血清C反应蛋白水平在克罗恩病中的改变

目的 比较血清C反应蛋白(CRP)水平在不同肠道疾病、不同病变部位和不同活动度中的变化,评估CRP作为疾病活动度指标的价值.方法 收集CD患者42例,分为结肠组25例和小肠组17例,另收集溃疡性结肠炎(UC)患者23例和肠易激综合征(IBS)患者26例作为对照组.胶乳增强免疫透射比浊法检测血清高敏(hs)-CRP水平.结果 ①CD、UC、IBS组hs-CRP均值分别为(9.9±7.8)mg/L、(3.6±4.5)mg/L、(1.1±1.8)mg/L,CD组显著高于UC组和IBS组,差异有统计学意义(P＜0.01),三组hs-CRP超过正常值患者的比率分别为76.2%、30.4%和7.7%,CD组亦显著高于UC组和IBS组,差异有统计学意义(P＜0.01).②在CD患者中,结肠组的hs-CRP显著高于小肠组[(11.9±7.6)mg/L比(6.8±7.2)mg/L,P=0.04);结肠组hs-CRP超过正常值患者的比率较小肠组高,但差异无统计学意义(P＞0.05).③CD患者中,hs-CRP≥10 mg/L者18例,其中疾病缓解(疾病活动指标＜150)4例(4/17),轻度(150～220)3例(3/11),中度(221～450)10例(10/13),重度(＞450)1例(1/1);hs-CRP与CD疾病活动指标、红细胞沉降率有显著相关性(r分别为0.52和0.70,P值均＜0.01).结论 CRP作为疾病活动指标主要用于CD,病变仅累及小肠者的CRP升高程度显著低于结肠病变者,CD病情愈重CRP升高愈明显.     

CD4+CD25+ T细胞在溃疡性结肠炎中的表达及其临床意义

目的 研究溃疡性结肠炎(UC)患者外周血CD 4CD 25调节性T细胞比例的变化,探讨其在UC病理机制中的意义.方法 选择UC患者33例,对照组20例.用流式细胞仪检测外周血CD 4CD 25T细胞阳性率.用RT-PCR检测外周单个核细胞(PBMC)中Foxp3 mRNA的表达.用酶联免疫吸附试验检测血清中IL-10和TGF-β的浓度.结果 UC患者CD 4CD 25T细胞占CD 4T细胞的比例明显低于对照组(P＜0.01),并且与疾病的活动指数及血沉水平均呈显著负相关(R值分别为-0.660和-0.572,P值均＜0.01).UC患者Foxp3 mRNA的表达也明显低于对照组(P＜0.01).两组患者血清IL-10和TGF-β的浓度比较无明显差异(P＞0.05).结论 UC患者外周血CD 4CD 25 调节性T细胞明显降低,与疾病活动性相关,提示这类细胞可能在UC的病理机制中发挥作用.Foxp3表达降低可能是导致CD 4CD 25 T细胞发育障碍的重要因素.     

炎症性肠病血清学抗体的临床意义

背景:对于炎症性肠病(IBD),迄今尚无疾病诊断和监测的金标准。鉴于免疫系统在IBD发病中的重要作用,检测血清免疫特异性抗体水平对于IBD的诊断和鉴别诊断可能有一定价值。目的:探讨血清抗酿酒酵母抗体(ASCA)和核周型抗中性粒细胞胞质抗体(pANCA)在IBD中的临床意义。方法:连续纳入2015年2月—2016年5月苏州大学附属第一医院收治的IBD患者91例,其中克罗恩病(CD)52例,溃疡性结肠炎(UC)39例,36例排除IBD的胃肠道疾病患者作为对照组。分别采用ELISA法和间接免疫荧光法检测血清ASCA-IgG、IgA和pANCA。以临床诊断为金标准,采用四格表对ASCA、pANCA进行诊断试验评价;采用ROC曲线、Pearsonχ2检验、Fisher精确检验分析两种血清学抗体与IBD、CD、UC以及病变部位的关系。结果:血清ASCA-IgG和IgA均与CD相关(AUC=0.626和0.614),而UC仅与ASCA-IgA相关(AUC=0.486)。血清pANCA与IBD(r=0.342)、CD(r=-0.262)、UC(r=0.614)均相关,对IBD和UC的诊断敏感性和特异性优于CD(P0.05)。CD患者的ASCA-IgG与病变累及回肠末端相关(P0.05),pANCA与病变累及结肠相关(P0.05);UC患者的ASCA-IgG、IgA均与病变累及回肠末端相关(P0.05)。结论:血清ASCA、pANCA有助于在IBD诊断确立的基础上区分CD与UC,并可能对病变部位具有提示作用。ASCA可能与病变累及回肠末端相关,而pANCA则可能与病变累及结肠相关。     

