Background-The aetiology and pathophysiology of ulcerative colitis remains unclear; however, there is increasing recognition of the critical role of inflammatory cytokines in the pathogenesis of this disease. Among these, tumour necrosis factor a (TNFa) seems to play an important role. Aim-To study the effects of an engineered human monoclonal antibody to TNFa (CDP571) in the treatment of idiopathic ulcerative colitis in the cottontop tamarin. Methods-Six cottontop tamarins with confirmed ulcerative colitis received repeated doses of CDP571. Progression of disease was assessed by measuring both body weight and rectal biopsy pathology. Results-All animals showed a rapid improvement in clinical condition and rectal biopsy pathology that was maintained foliowing completion of the therapy. Conclusion-These studies indicate the efficacy of selective antibody therapy to TNFa for the treatment of ulcerative colitis in a primate and suggest that similar therapy in humans could be ofvalue. (Gut 1997; 40: 628-633)
Aims-To investigate the presence and distribution of vascular collagen type IV in colonic tissue in cases of angiodysplasia and age and sex matched controls. Methods-Sections of colon from seven cases of colonic angiodysplasia and eight age and sex matched controls were examined for the presence of collagen type IV in vessels of the mucosa and submucosa. Immunohistochemical staining was performed on paraYn wax embedded sections, and the degree of vascular staining for each marker compared between mucosa and submucosa and between cases and controls. Staining for endothelial markers P-selectin and factor VIII was used to control for non-specific diVerences in immunostaining. Results-In both the angiodysplastic tissues and approximately half the control tissues, staining for collagen type IV was considerably weaker in vessels in the mucosa than in the submucosa. In angiodysplasia, ectatic vessels in the mucosa appeared to contain less collagen type IV than similarly sized vessels in the submucosa, and perforating vessels appeared in many cases to lose staining at the level of the muscularis mucosae. No diVerences were found in staining intensity for the control endothelial markers between cases and controls. Conclusions-The apparent relative deficiency of collagen type IV in the mucosal vessels in angiodysplasia may be related to their susceptibility to ectasia and haemorrhage. The finding of a similar deficiency in half of the control cases may reflect a population at risk of this relatively common condition.
Background-MUC5AC is a secreted mucin aberrantly expressed by polypoid colorectal adenomas. It has been hypothesised that the "normal" surrounding colorectal mucosa expresses MUC5AC as a field change phenomenon that can be used to predict adenoma recurrence following resection. Aim-To determine if there is a field change of de novo MUC5AC expression in histologically normal rectal mucosa adjacent to villous and tubulovillous adenomas, and thus whether MUC5AC expression can be used as a marker of early tumour recurrence. Methods-In a prospective cohort study paired mucosal biopsies of adenomatous and macroscopically "normal" mucosa were obtained from 11 patients with villous and 11 patients with tubulovillous adenomas who underwent primary resection for purpose of cure. The tissues were studied to determine MUC5AC gene expression by immunohistochemistry and in situ hybridisation. Patients were followed up by flexible sigmoidoscopy to detect the presence of early local recurrence. Results-10 villous adenomas showed mature MUC5AC glycoprotein and all 11 expressed MUC5AC mRNA. Five tubulovillous adenomas showed mature MUC5AC glycoprotein and 10 expressed MUC5AC mRNA. Neoexpression of the MUC5AC mucin gene was not detected in any of the mucosal biopsies taken adjacent to either villous or tubulovillous adenomas, even in three patients with early, locally recurrent disease. Conclusions-Aberrant MUC5AC gene expression is not a "field change" in the colorectal mucosa in patients with rectal adenomas and therefore cannot be used to predict local recurrence of villous and tubulovillous adenomas. (J Clin Pathol 2000;53:100-104)
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