Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Lymphocyte and macrophage subpopulations in pelvic ileal pouches(British Medical Assosiation, 1991) de Silva, H.J.; Jones, M.; Prince, C.; Kettlewell, M.; Mortensen, N.J.; Jewell, D.P.This study aimed to characterise the mucosal cellular infiltrate in ileal reservoirs with and without pouchitis (reservoir ileitis). Intraepithelial lymphocyte counts were performed in biopsy specimens obtained from ileal pouches and compared with counts in normal ileum and normal colon. T lymphocyte and macrophage subpopulations were characterised immunohistochemically in pouch biopsy specimens using a panel of monoclonal antibodies. Normal ileum was used as a control. Intraepithelial lymphocyte densities (expressed as intraepithelial lymphocyte/100 epithelial cells) in pouches with and without pouchitis were significantly less than in normal ileum, and approached counts found in normal colon. There was no significant increase in counts even in pouchitis. There were no significant differences in the helper/inducer to suppressor/cytotoxic T cell (CD4:CD8) ratios between normal ileum and pouches with or without pouchitis, either in the epithelium or in the lamina propria. The proportions of RFD9+ (epithelioid cells and tingible body macrophages) and 3G8+ (CD16) macrophages were significantly higher in pouchitis compared with pouches without pouchitis or normal ileum. There were no significant differences between the three groups in the proportions of cells positive for the other macrophage markers (CD68, RFD1-dendritic cells, and RFD7-mature macrophages). The significance of low intraepithelial lymphocyte counts in ileal pouches is unknown, but this may be an adaptive response to the new luminal environment. Since an increase in RFD9+ macrophages occurs in inflammatory bowel disease, but does not occur as a non-specific response to an acute infective process, their presence in pouchitis suggests that effector mechanisms similar to those triggering the original ulcerative colitis may be operating in pouchitis.Item Mucosal characteristics of pelvic ileal pouches(British Medical Assosiation, 1991) de Silva, H.J.; Millard, P.R.; Kettlewell, M.; Mortensen, N.J.; Prince, C.; Jewell, D.P.This study aimed to investigate the degree of colonic metaplasia in ileo - anal pouches. Biopsy specimens from 25 patients with functioning pouches, eight of whom had pouchitis, were studied using routine histology, mucosal morphometry, mucin histochemistry, and immunoperoxidase staining with monoclonal antibodies directed towards a 40kD colonic protein and a small bowel specific disaccharidase-sucrase isomaltase. Thirteen patients (including all eight with pouchitis) had subtotal or total villous atrophy and crypt hyperplasia. In this group, nine had colorectal type sulphomucin and the 40kD colonic protein was detected in two. These changes were not observed in patients with less severe villous abnormalities. Sucrase-isomaltase activity was, however, present in all 25 pouch specimens. We conclude that although some ileal pouches acquire certain colonic characteristics, complete colonic metaplasia does not occur.Item Crypt cell proliferation and HLA-DR expression in pelvic ileal pouches(BMJ Publishing Group, 1990) de Silva, H.J.; Gatter, K.C.; Millard, P.R.; Kettlewell, M.; Mortensen, N.J.; Jewell, D.P.To investigate the nature of the morphological changes that occur in ileal pouches, 26 biopsy specimens from patients with functioning ileo-anal pouches (eight with pouchitis) were studied. Normal ileum (n = 10) was used as a control. Mucosal morphometry (using linear measurements), crypt cell proliferation (CCP) (using the monoclonal antibody Ki67), and epithelial HLA-DR expression (monoclonal antibody CR3/43) were assessed. CCP (expressed as the percentage of Ki67 positive nuclei for each crypt) was significantly higher in pouches with pouchitis, compared with those without, and in pouches without pouchitis compared with normal ileum. CCP values in some pouches without pouchitis approached values found in those with pouchitis. CCP was related inversely to villous height and an index of villous atrophy (VH/TMT), and directly to crypt depth. In the presence of pouchitis there was intense epithelial HLA-DR expression that extended into the crypts. In some pouches with high CCP values, but without clinically important inflammation, surface epithelial HLA-DR expression was weak and patchy. It is concluded that villous atrophy and crypt hyperplasia in ileal pouches are associated with high CCP values. These may be increased even in the absence of active inflammation, and this increase may occur as a response to the new luminal environment.