A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis
Type 1 cytokines are overexpressed in psoriatic plaques. This trial evaluated a monoclonal antibody against interleukin-12 and interleukin-23 in patients with psoriasis. Response rates at 12 weeks were significantly higher in patients treated with interleukin-12/23 monoclonal antibody than in those...
Gespeichert in:
| Veröffentlicht in: | The New England journal of medicine 2007-02, Vol.356 (6), p.580-592 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 592 |
|---|---|
| container_issue | 6 |
| container_start_page | 580 |
| container_title | The New England journal of medicine |
| container_volume | 356 |
| creator | Krueger, Gerald G Langley, Richard G Leonardi, Craig Yeilding, Newman Guzzo, Cynthia Wang, Yuhua Dooley, Lisa T Lebwohl, Mark |
| description | Type 1 cytokines are overexpressed in psoriatic plaques. This trial evaluated a monoclonal antibody against interleukin-12 and interleukin-23 in patients with psoriasis. Response rates at 12 weeks were significantly higher in patients treated with interleukin-12/23 monoclonal antibody than in those treated with placebo. Four percent of patients who received interleukin-12/23 monoclonal antibody and 1% of those who received placebo had serious adverse events. Larger studies of longer duration are needed to assess the effectiveness and safety of interleukin-12/23 monoclonal antibody for psoriasis.
In patients with psoriasis, response rates at 12 weeks were significantly higher in those treated with interleukin-12/23 monoclonal antibody than in those treated with placebo.
Psoriasis is a chronic inflammatory skin disorder affecting 2 to 3% of the world's population.
1
,
2
Psoriasis affects the physical and emotional well-being of patients, and its effect on quality of life is similar to that seen with other major medical diseases.
3
Significant unmet need remains for safe, highly effective, and convenient treatments. Aberrant type 1 immune responses have been linked to the pathogenesis of psoriasis,
4
–
7
and cytokines that elicit these immune responses (e.g., interleukin-12 and interleukin-23) may represent appropriate therapeutic targets.
8
Interleukin-12 p40 is overexpressed in psoriasis plaques,
9
and preclinical studies implicate this cytokine in the pathogenesis of . . . |
| doi_str_mv | 10.1056/NEJMoa062382 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_68990697</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68990697</sourcerecordid><originalsourceid>FETCH-LOGICAL-c597t-3caff79e501067e70e96203aa6e1b77ae65ee006aa4cf8678647c242aa61a15e3</originalsourceid><addsrcrecordid>eNqF0U1rFEEQBuBGFLOJ3jxLI-rJMdXf3cclJCayUQ_xPNR2anDWme7YPXPIv3fCLkREsC51eXiLqmLslYCPAow9_XL--TojWKm8fMJWwijVaA32KVsBSN9oF9QRO651B0sJHZ6zI-Gkd9r5Fdus-eU8YuJXaaIy0PyzT42Qp1Lx65xyHHLCga_T1G_z7T3vcuHTD-I3hXAaKU08d_xbzaXH2tcX7FmHQ6WXh37Cvl-c35xdNpuvn67O1psmmuCmRkXsOhfIgADryAEFK0EhWhJb55CsIQKwiDp23jpvtYtSywUIFIbUCXu_z70r-ddMdWrHvkYaBkyU59paHwLY4P4LxWLAeLnAN3_BXZ7LsnptpVRBmgBqQR_2KJZca6GuvSv9iOW-FdA-_KL98xcLf33InLcj3T7iw_EX8O4AsEYcuoIp9vXReQNGhwf3du_GsbaJduO_5_0GvduZ9w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>223925903</pqid></control><display><type>article</type><title>A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>New England Journal of Medicine</source><creator>Krueger, Gerald G ; Langley, Richard G ; Leonardi, Craig ; Yeilding, Newman ; Guzzo, Cynthia ; Wang, Yuhua ; Dooley, Lisa T ; Lebwohl, Mark</creator><creatorcontrib>Krueger, Gerald G ; Langley, Richard G ; Leonardi, Craig ; Yeilding, Newman ; Guzzo, Cynthia ; Wang, Yuhua ; Dooley, Lisa T ; Lebwohl, Mark ; CNTO 1275 Psoriasis Study Group</creatorcontrib><description>Type 1 cytokines are overexpressed in psoriatic plaques. This trial evaluated a monoclonal antibody against interleukin-12 and interleukin-23 in patients with psoriasis. Response rates at 12 weeks were significantly higher in patients treated with interleukin-12/23 monoclonal antibody than in those treated with placebo. Four percent of patients who received interleukin-12/23 monoclonal antibody and 1% of those who received placebo had serious adverse events. Larger studies of longer duration are needed to assess the effectiveness and safety of interleukin-12/23 monoclonal antibody for psoriasis.
