NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype–phenotype analysis
OBJECTIVESThree recently identified NOD2/CARD15 mutations have been described associated with an increased susceptibility Crohn's disease (CD). Our aim was to examine the potential association of these NOD2 mutations with CD and different subsets of CD phenotypes in our population. METHODSTwo h...
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| Veröffentlicht in: | European journal of gastroenterology & hepatology 2004-01, Vol.16 (1), p.55-62 |
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| creator | Heresbach, Denis Gicquel-Douabin, Véronique Birebent, Brigitte D'halluin, Pierre-Nicolas Heresbach-Le Berre, Nathalie Dreano, Stéphane Siproudhis, Laurent Dabadie, Alain Gosselin, Michel Mosser, Jean Semana, Gilbert Bretagne, Jean-François Yaouanq, Jacqueline |
| description | OBJECTIVESThree recently identified NOD2/CARD15 mutations have been described associated with an increased susceptibility Crohn's disease (CD). Our aim was to examine the potential association of these NOD2 mutations with CD and different subsets of CD phenotypes in our population.
METHODSTwo hundred and five well-defined CD patients from north-western France and 95 ethnically matched healthy controls were genotyped for mutations R702W, G908R and Leu1007insC by DNA sequencing. Allele and genotype frequencies of NOD2 variants were examined in the whole series of CD and in different subgroups of CD phenotypes defined by the clinical characteristics of the Vienna classification (age at diagnosis, location and behaviour) or by histological features (granuloma).
RESULTSCarriers of at least one NOD2/CARD15 variant were significantly more frequent in CD than in controls (38.0% versus 20.0%, P < 0.002), and the R702W allele was the most significant contributor to this NOD2 association with CD. Homozygotes and compound heterozygotes combined had a higher risk of CD (odds ratio = 12.0, P < 0.0026) than simple heterozygotes for any variant (odds ratio = 2.2, P < 0.013) compared with subjects with no variant. Univariate analysis revealed that carriage of at least one NOD2 mutation was significantly associated with ileal involvement (P < 0.03), and stricturing evolution (P < 0.0015). Granuloma was associated with an excess of the R702W allele (16.1% versus 8.0%, Pc < 0.035), and was correlated with a young age at diagnosis, whatever the NOD2/CARD15 genotype. Multivariate analysis demonstrated that carriage of NOD2/CARD15 mutants, especially R702W, was primarily and independently associated both with stricturing evolution of CD and the presence of granuloma.
CONCLUSIONSIn our population, all NOD2/CARD15 mutant genotypes, especially compound heterozygosity, were found to increase the risk of CD, but R702W was the sole allele showing a significant association with CD. In addition, we confirm the positive and independent association of the R702W mutation with stricturing behaviour and describe a second one with the presence of granuloma. |
| doi_str_mv | 10.1097/00042737-200401000-00009 |
| format | Article |
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METHODSTwo hundred and five well-defined CD patients from north-western France and 95 ethnically matched healthy controls were genotyped for mutations R702W, G908R and Leu1007insC by DNA sequencing. Allele and genotype frequencies of NOD2 variants were examined in the whole series of CD and in different subgroups of CD phenotypes defined by the clinical characteristics of the Vienna classification (age at diagnosis, location and behaviour) or by histological features (granuloma).
RESULTSCarriers of at least one NOD2/CARD15 variant were significantly more frequent in CD than in controls (38.0% versus 20.0%, P < 0.002), and the R702W allele was the most significant contributor to this NOD2 association with CD. Homozygotes and compound heterozygotes combined had a higher risk of CD (odds ratio = 12.0, P < 0.0026) than simple heterozygotes for any variant (odds ratio = 2.2, P < 0.013) compared with subjects with no variant. Univariate analysis revealed that carriage of at least one NOD2 mutation was significantly associated with ileal involvement (P < 0.03), and stricturing evolution (P < 0.0015). Granuloma was associated with an excess of the R702W allele (16.1% versus 8.0%, Pc < 0.035), and was correlated with a young age at diagnosis, whatever the NOD2/CARD15 genotype. Multivariate analysis demonstrated that carriage of NOD2/CARD15 mutants, especially R702W, was primarily and independently associated both with stricturing evolution of CD and the presence of granuloma.
