizures; skin hypopigmentation; eczema; and demyelination in the central nervous system. (From Adams et al., Principles of Neurology, 6th ed, p952). [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH]
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Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which vegetable proteins is available. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] 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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or
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their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for
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exploring or sounding body cavities. [NIH] Product Labeling: Use of written, printed, or graphic materials upon or accompanying a product or its container or wrapper. It includes purpose, effect, description, directions, hazards, warnings, and other relevant information. [NIH] Progeny: The offspring produced in any generation. [NIH] Progeria: An abnormal congenital condition characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying, hair loss, hearing loss, cataracts, arthritis,osteoporosis, diabetes mellitus, atrophy of subcutaneous fat, skeletal hypoplasia, and accelerated atherosclerosis. Many affected individuals develop malignant tumors, especially sarcomas. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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] Proteus: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in the intestines of humans and a wide variety of animals, as well as in manure, soil, and polluted waters. Its species are pathogenic, causing urinary tract infections and are also considered secondary invaders, causing septic lesions at other sites of the body. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other
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aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] 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] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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]
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Radioactive: Giving off radiation. [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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] Reproduction Techniques: Methods pertaining to the generation of new individuals. [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] Research Support: Financial support of research activities. [NIH]
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Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [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]
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Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoidal: S-shaped; shaped like the letter sigma. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] 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]
Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] 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] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Steatosis: Fatty degeneration. [EU]
200
Phenylketonuria
Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striate: Recurrent branch of the anterior cerebral artery which supplies the anterior limb of the internal capsule. [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] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfites: Inorganic salts of sulfurous acid. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH]
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Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Testicular: Pertaining to a testis. [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.
202
Phenylketonuria
[NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of
