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Biomedical subjects

M Kettlewell

Publications and source records attributed to M Kettlewell.

At least 19 recordsLinked to original sources
PubMed1996

Smoking may prevent pouchitis in patients with restorative proctocolectomy for ulcerative colitis.

Epidemiological studies have shown an increased risk of ulcerative colitis (UC) in non-smokers and particularly recent ex-smokers. Patients with UC have an increased risk of pouchitis following ileal pouch-anal anastomosis, which may be a manifestation of the original disease susceptibility. The aim of this study was to test the hypothesis that smoking habit may influence the incidence of pouchitis. All patients with a functioning pouch > or = 12 months at one centre were assessed. Patients were excluded if (a) the original indication was not UC (n = 5), (b) the excised pouch showed histology diagnostic of Crohn's disease (n = 2), and (c) data were inadequate (n = 4). Smoking data were collected by questionnaire, or direct interview, or both. Ex-smokers were those who had stopped smoking < 7 years before colectomy. Non-smokers included ex-smokers who had stopped > 7 years before colectomy. Pouchitis was defined as an increase in stool frequency > 8/day with acute inflammation on biopsy specimen histology. Each presentation requiring treatment was regarded as an episode. For comparison smoking habit was assessed with regard to three other adverse outcomes - haemorrhage, sepsis, and pouch excision. Of 72 non-smokers (mean follow up 3.5 years) 18 had 46 episodes of pouchitis. Of 12 ex-smokers (mean follow up 3.3 years) four patients have had 14 episodes of pouchitis. Only one smoker from 17 has had a single episode of pouchitis. This shows that smokers have significantly less episodes of pouchitis compared with non-smokers (p = 0.0005) and ex-smokers (p = 0.05). There was no association of smoking habit with other adverse outcomes.

Adult↗
PubMed1994

Pouch-vaginal fistula after restorative proctocolectomy: aetiology and management.

Pouch-vaginal fistula is a rare complication following restorative proctocolectomy. Seven patients who developed such a fistula are presented. Six pouch-vaginal fistulas occurred at the level of the pouch-anal anastomosis and one 3 cm above the anastomosis, level with the posterior vaginal fornix. The anastomosis had been hand-sewn in four patients (following mucosectomy) and stapled in three. Five fistulas presented within the perioperative period (median 16 (range 10-30) days) and two at 186 and 273 days. Treatment was successful in the patients who presented early, and these remain continent with functioning pouches. If not already present (two patients), an ileostomy was raised. Repair was by endovaginal flap advancement, combined with fistulotomy and sphincter repair in two patients. Treatment was unsuccessful in the two patients who presented late; in both the diagnosis was revised to Crohn's disease, necessitating pouch excision.

Adolescent↗
PubMed1994

Expression of colonic antigens by goblet and columnar epithelial cells in ileal pouch mucosa: their association with inflammatory change and faecal stasis.

AIMS: To investigate colonic metaplasia of goblet and columnar epithelial cells in ileal pouch mucosa; to correlate this with the degree of morphological and inflammatory change; and to assess whether such changes are related to the presence of faecal stasis. METHODS: Biopsy specimens of ileal pouch mucosa were taken from 31 patients (30 with ulcerative colitis, one with familial adenomatous polyposis) either before (eight patients) or after (23 patients) ileostomy closure. A simple morphological technique was used to assess changes in villous height. Inflammatory change was estimated using an established scoring system for pouchitis, and acquisition of colonic antigens was determined by immunohistochemistry using three monoclonal antibodies which recognise components of the two major epithelial cell types in the colorectum. The degree of staining with the monoclonal antibodies was graded and the grades correlated with an index of villous atrophy and with the inflammatory scores. RESULTS: Five of eight (63%) pre-closure and 15 of 23 (65%) post-closure biopsy specimens showed increased staining with an antibody against components of columnar epithelial cells. One of eight (12%) pre-closure and 15 of 23 (65%) post-closure biopsy specimens stained with an antibody for colonic mucin. Although both types of staining showed a positive correlation with the pouchitis score, they also occurred in the absence of inflammation. CONCLUSIONS: Both goblet and columnar cells acquire colonic characteristics which are incomplete, but may represent a true adaptive response as they can develop in the absence of inflammation. As the change in goblet cells occurs after ileostomy closure, faecal stasis is likely to be a major contributory factor. Changes in columnar cells may occur before ileostomy closure in the absence of faecal stasis.

Autoantigens↗
PubMed1993

Cap polyposis--an unusual cause of diarrhoea.

