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<title xml:lang="en">Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data</title>
<author>
<name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name>
</author>
<author>
<name sortKey="Langbehn, Douglas R" sort="Langbehn, Douglas R" uniqKey="Langbehn D" first="Douglas R" last="Langbehn">Douglas R. Langbehn</name>
</author>
<author>
<name sortKey="Leavitt, Blair R" sort="Leavitt, Blair R" uniqKey="Leavitt B" first="Blair R" last="Leavitt">Blair R. Leavitt</name>
</author>
<author>
<name sortKey="Roos, Raymund A C" sort="Roos, Raymund A C" uniqKey="Roos R" first="Raymund A C" last="Roos">Raymund A C. Roos</name>
</author>
<author>
<name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name>
</author>
<author>
<name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name>
</author>
<author>
<name sortKey="Kennard, Christopher" sort="Kennard, Christopher" uniqKey="Kennard C" first="Christopher" last="Kennard">Christopher Kennard</name>
</author>
<author>
<name sortKey="Hicks, Stephen L" sort="Hicks, Stephen L" uniqKey="Hicks S" first="Stephen L" last="Hicks">Stephen L. Hicks</name>
</author>
<author>
<name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C" last="Fox">Nick C. Fox</name>
</author>
<author>
<name sortKey="Scahill, Rachael I" sort="Scahill, Rachael I" uniqKey="Scahill R" first="Rachael I" last="Scahill">Rachael I. Scahill</name>
</author>
<author>
<name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name>
</author>
<author>
<name sortKey="Tobin, Allan J" sort="Tobin, Allan J" uniqKey="Tobin A" first="Allan J" last="Tobin">Allan J. Tobin</name>
</author>
<author>
<name sortKey="Rosas, H Diana" sort="Rosas, H Diana" uniqKey="Rosas H" first="H Diana" last="Rosas">H Diana Rosas</name>
</author>
<author>
<name sortKey="Johnson, Hans" sort="Johnson, Hans" uniqKey="Johnson H" first="Hans" last="Johnson">Hans Johnson</name>
</author>
<author>
<name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name>
</author>
<author>
<name sortKey="Landwehrmeyer, Bernhard" sort="Landwehrmeyer, Bernhard" uniqKey="Landwehrmeyer B" first="Bernhard" last="Landwehrmeyer">Bernhard Landwehrmeyer</name>
</author>
<author>
<name sortKey="Stout, Julie C" sort="Stout, Julie C" uniqKey="Stout J" first="Julie C" last="Stout">Julie C. Stout</name>
</author>
</titleStmt>
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<idno type="wicri:source">PMC</idno>
<idno type="pmid">19646924</idno>
<idno type="pmc">3725974</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725974</idno>
<idno type="RBID">PMC:3725974</idno>
<idno type="doi">10.1016/S1474-4422(09)70170-X</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">001E06</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001E06</idno>
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<biblStruct>
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<title xml:lang="en" level="a" type="main">Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data</title>
<author>
<name sortKey="Tabrizi, Sarah J" sort="Tabrizi, Sarah J" uniqKey="Tabrizi S" first="Sarah J" last="Tabrizi">Sarah J. Tabrizi</name>
</author>
<author>
<name sortKey="Langbehn, Douglas R" sort="Langbehn, Douglas R" uniqKey="Langbehn D" first="Douglas R" last="Langbehn">Douglas R. Langbehn</name>
</author>
<author>
<name sortKey="Leavitt, Blair R" sort="Leavitt, Blair R" uniqKey="Leavitt B" first="Blair R" last="Leavitt">Blair R. Leavitt</name>
</author>
<author>
<name sortKey="Roos, Raymund A C" sort="Roos, Raymund A C" uniqKey="Roos R" first="Raymund A C" last="Roos">Raymund A C. Roos</name>
</author>
<author>
<name sortKey="Durr, Alexandra" sort="Durr, Alexandra" uniqKey="Durr A" first="Alexandra" last="Durr">Alexandra Durr</name>
</author>
<author>
<name sortKey="Craufurd, David" sort="Craufurd, David" uniqKey="Craufurd D" first="David" last="Craufurd">David Craufurd</name>
</author>
<author>
<name sortKey="Kennard, Christopher" sort="Kennard, Christopher" uniqKey="Kennard C" first="Christopher" last="Kennard">Christopher Kennard</name>
</author>
<author>
<name sortKey="Hicks, Stephen L" sort="Hicks, Stephen L" uniqKey="Hicks S" first="Stephen L" last="Hicks">Stephen L. Hicks</name>
</author>
<author>
<name sortKey="Fox, Nick C" sort="Fox, Nick C" uniqKey="Fox N" first="Nick C" last="Fox">Nick C. Fox</name>
</author>
<author>
<name sortKey="Scahill, Rachael I" sort="Scahill, Rachael I" uniqKey="Scahill R" first="Rachael I" last="Scahill">Rachael I. Scahill</name>
</author>
<author>