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ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tryptophan Hydroxylase: An enzyme that catalyzes the hydroxylation of tryptophan to 5hydroxytryptophan in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of serotonin. EC 1.14.16.4 [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [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] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [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]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [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] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [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]
204
Phenylketonuria
Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetable Proteins: Proteins which are present in or isolated from vegetables or vegetable products used as food. The concept is distinguished from plant proteins which refers to nondietary proteins from plants. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [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] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border
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205
of the fifth thoracic vertebra. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Dehydrogenase: An enzyme that catalyzes the oxidation of xanthine in the presence of NAD+ to form urate and NADH. It acts also on a variety of other purines and aldehydes. EC 1.1.1.204. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
207
INDEX 5 5-Hydroxytryptophan, 98, 155, 203 A Abdomen, 155, 162, 183, 190, 200 Abortion, 155, 193 Acantholysis, 155, 190 Acceptor, 155, 183, 189 Acetone, 155, 182 Acetylcholine, 155, 165, 188 Acetylcholinesterase, 26, 61, 155 Acidity, 3, 155 Acidosis, 15, 155, 169 Acquired Immunodeficiency Syndrome, 12, 155 Acremonium, 155, 164 Acrodermatitis, 111, 155 Acyl, 98, 155 Adaptation, 9, 91, 155, 192 Adenine, 156, 195 Adenosine, 104, 156, 191 Adenosine Triphosphate, 104, 156, 191 Adenovirus, 40, 156 Adjustment, 26, 37, 59, 76, 155, 156 Adrenal Glands, 156 Adrenal Hyperplasia, Congenital, 140, 156 Adrenal insufficiency, 113, 156 Adrenal Medulla, 156, 164, 172, 188 Adrenergic, 156, 170, 172, 200, 203 Adsorption, 99, 156, 191 Adsorptive, 156 Adverse Effect, 156, 198 Aerobic, 156, 203 Affinity, 23, 156, 157, 160, 199 Agonist, 157, 170 Albumin, 157, 189 Aldehydes, 157, 205 Algorithms, 157, 162 Alkaline, 155, 157, 158, 163, 201 Alkaptonuria, 21, 157, 189 Alleles, 30, 43, 157, 178, 183 Allylamine, 157 Alpha-fetoprotein, 108, 157, 174 Alternative medicine, 118, 157 Ameliorating, 104, 157 Amine, 33, 45, 157, 178 Amino Acid Sequence, 101, 102, 158, 159, 173
Ammonia, 14, 24, 25, 123, 157, 158, 176, 179 Ammonium Sulfate, 103, 158 Amphetamine, 158, 161 Ampulla, 158, 165 Anaemia, 50, 99, 158, 185 Anaerobic, 158, 194 Anaesthesia, 158, 180 Anal, 158, 183 Analogous, 19, 158, 202 Analytes, 8, 21, 158 Anaphylatoxins, 158, 166 Anatomical, 158, 164, 171, 180, 186, 197 Androgens, 158, 160 Anemia, 12, 133, 158, 174, 195 Animal model, 13, 20, 159 Anions, 157, 159, 181 Annealing, 159, 192 Anthropology, 52, 159 Antibacterial, 159, 165, 199, 204 Antibiotic, 159, 163, 165, 190, 197, 199, 201 Antibodies, 10, 159, 177, 178, 184, 192 Antibody, 157, 159, 166, 177, 179, 180, 185, 199 Anticoagulant, 159, 194 Antidepressant, 155, 159 Antiepileptic, 155, 159 Antigen, 156, 159, 166, 179, 180, 185, 186 Antigen-Antibody Complex, 159, 166 Anti-infective, 159, 174, 179 Anti-Infective Agents, 159, 174 Antineoplastic, 159, 162 Antioxidant, 159, 189 Anus, 158, 159, 162, 166, 181 Arachidonate 15-Lipoxygenase, 159, 183 Arachidonate Lipoxygenases, 160, 183 Arginine, 158, 160, 188, 203 Aromatase, 9, 160 Aromatic, 4, 22, 104, 160, 161, 191 Arterial, 157, 160, 179, 194, 201 Arteries, 160, 162, 167, 186 Arterioles, 160, 162, 163 Aspartame, 35, 37, 138, 139, 140, 141, 160 Aspartate, 77, 160 Aspartic, 160 Aspartic Acid, 160 Assay, 4, 7, 36, 38, 39, 77, 152, 160, 197 Astringents, 160, 185
208
Phenylketonuria