CONCLUSIONSIn our population, all NOD2/CARD15 mutant genotypes, especially compound heterozygosity, were found to increase the risk of CD, but R702W was the sole allele showing a significant association with CD. In addition, we confirm the positive and independent association of the R702W mutation with stricturing behaviour and describe a second one with the presence of granuloma.]]></description><identifier>ISSN: 0954-691X</identifier><identifier>EISSN: 1473-5687</identifier><identifier>DOI: 10.1097/00042737-200401000-00009</identifier><identifier>PMID: 15095853</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins, Inc</publisher><subject>Adolescent ; Adult ; Aged ; Analysis of Variance ; Biological and medical sciences ; Carrier Proteins - genetics ; Child ; Crohn Disease - genetics ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Frequency ; Genetic Predisposition to Disease - genetics ; Granuloma - genetics ; Heterozygote ; Homozygote ; Humans ; Intracellular Signaling Peptides and Proteins ; Male ; Medical sciences ; Middle Aged ; Mutation - genetics ; Nod2 Signaling Adaptor Protein ; Other diseases. Semiology ; Polymorphism, Genetic - genetics ; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><ispartof>European journal of gastroenterology & hepatology, 2004-01, Vol.16 (1), p.55-62</ispartof><rights>2004 Lippincott Williams & Wilkins, Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3319-748fe19418b27bb72c0f65b2ace503bd17e2ffdc3b4c852026f08923c22558353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15560696$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15095853$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heresbach, Denis</creatorcontrib><creatorcontrib>Gicquel-Douabin, Véronique</creatorcontrib><creatorcontrib>Birebent, Brigitte</creatorcontrib><creatorcontrib>D'halluin, Pierre-Nicolas</creatorcontrib><creatorcontrib>Heresbach-Le Berre, Nathalie</creatorcontrib><creatorcontrib>Dreano, Stéphane</creatorcontrib><creatorcontrib>Siproudhis, Laurent</creatorcontrib><creatorcontrib>Dabadie, Alain</creatorcontrib><creatorcontrib>Gosselin, Michel</creatorcontrib><creatorcontrib>Mosser, Jean</creatorcontrib><creatorcontrib>Semana, Gilbert</creatorcontrib><creatorcontrib>Bretagne, Jean-François</creatorcontrib><creatorcontrib>Yaouanq, Jacqueline</creatorcontrib><title>NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype–phenotype analysis</title><title>European journal of gastroenterology & hepatology</title><addtitle>Eur J Gastroenterol Hepatol</addtitle><description><![CDATA[OBJECTIVESThree recently identified NOD2/CARD15 mutations have been described associated with an increased susceptibility Crohn's disease (CD). Our aim was to examine the potential association of these NOD2 mutations with CD and different subsets of CD phenotypes in our population.
METHODSTwo hundred and five well-defined CD patients from north-western France and 95 ethnically matched healthy controls were genotyped for mutations R702W, G908R and Leu1007insC by DNA sequencing. Allele and genotype frequencies of NOD2 variants were examined in the whole series of CD and in different subgroups of CD phenotypes defined by the clinical characteristics of the Vienna classification (age at diagnosis, location and behaviour) or by histological features (granuloma).
RESULTSCarriers of at least one NOD2/CARD15 variant were significantly more frequent in CD than in controls (38.0% versus 20.0%, P < 0.002), and the R702W allele was the most significant contributor to this NOD2 association with CD. Homozygotes and compound heterozygotes combined had a higher risk of CD (odds ratio = 12.0, P < 0.0026) than simple heterozygotes for any variant (odds ratio = 2.2, P < 0.013) compared with subjects with no variant. Univariate analysis revealed that carriage of at least one NOD2 mutation was significantly associated with ileal involvement (P < 0.03), and stricturing evolution (P < 0.0015). Granuloma was associated with an excess of the R702W allele (16.1% versus 8.0%, Pc < 0.035), and was correlated with a young age at diagnosis, whatever the NOD2/CARD15 genotype. Multivariate analysis demonstrated that carriage of NOD2/CARD15 mutants, especially R702W, was primarily and independently associated both with stricturing evolution of CD and the presence of granuloma.
