Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects
Identifieur interne : 000C70 ( Main/Corpus ); précédent : 000C69; suivant : 000C71Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects
Auteurs : K. Shannak ; A. Rajput ; B. Rozdilsky ; S. Kish ; J. Gilbert ; O. HornykiewiczSource :
- Brain Research [ 0006-8993 ] ; 1993.
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- KwdEn :
Abstract
In order to determine whether, besides the severe striatal dopamine (DA) loss, other brain neurotransmitter changes may be a constant biochemical feature of idiopathic Parkinson's disease (iPD), we measured the concentration of the three major brain monoamines noradrenaline (NA), DA, and serotonin (5-HT) and their metabolites in five rostro-caudal subdivisions of the hypothalamus of eight control patients and nine patients with morphologically confirmed iPD. In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA(−52%, P < 0.05),DA(−25%),and5-HT(−26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.
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DOI: 10.1016/0006-8993(94)91761-2
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects</title><author><name sortKey="Shannak, K" sort="Shannak, K" uniqKey="Shannak K" first="K." last="Shannak">K. Shannak</name><affiliation><mods:affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</mods:affiliation></affiliation></author><author><name sortKey="Rajput, A" sort="Rajput, A" uniqKey="Rajput A" first="A." last="Rajput">A. Rajput</name><affiliation><mods:affiliation>University of Saskatoon, Saskatoon, Sask., Canada</mods:affiliation></affiliation></author><author><name sortKey="Rozdilsky, B" sort="Rozdilsky, B" uniqKey="Rozdilsky B" first="B." last="Rozdilsky">B. Rozdilsky</name><affiliation><mods:affiliation>University of Saskatoon, Saskatoon, Sask., Canada</mods:affiliation></affiliation></author><author><name sortKey="Kish, S" sort="Kish, S" uniqKey="Kish S" first="S." last="Kish">S. Kish</name><affiliation><mods:affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</mods:affiliation></affiliation></author><author><name sortKey="Gilbert, J" sort="Gilbert, J" uniqKey="Gilbert J" first="J." last="Gilbert">J. Gilbert</name><affiliation><mods:affiliation>Victoria Hospital, London, Ont., Canada</mods:affiliation></affiliation></author><author><name sortKey="Hornykiewicz, O" sort="Hornykiewicz, O" uniqKey="Hornykiewicz O" first="O." last="Hornykiewicz">O. Hornykiewicz</name><affiliation><mods:affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:4102B406468C0B6BA9172B93AD50607D80772547</idno><date when="1994" year="1994">1994</date><idno type="doi">10.1016/0006-8993(94)91761-2</idno><idno type="url">https://api.istex.fr/document/4102B406468C0B6BA9172B93AD50607D80772547/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000C70</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects</title><author><name sortKey="Shannak, K" sort="Shannak, K" uniqKey="Shannak K" first="K." last="Shannak">K. Shannak</name><affiliation><mods:affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</mods:affiliation></affiliation></author><author><name sortKey="Rajput, A" sort="Rajput, A" uniqKey="Rajput A" first="A." last="Rajput">A. Rajput</name><affiliation><mods:affiliation>University of Saskatoon, Saskatoon, Sask., Canada</mods:affiliation></affiliation></author><author><name sortKey="Rozdilsky, B" sort="Rozdilsky, B" uniqKey="Rozdilsky B" first="B." last="Rozdilsky">B. Rozdilsky</name><affiliation><mods:affiliation>University of Saskatoon, Saskatoon, Sask., Canada</mods:affiliation></affiliation></author><author><name sortKey="Kish, S" sort="Kish, S" uniqKey="Kish S" first="S." last="Kish">S. Kish</name><affiliation><mods:affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</mods:affiliation></affiliation></author><author><name sortKey="Gilbert, J" sort="Gilbert, J" uniqKey="Gilbert J" first="J." last="Gilbert">J. Gilbert</name><affiliation><mods:affiliation>Victoria Hospital, London, Ont., Canada</mods:affiliation></affiliation></author><author><name sortKey="Hornykiewicz, O" sort="Hornykiewicz, O" uniqKey="Hornykiewicz O" first="O." last="Hornykiewicz">O. Hornykiewicz</name><affiliation><mods:affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Brain Research</title><title level="j" type="abbrev">BRES</title><idno