Astrocytes, 15, 160, 186 Ataxia, 11, 133, 160, 201 Atrophy, 133, 155, 161, 173, 194 Atypical, 10, 98, 161, 191 Auditory, 67, 78, 161, 173 B Bacteria, 11, 155, 156, 159, 161, 169, 173, 177, 178, 186, 192, 194, 199, 202, 203 Bacterial Physiology, 156, 161 Bacteriophage, 161, 202 Basal Ganglia, 160, 161, 179 Basal Ganglia Diseases, 160, 161, 179 Base, 156, 161, 168, 169, 173, 182, 192 Benzoic Acid, 112, 161 Bile, 19, 161, 175, 178, 183, 200 Bile Acids, 161, 200 Bile Acids and Salts, 161 Biliary, 161, 165 Biochemical, 16, 19, 27, 62, 64, 65, 71, 73, 82, 157, 161, 198 Bioengineering, 16, 21, 128, 161 Biogenic Amines, 26, 161 Biopterin, 6, 71, 98, 162 Biotechnology, 23, 24, 109, 118, 129, 132, 133, 134, 162 Bladder, 162, 167, 188, 194, 203 Blastocyst, 162, 167, 171, 191 Bleomycin, 21, 111, 162 Blister, 162, 190 Blood Glucose, 162, 177, 181 Blood Platelets, 162, 198 Blood pressure, 162, 163, 179, 186, 199 Blood vessel, 162, 163, 164, 171, 178, 182, 199, 200, 201, 202, 204 Blood-Brain Barrier, 46, 55, 100, 162, 183 Body Fluids, 103, 162, 199 Bone Marrow, 12, 162, 176, 177, 184, 199 Bone Marrow Transplantation, 12, 162 Bowel, 158, 162, 169, 188, 200 Bowel Movement, 162, 170, 200 Bradykinin, 162, 188 Brain Stem, 162, 164 Branch, 73, 109, 130, 149, 163, 190, 195, 199, 200, 201 Breakdown, 102, 163, 169, 175 Broad-spectrum, 163, 164 Bronchial, 163, 178 C Calcium, 163, 166, 190, 201 Capillary, 7, 162, 163, 204 Capsid, 163, 204 Carbohydrate, 101, 108, 163, 176, 189
Carcinogen, 9, 163 Carcinogenesis, 9, 163 Carcinogenic, 163, 194, 200 Carcinoma, 20, 163 Cardiac, 157, 163, 171, 172, 177, 187, 200 Cardiovascular, 7, 29, 158, 163, 198 Cardiovascular disease, 7, 163 Carnitine, 73, 163 Case report, 56, 85, 87, 163 Catabolism, 10, 163 Catalytic Domain, 6, 22, 32, 163 Cataracts, 163, 194 Catecholamine, 10, 22, 164, 170 Catheter, 12, 164 Cations, 164, 181 Causal, 103, 164, 178, 198 Celiac Disease, 109, 164 Cell Division, 133, 161, 164, 192 Cell membrane, 19, 164, 191 Cephalosporins, 21, 164 Cerebellar, 15, 160, 164, 196, 203 Cerebellum, 15, 164, 196 Cerebral, 15, 24, 28, 29, 59, 67, 73, 100, 160, 161, 162, 164, 168, 171, 172, 174, 200 Cerebral Cortex, 160, 164 Cerebrospinal, 15, 33, 164 Cerebrospinal fluid, 15, 33, 164 Cerebrovascular, 7, 161, 163, 164, 201 Cerebrum, 164, 203 Chemotactic Factors, 164, 166 Chemotherapy, 12, 164 Chin, 164, 185 Chiropractic, 138, 165 Cholecystitis, 112, 165 Cholera, 165, 198 Cholestasis, 19, 165 Cholesterol, 7, 161, 165, 167, 175, 178, 183, 200 Choline, 32, 155, 165 Chromatin, 165 Chromosomal, 165, 192 Chromosome, 165, 183 Chronic, 8, 108, 111, 133, 140, 165, 172, 175, 180, 182, 190, 192, 197, 200 Chronic renal, 165, 192 Cirrhosis, 20, 111, 165, 177 CIS, 13, 165 Clavulanic Acid, 21, 165 Clear cell carcinoma, 165, 169 Clinical Medicine, 165, 193 Clinical trial, 4, 93, 94, 129, 165, 167, 194, 196
Index 209
Cloning, 162, 165 Codons, 101, 105, 165 Cofactor, 5, 6, 10, 14, 17, 23, 165, 194, 201 Collagen, 158, 166, 174, 175, 192 Collapse, 163, 166 Colloidal, 157, 166, 171 Colon, 133, 166, 182 Complement, 12, 13, 22, 158, 166, 167, 184 Complement 3, 166 Complement Activation, 158, 166 Complement Factor D, 12, 13, 166 Complementary and alternative medicine, 81, 89, 166 Complementary medicine, 81, 167 Compliance, 30, 47, 167 Computational Biology, 129, 132, 167 Computed tomography, 32, 167 Computerized tomography, 167 Conception, 39, 155, 167, 174, 193 Congestive heart failure, 20, 167 Conjugated, 161, 167, 168 Connective Tissue, 162, 166, 167, 169, 174, 175, 189, 197 Contamination, 112, 167 Contraindications, ii, 167 Control group, 3, 167 Coordination, 164, 167 Coronary, 7, 163, 167, 168, 178, 186 Coronary heart disease, 7, 163, 167, 178 Coronary Thrombosis, 168, 186 Corpuscle, 168, 172 Cortex, 6, 70, 168, 173, 196 Cortical, 15, 42, 168, 197, 201 Cortical Blindness, 42, 168 Cranial, 72, 164, 168, 190 Curative, 168, 188, 201 Cyclic, 168, 177, 188, 193 Cytochrome, 160, 168 Cytoplasm, 164, 168, 172 D Decarboxylation, 161, 168, 178, 203 Degenerative, 168, 178 Delusions, 168, 195 Dementia, 155, 168 Denaturation, 168, 192 Dendrites, 168, 188 Density, 20, 21, 32, 168, 178, 183, 189 Dental Care, 112, 113, 169 Dental Caries, 4, 169 Deoxyribonucleic, 102, 169 Deoxyribonucleic acid, 102, 169 Deoxyribonucleotides, 169
