CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study
Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commerc...
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| Veröffentlicht in: | Journal of clinical immunology 2004-11, Vol.24 (6), p.693-701 |
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| creator | Cooper, C L Davis, H L Morris, M L Efler, S M Adhami, M Al Krieg, A M Cameron, D W Heathcote, J |
| description | Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p |
| doi_str_mv | 10.1007/s10875-004-6244-3 |
| format | Article |
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We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.</description><identifier>ISSN: 0271-9142</identifier><identifier>EISSN: 1573-2592</identifier><identifier>DOI: 10.1007/s10875-004-6244-3</identifier><identifier>PMID: 15622454</identifier><identifier>CODEN: JCIMDO</identifier><language>eng</language><publisher>Netherlands: Springer Nature B.V</publisher><subject>Adjuvants, Immunologic - administration & dosage ; Adjuvants, Immunologic - toxicity ; Adolescent ; Adult ; Antibody Formation ; Double-Blind Method ; Female ; Hepatitis B Surface Antigens - administration & dosage ; Hepatitis B Surface Antigens - immunology ; Hepatitis B Vaccines - administration & dosage ; Hepatitis B Vaccines - toxicity ; Humans ; Immunophenotyping ; Male ; Membrane Glycoproteins - agonists ; Oligodeoxyribonucleotides - administration & dosage ; Oligodeoxyribonucleotides - toxicity ; Receptors, Cell Surface - agonists ; T-Lymphocytes - immunology ; T-Lymphocytes, Cytotoxic - immunology ; Toll-Like Receptor 9 ; Toll-Like Receptors ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - toxicity</subject><ispartof>Journal of clinical immunology, 2004-11, Vol.24 (6), p.693-701</ispartof><rights>Springer Science+Business Media, Inc. 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-c5e9926c04639be8da61add1080e56830aec3386128aa3ec1decc31363f6b03c3</citedby><cites>FETCH-LOGICAL-c392t-c5e9926c04639be8da61add1080e56830aec3386128aa3ec1decc31363f6b03c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15622454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cooper, C L</creatorcontrib><creatorcontrib>Davis, H L</creatorcontrib><creatorcontrib>Morris, M L</creatorcontrib><creatorcontrib>Efler, S M</creatorcontrib><creatorcontrib>Adhami, M Al</creatorcontrib><creatorcontrib>Krieg, A M</creatorcontrib><creatorcontrib>Cameron, D W</creatorcontrib><creatorcontrib>Heathcote, J</creatorcontrib><title>CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study</title><title>Journal of clinical immunology</title><addtitle>J Clin Immunol</addtitle><description>Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.</description><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Adjuvants, Immunologic - toxicity</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Antibody Formation</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Hepatitis B Surface Antigens - administration & dosage</subject><subject>Hepatitis B Surface Antigens - immunology</subject><subject>Hepatitis B Vaccines - administration & dosage</subject><subject>Hepatitis B Vaccines - toxicity</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Male</subject><subject>Membrane Glycoproteins - agonists</subject><subject>Oligodeoxyribonucleotides - administration & dosage</subject><subject>Oligodeoxyribonucleotides - toxicity</subject><subject>Receptors, Cell Surface - agonists</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>Toll-Like Receptor 9</subject><subject>Toll-Like Receptors</subject><subject>Vaccines, Synthetic - administration & dosage</subject><subject>Vaccines, Synthetic - toxicity</subject><issn>0271-9142</issn><issn>1573-2592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpFkc1qGzEUhUVpaNy0D9BNuXRdJfqZ0Yy6a0yaGAwJIe1WaCTZlpmR3JEUMo_St-0EG7K6m_OdC-dD6Asll5SQ5ipR0jY1JqTCglUV5u_QgtYNx6yW7D1aENZQLGnFztHHlPaEEC5Y_QGd01owVtXVAv1bPtxCI4n8DjqAH4YSYsp-KL3OcZzgaf0oQW9j8ClD7P02WhdfplBM72L21s1cAm335VmHDDnCTdi60b_ga7i7_gPP2hgfHPgAO6f7vJvmcOlz-gEabCxd73DX-2DhsNPJwepqtYKUi50-obON7pP7fLoX6Pevm6flHV7f366WP9fYcMkyNrWTkglDKsFl51qrBdXWzssQV4uWE-0M562grNWaO0OtM4ZTLvhGdIQbfoG-HXsPY_xbXMpqH8sY5peKUdG2ktF2DtFjyIwxpdFt1GH0gx4nRYl6daGOLtTsQr26UHxmvp6KSzc4-0acxuf_AcPNhKI</recordid><startdate>20041101</startdate><enddate>20041101</enddate><creator>Cooper, C L</creator><creator>Davis, H L</creator><creator>Morris, M L</creator><creator>Efler, S M</creator><creator>Adhami, M Al</creator><creator>Krieg, A M</creator><creator>Cameron, D W</creator><creator>Heathcote, J</creator><general>Springer Nature B.V</general><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>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</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>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>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20041101</creationdate><title>CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study</title><author>Cooper, C L ; Davis, H L ; Morris, M L ; Efler, S M ; Adhami, M Al ; Krieg, A M ; Cameron, D W ; Heathcote, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-c5e9926c04639be8da61add1080e56830aec3386128aa3ec1decc31363f6b03c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adjuvants, Immunologic - administration & dosage</topic><topic>Adjuvants, Immunologic - toxicity</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Antibody Formation</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Hepatitis B Surface Antigens - administration & dosage</topic><topic>Hepatitis B Surface Antigens - immunology</topic><topic>Hepatitis B Vaccines - administration & dosage</topic><topic>Hepatitis B Vaccines - toxicity</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Male</topic><topic>Membrane Glycoproteins - agonists</topic><topic>Oligodeoxyribonucleotides - administration & dosage</topic><topic>Oligodeoxyribonucleotides - toxicity</topic><topic>Receptors, Cell Surface - agonists</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Toll-Like Receptor 9</topic><topic>Toll-Like Receptors</topic><topic>Vaccines, Synthetic - administration & dosage</topic><topic>Vaccines, Synthetic - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cooper, C L</creatorcontrib><creatorcontrib>Davis, H L</creatorcontrib><creatorcontrib>Morris, M L</creatorcontrib><creatorcontrib>Efler, S M</creatorcontrib><creatorcontrib>Adhami, M Al</creatorcontrib><creatorcontrib>Krieg, A M</creatorcontrib><creatorcontrib>Cameron, D W</creatorcontrib><creatorcontrib>Heathcote, J</creatorcontrib><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>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>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>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>Biological Science Database</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><jtitle>Journal of clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cooper, C L</au><au>Davis, H L</au><au>Morris, M L</au><au>Efler, S M</au><au>Adhami, M Al</au><au>Krieg, A M</au><au>Cameron, D W</au><au>Heathcote, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study</atitle><jtitle>Journal of clinical immunology</jtitle><addtitle>J Clin Immunol</addtitle><date>2004-11-01</date><risdate>2004</risdate><volume>24</volume><issue>6</issue><spage>693</spage><epage>701</epage><pages>693-701</pages><issn>0271-9142</issn><eissn>1573-2592</eissn><coden>JCIMDO</coden><abstract>Oligodeoxynucleotides containing immunostimulatory CpG motifs (CpG ODN) act as potent Th1-like immune enhancers with many antigens in animal models. We have extended these observations to the first clinical evaluation of the safety, tolerability and immunogenicity of CPG 7909 when added to a commercial HBV vaccine. In a randomized, double-blind phase I dose escalation study, healthy volunteers aged 18-35 years were vaccinated at 0, 4 and 24 weeks by intramuscular injection with Engerix-B (GlaxoSmithKline). The regular adult dose of 20 microg recombinant hepatitis B surface antigen (HBsAg) adsorbed to alum was administered mixed with saline (control) or with CPG 7909 at one of three doses (0.125, 0.5 or 1.0 mg). HBsAg-specific antibody responses (anti-HBs) appeared significantly sooner and were significantly higher at all timepoints up to and including 24 weeks in CPG 7909 recipients compared to control subjects (p< or = 0.001). Strikingly, most CpG 7909-vaccinated subjects developed protective levels of anti-HBs IgG within just two weeks of the priming vaccine dose. A trend towards higher rates of positive cytotoxic T cell lymphocyte responses was noted in the two higher dose groups of CPG 7909 compared to controls. The most frequently reported adverse events were injection site reactions, flu-like symptoms and headache. While these were more frequent in CPG 7909 groups than in the control group (p<0.0001), most were reported to be of mild to moderate intensity regardless of group. In summary, CPG 7909 as an adjuvant to Engerix-B was well-tolerated and enhanced vaccine immunogenicity. CPG 7909 may allow the development of a two-dose prophylactic HBV vaccine.</abstract><cop>Netherlands</cop><pub>Springer Nature B.V</pub><pmid>15622454</pmid><doi>10.1007/s10875-004-6244-3</doi><tpages>9</tpages></addata></record> |
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| subjects | Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - toxicity Adolescent Adult Antibody Formation Double-Blind Method Female Hepatitis B Surface Antigens - administration & dosage Hepatitis B Surface Antigens - immunology Hepatitis B Vaccines - administration & dosage Hepatitis B Vaccines - toxicity Humans Immunophenotyping Male Membrane Glycoproteins - agonists Oligodeoxyribonucleotides - administration & dosage Oligodeoxyribonucleotides - toxicity Receptors, Cell Surface - agonists T-Lymphocytes - immunology T-Lymphocytes, Cytotoxic - immunology Toll-Like Receptor 9 Toll-Like Receptors Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - toxicity |
| title | CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind phase I/II study |
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