In patients with psoriasis, response rates at 12 weeks were significantly higher in those treated with interleukin-12/23 monoclonal antibody than in those treated with placebo.
Psoriasis is a chronic inflammatory skin disorder affecting 2 to 3% of the world's population.
1
,
2
Psoriasis affects the physical and emotional well-being of patients, and its effect on quality of life is similar to that seen with other major medical diseases.
3
Significant unmet need remains for safe, highly effective, and convenient treatments. Aberrant type 1 immune responses have been linked to the pathogenesis of psoriasis,
4
–
7
and cytokines that elicit these immune responses (e.g., interleukin-12 and interleukin-23) may represent appropriate therapeutic targets.
8
Interleukin-12 p40 is overexpressed in psoriasis plaques,
9
and preclinical studies implicate this cytokine in the pathogenesis of . . .</description><identifier>ISSN: 0028-4793</identifier><identifier>EISSN: 1533-4406</identifier><identifier>DOI: 10.1056/NEJMoa062382</identifier><identifier>PMID: 17287478</identifier><identifier>CODEN: NEJMAG</identifier><language>eng</language><publisher>Boston, MA: Massachusetts Medical Society</publisher><subject>Adult ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Biological and medical sciences ; Cytokines ; Dermatology ; Double-Blind Method ; Female ; General aspects ; Humans ; Immunologic Factors - therapeutic use ; Interleukin-12 - immunology ; Interleukin-23 - immunology ; Light therapy ; Male ; Medical sciences ; Middle Aged ; Pathogenesis ; Patients ; Psoriasis ; Psoriasis - drug therapy ; Psoriasis - immunology ; Psoriasis. Parapsoriasis. Lichen ; Quality of life ; Treatment Outcome</subject><ispartof>The New England journal of medicine, 2007-02, Vol.356 (6), p.580-592</ispartof><rights>Copyright © 2007 Massachusetts Medical Society. All rights reserved.</rights><rights>2007 INIST-CNRS</rights><rights>Copyright 2007 Massachusetts Medical Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c597t-3caff79e501067e70e96203aa6e1b77ae65ee006aa4cf8678647c242aa61a15e3</citedby><cites>FETCH-LOGICAL-c597t-3caff79e501067e70e96203aa6e1b77ae65ee006aa4cf8678647c242aa61a15e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.nejm.org/doi/pdf/10.1056/NEJMoa062382$$EPDF$$P50$$Gmms$$H</linktopdf><linktohtml>$$Uhttps://www.nejm.org/doi/full/10.1056/NEJMoa062382$$EHTML$$P50$$Gmms$$H</linktohtml><link.rule.ids>314,776,780,2746,2747,26080,27901,27902,52357,54039</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18505498$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17287478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krueger, Gerald G</creatorcontrib><creatorcontrib>Langley, Richard G</creatorcontrib><creatorcontrib>Leonardi, Craig</creatorcontrib><creatorcontrib>Yeilding, Newman</creatorcontrib><creatorcontrib>Guzzo, Cynthia</creatorcontrib><creatorcontrib>Wang, Yuhua</creatorcontrib><creatorcontrib>Dooley, Lisa T</creatorcontrib><creatorcontrib>Lebwohl, Mark</creatorcontrib><creatorcontrib>CNTO 1275 Psoriasis Study Group</creatorcontrib><title>A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis</title><title>The New England journal of medicine</title><addtitle>N Engl J Med</addtitle><description>Type 1 cytokines are overexpressed in psoriatic plaques. This trial evaluated a monoclonal antibody against interleukin-12 and interleukin-23 in patients with psoriasis. Response rates at 12 weeks were significantly higher in patients treated with interleukin-12/23 monoclonal antibody than in those treated with placebo. Four percent of patients who received interleukin-12/23 monoclonal antibody and 1% of those who received placebo had serious adverse events. Larger studies of longer duration are needed to assess the effectiveness and safety of interleukin-12/23 monoclonal antibody for psoriasis.