CONCLUSIONSIn our population, all NOD2/CARD15 mutant genotypes, especially compound heterozygosity, were found to increase the risk of CD, but R702W was the sole allele showing a significant association with CD. In addition, we confirm the positive and independent association of the R702W mutation with stricturing behaviour and describe a second one with the presence of granuloma.]]></description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Child</subject><subject>Crohn Disease - genetics</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Granuloma - genetics</subject><subject>Heterozygote</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Nod2 Signaling Adaptor Protein</subject><subject>Other diseases. Semiology</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><issn>0954-691X</issn><issn>1473-5687</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKxDAUhoMoOl5eQbpRV9VcmiZ1J-MVREEU3IU0c2qr6cWcGWR2voNv6JNYnXrZuAg5h3z_OfCFkIjRfUYzdUApTbgSKuZ9QVnfxv2h2RIZsUSJWKZaLZMRzWQSpxm7XyPriI-UMiWYWiVrTPZPWooRubm6PuYH46ObYyajB2gg6lo_r9vQlRXWGFVNNA5t2exhNKkQLMJhZD_Bdjrv4P31rSuHOrKN9XOscJOsFNYjbA33Brk7Pbkdn8eX12cX46PL2AnBslglugCWJUznXOW54o4Wqcy5dSCpyCdMAS-KiRN54rTklKcF1RkXjnMptZBig-wu5nahfZ4BTk1doQPvbQPtDI1iOuFM8R7UC9CFFjFAYbpQ1TbMDaPm06f59ml-fJovn310e9gxy2uY_AYHgT2wMwAWnfVFsI2r8A8nU5pmac8lC-6l9VMI-ORnLxBMCdZPS_Pff4oPh0yMMg</recordid><startdate>200401</startdate><enddate>200401</enddate><creator>Heresbach, Denis</creator><creator>Gicquel-Douabin, Véronique</creator><creator>Birebent, Brigitte</creator><creator>D'halluin, Pierre-Nicolas</creator><creator>Heresbach-Le Berre, Nathalie</creator><creator>Dreano, Stéphane</creator><creator>Siproudhis, Laurent</creator><creator>Dabadie, Alain</creator><creator>Gosselin, Michel</creator><creator>Mosser, Jean</creator><creator>Semana, Gilbert</creator><creator>Bretagne, Jean-François</creator><creator>Yaouanq, Jacqueline</creator><general>Lippincott Williams & Wilkins, Inc</general><general>Lippincott Williams & Wilkins</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>7X8</scope></search><sort><creationdate>200401</creationdate><title>NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype–phenotype analysis</title><author>Heresbach, Denis ; Gicquel-Douabin, Véronique ; Birebent, Brigitte ; D'halluin, Pierre-Nicolas ; Heresbach-Le Berre, Nathalie ; Dreano, Stéphane ; Siproudhis, Laurent ; Dabadie, Alain ; Gosselin, Michel ; Mosser, Jean ; Semana, Gilbert ; Bretagne, Jean-François ; Yaouanq, Jacqueline</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3319-748fe19418b27bb72c0f65b2ace503bd17e2ffdc3b4c852026f08923c22558353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Analysis of Variance</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Child</topic><topic>Crohn Disease - genetics</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Granuloma - genetics</topic><topic>Heterozygote</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mutation - genetics</topic><topic>Nod2 Signaling Adaptor Protein</topic><topic>Other diseases. Semiology</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heresbach, Denis</creatorcontrib><creatorcontrib>Gicquel-Douabin, Véronique</creatorcontrib><creatorcontrib>Birebent, Brigitte</creatorcontrib><creatorcontrib>D'halluin, Pierre-Nicolas</creatorcontrib><creatorcontrib>Heresbach-Le Berre, Nathalie</creatorcontrib><creatorcontrib>Dreano, Stéphane</creatorcontrib><creatorcontrib>Siproudhis, Laurent</creatorcontrib><creatorcontrib>Dabadie, Alain</creatorcontrib><creatorcontrib>Gosselin, Michel</creatorcontrib><creatorcontrib>Mosser, Jean</creatorcontrib><creatorcontrib>Semana, Gilbert</creatorcontrib><creatorcontrib>Bretagne, Jean-François</creatorcontrib><creatorcontrib>Yaouanq, Jacqueline</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>MEDLINE - Academic</collection><jtitle>European journal of gastroenterology & hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heresbach, Denis</au><au>Gicquel-Douabin, Véronique</au><au>Birebent, Brigitte</au><au>D'halluin, Pierre-Nicolas</au><au>Heresbach-Le Berre, Nathalie</au><au>Dreano, Stéphane</au><au>Siproudhis, Laurent</au><au>Dabadie, Alain</au><au>Gosselin, Michel</au><au>Mosser, Jean</au><au>Semana, Gilbert</au><au>Bretagne, Jean-François</au><au>Yaouanq, Jacqueline</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype–phenotype analysis</atitle><jtitle>European journal of gastroenterology & hepatology</jtitle><addtitle>Eur J Gastroenterol Hepatol</addtitle><date>2004-01</date><risdate>2004</risdate><volume>16</volume><issue>1</issue><spage>55</spage><epage>62</epage><pages>55-62</pages><issn>0954-691X</issn><eissn>1473-5687</eissn><abstract><![CDATA[OBJECTIVESThree recently identified NOD2/CARD15 mutations have been described associated with an increased susceptibility Crohn's disease (CD). Our aim was to examine the potential association of these NOD2 mutations with CD and different subsets of CD phenotypes in our population.
METHODSTwo hundred and five well-defined CD patients from north-western France and 95 ethnically matched healthy controls were genotyped for mutations R702W, G908R and Leu1007insC by DNA sequencing. Allele and genotype frequencies of NOD2 variants were examined in the whole series of CD and in different subgroups of CD phenotypes defined by the clinical characteristics of the Vienna classification (age at diagnosis, location and behaviour) or by histological features (granuloma).
RESULTSCarriers of at least one NOD2/CARD15 variant were significantly more frequent in CD than in controls (38.0% versus 20.0%, P < 0.002), and the R702W allele was the most significant contributor to this NOD2 association with CD. Homozygotes and compound heterozygotes combined had a higher risk of CD (odds ratio = 12.0, P < 0.0026) than simple heterozygotes for any variant (odds ratio = 2.2, P < 0.013) compared with subjects with no variant. Univariate analysis revealed that carriage of at least one NOD2 mutation was significantly associated with ileal involvement (P < 0.03), and stricturing evolution (P < 0.0015). Granuloma was associated with an excess of the R702W allele (16.1% versus 8.0%, Pc < 0.035), and was correlated with a young age at diagnosis, whatever the NOD2/CARD15 genotype. Multivariate analysis demonstrated that carriage of NOD2/CARD15 mutants, especially R702W, was primarily and independently associated both with stricturing evolution of CD and the presence of granuloma.
CONCLUSIONSIn our population, all NOD2/CARD15 mutant genotypes, especially compound heterozygosity, were found to increase the risk of CD, but R702W was the sole allele showing a significant association with CD. In addition, we confirm the positive and independent association of the R702W mutation with stricturing behaviour and describe a second one with the presence of granuloma.]]></abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins, Inc</pub><pmid>15095853</pmid><doi>10.1097/00042737-200401000-00009</doi><tpages>8</tpages></addata></record> |
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| ispartof | European journal of gastroenterology & hepatology, 2004-01, Vol.16 (1), p.55-62 |
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| subjects | Adolescent Adult Aged Analysis of Variance Biological and medical sciences Carrier Proteins - genetics Child Crohn Disease - genetics Female Gastroenterology. Liver. Pancreas. Abdomen Gene Frequency Genetic Predisposition to Disease - genetics Granuloma - genetics Heterozygote Homozygote Humans Intracellular Signaling Peptides and Proteins Male Medical sciences Middle Aged Mutation - genetics Nod2 Signaling Adaptor Protein Other diseases. Semiology Polymorphism, Genetic - genetics Stomach. Duodenum. Small intestine. Colon. Rectum. Anus |
| title | NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype–phenotype analysis |
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