Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study
Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such p...
Gespeichert in:
| Veröffentlicht in: | Neuroendocrinology 2006-01, Vol.83 (1), p.12-19 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 19 |
|---|---|
| container_issue | 1 |
| container_start_page | 12 |
| container_title | Neuroendocrinology |
| container_volume | 83 |
| creator | Arwert, Lucia I. Veltman, Dick J. Deijen, Jan Berend van Dam, P. Sytze Drent, Madeleine L. |
| description | Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging. |
| doi_str_mv | 10.1159/000093337 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pasca</sourceid><recordid>TN_cdi_pascalfrancis_primary_17880118</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20628279</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-db774ea1732e28099430a8895d7373241f76eb222995e0fedf6b70f0bdf9604e3</originalsourceid><addsrcrecordid>eNqF0c9rFDEUB_AgLXatPXgWJAgWPIzmx2x-eCtrf0FFaet5yMy8bNPOJmuSUfbeP9wsu2yhl-byQvJ5L4QvQu8o-ULpVH8lZWnOuXyFJrRmvCJU13toQghTFVd8eoDepHRfFNOcvUYHVEgiNaUT9HhqLXQ54WDxeQz_8h2-CHERPOCbsU3Z5TG74PHtHUSzXOGynYW5d9n9BXw2-m596_wcO_-8_ztY1znwGf8yeV3TN3yy6zED_nF9iW_y2K_eon1rhgRH23qIfp-d3s4uqquf55ezk6uqq5nIVd9KWYOhkjNgimhdc2KU0tNe8nJWUysFtIwxradALPRWtJJY0vZWC1IDP0THm7nLGP6MkHKzcKmDYTAewpgaoYjQVJEXISOCKSZ1gR-fwfswxvK5YmStqBZcFPR5g7oYUopgm2V0CxNXDSXNOsBmF2CxH7YDx3YB_ZPcJlbApy0wqTODjcZ3Lj05qRShVBX3fuMeTJxD3IHNM_8BqcOqqQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>274819636</pqid></control><display><type>article</type><title>Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study</title><source>MEDLINE</source><source>Karger Journals</source><creator>Arwert, Lucia I. ; Veltman, Dick J. ; Deijen, Jan Berend ; van Dam, P. Sytze ; Drent, Madeleine L.</creator><creatorcontrib>Arwert, Lucia I. ; Veltman, Dick J. ; Deijen, Jan Berend ; van Dam, P. Sytze ; Drent, Madeleine L.</creatorcontrib><description>Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.</description><identifier>ISSN: 0028-3835</identifier><identifier>EISSN: 1423-0194</identifier><identifier>DOI: 10.1159/000093337</identifier><identifier>PMID: 16707911</identifier><identifier>CODEN: NUNDAJ</identifier><language>eng</language><publisher>Basel, Switzerland: Karger</publisher><subject>Adolescent ; Adult ; Biological and medical sciences ; Brain - pathology ; Brain - physiopathology ; Cerebral Cortex - pathology ; Cerebral Cortex - physiopathology ; Cognition - drug effects ; Cognition Disorders - drug therapy ; Cognition Disorders - etiology ; Cognition Disorders - physiopathology ; Double-Blind Method ; Dwarfism, Pituitary - complications ; Dwarfism, Pituitary - drug therapy ; Dwarfism, Pituitary - physiopathology ; Female ; Fundamental and applied biological sciences. Psychology ; Growth Hormone - deficiency ; Growth Hormone - pharmacology ; Growth Hormone - therapeutic use ; Humans ; Insulin-Like Growth Factor I - analysis ; Magnetic Resonance Imaging ; Male ; Memory - drug effects ; Memory - physiology ; Neuropsychological Tests ; Original Paper ; Time Factors ; Vertebrates: endocrinology</subject><ispartof>Neuroendocrinology, 2006-01, Vol.83 (1), p.12-19</ispartof><rights>2006 S. Karger AG, Basel</rights><rights>2006 INIST-CNRS</rights><rights>Copyright (c) 2006 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-db774ea1732e28099430a8895d7373241f76eb222995e0fedf6b70f0bdf9604e3</citedby><cites>FETCH-LOGICAL-c426t-db774ea1732e28099430a8895d7373241f76eb222995e0fedf6b70f0bdf9604e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17880118$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16707911$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Arwert, Lucia I.</creatorcontrib><creatorcontrib>Veltman, Dick J.</creatorcontrib><creatorcontrib>Deijen, Jan Berend</creatorcontrib><creatorcontrib>van Dam, P. Sytze</creatorcontrib><creatorcontrib>Drent, Madeleine L.