A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity
OBJECTIVE To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis‐related factors. MATERIALS AND METHODS Using D2‐40 antibody as a lymphatic marker, lymph vessels were counted in tissue sections of 150 clear...
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| creator | Baldewijns, Marcella M. Roskams, Tania Ballet, Vera Van den Eynden, Gert G. Van Laere, Steven J. Van der Auwera, Ilse Lerut, Evelyne De Bruïne, Adriaan P. Thijssen, Victor L. Vermeulen, Peter B. Van Poppel, Hein |
| description | OBJECTIVE
To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis‐related factors.
MATERIALS AND METHODS
Using D2‐40 antibody as a lymphatic marker, lymph vessels were counted in tissue sections of 150 clear‐cell RCCs (ccRCC) and 61 non‐neoplastic controls, using the Chalkley method, which measures the relative lymph vessel area (LVA). Double‐staining with Ki67 and D2‐40 was used to assess active lymphangiogenesis. In a subset of 25 ccRCCs and nine non‐neoplastic controls mRNA expression levels of lymphangiogenic factors were determined by real‐time quantitative reverse transcription‐polymerase chain reaction.
RESULTS
LVA was higher in normal renal tissue than in both intra‐ and peri‐tumoral LVA (P |
| doi_str_mv | 10.1111/j.1464-410X.2008.08272.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67409732</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67409732</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4782-fe4bffe35d0d04a3bc1543a207fde48d6fbe0cf7c606415f1cb1cbe4681a59fc3</originalsourceid><addsrcrecordid>eNqNkc9u3CAQxlHVqEnTvkLFpb2tCwaD99BDGjX9o0i5NFJvCOMhZYVhC95kfesj5Bn7JMW7m_TYoJEYwe8bhvkQwpRUtKz3q4pywReckh9VTUhbkbaWdbV9hk4eL54_5GQpjtHLnFeElAPRvEDHdEkbzoU8Qdsz7OMdtgl-bSCYCUeL_TSsf-IQe8ADjDqXcBm7gI0Hnf78vjfgPU4QtMe71OhkXIiDxoVL4PUIPR7jrvKumA43Lt5AcAZrM7pbN06v0JHVPsPrw36Kri8-fT__sri8-vz1_OxyYbhs64UF3lkLrOlJT7hmnSmdM10TaXvgbS9sB8RYaQQRnDaWmq4EcNFS3SytYafo3b7uOsXyxTyqweW5ax0gbrISsgxIsvq_YJmzZI2UBWz3oEkx5wRWrZMbdJoUJWq2R63UPHk1uzDLWrWzR22L9M3hjU03QP9PePCjAG8PgM5Ge5t0MC4_cjVtGBOsKdyHPXfnPExPbkB9_HY9Z-wv6mivDg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20073577</pqid></control><display><type>article</type><title>A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Baldewijns, Marcella M. ; Roskams, Tania ; Ballet, Vera ; Van den Eynden, Gert G. ; Van Laere, Steven J. ; Van der Auwera, Ilse ; Lerut, Evelyne ; De Bruïne, Adriaan P. ; Thijssen, Victor L. ; Vermeulen, Peter B. ; Van Poppel, Hein</creator><creatorcontrib>Baldewijns, Marcella M. ; Roskams, Tania ; Ballet, Vera ; Van den Eynden, Gert G. ; Van Laere, Steven J. ; Van der Auwera, Ilse ; Lerut, Evelyne ; De Bruïne, Adriaan P. ; Thijssen, Victor L. ; Vermeulen, Peter B. ; Van Poppel, Hein</creatorcontrib><description>OBJECTIVE
To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis‐related factors.
MATERIALS AND METHODS
Using D2‐40 antibody as a lymphatic marker, lymph vessels were counted in tissue sections of 150 clear‐cell RCCs (ccRCC) and 61 non‐neoplastic controls, using the Chalkley method, which measures the relative lymph vessel area (LVA). Double‐staining with Ki67 and D2‐40 was used to assess active lymphangiogenesis. In a subset of 25 ccRCCs and nine non‐neoplastic controls mRNA expression levels of lymphangiogenic factors were determined by real‐time quantitative reverse transcription‐polymerase chain reaction.