'Cap polyposis' is a poorly recognised condition with distinct clinical, sigmoidoscopic, and pathological features that may be confused with other inflammatory conditions of the large intestine including pseudomembranous colitis and idiopathic chronic inflammatory bowel disease. The pathogenesis is unknown but on the basis of the characteristic histological appearances, which are similar to those seen in situations where mucosal prolapse is the underlying mechanism, it has been suggested that the latter may be an important aetiological factor. Two cases are described. Histological features in the first (presence of intramucosal elastin) and clinical features in the second (rectal prolapse) support the above hypothesis.

Aged↗
PubMed1991

Mucosal characteristics of pelvic ileal pouches.

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.

Adenomatous Polyposis Coli↗
PubMed1991

Lymphocyte and macrophage subpopulations in pelvic ileal pouches.

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.

Adolescent↗
PubMed1991

Effects of the faecal stream and stasis on the ileal pouch mucosa.

This study aimed to investigate the effects of the faecal stream and stasis on the mucosa of ileal pouches. Nine patients were followed up. Two pouch biopsy specimens were obtained from each at the time of pouch formation, ileostomy closure, and three, six, and 12 months after operation. None developed pouchitis. Two pouch biopsy specimens each were also obtained from 20 patients (six with pouchitis), whose pouches had been functioning for at least a year and in whom pouch evacuation was assessed by radioisotope labelled artificial stool. Biopsy specimens were assessed for the degree of acute and chronic inflammation, mucin type (high iron diamine-alcian blue stain), a morphometric index of villous atrophy (villous height:total mucosal thickness), and crypt cell proliferation (using the monoclonal antibody Ki67). Mean values from the two biopsy specimens were obtained for each parameter. After three months of pouch function, the scores for acute and chronic inflammation, the degree of sulphomucin, and crypt cell proliferation were significantly higher, and the index of villous atrophy was significantly lower (indicating a greater degree of villous atrophy), than at pouch formation or at ileostomy closure. The values at pouch formation and ileostomy closure were similar. For all parameters, the changes seen at six and 12 months were not significantly different from those at three months. There was no significant correlation between the efficiency of pouch evacuation and any of the mucosal changes. It is concluded that exposure to the faecal stream is necessary for changes to take place in the pouch mucosa, although the amount of stasis, as measured by radioisotopic evacuation studies, seems to be irrelevant. The mucosal changes occur soon after ileostomy closure and then remain stable for at least one year.

Adult↗
PubMed1990

Crypt cell proliferation and HLA-DR expression in pelvic ileal pouches.

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.

Adenomatous Polyposis Coli↗
PubMed1986

The metabolic consequences of infusing emulsions containing medium chain triglycerides for parenteral nutrition: a comparative study with conventional lipid.

In order to test the hypothesis that medium chain triglycerides (MCT's) are a safe and potentially superior energy source during parenteral nutrition 13 patients were entered into a randomised cross over trial. They received either a long chain triglyceride emulsion (LCT) or a 50% medium chain (MCT)/50% LCT mixture as part of their energy supply. Nitrogen balance was significantly better when MCT/LCT was infused and the greater levels of plasma ketones and lower plasma triglyceride levels suggested that MCT was more readily metabolised in these patients. Routine haematology, biochemistry and liver function tests gave no indication of harmful side effects from MCT.

Adult↗
PubMed1980

Gastrin levels in chronic renal failure, hemodialysis and renal transplant patients.

Basal serum gastrin levels have been studied in chronic renal failure (CRF), hemodialysis (MHDT) and renal transplant patients. There was no significant difference between the levels in CRF and controls and between anephric and nephric MHDT patients. However, levels in transplant patients were lower than those in the other groups. There was no relationship between fasting gastrin levels and peptic ulceration in any of the groups studied. It is doubtful whether basal gastrin estimations are of much value in management of these patients.

Gastrins↗
PubMed1978

Liver function and lactate metabolism in the ill surgical patient.

Liver function and lactate metabolism were investigated in non-shocked, severely ill surgical patients. Fasting venous blood lactate concentration was increased and plasma liver function tests were abnormal in ill patients compared with controls. Ill patients were glucose-intolerant and blood lactate changes following intravenous glucose infusion were similar in both ill and control patients. Blood lactate half-life was increased in ill patients following a sodium L-lactate infusion, suggesting that the increased fasting lactate concentration may have been due to decreased hepatic removal rather than to increased peripheral production of lactate.

Aged↗
PubMed1977

The complications of intravenous Corynebacterium parvum infusion.

100 intravenous infusions of Corynebacterium parvum were given to thirty-six patients at a dose of 5 mg/m2. Fever and rigors occurred in all patients but these acute side effects were acceptable to all but two patients. Seventeen patients suffered a delayed fall in blood pressure, which was marked in eight of them but was generally well tolerated. One patient died 18 hr after infusion from extensive myocardial infarction. Herpes labialis complicated the first infusion in nine instances, which may reflect transient immunosuppression following immunotherapy.

Aged↗