清洁世界组织（Clean Up the World）成立于1993年,是一家致力于调动全球基层社区清洁、改善和保护地方环境的国际环保组织,总部位于澳大利亚的悉尼市。1987年,澳大利亚人伊恩基南（Ian Kiernan）驾单人帆船环绕地球时,看到漂浮在海面...清洁世界组织（Clean Up the World）成立于1993年,是一家致力于调动全球基层社区清洁、改善和保护地方环境的国际环保组织,总部位于澳大利亚的悉尼市。1987年,澳大利亚人伊恩基南（Ian Kiernan）驾单人帆船环绕地球时,看到漂浮在海面上的垃圾,萌生了发起这一活动的想法。返回到悉尼后,他在朋友的帮助下发起了＂清洁悉尼港日”（CleanUpSydneyHarbourDay）行动。展开更多
AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 hea...AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.展开更多
Background and aims:Crohn’s disease(CD)and intestinal tuberculosis(ITB)are both chronic granulomatous conditions with similar phenotypic presentations.Hence,there is need for a biomarker to differentiate between both...Background and aims:Crohn’s disease(CD)and intestinal tuberculosis(ITB)are both chronic granulomatous conditions with similar phenotypic presentations.Hence,there is need for a biomarker to differentiate between both these two diseases.This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of ITB and CD in comparison with controls.To evaluate the role of T regulatory cells,forkhead box P3(FOXP3)mRNA expression was quantified in serum as well as in colonic biopsies from patients with ITB and with the controls.Methods:Paired samples,including serum and colonic biopsies,were taken from 33 study subjects(CD,ITB and controls),and total RNA was extracted.Human whole genome gene expression microarray analysis was performed using the Illumina HumanWG-6 BeadChip Kit with six total RNA samples of the three groups in duplicates.Real-time PCR for FOXP3 mRNA expression was analyzed in serum samples and colonic biopsy samples(4-CD,5-ITB,4-controls).Results:In CD and ITB there was 1.5-fold upregulation of 92 and 382 genes and 1.5-fold downregulation of 91 and 256 genes,respectively.Peroxisome proliferators via the PPARc pathway were most significantly downregulated(P<0.005)in CD.Additionally,the IL4/5/6 signaling pathways and Toll-like receptor signaling pathway were identified as significantly differentially regulated(P<0.005)at>2-fold change.In ITB,the complement activation pathway,specifically the classical pathway,was the most significantly upregulated.FOXP3 mRNA expression was significantly elevated in colonic biopsies obtained from ITB patients as compared with CD cases(4.7062.21 vs 1.4860.31,P=0.016).Conclusions:FOXP3 mRNA expression in colonic mucosa could be a discriminatory marker between ITB and CD.Upregulation of the complement activation pathway in ITB suggests that pathogenetic mechanisms for ITB are similar to those of pulmonary tuberculosis.In CD,downregulation of PPARc was seen in colonic tissue,suggesting that restoration of PPARc-dependent anti-microbial barrier function may be a therapeutic target.展开更多
Background:Surgery in Crohn’s disease(CD)may be associated with poor prognosis and clinical and surgical recurrence.The aim of this study was to describe and compare the post-operative management and outcomes of pati...Background:Surgery in Crohn’s disease(CD)may be associated with poor prognosis and clinical and surgical recurrence.The aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent surgeries.Methods:Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010.Data were retrospectively collected from the medical records.Results:Data from 314 patients were analysed,of whom 262(83%)underwent first surgery and 52(17%)referred to previous CD surgeries.Baseline characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients(P=0.03).After surgery,a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery(P=0.04).In re-operated patients,time to clinical recurrence was not associated with the fact of receiving or not prophylaxis,whereas,in patients with first surgery,recurrence-free survival was greater when prophylaxis was received(P=0.03).Conclusions:After surgery,a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first surgery.Although prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time,it did not significantly reduce the risk of further recurrence in patients with previous surgeries.This suggests that effective prophylactic therapies are still needed in this subset of patients.展开更多
文摘清洁世界组织（Clean Up the World）成立于1993年,是一家致力于调动全球基层社区清洁、改善和保护地方环境的国际环保组织,总部位于澳大利亚的悉尼市。1987年,澳大利亚人伊恩基南（Ian Kiernan）驾单人帆船环绕地球时,看到漂浮在海面上的垃圾,萌生了发起这一活动的想法。返回到悉尼后,他在朋友的帮助下发起了＂清洁悉尼港日”（CleanUpSydneyHarbourDay）行动。
文摘AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%,P<0.0001). SNP8/R702W (10.8% vs 6%, P= 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P= 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (ORhet=1.71, 95%CI=1.12-2.6, P= 0.0001, ORtwo-risk alleles = 25.2, 95%CI =4.37- ,P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P=0.0006), ileal disease (81.9% (?) 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P= 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69,95%CI = 1.13-2.55, P= 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P= 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/ CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.