RESULTS
LVA was higher in normal renal tissue than in both intra‐ and peri‐tumoral LVA (P < 0.001). LVA in the tumour periphery was higher than in the tumour parenchyma (P < 0.001). Lymphatic endothelial cell proliferation (LECP) was identified in 8.2% of the control sections and was higher than the intratumoral LECP fraction (LECP%, 2.6%; P = 0.02) and the peritumoral LECP% (6.5%; P > 0.05). Compared with controls, ccRCC specimens had higher mRNA expression levels of vascular endothelial growth factor (VEGF)‐A and VEGF‐C, but lower expression levels of VEGF‐D and Prox‐1 (all P < 0.001).
CONCLUSION
Our results show that there is only limited ongoing lymphangiogenesis in ccRCC. Given that several growth factors stimulate both angiogenesis and lymphangiogenesis, our observation indirectly indicates that haemangiogenesis predominates in ccRCC. This finding might provide better understanding of why ccRCCs prefer haematogenous dissemination to lymphatic spread.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1111/j.1464-410X.2008.08272.x</identifier><identifier>PMID: 19154467</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Carcinoma, Renal Cell - secondary ; Female ; Hematologic and hematopoietic diseases ; Humans ; Immunohistochemistry ; Kidney Neoplasms - pathology ; Kidneys ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Lymph Nodes - pathology ; lymphangiogenesis ; Lymphangiogenesis - physiology ; Lymphatic Metastasis ; Lymphatic Vessels - pathology ; Male ; Medical sciences ; Membrane Glycoproteins - metabolism ; Middle Aged ; Nephrology. Urinary tract diseases ; podoplanin ; prox‐1 ; renal carcinoma ; Reverse Transcriptase Polymerase Chain Reaction ; Tumors of the urinary system ; Vascular Endothelial Growth Factor Receptor-3 - metabolism ; Vascular Endothelial Growth Factors - metabolism ; VEGF ; Young Adult</subject><ispartof>BJU international, 2009-06, Vol.103 (12), p.1626-1631</ispartof><rights>2009 THE AUTHORS. JOURNAL COMPILATION © 2009 BJU INTERNATIONAL</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4782-fe4bffe35d0d04a3bc1543a207fde48d6fbe0cf7c606415f1cb1cbe4681a59fc3</citedby><cites>FETCH-LOGICAL-c4782-fe4bffe35d0d04a3bc1543a207fde48d6fbe0cf7c606415f1cb1cbe4681a59fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1464-410X.2008.08272.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1464-410X.2008.08272.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21533635$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19154467$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baldewijns, Marcella M.</creatorcontrib><creatorcontrib>Roskams, Tania</creatorcontrib><creatorcontrib>Ballet, Vera</creatorcontrib><creatorcontrib>Van den Eynden, Gert G.</creatorcontrib><creatorcontrib>Van Laere, Steven J.</creatorcontrib><creatorcontrib>Van der Auwera, Ilse</creatorcontrib><creatorcontrib>Lerut, Evelyne</creatorcontrib><creatorcontrib>De Bruïne, Adriaan P.</creatorcontrib><creatorcontrib>Thijssen, Victor L.</creatorcontrib><creatorcontrib>Vermeulen, Peter B.</creatorcontrib><creatorcontrib>Van Poppel, Hein</creatorcontrib><title>A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>OBJECTIVE
To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis‐related factors.
MATERIALS AND METHODS
Using D2‐40 antibody as a lymphatic marker, lymph vessels were counted in tissue sections of 150 clear‐cell RCCs (ccRCC) and 61 non‐neoplastic controls, using the Chalkley method, which measures the relative lymph vessel area (LVA). Double‐staining with Ki67 and D2‐40 was used to assess active lymphangiogenesis. In a subset of 25 ccRCCs and nine non‐neoplastic controls mRNA expression levels of lymphangiogenic factors were determined by real‐time quantitative reverse transcription‐polymerase chain reaction.
RESULTS
LVA was higher in normal renal tissue than in both intra‐ and peri‐tumoral LVA (P < 0.001). LVA in the tumour periphery was higher than in the tumour parenchyma (P < 0.001). Lymphatic endothelial cell proliferation (LECP) was identified in 8.2% of the control sections and was higher than the intratumoral LECP fraction (LECP%, 2.6%; P = 0.02) and the peritumoral LECP% (6.5%; P > 0.05). Compared with controls, ccRCC specimens had higher mRNA expression levels of vascular endothelial growth factor (VEGF)‐A and VEGF‐C, but lower expression levels of VEGF‐D and Prox‐1 (all P < 0.001).