type="ISSN">0006-8993</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1993">1993</date><biblScope unit="volume">639</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="33">33</biblScope><biblScope unit="page" to="41">41</biblScope></imprint><idno type="ISSN">0006-8993</idno></series><idno type="istex">4102B406468C0B6BA9172B93AD50607D80772547</idno><idno type="DOI">10.1016/0006-8993(94)91761-2</idno><idno type="PII">0006-8993(94)91761-2</idno><idno type="ArticleID">94917612</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8993</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine</term><term>Hypothalamus</term><term>Monoamine</term><term>Noradrenaline</term><term>Parkinson's disease</term><term>Serotonin</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In order to determine whether, besides the severe striatal dopamine (DA) loss, other brain neurotransmitter changes may be a constant biochemical feature of idiopathic Parkinson's disease (iPD), we measured the concentration of the three major brain monoamines noradrenaline (NA), DA, and serotonin (5-HT) and their metabolites in five rostro-caudal subdivisions of the hypothalamus of eight control patients and nine patients with morphologically confirmed iPD. In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA(−52%, P < 0.05),DA(−25%),and5-HT(−26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>K. Shannak</name><affiliations><json:string>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</json:string></affiliations></json:item><json:item><name>A. Rajput</name><affiliations><json:string>University of Saskatoon, Saskatoon, Sask., Canada</json:string></affiliations></json:item><json:item><name>B. Rozdilsky</name><affiliations><json:string>University of Saskatoon, Saskatoon, Sask., Canada</json:string></affiliations></json:item><json:item><name>S. Kish</name><affiliations><json:string>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</json:string></affiliations></json:item><json:item><name>J. Gilbert</name><affiliations><json:string>Victoria Hospital, London, Ont., Canada</json:string></affiliations></json:item><json:item><name>O. Hornykiewicz</name><affiliations><json:string>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Hypothalamus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Noradrenaline</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Serotonin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Monoamine</value></json:item></subject><articleId><json:string>94917612</json:string></articleId><language><json:string>eng</json:string></language><abstract>In order to determine whether, besides the severe striatal dopamine (DA) loss, other brain neurotransmitter changes may be a constant biochemical feature of idiopathic Parkinson's disease (iPD), we measured the concentration of the three major brain monoamines noradrenaline (NA), DA, and serotonin (5-HT) and their metabolites in five rostro-caudal subdivisions of the hypothalamus of eight control patients and nine patients with morphologically confirmed iPD. In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA(−52%, P > 0.05),DA(−25%),and5-HT(−26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.</abstract><qualityIndicators><score>7.772</score><pdfVersion>1.3</pdfVersion><pdfPageSize>648 x 864 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>6</keywordCount><abstractCharCount>1560</abstractCharCount><pdfWordCount>5661</pdfWordCount><pdfCharCount>37061</pdfCharCount><pdfPageCount>9</pdfPageCount><abstractWordCount>231</abstractWordCount></qualityIndicators><title>Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects</title><pii><json:string>0006-8993(94)91761-2</json:string></pii><genre><json:string>research-article</json:string></genre><serie><volume>Vol. 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1R8</affiliation></author><author><persName><forename type="first">A.</forename><surname>Rajput</surname></persName><affiliation>University of Saskatoon, Saskatoon, Sask., Canada</affiliation></author><author><persName><forename type="first">B.</forename><surname>Rozdilsky</surname></persName><affiliation>University of Saskatoon, Saskatoon, Sask., Canada</affiliation></author><author><persName><forename type="first">S.</forename><surname>Kish</surname></persName><affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</affiliation></author><author><persName><forename type="first">J.