<name sortKey="Borowsky, Beth" sort="Borowsky, Beth" uniqKey="Borowsky B" first="Beth" last="Borowsky">Beth Borowsky</name>
</author>
<author>
<name sortKey="Tobin, Allan J" sort="Tobin, Allan J" uniqKey="Tobin A" first="Allan J" last="Tobin">Allan J. Tobin</name>
</author>
<author>
<name sortKey="Rosas, H Diana" sort="Rosas, H Diana" uniqKey="Rosas H" first="H Diana" last="Rosas">H Diana Rosas</name>
</author>
<author>
<name sortKey="Johnson, Hans" sort="Johnson, Hans" uniqKey="Johnson H" first="Hans" last="Johnson">Hans Johnson</name>
</author>
<author>
<name sortKey="Reilmann, Ralf" sort="Reilmann, Ralf" uniqKey="Reilmann R" first="Ralf" last="Reilmann">Ralf Reilmann</name>
</author>
<author>
<name sortKey="Landwehrmeyer, Bernhard" sort="Landwehrmeyer, Bernhard" uniqKey="Landwehrmeyer B" first="Bernhard" last="Landwehrmeyer">Bernhard Landwehrmeyer</name>
</author>
<author>
<name sortKey="Stout, Julie C" sort="Stout, Julie C" uniqKey="Stout J" first="Julie C" last="Stout">Julie C. Stout</name>
</author>
</analytic>
<series>
<title level="j">Lancet neurology</title>
<idno type="ISSN">1474-4422</idno>
<idno type="eISSN">1474-4465</idno>
<imprint>
<date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
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<textClass></textClass>
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<front>
<div type="abstract" xml:lang="en">
<title>Summary</title>
<sec id="S1">
<title>Background</title>
<p id="P1">Huntington’s disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated
<italic>HTT</italic>
and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD.</p>
</sec>
<sec id="S3">
<title>Findings</title>
<p id="P3">The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease.</p>
</sec>
<sec id="S4">
<title>Interpretation</title>
<p id="P4">We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in
<italic>HTT</italic>
expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials.</p>
</sec>
<sec id="S5">
<title>Funding</title>
<p id="P5">CHDI/High Q Foundation.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">101139309</journal-id>
<journal-id journal-id-type="pubmed-jr-id">30413</journal-id>
<journal-id journal-id-type="nlm-ta">Lancet Neurol</journal-id>
<journal-id journal-id-type="iso-abbrev">Lancet Neurol</journal-id>
<journal-title-group>
<journal-title>Lancet neurology</journal-title>
</journal-title-group>
<issn pub-type="ppub">1474-4422</issn>
<issn pub-type="epub">1474-4465</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">19646924</article-id>
<article-id pub-id-type="pmc">3725974</article-id>
<article-id pub-id-type="doi">10.1016/S1474-4422(09)70170-X</article-id>
<article-id pub-id-type="manuscript">NIHMS173425</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Biological and clinical manifestations of Huntington’s disease in the longitudinal TRACK-HD study: cross-sectional analysis of baseline data</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Tabrizi</surname>
<given-names>Sarah J</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Langbehn</surname>
<given-names>Douglas R</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Leavitt</surname>
<given-names>Blair R</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Roos</surname>
<given-names>Raymund A C</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Durr</surname>
<given-names>Alexandra</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Craufurd</surname>
<given-names>David</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kennard</surname>
<given-names>Christopher</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hicks</surname>
<given-names>Stephen L</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fox</surname>
<given-names>Nick C</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Scahill</surname>
<given-names>Rachael I</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Borowsky</surname>
<given-names>Beth</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tobin</surname>
<given-names>Allan J</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rosas</surname>
<given-names>H Diana</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Johnson</surname>
<given-names>Hans</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Reilmann</surname>
<given-names>Ralf</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Landwehrmeyer</surname>
<given-names>Bernhard</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stout</surname>
<given-names>Julie C</given-names>
</name>
</contrib>
<on-behalf-of>and the TRACK-HD investigators</on-behalf-of>