</creatorcontrib><title>Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study</title><title>Neuroendocrinology</title><addtitle>Neuroendocrinology</addtitle><description>Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Brain - pathology</subject><subject>Brain - physiopathology</subject><subject>Cerebral Cortex - pathology</subject><subject>Cerebral Cortex - physiopathology</subject><subject>Cognition - drug effects</subject><subject>Cognition Disorders - drug therapy</subject><subject>Cognition Disorders - etiology</subject><subject>Cognition Disorders - physiopathology</subject><subject>Double-Blind Method</subject><subject>Dwarfism, Pituitary - complications</subject><subject>Dwarfism, Pituitary - drug therapy</subject><subject>Dwarfism, Pituitary - physiopathology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Growth Hormone - deficiency</subject><subject>Growth Hormone - pharmacology</subject><subject>Growth Hormone - therapeutic use</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor I - analysis</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Memory - drug effects</subject><subject>Memory - physiology</subject><subject>Neuropsychological Tests</subject><subject>Original Paper</subject><subject>Time Factors</subject><subject>Vertebrates: endocrinology</subject><issn>0028-3835</issn><issn>1423-0194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqF0c9rFDEUB_AgLXatPXgWJAgWPIzmx2x-eCtrf0FFaet5yMy8bNPOJmuSUfbeP9wsu2yhl-byQvJ5L4QvQu8o-ULpVH8lZWnOuXyFJrRmvCJU13toQghTFVd8eoDepHRfFNOcvUYHVEgiNaUT9HhqLXQ54WDxeQz_8h2-CHERPOCbsU3Z5TG74PHtHUSzXOGynYW5d9n9BXw2-m596_wcO_-8_ztY1znwGf8yeV3TN3yy6zED_nF9iW_y2K_eon1rhgRH23qIfp-d3s4uqquf55ezk6uqq5nIVd9KWYOhkjNgimhdc2KU0tNe8nJWUysFtIwxradALPRWtJJY0vZWC1IDP0THm7nLGP6MkHKzcKmDYTAewpgaoYjQVJEXISOCKSZ1gR-fwfswxvK5YmStqBZcFPR5g7oYUopgm2V0CxNXDSXNOsBmF2CxH7YDx3YB_ZPcJlbApy0wqTODjcZ3Lj05qRShVBX3fuMeTJxD3IHNM_8BqcOqqQ</recordid><startdate>20060101</startdate><enddate>20060101</enddate><creator>Arwert, Lucia I.</creator><creator>Veltman, Dick J.</creator><creator>Deijen, Jan Berend</creator><creator>van Dam, P. Sytze</creator><creator>Drent, Madeleine L.</creator><general>Karger</general><general>S. Karger AG</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20060101</creationdate><title>Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study</title><author>Arwert, Lucia I. ; Veltman, Dick J. ; Deijen, Jan Berend ; van Dam, P. Sytze ; Drent, Madeleine L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-db774ea1732e28099430a8895d7373241f76eb222995e0fedf6b70f0bdf9604e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Brain - pathology</topic><topic>Brain - physiopathology</topic><topic>Cerebral Cortex - pathology</topic><topic>Cerebral Cortex - physiopathology</topic><topic>Cognition - drug effects</topic><topic>Cognition Disorders - drug therapy</topic><topic>Cognition Disorders - etiology</topic><topic>Cognition Disorders - physiopathology</topic><topic>Double-Blind Method</topic><topic>Dwarfism, Pituitary - complications</topic><topic>Dwarfism, Pituitary - drug therapy</topic><topic>Dwarfism, Pituitary - physiopathology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Growth Hormone - deficiency</topic><topic>Growth Hormone - pharmacology</topic><topic>Growth Hormone - therapeutic use</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor I - analysis</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Memory - drug effects</topic><topic>Memory - physiology</topic><topic>Neuropsychological Tests</topic><topic>Original Paper</topic><topic>Time Factors</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arwert, Lucia I.</creatorcontrib><creatorcontrib>Veltman, Dick J.</creatorcontrib><creatorcontrib>Deijen, Jan Berend</creatorcontrib><creatorcontrib>van Dam, P. Sytze</creatorcontrib><creatorcontrib>Drent, Madeleine L.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Neuroendocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arwert, Lucia I.</au><au>Veltman, Dick J.