In patients with psoriasis, response rates at 12 weeks were significantly higher in those treated with interleukin-12/23 monoclonal antibody than in those treated with placebo.
Psoriasis is a chronic inflammatory skin disorder affecting 2 to 3% of the world's population.
1
,
2
Psoriasis affects the physical and emotional well-being of patients, and its effect on quality of life is similar to that seen with other major medical diseases.
3
Significant unmet need remains for safe, highly effective, and convenient treatments. Aberrant type 1 immune responses have been linked to the pathogenesis of psoriasis,
4
–
7
and cytokines that elicit these immune responses (e.g., interleukin-12 and interleukin-23) may represent appropriate therapeutic targets.
8
Interleukin-12 p40 is overexpressed in psoriasis plaques,
9
and preclinical studies implicate this cytokine in the pathogenesis of . . .</description><subject>Adult</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Cytokines</subject><subject>Dermatology</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>General aspects</subject><subject>Humans</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Interleukin-12 - immunology</subject><subject>Interleukin-23 - immunology</subject><subject>Light therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Psoriasis</subject><subject>Psoriasis - drug therapy</subject><subject>Psoriasis - immunology</subject><subject>Psoriasis. Parapsoriasis. Lichen</subject><subject>Quality of life</subject><subject>Treatment Outcome</subject><issn>0028-4793</issn><issn>1533-4406</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF0U1rFEEQBuBGFLOJ3jxLI-rJMdXf3cclJCayUQ_xPNR2anDWme7YPXPIv3fCLkREsC51eXiLqmLslYCPAow9_XL--TojWKm8fMJWwijVaA32KVsBSN9oF9QRO651B0sJHZ6zI-Gkd9r5Fdus-eU8YuJXaaIy0PyzT42Qp1Lx65xyHHLCga_T1G_z7T3vcuHTD-I3hXAaKU08d_xbzaXH2tcX7FmHQ6WXh37Cvl-c35xdNpuvn67O1psmmuCmRkXsOhfIgADryAEFK0EhWhJb55CsIQKwiDp23jpvtYtSywUIFIbUCXu_z70r-ddMdWrHvkYaBkyU59paHwLY4P4LxWLAeLnAN3_BXZ7LsnptpVRBmgBqQR_2KJZca6GuvSv9iOW-FdA-_KL98xcLf33InLcj3T7iw_EX8O4AsEYcuoIp9vXReQNGhwf3du_GsbaJduO_5_0GvduZ9w</recordid><startdate>20070208</startdate><enddate>20070208</enddate><creator>Krueger, Gerald G</creator><creator>Langley, Richard G</creator><creator>Leonardi, Craig</creator><creator>Yeilding, Newman</creator><creator>Guzzo, Cynthia</creator><creator>Wang, Yuhua</creator><creator>Dooley, Lisa T</creator><creator>Lebwohl, Mark</creator><general>Massachusetts Medical Society</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>0TZ</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K0Y</scope><scope>LK8</scope><scope>M0R</scope><scope>M0T</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20070208</creationdate><title>A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis</title><author>Krueger, Gerald G ; Langley, Richard G ; Leonardi, Craig ; Yeilding, Newman ; Guzzo, Cynthia ; Wang, Yuhua ; Dooley, Lisa T ; Lebwohl, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c597t-3caff79e501067e70e96203aa6e1b77ae65ee006aa4cf8678647c242aa61a15e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adult</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Cytokines</topic><topic>Dermatology</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>General aspects</topic><topic>Humans</topic><topic>Immunologic Factors - therapeutic use</topic><topic>Interleukin-12 - immunology</topic><topic>Interleukin-23 - immunology</topic><topic>Light therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Psoriasis</topic><topic>Psoriasis - drug therapy</topic><topic>Psoriasis - immunology</topic><topic>Psoriasis. Parapsoriasis. Lichen</topic><topic>Quality of life</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Krueger, Gerald G</creatorcontrib><creatorcontrib>Langley, Richard G</creatorcontrib><creatorcontrib>Leonardi, Craig</creatorcontrib><creatorcontrib>Yeilding, Newman</creatorcontrib><creatorcontrib>Guzzo, Cynthia</creatorcontrib><creatorcontrib>Wang, Yuhua</creatorcontrib><creatorcontrib>Dooley, Lisa