PTPN22在溃疡性结肠炎中的表达及其临床意义

背景:溃疡性结肠炎(UC)的发生、发展与T细胞过度活化有关,蛋白酪氨酸磷酸酶非受体型22(PTPN22)参与T细胞活化的负性调节。目的:探讨PTPN22在UC中的表达及其临床意义。方法:纳入2010年7月～2012年7月武汉市中心医院、武汉大学中南医院就诊的UC患者60例,同时纳入35例IBS患者作为对照组。采用实时定量PCR法检测患者肠黏膜PTPN22 mRNA表达水平。采用全自动红细胞沉降系统分析仪检测血清ESR水平。采用速率散射比浊法检测血清CRP水平。结果:活动期UC患者肠黏膜PTPN22 mRNA表达水平与缓解期UC患者和对照组相比显著升高(P=0.007;P=0.021)。UC患者肠黏膜PTPN22 mRNA表达水平与血清ESR和CRP水平呈正相关(r=0.63,P=0.005;r=0.58,P<0.01)。UC患者疾病严重程度和病变范围与肠黏膜PTPN22 mRNA表达水平呈正相关(r=0.51,P<0.01;r=0.44,P<0.01)。中重度UC患者肠黏膜PTPN22 mRNA表达水平与轻度UC患者相比显著升高(P=0.005),病变位于广泛结肠者肠黏膜PTPN22 mRNA表达水平与病变位于左半结肠和直肠者相比显著升高(P=0.029;P=0.008)。结论:PTPN22 mRNA表达水平与UC疾病活动性、严重程度和病变范围相关。PTPN22可能在UC发病机制中发挥重要作用。     

炎症性肠病与睡眠障碍的相关性研究

目的探讨炎症性肠病(inflammatory bowel disease,IBD)患者主观睡眠不良与疾病活动度及相关炎症指标之间的关系。方法选取2018年1月至2019年3月于武汉大学人民医院消化内科住院治疗的116例IBD患者(54例CD和62例UC)为研究对象,另选取120名健康体检者为对照组;收集纳入对象的一般临床信息及ESR、CRP、NLR等相关疾病检查结果,分别采用CD活动指数(CDAI)与UC Mayo评分进行疾病活动度的评分,同时对所有纳入对象采用匹兹堡睡眠质量指数量表(Pittsburgh sleep quality index, PSQI)进行问卷调查。结果 IBD组PSQI评分显著高于对照组(P0.05);CD与UC患者中不同临床活动期间PSQI得分差异均有显著统计学意义(P0.01); CD的PSQI最佳临界值为7.5分(灵敏度为67%,特异度为87%),诊断价值AUC=0.794,95%CI:0.712～0.876),UC的PSQI最佳临界值为7.5分(灵敏度为66%,特异度为87%),诊断价值AUC=0.843,95%CI:0.784～0.903;CD与UC患者血清ESR、CRP、NLR水平与其PSQI得分均呈正相关(ESR:r=0.519、0.54;CRP:r=0.573、0.584;NLR:r=0.425、0.382;P0.01)。结论 IBD患者的疾病活动度与其睡眠障碍之间存在密切关联,PSQI评分可以作为评估患者炎症活动性的另一种非侵入性检测方法。     