<aff id="A1">UCL Institute of Neurology, University College London, Queen Square, London, UK (S J Tabrizi, N C Fox, R I Scahill); Departments of Psychiatry and Biostatistics, University of Iowa, Iowa City, IA, USA (D R Langbehn); Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada (B R Leavitt); Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands (R A C Roos); Department of Genetics and Cytogenetics, and INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France (A Durr); Medical Genetics Research Group, St. Mary’s Hospital, Manchester, UK (D Craufurd); Department of Clinical Neurology, University of Oxford, Oxford, UK (C Kennard, S L Hicks); CHDI Management/CHDI Foundation, New York, NY, USA (B Borowsky, A J Tobin); Massachusetts General Hospital Department of Neurology, Harvard, Charlestown, MA, USA (H D Rosas); Department of Psychiatry, University of Iowa, Iowa City, IA, USA (H Johnson); Department of Neurology, University of Münster, Münster, Germany (R Reilmann); Department of Neurology, Ulm University, Ulm, Germany (B Landwehrmeyer); School of Psychology, Psychiatry, and Psychological Medicine, Monash University, Clayton Campus, VIC, Australia (J C Stout); and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA (J C Stout)</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">Correspondence to: Sarah Tabrizi, TRACK-HD, Box, 104, UCL Institute of Neurology, University College London, Department of Neurodegenerative Disease, Queen Square, London, WC1N 3BG, UK,
<email>sarah.tabrizi@prion.ucl.ac.uk</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>29</day>
<month>1</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub">
<day>29</day>
<month>7</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="ppub">
<month>9</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>29</day>
<month>7</month>
<year>2013</year>
</pub-date>
<volume>8</volume>
<issue>9</issue>
<fpage>791</fpage>
<lpage>801</lpage>
<abstract>
<title>Summary</title>
<sec id="S1">
<title>Background</title>
<p id="P1">Huntington’s disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. Our aim was to identify sensitive and reliable biomarkers in premanifest carriers of mutated
<italic>HTT</italic>
and in individuals with early HD that could provide essential methodology for the assessment of therapeutic interventions.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">This multicentre study uses an extensive battery of novel assessments, including multi-site 3T MRI, clinical, cognitive, quantitative motor, oculomotor, and neuropsychiatric measures. Blinded analyses were done on the baseline cross-sectional data from 366 individuals: 123 controls, 120 premanifest (pre-HD) individuals, and 123 patients with early HD.</p>
</sec>
<sec id="S3">
<title>Findings</title>
<p id="P3">The first participant was enrolled in January, 2008, and all assessments were completed by August, 2008. Cross-sectional analyses identified significant changes in whole-brain volume, regional grey and white matter differences, impairment in a range of voluntary neurophysiological motor, and oculomotor tasks, and cognitive and neuropsychiatric dysfunction in premanifest HD gene carriers with normal motor scores through to early clinical stage 2 disease.</p>
</sec>
<sec id="S4">
<title>Interpretation</title>
<p id="P4">We show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Our results provide evidence for quantifiable biological and clinical alterations in
<italic>HTT</italic>
expansion carriers compared with age-matched controls. Many parameters differ from age-matched controls in a graded fashion and show changes of increasing magnitude across our cohort, who range from about 16 years from predicted disease diagnosis to early HD. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials.</p>
</sec>
<sec id="S5">
<title>Funding</title>
<p id="P5">CHDI/High Q Foundation.</p>
</sec>
</abstract>
<funding-group>
<award-group>
<funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS042861-05 || NS</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>R01 NS042861-04 || NS</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>P01 NS058793-02 || NS</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Institute of Neurological Disorders and Stroke : NINDS</funding-source>
<award-id>P01 NS058793-01A10001 || NS</award-id>
</award-group>
<award-group>
<funding-source country="United States">National Center for Research Resources : NCRR</funding-source>
<award-id>M01 RR001066-305062 || RR</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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