Depressive Disorder, 169, 183 Dermal, 31, 169 Dermis, 169, 202 DES, 77, 158, 169 Detoxification, 19, 169 Developed Countries, 169, 174 Diabetes Mellitus, 71, 113, 169, 176, 177, 194 Diabetic Ketoacidosis, 169, 182 Diagnostic procedure, 97, 118, 169 Diastolic, 169, 179 Dietary Proteins, 169, 204 Dietitian, 111, 169 Digestion, 161, 162, 169, 183, 200 Digestive system, 95, 112, 169 Dihydropteridine Reductase, 29, 170, 191 Dihydrotestosterone, 170, 196 Dilatation, 155, 170, 193 Direct, iii, 14, 34, 77, 165, 170, 179, 196, 201 Dissociation, 156, 170, 181 Distal, 170, 171 Diurnal, 66, 87, 170 Dopa, 7, 35, 36, 170, 183 Dopamine, 6, 18, 23, 59, 158, 170, 183, 186, 188, 191 Drug Interactions, 122, 170 Drug Monitoring, 21, 170 Duodenum, 161, 170, 200 Dysplasia, 133, 170 Dystonia, 23, 170 Dystrophy, 20, 111, 133, 170 E Eating Disorders, 109, 170 Ectopic, 13, 170 Effector, 23, 155, 166, 170 Efficacy, 14, 170 Electrode, 7, 171 Electroencephalography, 72, 171 Electrolyte, 81, 171, 199 Electrophoresis, 7, 171 Elementary Particles, 171, 184, 195 Emaciation, 155, 171 Embryo, 155, 162, 171, 174, 180, 193, 199 Embryo Transfer, 171, 193 Empirical, 100, 171 Enamel, 169, 171, 182 Encephalocele, 171, 188 Endogenous, 21, 106, 170, 171, 172 Endorphins, 171, 188 Endothelial cell, 162, 171, 201 Endothelium, 171, 188 Endothelium-derived, 171, 188
210
Phenylketonuria
Endotoxins, 166, 172 End-stage renal, 165, 172, 192 Energy Intake, 61, 172 Enhancer, 13, 172 Enkephalins, 172, 188 Enterocytes, 20, 172 Enteropeptidase, 172, 203 Environmental Exposure, 172, 189 Environmental Health, 71, 72, 128, 130, 172 Enzymatic, 10, 26, 36, 98, 100, 158, 161, 163, 166, 169, 172, 178, 192 Epidermal, 31, 172, 182, 185 Epidermis, 155, 162, 169, 172, 182, 190, 193 Epinephrine, 156, 161, 170, 172, 188, 203 Epithelium, 171, 172, 182 Erythrocyte Membrane, 49, 61, 84, 172 Erythrocytes, 158, 162, 172, 178, 196 Esophagus, 170, 172, 200 Essential Tremor, 133, 172 Estrogen, 9, 160, 173 Evoked Potentials, 35, 36, 39, 64, 67, 78, 83, 173 Excipients, 173, 174, 191 Excitation, 173, 188 Exogenous, 14, 156, 171, 173 Exon, 25, 55, 56, 173 Extracellular, 160, 167, 173, 174, 186, 199, 201 Extracellular Matrix, 167, 173, 174 Extracellular Space, 173, 186 Extraction, 21, 173 Extrapyramidal, 170, 173 Eye Color, 10, 173 Eye Infections, 156, 173 F Facial, 50, 111, 173 Facial Hemiatrophy, 111, 173 Family Planning, 129, 173 Fat, 101, 109, 161, 162, 167, 173, 182, 183, 189, 192, 194, 197, 199 Fatty acids, 46, 84, 157, 169, 173, 183 Fatty Liver, 111, 173 Febrile, 173, 199 Ferritin, 20, 173 Fertilization in Vitro, 173, 193 Fetal Alcohol Syndrome, 33, 72, 108, 174 Fetal Development, 174, 188 Fetoprotein, 174 Fetus, 155, 157, 174, 191, 193, 199, 200 Fibroblasts, 31, 174
Fibrosis, 20, 28, 71, 108, 112, 133, 140, 157, 174, 197 Filtration, 23, 174 Flatus, 174, 175 Flavoring Agents, 174, 191 Folate, 65, 78, 174 Fold, 20, 174 Folic Acid, 108, 174 Food Additives, 109, 112, 174 Food Exchange, 111, 174 Food Habits, 100, 174 Food Preferences, 174 Food Preservatives, 174 Fossa, 164, 174 Fractionation, 158, 174 Frontal Lobe, 33, 58, 174 Fructose, 43, 112, 174, 175 Fructose Intolerance, 43, 112, 175 Fungi, 173, 175, 177, 186, 205 Fungistatic, 161, 175 Fungus, 164, 175 G Galactosemia, 110, 111, 112, 140, 175 Gallbladder, 161, 165, 170, 175 Gallstones, 161, 175, 178 Ganglia, 155, 161, 175, 187, 190 Gangrenous, 175, 198 Gas, 60, 158, 174, 175, 179, 188, 200 Gastric, 163, 175, 178 Gastrin, 175, 179 Gastrointestinal, 112, 162, 172, 175, 198, 200 Gastrointestinal tract, 175, 198 Gelatin, 175, 176, 201 Gene Expression, 134, 175 Gene Therapy, 4, 11, 12, 13, 14, 19, 31, 40, 52, 63, 76, 156, 175 Genetic Screening, 140, 176 Genetic testing, 176, 192 Genotype, 30, 34, 35, 42, 43, 51, 62, 75, 176, 191 Gland, 156, 176, 184, 189, 190, 194, 197, 200, 202 Gluconeogenesis, 175, 176 Glucose, 15, 19, 21, 133, 162, 169, 175, 176, 177, 181 Glucose Intolerance, 169, 176 Glutamate, 15, 112, 176 Glutamic Acid, 174, 176, 188 Glutamine, 15, 176 Glutathione Peroxidase, 77, 86, 176, 198 Gluten, 164, 176