克罗恩病和溃疡性结肠炎食物不耐受的差异分析

背景:炎症性肠病(IBD)的发生、发展与饮食关系密切,食物不耐受在IBD中的发生情况及其与IBD的关系尚不十分清楚。目的:探讨活动期克罗恩病(CD)和溃疡性结肠炎(UC)患者中食物不耐受的差异。方法:选取2016年1月—2017年11月中南大学湘雅医院确诊的活动期134例CD、67例UC患者和42名正常对照者。以ELISA法检测14种食物的血清特异性IgG,据此评价食物不耐受情况,分析CD和UC患者食物不耐受的差异。结果:CD和UC患者食物不耐受阳性率均显著高于对照组(P 0. 001),CD患者又明显高于UC患者(P 0. 001)。三组间食物不耐受程度相比差异有统计学意义(F=46. 707,P 0. 001)。CD患者4种和6种食物不耐受的发生率均明显高于UC患者(P 0. 001)。与UC患者相比,病变累及结肠的CD患者的食物不耐受率无明显差异(P=0. 100),而累及小肠的CD患者明显升高(P=0. 010)。多元Logistic回归分析显示,食物不耐受≥4种为病变累及小肠的CD的危险因素(P=0. 040)。结论:CD和UC患者的食物不耐受阳性率均明显高于对照组,CD患者食物不耐受发生率高、程度重、种类多,病变累及小肠的CD患者的食物不耐受发生率明显高于结肠型CD和UC患者,食物不耐受≥4种可能为小肠型CD的预测因素。     

活动期炎症性肠病患者血清内脂素水平及其临床意义

背景:近年炎症性肠病(IBD)的发病率呈逐年增长趋势,但其发病机制目前仍不明确。既往研究发现一些脂肪因子在肠道炎症调节中起关键作用。目的:探讨脂肪细胞因子内脂素(visfatin)在IBD中的作用及其临床意义。方法:收集2015年5月—2015年12月苏州大学附属第一医院和苏州市立医院91例活动期IBD患者,包括61例克罗恩病(CD)和30例溃疡性结肠炎(UC),以ELISA法检测血清内脂素水平。48名健康体检者作为对照组。分析血清内脂素水平与IBD患者临床特征的关系,以ROC曲线评估血清内脂素水平对IBD的诊断效能。结果:活动期CD和UC患者的血清内脂素水平显著高于对照组[(385.24±112.64)pg/mL和(378.91±118.57)pg/mL对(321.11±96.27)pg/mL,P均0.05]。血清内脂素水平与UC患者的疾病活动性Mayo评分呈显著正相关(r=0.398,P0.05),与CD患者的疾病活动性以及IBD患者的临床常用炎性指标CRP、ESR和病变部位均无关(P均0.05)。血清内脂素水平诊断CD和UC的ROC曲线下面积(AUC)分别为0.654和0.622,诊断准确性较低。结论:血清内脂素水平可能与IBD炎症活动有一定关联,并可能成为活动期UC的临床指标。     

活动期溃疡性结肠炎患者血清vaspin水平及其临床意义

脂肪细胞因子与机体内能量稳定相关,并介导多种免疫应答和炎症反应。内脏脂肪特异性丝氨酸蛋白酶抑制剂vaspin是近年发现的一种与炎症反应有关的脂肪细胞因子。目的:检测活动期溃疡性结肠炎(UC)患者的血清vaspin水平并探讨其临床意义。方法:选取2008年1月~2013年4月苏州市立医院收治的150例活动期UC患者,以150名健康体检者作为正常对照组。采用ELISA法检测血清vaspin水平,并分析其与UC临床特征的相关性。结果:UC患者血清vaspin水平显著高于正常对照者[(1.86±0.38)μg/L对(0.96±0.43)μg/L,P0.01],并与血清CRP水平和疾病活动指数呈显著正相关(r=0.628,P0.01;r=0.514,P0.05),与血清ESR水平和病变部位无关(r=0.098,P0.05;r=0.124,P0.0)5)。结论:Vaspin可能在UC发生、发展的病理生理机制中发挥重要作用。     