</forename><surname>Gilbert</surname></persName><affiliation>Victoria Hospital, London, Ont., Canada</affiliation></author><author><persName><forename type="first">O.</forename><surname>Hornykiewicz</surname></persName><affiliation>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</affiliation></author></analytic><monogr><title level="j">Brain Research</title><title level="j" type="abbrev">BRES</title><idno type="pISSN">0006-8993</idno><idno type="PII">S0006-8993(00)X1196-1</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1993"></date><biblScope unit="volume">639</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="33">33</biblScope><biblScope unit="page" to="41">41</biblScope></imprint></monogr><idno type="istex">4102B406468C0B6BA9172B93AD50607D80772547</idno><idno type="DOI">10.1016/0006-8993(94)91761-2</idno><idno type="PII">0006-8993(94)91761-2</idno><idno type="ArticleID">94917612</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1994</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>In order to determine whether, besides the severe striatal dopamine (DA) loss, other brain neurotransmitter changes may be a constant biochemical feature of idiopathic Parkinson's disease (iPD), we measured the concentration of the three major brain monoamines noradrenaline (NA), DA, and serotonin (5-HT) and their metabolites in five rostro-caudal subdivisions of the hypothalamus of eight control patients and nine patients with morphologically confirmed iPD. In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA(−52%, P < 0.05),DA(−25%),and5-HT(−26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Parkinson's disease</term></item><item><term>Hypothalamus</term></item><item><term>Dopamine</term></item><item><term>Noradrenaline</term></item><item><term>Serotonin</term></item><item><term>Monoamine</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1993-10-19">Registration</change><change when="1993">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.0.1//EN//XML" URI="art501.dtd" name="istex:docType"></istex:docType><istex:document><article version="5.0" xml:lang="en" docsubtype="fla"><item-info><jid>BRES</jid><aid>94917612</aid><ce:pii>0006-8993(94)91761-2</ce:pii><ce:doi>10.1016/0006-8993(94)91761-2</ce:doi><ce:copyright type="unknown" year="1994">Elsevier Science B.V. All rights reserved</ce:copyright></item-info><head><ce:title>Noradrenaline, dopamine and serotonin levels and metabolism in the human hypothalamus: observations in Parkinson's disease and normal subjects</ce:title><ce:author-group><ce:author><ce:given-name>K.</ce:given-name><ce:surname>Shannak</ce:surname><ce:cross-ref refid="cor1"><ce:sup loc="post">*</ce:sup></ce:cross-ref><ce:cross-ref refid="aff1"><ce:sup loc="post">a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>A.</ce:given-name><ce:surname>Rajput</ce:surname><ce:cross-ref refid="aff2"><ce:sup loc="post">b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>B.</ce:given-name><ce:surname>Rozdilsky</ce:surname><ce:cross-ref refid="aff2"><ce:sup loc="post">b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>S.</ce:given-name><ce:surname>Kish</ce:surname><ce:cross-ref refid="aff1"><ce:sup loc="post">a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>J.</ce:given-name><ce:surname>Gilbert</ce:surname><ce:cross-ref refid="aff3"><ce:sup loc="post">c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>O.</ce:given-name><ce:surname>Hornykiewicz</ce:surname><ce:cross-ref refid="aff1"><ce:sup loc="post">a</ce:sup></ce:cross-ref><ce:cross-ref refid="aff4"><ce:sup loc="post">d</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="aff1"><ce:label>a</ce:label><ce:textfn>Clarke Institute of Psychiatry, 250 College Street, Toronto, Ont. ,CanadaM5T 1R8</ce:textfn></ce:affiliation><ce:affiliation id="aff2"><ce:label>b</ce:label><ce:textfn>University of Saskatoon, Saskatoon, Sask., Canada</ce:textfn></ce:affiliation><ce:affiliation id="aff3"><ce:label>c</ce:label><ce:textfn>Victoria Hospital, London, Ont., Canada</ce:textfn></ce:affiliation><ce:affiliation id="aff4"><ce:label>d</ce:label><ce:textfn>Institute of Biochemical Pharmacology, University of Vienna, Vienna, Austria</ce:textfn></ce:affiliation><ce:correspondence id="cor1"><ce:label>*</ce:label><ce:text>Corresponding author.