Index 211
Glycine, 158, 161, 176, 188, 198 Glycogen, 19, 57, 176 Glycogen Storage Disease, 57, 176 Glycolysis, 15, 177 Goblet Cells, 172, 177 Governing Board, 177, 193 Graft, 111, 177, 179 Graft-versus-host disease, 111, 177 Gram-negative, 177, 194, 197 Gram-Negative Bacteria, 177, 197 Granule, 15, 177 Grasses, 174, 177 Guanylate Cyclase, 177, 188 H Haplotypes, 30, 177 Haptens, 157, 177 Heart attack, 163, 177 Heart failure, 177 Heme, 5, 21, 168, 177, 193, 203 Hemochromatosis, 20, 177 Hemoglobin, 159, 172, 177, 178, 182, 193 Hemoglobinopathies, 176, 178 Hemoglobinuria, 133, 178 Hemolysis, 172, 178 Hemolytic, 178, 195 Hemophilia, 12, 133, 178 Hemorrhage, 178, 200 Hemostasis, 178, 198 Hepatic, 13, 19, 20, 40, 63, 157, 175, 178, 186, 191, 193 Hepatitis, 111, 178 Hepatocyte, 12, 13, 19, 165, 178 Hereditary, 20, 43, 155, 178, 197 Heredity, 175, 176, 178 Heterogeneity, 43, 157, 178 Heterozygotes, 35, 37, 63, 178 High blood cholesterol, 109, 178 Histamine, 112, 158, 161, 178, 179 Histidine, 178 Homeostasis, 20, 179 Homogeneous, 5, 179 Homologous, 157, 175, 178, 179, 201 Hormonal, 9, 161, 179 Hormone, 36, 82, 169, 172, 175, 179, 181, 190, 201, 202 Host, 161, 179, 204 Hybrid, 13, 179 Hydrogen, 155, 157, 161, 163, 168, 176, 179, 183, 186, 189, 195 Hydrogen Peroxide, 176, 179, 183 Hydrogenation, 98, 179 Hydrolysis, 155, 160, 179, 194, 203
Hydroxylation, 5, 10, 21, 98, 105, 179, 203 Hydroxyproline, 158, 166, 179 Hyperammonemia, 11, 179 Hyperglycemia, 113, 179 Hyperlipidemia, 9, 179 Hypertension, 10, 109, 163, 179 Hyperthyroidism, 113, 179 Hypoglycemia, 113, 175, 179 Hypokinesia, 179, 190 Hypoplasia, 53, 179, 194 Hypothyroidism, 18, 53, 58, 108, 113, 140, 179 I Id, 79, 88, 141, 142, 148, 150, 180 Idiopathic, 155, 180 Immune response, 12, 13, 159, 177, 180, 184, 200, 204 Immune system, 180, 184, 203, 204 Immunity, 155, 180 Immunodeficiency, 133, 155, 180 Immunology, 19, 156, 180 Impairment, 15, 45, 64, 101, 106, 160, 165, 173, 180, 185, 195 Implantation, 167, 180 In situ, 10, 17, 21, 180 In vitro, 3, 17, 37, 171, 176, 180, 192, 197 In vivo, 9, 11, 13, 21, 29, 31, 45, 83, 176, 180, 186 Incision, 180, 181 Indicative, 103, 108, 180, 190, 204 Induction, 9, 158, 180 Infancy, 7, 70, 84, 180, 191 Infarction, 168, 180, 186 Infection, 16, 155, 159, 164, 173, 180, 184, 189, 190, 198, 200, 202, 204 Inflammation, 155, 157, 165, 173, 174, 175, 178, 180, 192, 197 Ingestion, 35, 175, 181, 192, 201 Inner ear, 181, 204 Inotropic, 170, 181 Insecticides, 181, 205 Insight, 22, 23, 181 Insulin, 9, 113, 169, 181, 182 Insulin-dependent diabetes mellitus, 9, 181 Intestinal, 20, 164, 172, 181, 184, 190 Intestinal Mucosa, 164, 172, 181 Intestines, 175, 181, 194 Intracellular, 180, 181, 188, 196, 198 Intravascular, 12, 13, 181 Intrinsic, 157, 181 Invasive, 6, 16, 180, 181, 184
212
Phenylketonuria
Involuntary, 161, 172, 181, 187 Ion Channels, 160, 181 Ion Exchange, 181 Ionization, 181 Ions, 21, 155, 161, 170, 171, 179, 181 Iontophoresis, 21, 181 Iris, 173, 181 Ischemia, 161, 182 Isoleucine, 66, 100, 123, 182 Isozymes, 182, 195 K Kb, 128, 182 Keratin, 182 Keratinocytes, 31, 182 Keratolytic, 169, 182 Ketone Bodies, 15, 155, 169, 182 Ketonuria, 106, 182 Kidney Disease, 12, 95, 128, 133, 182 Kinetic, 5, 23, 182 L Labile, 166, 182 Large Intestine, 170, 181, 182, 196, 199 Lens, 163, 182, 197 Lethargy, 179, 182 Leucine, 66, 100, 123, 182 Leukemia, 133, 176, 182 Leukocytes, 162, 164, 183 Levodopa, 170, 183 Library Services, 148, 183 Ligament, 183, 194 Linkage, 48, 52, 183 Linkage Disequilibrium, 52, 183 Lipid, 48, 74, 84, 165, 181, 183, 189, 203 Lipid Peroxidation, 183, 189 Lipopolysaccharides, 183, 197 Lipoprotein, 177, 178, 183, 204 Lipoxygenase, 21, 160, 183 Lithium, 21, 183 Liver cancer, 157, 183 Liver Transplantation, 111, 183 Localization, 56, 183 Localized, 6, 10, 49, 111, 169, 180, 183, 186, 192, 197 Longitudinal study, 25, 49, 183 Lymphatic, 171, 180, 184, 199 Lymphocyte, 155, 159, 184, 185 Lymphocyte Count, 155, 184 Lymphoid, 159, 184 Lymphoma, 133, 184 Lysine, 184, 203