CONCLUSION
Our results show that there is only limited ongoing lymphangiogenesis in ccRCC. Given that several growth factors stimulate both angiogenesis and lymphangiogenesis, our observation indirectly indicates that haemangiogenesis predominates in ccRCC. This finding might provide better understanding of why ccRCCs prefer haematogenous dissemination to lymphatic spread.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Renal Cell - secondary</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Kidney Neoplasms - pathology</subject><subject>Kidneys</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Lymph Nodes - pathology</subject><subject>lymphangiogenesis</subject><subject>Lymphangiogenesis - physiology</subject><subject>Lymphatic Metastasis</subject><subject>Lymphatic Vessels - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Middle Aged</subject><subject>Nephrology. Urinary tract diseases</subject><subject>podoplanin</subject><subject>prox‐1</subject><subject>renal carcinoma</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Tumors of the urinary system</subject><subject>Vascular Endothelial Growth Factor Receptor-3 - metabolism</subject><subject>Vascular Endothelial Growth Factors - metabolism</subject><subject>VEGF</subject><subject>Young Adult</subject><issn>1464-4096</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u3CAQxlHVqEnTvkLFpb2tCwaD99BDGjX9o0i5NFJvCOMhZYVhC95kfesj5Bn7JMW7m_TYoJEYwe8bhvkQwpRUtKz3q4pywReckh9VTUhbkbaWdbV9hk4eL54_5GQpjtHLnFeElAPRvEDHdEkbzoU8Qdsz7OMdtgl-bSCYCUeL_TSsf-IQe8ADjDqXcBm7gI0Hnf78vjfgPU4QtMe71OhkXIiDxoVL4PUIPR7jrvKumA43Lt5AcAZrM7pbN06v0JHVPsPrw36Kri8-fT__sri8-vz1_OxyYbhs64UF3lkLrOlJT7hmnSmdM10TaXvgbS9sB8RYaQQRnDaWmq4EcNFS3SytYafo3b7uOsXyxTyqweW5ax0gbrISsgxIsvq_YJmzZI2UBWz3oEkx5wRWrZMbdJoUJWq2R63UPHk1uzDLWrWzR22L9M3hjU03QP9PePCjAG8PgM5Ge5t0MC4_cjVtGBOsKdyHPXfnPExPbkB9_HY9Z-wv6mivDg</recordid><startdate>200906</startdate><enddate>200906</enddate><creator>Baldewijns, Marcella M.</creator><creator>Roskams, Tania</creator><creator>Ballet, Vera</creator><creator>Van den Eynden, Gert G.</creator><creator>Van Laere, Steven J.</creator><creator>Van der Auwera, Ilse</creator><creator>Lerut, Evelyne</creator><creator>De Bruïne, Adriaan P.</creator><creator>Thijssen, Victor L.</creator><creator>Vermeulen, Peter B.</creator><creator>Van Poppel, Hein</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200906</creationdate><title>A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity</title><author>Baldewijns, Marcella M. ; Roskams, Tania ; Ballet, Vera ; Van den Eynden, Gert G. ; Van Laere, Steven J. ; Van der Auwera, Ilse ; Lerut, Evelyne ; De Bruïne, Adriaan P. ; Thijssen, Victor L. ; Vermeulen, Peter B. ; Van Poppel, Hein</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4782-fe4bffe35d0d04a3bc1543a207fde48d6fbe0cf7c606415f1cb1cbe4681a59fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Renal Cell - secondary</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Kidney Neoplasms - pathology</topic><topic>Kidneys</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Lymph Nodes - pathology</topic><topic>lymphangiogenesis</topic><topic>Lymphangiogenesis - physiology</topic><topic>Lymphatic Metastasis</topic><topic>Lymphatic Vessels - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Middle Aged</topic><topic>Nephrology. Urinary tract diseases</topic><topic>podoplanin</topic><topic>prox‐1</topic><topic>renal carcinoma</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Tumors of the urinary system</topic><topic>Vascular Endothelial Growth Factor Receptor-3 - metabolism</topic><topic>Vascular Endothelial Growth Factors - metabolism</topic><topic>VEGF</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baldewijns, Marcella M.