白介素-1 7在溃疡性结肠炎表达的研究

目的研究白介素-17(IL-17)在溃疡性结肠炎(UC)的表达和分泌及与疾病活动性的关系.方法用ELISA法测定UC患者及正常对照者血清或细胞培养液中,IL-17、IL-6和IL-8的浓度,逆转录聚合酶链反应(RT-PCT)测定IL-17mRNA的表达.结果32例UC患者外周血中IL-17,IL-6和IL-8的浓度与40例正常对照者比较,差异无显著性(P＞0.05),但外周血CD+4T细胞在PMA和抗CD3的刺激下,表达IL17mRNA及分泌IL-17的水平均明显高于对照组[(23.6±5.7)pg/ml和(13.1±3.2)pg/ml,P＜0.01].UC患者病变部位的黏膜固有层CD+4T细胞(LP-CD+4T)与非受累部位的LP-CD+4T细胞比较,它们表达大量的IL-17mRNA并自发分泌大量的IL-17蛋白,且IL-17浓度与该部位的单个核细胞(LPMC)分泌的IL-6,以及患者外周血中的C-反应蛋白,血沉均呈显著正相关.在刺激剂的作用下,病变部位的LP-CD+4T细胞IL-17的分泌进一步增加,且明显高于非受累部位LP-CD+4T细胞的分泌水平.另外,UC病变部位LPMC分泌的IL-6和IL-8的水平均明显高于非受累部位的LPMC,但在培养液中加入抗IL-17单克隆抗体后,LPMC细胞IL-6和IL-8的分泌均明显被抑制.结论UC患者病变部位的LP-CD+4T细胞表达和分泌IL-17明显增加,并与疾病的活动性呈正相关.抗IL-17抗体可明显抑制LMPC产生炎性细胞因子.IL-6和IL-8.结果说明,IL-17在UC肠道的炎症病理中起重要作用;阻断IL-17的分泌可能是治疗UC的一种有效手段.     

α1-酸性糖蛋白在溃疡性结肠炎患者血清中的检测及意义

目的:探讨血清α1-酸性糖蛋白(α1-AGP)的检测在溃疡性结肠炎(UC)活动性评估中的意义.方法:选取UC患者100例和对照40例, 用散射免疫比浊法测定血清α1-AGP的含量, 同时检测血沉(erythrocyte sedimentation rate, ESR).UC疾病活动性根据Mayo评分标准判定.结果:UC活动期血清α1-AGP含量显著高于缓解期组和对照组(1446.0 mg/L±543.6 mg/L vs857.2 mg/L±310.9 mg/L, 653.7 mg/L±308.9mg/L, 均P <0.01), 缓解期组与对照组比较差异也有统计学意义(P <0.05);活动期组轻、中、重度3级之间差异有统计学意义;血清血清α1-AGP含量与疾病活动指数显著相关(r = 0.777,P <0.001).结论:血清α1-AGP能客观地反映UC的炎症活动情况, 对UC患者活动性评估具有一定的临床应用价值.     

Influence of inflammatory bowel disease on intestinal microflora.

The microflora of the jejunum, ileum, and colon has been studied from operative samples in Crohn's disease (n = 30), ulcerative colitis (n = 15), and controls (n = 40). There was no significant difference in the flora of patients with ulcerative colitis compared with controls. In Crohn's disease there was a significant increase in E. coli (P less than 0.001) and B. fragilis (P less than 0.001) in the ileum and of E. coli (P less than 0.001) and lactobacilli (P less than 0.01) in the colon. The abnormal ileal flora in Crohn's disease was unrelated to serological evidence of disease activity (indices: ESR, serum albumin, serum seromucoids), diameter of the ileum, or excision of the ileocaecal valve. The abnormal colonic flora in Crohn's disease was not related to presence of macroscopic colitis.     

Serum zinc, copper, and selenium levels in inflammatory bowel disease: effect of total enteral nutrition on trace element status

Serum levels of zinc, copper, and selenium, and alkaline phosphatase activity were prospectively studied in 29 patients with inflammatory bowel disease. Fifteen patients had extensive active colitis (active colitis group). Seven patients had active, and seven cases inactive small bowel or ileocecal Crohn's disease (small bowel disease group). Ninety-three healthy subjects acted as controls. Serum trace element levels were considered in relation to vitamin A and E levels, nutritional parameters, the activity of the disease, and the recent intake of steroids. The effect of total enteral nutrition on serum trace elements was studied in seven cases. Serum zinc levels were lower and serum copper levels higher in the active colitis group than in controls (p = 0.0007, and p = 0.02, respectively). More than 50% of patients with active colonic or small bowel disease showed zinc levels below the 15th percentile of the control group. Serum zinc levels correlated with plasma vitamin A in acute colitis (r = 0.67; p = 0.006), and with both serum albumin concentration (r = 0.76; p = 0.002) and disease activity score (r = -0.67, p = 0.009) in patients with small bowel disease. The copper:zinc ratio was higher in the active colitis group than in controls (p = 0.002). In spite of the increase in serum albumin levels and the decrease in disease activity, serum zinc levels remained low after total enteral nutrition. The implications of the abnormal trace element status in patients with inflammatory bowel disease are discussed.     