</ce:text></ce:correspondence></ce:author-group><ce:date-accepted day="19" month="10" year="1993"></ce:date-accepted><ce:abstract id="ab1" class="author" xml:lang="en"><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para view="all" id="simple-para.0010">In order to determine whether, besides the severe striatal dopamine (DA) loss, other brain neurotransmitter changes may be a constant biochemical feature of idiopathic Parkinson's disease (iPD), we measured the concentration of the three major brain monoamines noradrenaline (NA), DA, and serotonin (5-HT) and their metabolites in five rostro-caudal subdivisions of the hypothalamus of eight control patients and nine patients with morphologically confirmed iPD. In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA(−52%, P < 0.05),DA(−25%),and5-HT(−26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword" xml:lang="en"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Parkinson's disease</ce:text></ce:keyword><ce:keyword><ce:text>Hypothalamus</ce:text></ce:keyword><ce:keyword><ce:text>Dopamine</ce:text></ce:keyword><ce:keyword><ce:text>Noradrenaline</ce:text></ce:keyword><ce:keyword><ce:text>Serotonin</ce:text></ce:keyword><ce:keyword><ce:text>Monoamine</ce:text></ce:keyword></ce:keywords></head><tail view="all"><ce:bibliography view="all" id="bibliography.0010"><ce:section-title>Reference</ce:section-title><ce:bibliography-sec id="bibliography-sec.0010"><ce:bib-reference id="bib1"><ce:label>[1]</ce:label><sb:reference><sb:contribution langtype="en"><sb:authors><sb:author><ce:surname>Adolfsson</ce:surname><ce:given-name>R.</ce:given-name></sb:author><sb:author><ce:surname>Gottfries</ce:surname><ce:given-name>C.G.</ce:given-name></sb:author><sb:author><ce:surname>Roos</ce:surname><ce:given-name>B.E.</ce:given-name></sb:author><sb:author><ce:surname>Winblad</ce:surname><ce:given-name>B.</ce:given-name></sb:author></sb:authors><sb:title><sb:maintitle>Post-mortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and a review of the literature</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. 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In the whole hypothalamus of the iPD patients we found a mild to moderate mean reduction of NA(−52%, P < 0.05),DA(−25%),and5-HT(−26%). At the subregional level, the most consistently affected area was the intermediate subdivision of the hypothalamus proper where all three monoamines were statistically significantly reduced. Evaluation of individual patient values indicated that, in contrast to the constant and severe DA reduction present in putamen of each of the iPD patients (DA loss ranging from 96% to 99%), several of these patients had whole (and subregional) hypothalamic monoamine values well within the range of controls. We conclude that, although possibly involved in autonomic and/or endocrine disturbances in some patients with iPD, none of the observed monoamine changes in the hypothalamus is an obligatory feature of iPD. Our study demonstrates the need for evaluation of individual patient values rather than mean differences in order to permit valid conclusions to be drawn as to whether an observed neurochemical change can be regarded as specific to a given brain disorder.</abstract><subject lang="en"><genre>Keywords</genre><topic>Parkinson's disease</topic><topic>Hypothalamus</topic><topic>Dopamine</topic><topic>Noradrenaline</topic><topic>Serotonin</topic><topic>Monoamine</topic></subject><relatedItem type="host"><titleInfo><title>Brain Research</title></titleInfo><titleInfo type="abbreviated"><title>BRES</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">19940307</dateIssued></originInfo><identifier type="ISSN">0006-8993</identifier><identifier type="PII">S0006-8993(00)X1196-1</identifier><part><detail type="volume"><number>639</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>179</end></extent><extent unit="pages"><start>33</start><end>41</end></extent></part></relatedItem><identifier type="istex">4102B406468C0B6BA9172B93AD50607D80772547</identifier><identifier type="DOI">10.1016/0006-8993(94)91761-2</identifier><identifier type="PII">0006-8993(94)91761-2</identifier><identifier type="ArticleID">94917612</identifier><accessCondition type="use and reproduction" contentType="">© 1994Elsevier Science B.V. 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