</creatorcontrib><creatorcontrib>Roskams, Tania</creatorcontrib><creatorcontrib>Ballet, Vera</creatorcontrib><creatorcontrib>Van den Eynden, Gert G.</creatorcontrib><creatorcontrib>Van Laere, Steven J.</creatorcontrib><creatorcontrib>Van der Auwera, Ilse</creatorcontrib><creatorcontrib>Lerut, Evelyne</creatorcontrib><creatorcontrib>De Bruïne, Adriaan P.</creatorcontrib><creatorcontrib>Thijssen, Victor L.</creatorcontrib><creatorcontrib>Vermeulen, Peter B.</creatorcontrib><creatorcontrib>Van Poppel, Hein</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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baldewijns, Marcella M.</au><au>Roskams, Tania</au><au>Ballet, Vera</au><au>Van den Eynden, Gert G.</au><au>Van Laere, Steven J.</au><au>Van der Auwera, Ilse</au><au>Lerut, Evelyne</au><au>De Bruïne, Adriaan P.</au><au>Thijssen, Victor L.</au><au>Vermeulen, Peter B.</au><au>Van Poppel, Hein</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2009-06</date><risdate>2009</risdate><volume>103</volume><issue>12</issue><spage>1626</spage><epage>1631</epage><pages>1626-1631</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><abstract>OBJECTIVE
To assess ongoing lymphangiogenesis in renal cell carcinoma (RCC) by histomorphometry and by quantifying mRNA expression levels of lymphangiogenesis‐related factors.
MATERIALS AND METHODS
Using D2‐40 antibody as a lymphatic marker, lymph vessels were counted in tissue sections of 150 clear‐cell RCCs (ccRCC) and 61 non‐neoplastic controls, using the Chalkley method, which measures the relative lymph vessel area (LVA). Double‐staining with Ki67 and D2‐40 was used to assess active lymphangiogenesis. In a subset of 25 ccRCCs and nine non‐neoplastic controls mRNA expression levels of lymphangiogenic factors were determined by real‐time quantitative reverse transcription‐polymerase chain reaction.
RESULTS
LVA was higher in normal renal tissue than in both intra‐ and peri‐tumoral LVA (P < 0.001). LVA in the tumour periphery was higher than in the tumour parenchyma (P < 0.001). Lymphatic endothelial cell proliferation (LECP) was identified in 8.2% of the control sections and was higher than the intratumoral LECP fraction (LECP%, 2.6%; P = 0.02) and the peritumoral LECP% (6.5%; P > 0.05). Compared with controls, ccRCC specimens had higher mRNA expression levels of vascular endothelial growth factor (VEGF)‐A and VEGF‐C, but lower expression levels of VEGF‐D and Prox‐1 (all P < 0.001).
CONCLUSION
Our results show that there is only limited ongoing lymphangiogenesis in ccRCC. Given that several growth factors stimulate both angiogenesis and lymphangiogenesis, our observation indirectly indicates that haemangiogenesis predominates in ccRCC. This finding might provide better understanding of why ccRCCs prefer haematogenous dissemination to lymphatic spread.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19154467</pmid><doi>10.1111/j.1464-410X.2008.08272.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biological and medical sciences Carcinoma, Renal Cell - secondary Female Hematologic and hematopoietic diseases Humans Immunohistochemistry Kidney Neoplasms - pathology Kidneys Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Lymph Nodes - pathology lymphangiogenesis Lymphangiogenesis - physiology Lymphatic Metastasis Lymphatic Vessels - pathology Male Medical sciences Membrane Glycoproteins - metabolism Middle Aged Nephrology. Urinary tract diseases podoplanin prox‐1 renal carcinoma Reverse Transcriptase Polymerase Chain Reaction Tumors of the urinary system Vascular Endothelial Growth Factor Receptor-3 - metabolism Vascular Endothelial Growth Factors - metabolism VEGF Young Adult |
| title | A low frequency of lymph node metastasis in clear‐cell renal cell carcinoma is related to low lymphangiogenic activity |
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