Antineutrophil cytoplasm autoantibodies against bactericidal/permeability-increasing protein in inflammatory bowel disease.

BACKGROUND: Bactericidal/permeability-increasing protein (BPI), a constituent of primary neutrophil granules, is a potent natural antibiotic and an antineutrophil cytoplasm antibody (ANCA) antigen in cases of vasculitis in which the target antigen is neither myeloperoxidase (MPO) nor proteinase-3 (PR3). AIM: To investigate BPI as a possible target antigen for ANCAs in inflammatory bowel disease. METHODS: ANCAs were detected by routine immunofluorescence (IIF) and solid phase enzyme linked immunosorbent assay (ELISA) performed for antibodies to the purified neutrophil granule proteins; MPO, PR3, cathepsin-G, lactoferrin, and BPI in serum samples from 88 patients with inflammatory bowel disease (36 with Crohn's disease, 52 with ulcerative colitis). Thirty patients with bacterial enteritis acted as controls. RESULTS: Significantly more patients with ulcerative colitis were ANCA positive by IIF (60%) than patients with Crohn's disease (28%) or infectious enteritis (23%) (p < 0.001). IgG anti-BPI antibodies were present in 29% of patients with ulcerative colitis, 14% of patients with Crohn's disease, and 23% of patients with infectious enteritis, occurring in 44% of those patients with inflammatory bowel disease who were ANCA positive by IIF. Antibodies to other ANCA antigens were rare. The presence of ANCAs was not related to either disease activity or extent; presence of anti-BPI antibodies was significantly related to both a lower serum albumin concentration (p = 0.001) and a higher erythrocyte sedimentation rate (p = 0.02) in patients with ulcerative colitis, and to colonic involvement in patients with Crohn's disease (p = 0.01). CONCLUSION: BPI is a significant minority target antigen for ANCAs in inflammatory bowel disease that seems related to colonic Crohn's disease and disease activity in ulcerative colitis. Anti-BPI antibodies occur in infectious enteritis.     

Determining disease activity in inflammatory bowel disease

To provide a stronger relationship between clinical assessment of disease activity and laboratory measurements, we studied hemoglobin concentrations, sedimentation rates, and the serum levels of albumin and of seromucoids in 86 patients; first when seriously ill with either ulcerative colitis or Crohn's disease, and then again when they were well. Only albumin and seromucoids were separated clearly in the two states: hemoglobin and sedimentation rates showed significant overlap. Paired correlation tests between 10 laboratory variables in 149 patients with Crohn's disease of varying severity revealed a highly significant correlation between seromucoids and albumin (r = 0.71). Both variables correlated with six others, but at lower levels. Processing the correlation matrix by factor analysis suggested that the serum levels of albumin and seromucoid are indicators of the same effect--disease activity. A simple index using only hemoglobin, albumin, and seromucoid values, was derived from this analysis, positive values indicating health and negative ill health. Serum levels of albumin and seromucoids provide the essential data to determine disease activity at routine follow-up of inflammatory bowel disease or to indicate the success or failure of therapeutic regimens, overriding any arbitrary clinical assessment.     

Increased serum levels of YKL-40 in patients with inflammatory bowel disease

BACKGROUND AND AIMS: Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. PATIENTS AND METHODS: YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. RESULTS: Mean serum YKL-40 levels were 102.6+/-82.7 ng/ml in ulcerative colitis patients and 112.2+/-83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1+/-21.4 ng/ml) but not significantly different from inflammatory controls (77.8+/-23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. CONCLUSION: Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis.     

Cholelithiasis in inflammatory bowel disease

Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis.     