M Magnetic Resonance Imaging, 27, 51, 57, 184 Magnetic Resonance Spectroscopy, 31, 57, 184 Major Histocompatibility Complex, 177, 184 Malabsorption, 133, 164, 184 Malformation, 101, 184 Malignant, 72, 133, 155, 159, 183, 184, 187, 194 Malignant tumor, 184, 194 Malnutrition, 157, 161, 184, 187 Mammary, 9, 184 Manic, 183, 184, 195 Manic-depressive psychosis, 184, 195 Maple Syrup Urine Disease, 14, 15, 74, 110, 111, 140, 184 Mass Screening, 54, 75, 184 Mastitis, 184, 198 Meat, 99, 185 Mediate, 170, 185 Mediator, 170, 185, 198 MEDLINE, 129, 132, 134, 185 Megaloblastic, 174, 185 Melanin, 152, 182, 185, 191, 203 Melanocytes, 185 Melanoma, 133, 185 Membrane, 77, 160, 164, 166, 173, 177, 181, 185, 186, 187, 191, 197 Memory, 7, 17, 26, 32, 70, 168, 185 Meninges, 164, 185 Mental deficiency, 88, 174, 185 Mental Disorders, 95, 103, 179, 185, 195 Mental Health, iv, 4, 71, 95, 128, 131, 185, 195 Mental Processes, 170, 185, 195 Mental Retardation, 5, 8, 11, 13, 15, 19, 63, 65, 73, 93, 101, 102, 110, 134, 139, 185 Mentors, 9, 185 Mercury, 7, 185 Metabolic disorder, 4, 11, 12, 13, 19, 22, 104, 106, 110, 176, 179, 185 MI, 110, 153, 186 Microbe, 186, 202 Microbiology, 156, 161, 186 Microdialysis, 74, 186 Microglia, 160, 186 Microorganism, 112, 165, 186, 204 Micro-organism, 169, 186, 198 Mineralization, 32, 186 Modification, 11, 15, 158, 186
Index 213
Molecule, 9, 105, 159, 161, 166, 170, 171, 173, 178, 179, 186, 189, 192, 196, 204 Monitor, 186, 188 Monoamine, 158, 186, 203 Monoamine Oxidase, 158, 186, 203 Monogenic, 13, 186 Mononuclear, 5, 21, 187 Monotherapy, 65, 78, 187 Morphogenesis, 174, 187 Motility, 187, 198 Mucins, 172, 177, 187 Mucosa, 187 Muscle Fibers, 187 Muscular Atrophy, 133, 187 Muscular Dystrophies, 170, 187 Myelin, 16, 187 Myeloma, 111, 187 Myocardium, 186, 187 Myotonic Dystrophy, 133, 187 N NCI, 1, 94, 127, 165, 187 Need, 3, 13, 17, 99, 100, 107, 110, 119, 122, 123, 130, 143, 156, 165, 176, 187 Neonatal, 11, 36, 39, 53, 56, 60, 62, 72, 75, 111, 187 Neonatal Screening, 36, 56, 75, 187 Neoplasia, 133, 187 Neoplasm, 187 Neoplastic, 9, 184, 187 Nephropathy, 182, 187 Nerve, 99, 156, 160, 164, 165, 168, 185, 186, 187, 188, 197, 200, 203 Nervous System, 5, 22, 37, 98, 99, 100, 101, 102, 133, 152, 155, 158, 164, 173, 175, 176, 183, 185, 186, 187, 188, 190, 191, 198, 200, 203 Neural, 6, 108, 171, 174, 186, 188 Neural tube defects, 108, 174, 188 Neuromuscular, 155, 188 Neuromuscular Junction, 155, 188 Neuronal, 15, 72, 188 Neurons, 15, 77, 168, 175, 183, 188, 201 Neuropsychological Tests, 35, 36, 188 Neurotoxicity, 33, 72, 188 Niacin, 188, 203 Nitric Oxide, 23, 188 Nitrogen, 157, 158, 176, 188, 203 Norepinephrine, 156, 170, 188 Nuclear, 19, 161, 188 Nuclei, 175, 184, 188, 195 Nucleus, 161, 165, 168, 171, 187, 189, 195, 200, 201
Nutrition Assessment, 111, 189 Nutritional Status, 189 Nutritive Value, 174, 189 O Ochronosis, 157, 189 Odour, 160, 189 Oncogene, 133, 189 On-line, 21, 151, 189 Opacity, 163, 168, 189 Opportunistic Infections, 155, 189 Oral Health, 3, 189 Orofacial, 53, 189 Osteoporosis, 189, 194 Ovalbumin, 105, 189 Ovaries, 160, 189, 198 Oxidation, 5, 21, 104, 155, 159, 160, 168, 169, 176, 183, 189, 205 Oxidative Stress, 72, 189 P Palliative, 189, 201 Pancreas, 170, 177, 181, 189, 190, 203 Pancreatic, 133, 163, 190 Pancreatic cancer, 133, 190 Paneth Cells, 172, 190 Parathyroid, 113, 190, 201 Parathyroid Glands, 190 Parenteral, 172, 190 Parkinsonism, 6, 183, 190 Paroxysmal, 133, 190 Patch, 190, 202 Pathogenesis, 19, 28, 71, 102, 190 Pathologic, 14, 155, 167, 190 Pathophysiology, 14, 16, 111, 190 Patient Compliance, 13, 105, 111, 190 Patient Education, 111, 139, 146, 148, 153, 190 Pelvic, 190, 194 Pemphigus, 24, 155, 190 Penicillin, 190, 204 Peptide, 78, 158, 172, 182, 190, 194, 202 Peripheral Nervous System, 172, 188, 190, 200 Peripheral stem cells, 177, 190 Pharmaceutic Aids, 174, 190 Pharmacologic, 191, 202 Phenotype, 10, 13, 30, 42, 43, 51, 62, 75, 191 Phenyl, 16, 106, 123, 191 Phenylacetate, 9, 191 Phenylketonurias, 191 Phonophoresis, 181, 191 Phospholipids, 173, 183, 191