T</creatorcontrib><creatorcontrib>Lebwohl, Mark</creatorcontrib><creatorcontrib>CNTO 1275 Psoriasis Study Group</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>Pharma and Biotech Premium PRO</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>New England Journal of Medicine</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The New England journal of medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Krueger, Gerald G</au><au>Langley, Richard G</au><au>Leonardi, Craig</au><au>Yeilding, Newman</au><au>Guzzo, Cynthia</au><au>Wang, Yuhua</au><au>Dooley, Lisa T</au><au>Lebwohl, Mark</au><aucorp>CNTO 1275 Psoriasis Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis</atitle><jtitle>The New England journal of medicine</jtitle><addtitle>N Engl J Med</addtitle><date>2007-02-08</date><risdate>2007</risdate><volume>356</volume><issue>6</issue><spage>580</spage><epage>592</epage><pages>580-592</pages><issn>0028-4793</issn><eissn>1533-4406</eissn><coden>NEJMAG</coden><abstract>Type 1 cytokines are overexpressed in psoriatic plaques. This trial evaluated a monoclonal antibody against interleukin-12 and interleukin-23 in patients with psoriasis. Response rates at 12 weeks were significantly higher in patients treated with interleukin-12/23 monoclonal antibody than in those treated with placebo. Four percent of patients who received interleukin-12/23 monoclonal antibody and 1% of those who received placebo had serious adverse events. Larger studies of longer duration are needed to assess the effectiveness and safety of interleukin-12/23 monoclonal antibody for psoriasis.
In patients with psoriasis, response rates at 12 weeks were significantly higher in those treated with interleukin-12/23 monoclonal antibody than in those treated with placebo.
Psoriasis is a chronic inflammatory skin disorder affecting 2 to 3% of the world's population.
1
,
2
Psoriasis affects the physical and emotional well-being of patients, and its effect on quality of life is similar to that seen with other major medical diseases.
3
Significant unmet need remains for safe, highly effective, and convenient treatments. Aberrant type 1 immune responses have been linked to the pathogenesis of psoriasis,
4
–
7
and cytokines that elicit these immune responses (e.g., interleukin-12 and interleukin-23) may represent appropriate therapeutic targets.
8
Interleukin-12 p40 is overexpressed in psoriasis plaques,
9
and preclinical studies implicate this cytokine in the pathogenesis of . . .</abstract><cop>Boston, MA</cop><pub>Massachusetts Medical Society</pub><pmid>17287478</pmid><doi>10.1056/NEJMoa062382</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-4793 |
| ispartof | The New England journal of medicine, 2007-02, Vol.356 (6), p.580-592 |
| issn | 0028-4793 1533-4406 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68990697 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; New England Journal of Medicine |
| subjects | Adult Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Biological and medical sciences Cytokines Dermatology Double-Blind Method Female General aspects Humans Immunologic Factors - therapeutic use Interleukin-12 - immunology Interleukin-23 - immunology Light therapy Male Medical sciences Middle Aged Pathogenesis Patients Psoriasis Psoriasis - drug therapy Psoriasis - immunology Psoriasis. Parapsoriasis. Lichen Quality of life Treatment Outcome |
| title | A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T00%3A46%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Human%20Interleukin-12/23%20Monoclonal%20Antibody%20for%20the%20Treatment%20of%20Psoriasis&rft.jtitle=The%20New%20England%20journal%20of%20medicine&rft.au=Krueger,%20Gerald%20G&rft.aucorp=CNTO%201275%20Psoriasis%20Study%20Group&rft.date=2007-02-08&rft.volume=356&rft.issue=6&rft.spage=580&rft.epage=592&rft.pages=580-592&rft.issn=0028-4793&rft.eissn=1533-4406&rft.coden=NEJMAG&rft_id=info:doi/10.1056/NEJMoa062382&rft_dat=%3Cproquest_cross%3E68990697%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=223925903&rft_id=info:pmid/17287478&rfr_iscdi=true |