</au><au>Deijen, Jan Berend</au><au>van Dam, P. Sytze</au><au>Drent, Madeleine L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study</atitle><jtitle>Neuroendocrinology</jtitle><addtitle>Neuroendocrinology</addtitle><date>2006-01-01</date><risdate>2006</risdate><volume>83</volume><issue>1</issue><spage>12</spage><epage>19</epage><pages>12-19</pages><issn>0028-3835</issn><eissn>1423-0194</eissn><coden>NUNDAJ</coden><abstract>Patients with childhood-onset growth hormone (GH) deficiency (GHD) show impairments in mood and cognitive functioning which may resolve following GH substitution. Brain functional magnetic resonance imaging (fMRI) during performance of a memory task was used to assess the cerebral activity of such patients. Thirteen childhood-onset GHD patients (mean age 27.3 ± 6.9 years) were included in a double-blind, placebo-controlled study. The effects of 6 months of GH replacement or placebo therapy were studied using neuropsychological tests and fMRI. One patient was excluded from the study due to noncompliance with the protocol. Six months of GH substitution in these GHD patients resulted in improved memory functioning, both for long-term and working memory. fMRI showed activations during the working memory task in prefrontal, parietal, motor, and occipital cortices, as well as in the right thalamus and anterior cingulate cortex. Decreased activation in the ventrolateral prefrontal cortex was observed after GH treatment as compared with placebo treatment, indicating decreased effort and more efficient recruitment of the neural system involved. It can be concluded that GH treatment for 6 months improved the long-term as well as the working memory in patients with GHD, and this was associated with decreased brain activation in the ventrolateral prefrontal cortex. GH substitution in GHD patients is beneficial for cognitive functioning, the effects of which can be visualized by means of neuroimaging.</abstract><cop>Basel, Switzerland</cop><pub>Karger</pub><pmid>16707911</pmid><doi>10.1159/000093337</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-3835 |
| ispartof | Neuroendocrinology, 2006-01, Vol.83 (1), p.12-19 |
| issn | 0028-3835 1423-0194 |
| language | eng |
| recordid | cdi_pascalfrancis_primary_17880118 |
| source | MEDLINE; Karger Journals |
| subjects | Adolescent Adult Biological and medical sciences Brain - pathology Brain - physiopathology Cerebral Cortex - pathology Cerebral Cortex - physiopathology Cognition - drug effects Cognition Disorders - drug therapy Cognition Disorders - etiology Cognition Disorders - physiopathology Double-Blind Method Dwarfism, Pituitary - complications Dwarfism, Pituitary - drug therapy Dwarfism, Pituitary - physiopathology Female Fundamental and applied biological sciences. Psychology Growth Hormone - deficiency Growth Hormone - pharmacology Growth Hormone - therapeutic use Humans Insulin-Like Growth Factor I - analysis Magnetic Resonance Imaging Male Memory - drug effects Memory - physiology Neuropsychological Tests Original Paper Time Factors Vertebrates: endocrinology |
| title | Effects of Growth Hormone Substitution Therapy on Cognitive Functioning in Growth Hormone Deficient Patients: A Functional MRI Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T18%3A55%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pasca&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Effects%20of%20Growth%20Hormone%20Substitution%20Therapy%20on%20Cognitive%20Functioning%20in%20Growth%20Hormone%20Deficient%20Patients:%20A%20Functional%20MRI%20Study&rft.jtitle=Neuroendocrinology&rft.au=Arwert,%20Lucia%20I.&rft.date=2006-01-01&rft.volume=83&rft.issue=1&rft.spage=12&rft.epage=19&rft.pages=12-19&rft.issn=0028-3835&rft.eissn=1423-0194&rft.coden=NUNDAJ&rft_id=info:doi/10.1159/000093337&rft_dat=%3Cproquest_pasca%3E20628279%3C/proquest_pasca%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=274819636&rft_id=info:pmid/16707911&rfr_iscdi=true |