214
Phenylketonuria
Phosphorus, 163, 190, 191 Phosphorylation, 11, 191, 195 Photosensitivity, 191, 193 Physical Examination, 178, 191 Physiologic, 157, 170, 174, 179, 191, 196, 203 Pigmentation, 103, 191 Pilot study, 9, 17, 19, 53, 54, 191 Placenta, 160, 191 Plant Proteins, 192, 204 Plants, 160, 165, 176, 188, 192, 202, 203, 204 Plasma cells, 159, 187, 192 Plasmid, 12, 13, 192, 204 Plasticity, 37, 192 Platelet Aggregation, 158, 188, 192 Platelets, 188, 192 Pneumonia, 167, 192 Point Mutation, 43, 192 Poisoning, 185, 192 Polycystic, 133, 192 Polymerase, 77, 192 Polymerase Chain Reaction, 77, 192 Polymorphic, 70, 192 Polymorphism, 38, 60, 192 Polyunsaturated fat, 48, 49, 74, 82, 84, 85, 192 Porphyria, 111, 112, 192, 193 Porphyria Cutanea Tarda, 111, 193 Porphyria, Hepatic, 193 Porphyrins, 192, 193 Posterior, 158, 160, 164, 182, 189, 193 Postnatal, 5, 76, 174, 193 Postprandial, 85, 193 Practice Guidelines, 131, 141, 193 Preclinical, 12, 140, 193 Precursor, 7, 18, 98, 99, 155, 165, 170, 171, 172, 183, 188, 191, 193, 203, 204 Pregnancy Outcome, 50, 193 Prenatal, 38, 52, 70, 74, 108, 171, 174, 176, 193 Presumptive, 66, 87, 193 Presynaptic, 188, 193 Prevalence, 141, 193 Prickle, 155, 182, 193 Probe, 5, 11, 186, 193 Product Labeling, 141, 194 Progeny, 29, 194 Progeria, 111, 194 Progression, 6, 159, 194 Progressive, 19, 20, 106, 111, 165, 168, 173, 177, 187, 194
Promoter, 13, 194 Prone, 103, 194 Prospective study, 183, 194 Prostate, 9, 133, 194 Protease, 23, 194 Protein C, 23, 99, 105, 108, 157, 158, 161, 173, 182, 183, 194, 204 Protein Conformation, 23, 158, 182, 194 Protein S, 8, 19, 24, 26, 27, 47, 70, 81, 99, 101, 105, 109, 134, 162, 194, 201 Proteolytic, 99, 166, 172, 194 Proteus, 112, 194 Protocol, 12, 13, 194 Protons, 179, 184, 195 Protozoa, 186, 195 Psychiatric, 10, 71, 118, 185, 195 Psychiatry, 67, 76, 77, 195 Psychic, 185, 195, 197 Psychology, 8, 17, 36, 70, 71, 73, 86, 170, 195 Psychosis, 71, 195 Puberty, 78, 195 Public Health, 13, 20, 24, 41, 48, 52, 53, 54, 66, 71, 75, 86, 109, 110, 115, 131, 195 Public Policy, 129, 195 Purines, 195, 198, 205 Pyruvate Kinase, 70, 195 Q Quaternary, 194, 195 R Race, 170, 195 Racemic, 170, 195 Radiation, 171, 172, 174, 195, 196, 205 Radioactive, 60, 179, 180, 181, 188, 196 Randomized, 171, 196 Reagent, 103, 196 Reality Testing, 195, 196 Receptor, 20, 77, 156, 159, 170, 173, 196, 198 Receptors, Serotonin, 196, 198 Recombinant, 12, 13, 14, 19, 24, 25, 104, 118, 196, 204 Recombination, 175, 196 Reconstitution, 13, 196 Rectum, 159, 162, 166, 170, 174, 175, 182, 194, 196 Recurrence, 37, 184, 196 Red blood cells, 172, 178, 193, 196 Red Nucleus, 160, 196 Reductase, 10, 98, 160, 196 Refer, 1, 166, 171, 175, 183, 195, 196 Refraction, 196, 199
Index 215
Regeneration, 106, 196 Regimen, 170, 190, 196 Remission, 184, 196 Reproduction Techniques, 193, 196 Research Design, 4, 196 Research Support, 9, 196 Resolving, 11, 197 Restoration, 14, 196, 197 Retina, 168, 182, 197 Retinoblastoma, 133, 197 Retroviral vector, 175, 197 Rhamnose, 98, 197 Rheumatism, 111, 197 Rhinitis, 197, 198 Ribose, 156, 197 Rigidity, 190, 192, 197 Risk factor, 44, 194, 197 Ristocetin, 197, 204 Rod, 194, 197 S Salivary, 170, 190, 197 Salivary glands, 170, 197 Schizophrenia, 16, 71, 98, 99, 197 Scleroderma, 77, 111, 197 Sclerosis, 111, 133, 197 Secretion, 19, 156, 178, 180, 181, 186, 187, 197, 198 Sediment, 197 Sedimentation, 23, 166, 197 Seizures, 42, 102, 152, 190, 191, 197 Selenium, 36, 62, 77, 80, 82, 86, 198 Semen, 194, 198 Senescence, 194, 198 Septic, 194, 198 Septicaemia, 198 Sequencing, 192, 198 Serine, 198, 203 Serotonin, 10, 19, 23, 155, 161, 186, 188, 196, 198, 203 Serotypes, 13, 198 Serum, 5, 11, 13, 14, 19, 59, 73, 86, 100, 103, 108, 157, 158, 166, 196, 198 Sex Characteristics, 158, 195, 198, 201 Sex Determination, 133, 198 Side effect, 121, 123, 156, 198, 202 Sigmoidal, 23, 198 Signs and Symptoms, 112, 196, 198 Skeletal, 13, 14, 42, 158, 187, 194, 198 Skeleton, 198 Skull, 171, 188, 198 Small intestine, 170, 179, 181, 198, 203