基金This project was undertaken under the‘FIST’scheme of Department of Science and Technology,Government of India.In addition,support was taken from ICMR Senior Research Fellowship granted to VM.
文摘Background and aims:Crohn’s disease(CD)and intestinal tuberculosis(ITB)are both chronic granulomatous conditions with similar phenotypic presentations.Hence,there is need for a biomarker to differentiate between both these two diseases.This study aimed at genome-wide gene expression analysis of colonic biopsies from confirmed cases of ITB and CD in comparison with controls.To evaluate the role of T regulatory cells,forkhead box P3(FOXP3)mRNA expression was quantified in serum as well as in colonic biopsies from patients with ITB and with the controls.Methods:Paired samples,including serum and colonic biopsies,were taken from 33 study subjects(CD,ITB and controls),and total RNA was extracted.Human whole genome gene expression microarray analysis was performed using the Illumina HumanWG-6 BeadChip Kit with six total RNA samples of the three groups in duplicates.Real-time PCR for FOXP3 mRNA expression was analyzed in serum samples and colonic biopsy samples(4-CD,5-ITB,4-controls).Results:In CD and ITB there was 1.5-fold upregulation of 92 and 382 genes and 1.5-fold downregulation of 91 and 256 genes,respectively.Peroxisome proliferators via the PPARc pathway were most significantly downregulated(P<0.005)in CD.Additionally,the IL4/5/6 signaling pathways and Toll-like receptor signaling pathway were identified as significantly differentially regulated(P<0.005)at>2-fold change.In ITB,the complement activation pathway,specifically the classical pathway,was the most significantly upregulated.FOXP3 mRNA expression was significantly elevated in colonic biopsies obtained from ITB patients as compared with CD cases(4.7062.21 vs 1.4860.31,P=0.016).Conclusions:FOXP3 mRNA expression in colonic mucosa could be a discriminatory marker between ITB and CD.Upregulation of the complement activation pathway in ITB suggests that pathogenetic mechanisms for ITB are similar to those of pulmonary tuberculosis.In CD,downregulation of PPARc was seen in colonic tissue,suggesting that restoration of PPARc-dependent anti-microbial barrier function may be a therapeutic target.
基金This study was funded by Merck Sharp&Dohme of Spain,a subsidiary of Merck&Co.,Inc.,Kenilworth,New Jersey,USA.
文摘Background:Surgery in Crohn’s disease(CD)may be associated with poor prognosis and clinical and surgical recurrence.The aim of this study was to describe and compare the post-operative management and outcomes of patients with CD who underwent first vs recurrent surgeries.Methods:Observational study that included adult CD patients from 26 Spanish hospitals who underwent ileocolonic resection with ileocolonic anastomosis between January 2007 and December 2010.Data were retrospectively collected from the medical records.Results:Data from 314 patients were analysed,of whom 262(83%)underwent first surgery and 52(17%)referred to previous CD surgeries.Baseline characteristics were similar between the two groups except for a higher rate of stricturing behavior at diagnosis among re-operated patients(P=0.03).After surgery,a higher proportion of re-operated patients received prophylactic treatment with immunomodulators compared with patients with first surgery(P=0.04).In re-operated patients,time to clinical recurrence was not associated with the fact of receiving or not prophylaxis,whereas,in patients with first surgery,recurrence-free survival was greater when prophylaxis was received(P=0.03).Conclusions:After surgery,a higher proportion of patients with previous surgeries received prophylactic treatment with immunomodulators compared with patients with first surgery.Although prophylactic treatment was beneficial for preventing clinical recurrence in patients operated on for the first time,it did not significantly reduce the risk of further recurrence in patients with previous surgeries.This suggests that effective prophylactic therapies are still needed in this subset of patients.