Erythrocytic sedimentation rate as a measure of clinical activity in inflammatory bowel disease

To assess the reliability of the erythrocytic sedimentation rate (ESR) as a measure of clinical activity in inflammatory bowel disease, we analyzed the correlations of ESR with a global assessment of clinical activity in 77 patients with varying extents of Crohn's disease and ulcerative colitis. Analysis of all 141 ESR determinations in all 77 patients showed a highly significant correlation between mean ESR and clinical activity score (r = 0.54, p less than 0.001). Analysis of 133 ESR determinations in these 77 patients when their disease activity was either mild, moderate, or severe showed some significant differences among certain disease categories. The highest mean ESRs were in patients with the most extensive colon involvement (Crohn's colitis 40.7 +/- 3.3, universal ulcerative colitis 31.0 +/- 3.9), whereas the lowest mean ESRs were in patients with the most limited disease (ulcerative proctitis and proctosigmoiditis 19.2 +/- 2.1). The rate of increase in ESR with progressively increasing clinical activity from mild to moderate was the same in all disease categories, with the exception of Crohn's disease limited to the small bowel (ileitis or jejunoileitis), in which the ESR was relatively unchanged in a small sample of patients. By the time clinical activity became severe, however, patients in all disease categories manifested similarly high ESRs, with the exception of ulcerative proctitis in which the ESR remained low in the single patient tested.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum gastrin levels in patients with inflammatory bowel disease

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.     

Circulating von Willebrand factor in inflammatory bowel disease.

Raised circulating von Willebrand factor is a recognised marker of vascular injury. To evaluate the role of vascular injury in the pathogenesis of inflammatory bowel disease, serum von Willebrand factor in Crohn's disease, ulcerative colitis, confirmed bacterial diarrhoea, and healthy subjects was measured. von Willebrand factor values were raised in 9/14 patients (p = 0.007) with active Crohn's disease, 15/28 (p = 0.0004) with inactive Crohn's disease, 16/23 (p = 0.0003) with active ulcerative colitis, 9/27 (p = 0.04) with inactive ulcerative colitis, and 15/17 (p = 0.0001) patients with bacterial diarrhoea. Serum von Willebrand factor was unrelated to disease activity in Crohn's disease but was significantly raised in active (p = 0.02) compared with inactive ulcerative colitis. In contrast to controls, the detection of von Willebrand factor from inflammatory bowel disease sera and that from fractured endothelial cells was significantly inhibited by the reducing agent, dithiothreitol, suggesting the presence of an additional dithiothreitol sensitive form of the molecule derived from injured endothelial cells in inflammatory bowel disease. That serum von Willebrand factor is raised in quiescent as well as active Crohn's disease is compatible with the proposal that vascular injury is a fundamental abnormality in this disorder. The raised von Willebrand factor values in active inflammatory bowel disease and bacterial diarrhoea could be caused by either vascular injury, occurring secondary to bowel inflammation, or to an acute phase response resulting from endothelial cell stimulation by mediators released during the inflammatory process. Raised circulating von Willebrand factor could contribute to the increased risk of thrombosis associated with active inflammatory bowel disease.     

Increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing cytokine with overexpression in various pathological disorders, including tumour growth, chronic inflammation and tissue repair. Recent studies have shown significantly increased serum levels of VEGF in patients with inflammatory bowel disease. The origin of the circulating VEGF is still unknown. The present investigation examines the VEGF production by peripheral blood mononuclear cells (PBMCs) in patients with inflammatory bowel disease. METHODS: VEGF levels were measured in culture supernatants of unstimulated PBMCs of 27 patients with inflammatory bowel disease and 10 healthy volunteers using a solid phase ELISA. In addition, VEGF serum levels were determined. RESULTS: PBMCs of both active Crohn's disease patients (1142.6+/-483.9 pg/ml, P < 0.001, n = 12) and active ulcerative colitis patients (748.0+/-637.6 pg/ml, P = 0.006, n = 4) produced significantly higher amounts of VEGF compared with PBMCs of healthy volunteers (113.4+/-101.8 pg/ml, n = 10). In addition, there was a significantly increased VEGF production by PBMCs of patients with active disease compared with PBMCs of patients with quiescent Crohn's disease (261.6+/-254.8 pg/ml, P < 0.001, n = 7) and inactive ulcerative colitis (147.7+/-100.3 pg/ml, P = 0.02, n = 4). There was no significant difference in VEGF release between patients with inactive inflammatory bowel disease and healthy controls. CONCLUSIONS: Significantly increased VEGF production by PBMCs was found in patients with active Crohn's disease and active ulcerative colitis. The study helps to clarify one of the origins of the significantly enhanced VEGF serum levels in patients with active inflammatory bowel disease observed in recent studies.