Smooth muscle, 157, 158, 166, 178, 199, 200 Sodium, 103, 199 Soft tissue, 162, 198, 199 Solid tumor, 162, 199 Solvent, 98, 155, 199 Soma, 199 Somatic, 31, 63, 76, 190, 199 Soybean Oil, 192, 199 Specialist, 143, 199 Species, 172, 179, 194, 195, 199, 204, 205 Specificity, 23, 157, 160, 199 Spectroscopic, 21, 184, 199 Spectrum, 63, 75, 186, 199 Spina bifida, 188, 199 Spinal cord, 160, 163, 164, 165, 185, 187, 188, 190, 199 Spinous, 172, 182, 199 Spontaneous Abortion, 193, 199 Sporadic, 193, 197, 199 Sprue, 112, 199 Steatosis, 173, 199 Sterile, 190, 200 Steroid, 160, 161, 178, 200 Stillbirth, 193, 200 Stimulant, 158, 178, 200, 204 Stimulus, 171, 173, 181, 200, 201 Stomach, 170, 172, 175, 179, 181, 198, 200 Stool, 166, 182, 200 Strand, 60, 192, 200 Stress, 56, 75, 164, 189, 200 Striate, 168, 200 Stroke, 95, 128, 139, 163, 200 Subacute, 180, 200 Subclinical, 64, 180, 197, 200 Subcutaneous, 173, 175, 190, 194, 200 Substance P, 196, 197, 200 Substrate, 5, 15, 23, 163, 200, 203 Suction, 174, 200 Sulfites, 112, 200 Supplementation, 35, 36, 38, 39, 58, 59, 66, 73, 77, 78, 82, 83, 84, 85, 86, 87, 101, 200 Support group, 112, 200 Sympathomimetic, 158, 170, 172, 188, 200, 203 Symphysis, 164, 194, 200 Synapse, 156, 188, 193, 201, 203 Synaptic, 188, 201 Synergistic, 14, 201 Systemic, 111, 162, 172, 180, 197, 201 Systolic, 179, 201
216
Phenylketonuria
T Telangiectasia, 133, 201 Teratogen, 50, 201 Testicular, 160, 201 Testosterone, 196, 201 Tetany, 190, 201 Tetracycline, 24, 201 Thalamic, 160, 201 Thalamic Diseases, 160, 201 Therapeutics, 4, 122, 186, 201 Thermal, 170, 192, 201 Threonine, 82, 105, 106, 198, 201 Threshold, 179, 201 Thrombin, 192, 194, 201 Thrombomodulin, 194, 201 Thrombosis, 194, 200, 202 Thyroid, 36, 82, 113, 179, 190, 202, 203 Thyroid Gland, 179, 190, 202 Thyrotropin, 180, 202 Thyroxine, 157, 191, 202 Tomography, 29, 57, 167, 184, 202 Tonicity, 170, 178, 202 Tooth Preparation, 156, 202 Toxic, iv, 14, 20, 22, 102, 172, 177, 180, 198, 202, 204 Toxicity, 12, 13, 170, 185, 197, 202 Toxicology, 33, 72, 130, 202 Toxins, 14, 159, 172, 180, 202 Toxoplasmosis, 140, 202 Trace element, 102, 202 Trachea, 202 Transdermal, 21, 202 Transduction, 13, 19, 202 Transfection, 12, 162, 175, 202 Transgenes, 13, 202 Translation, 158, 202 Transmitter, 98, 99, 155, 160, 170, 181, 185, 188, 203 Tremor, 190, 203 Trypsin, 19, 172, 203, 205 Tryptophan, 10, 22, 50, 166, 198, 203 Tryptophan Hydroxylase, 10, 22, 203 Tuberous Sclerosis, 133, 203 Tyramine, 112, 161, 186, 203 Tyrosine, 4, 5, 6, 7, 10, 15, 19, 22, 23, 27, 35, 44, 47, 58, 59, 60, 66, 71, 73, 78, 82, 83, 85, 87, 89, 98, 99, 102, 103, 105, 170, 191, 203
U Ubiquinone, 59, 203 Unconscious, 180, 203 Urethra, 194, 203 Urinary, 194, 203, 205 Urinary tract, 194, 203 Urinary tract infection, 194, 203 Urine, 100, 103, 157, 162, 178, 182, 184, 203 Uroporphyrinogen Decarboxylase, 193, 203 V Vaccine, 194, 203 Vagina, 169, 204 Valine, 66, 100, 123, 204 Vancomycin, 21, 204 Vascular, 7, 13, 44, 157, 169, 171, 180, 188, 191, 202, 204 Vasodilator, 162, 170, 178, 204 Vector, 11, 12, 13, 14, 19, 202, 204 Vegetable Proteins, 99, 192, 204 Vein, 188, 204 Venous, 194, 204 Ventricles, 164, 204 Venules, 162, 163, 204 Veterinary Medicine, 129, 204 Villous, 164, 204 Viral, 11, 12, 13, 163, 202, 204 Viral vector, 11, 204 Virion, 104, 204 Virulence, 202, 204 Virus, 11, 13, 14, 19, 104, 155, 161, 163, 172, 197, 202, 204 Vitro, 204 Vivo, 9, 11, 13, 73, 204 W White blood cell, 159, 183, 184, 187, 192, 204 Windpipe, 202, 204 X Xanthine, 10, 205 Xanthine Dehydrogenase, 10, 205 Xenobiotics, 19, 205 Xenograft, 159, 205 X-ray, 21, 167, 188, 205 Y Yeasts, 175, 191, 205 Z Zygote, 167, 205 Zymogen, 194, 205
Index 217
218
Phenylketonuria
Index 219
220
Phenylketonuria
