Biomedical subjects
Publications and source records attributed to P J Kumar.
Bleeding from duodenal varices in portal hypertension may not be recognized, resulting in a delay in diagnosis. Early detection is important as duodenal varices are a potential source of massive hemorrhage. We report two cases with recurrent upper gastrointestinal hemorrhage in whom accurate diagnosis was made only after extensive investigation including repeated endoscopic examination.
Although intestinal tuberculosis is rare in this country, increasing numbers of patients are now being seen, particularly in the immigrant population. We present the history of a lady who had acute diarrhoea and in whom the radiological and endoscopic findings looked very similar to those seen in Crohn's disease. The radiological presentation included widespread aphthous ulceration, a feature that has rarely been reported in tuberculous colitis.
Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) are at an increased risk of gastroduodenal erosions, ulcers, and the associated complications of haemorrhage, perforation, and death. Many NSAID associated ulcers that bleed or perforate have been asymptomatic until the time of presentation and conversely many patients with dyspepsia do not have ulcers. Symptoms are a poor guide to the presence of an ulcer. During continued treatment with NSAIDs misoprostol is the best choice for NSAID induced gastroduodenal damage; it achieves higher rates of healing than other drugs in these circumstances. Misoprostol is superior to other drugs in the prevention of gastric damage but misoprostol and H2 antagonists are of similar benefit in the duodenum. Prophylactic studies have all used endoscopic damage as an endpoint, and much larger studies will be needed to show an effect of misoprostol on the incidence of ulcer complications. There are no clear guidelines as to which patients should receive prophylactic treatment with misoprostol but those particularly at risk of ulcer complications--that is, those with previous peptic ulceration, the elderly, medically unfit, patients receiving large doses of NSAIDs, and those patients receiving steroids in addition to NSAIDs--should be considered.
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Over a 10 year period a total of 102 teenage patients with coeliac disease were assessed on transfer from paediatric hospitals to an adult clinic. Fifty seven patients said they were on a strict gluten free diet; 36 were semistrict, and nine admitted to eating a normal diet. Jejunal mucosal abnormalities, however, suggested that many patients on the 'strict' diet were actually consuming gluten. All patients were well with biochemical parameters within the normal range. Height percentiles were not significantly different from the normal population but patients, as a group, were significantly lighter.
Treatment of patients with coeliac disease with a low gluten containing diet (LGD) remains controversial. We have studied jejunal morphology and antigluten (AG) antibody titres by ELISA in patients on a LGD of 2.5-5 g/day for three to 14 months (median six months) and compared results with patients on a strict gluten free diet (GFD) for six to 27 months (median 13 months). We found no significant difference in villous height or crypt depth (eight LGD v 10 GFD patients) or serum AG-IgA, -IgG, and IgM titres (13 LGD v 12 GFD patients). there was however, a significant increase (p less than 0.05) in intra-epithelial lymphocytes in those patients on a LGD. We conclude that adult coeliac patients can tolerate a LGD without gross morphological change and without initiating significant AG antibody responses.
Binding of 125I-crude gluten digest (Frazer's fraction III. FF-III) and 125I-concanavalin A (Con A) to isolated rat enterocytes and of 125I-FF-III to human enterocytes was investigated. Specific binding of 125I-FF-III to rat enterocytes was observed but binding was not inhibited by any of a range of simple and complex saccharides. although casein and bovine serum albumin displaced FF-III at high concentrations. Con A also bound to enterocytes in a specific manner and was inhibited by alpha-methyl-D-mannoside, confirming a lectin-mediated interaction. 125I-FF-III exhibited quantitatively similar specific binding to both normal human and coeliac enterocytes. The primary interaction of gliadin peptides with the enterocyte surface membrane is not lectin-mediated and unlikely to be of fundamental importance in the pathogenesis of coeliac disease.
We previously noted a region of amino acid sequence homology between A-gliadin, a major alpha-gliadin component known to activate coeliac disease, and the early region E1b protein of human adenovirus serotype 12 (Ad12), an adenovirus isolated from the human intestinal tract. In the present study sera from coeliac disease patients from the United Kingdom and the United States were assayed for neutralising antibody to Ad12 as evidence of past exposure to that virus and for antibody to synthetic peptides of A-gliadin from the region of shared sequence with the Ad12 E1b protein. Eighty nine per cent of untreated coeliac disease patients had evidence of previous Ad12 infection. There was also a significant increase in the prevalence of neutralising antibody to Ad12 among treated adults (33.3%) and children (30.8%) with coeliac disease compared with controls (0-12.8%) in the western USA and in London. There was no evidence for an increased prevalence of infection with a closely related adenovirus, adenovirus 18, or another enteric virus, Echovirus 11, among coeliac disease subjects. Additional studies documented that a region of A-gliadin that shares amino acid sequence homology with the adenovirus 12 E1b protein could be recognised as an antigenic determinant in active coeliac disease patients. Taken together, these data are compatible with the hypothesis that a viral protein may play a role in the pathogenesis of coeliac disease, perhaps by virtue of immunological cross reactivity between antigenic determinants shared by the viral protein and alpha-gliadins.
The agglutinating properties of a crude gluten digest, purified gliadin fractions and established plant lectins were investigated using mammalian erythrocytes, rat enterocytes and normal and coeliac human enterocytes as the target systems. Gliadin preparations failed to cause agglutination of any of the cells tested, whereas established pure plant lectins were active cell agglutinins. These studies indicate that gliadin peptides do not interact with intestinal cells in a polyvalent, lectin-like manner and as such cannot be regarded as true lectins. Mucosal damage in coeliac disease is unlikely therefore to be related to lectin-like activity of gliadin.
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Twenty-eight patients, thought to have coeliac disease and on gluten free diets, were put on a normal diet to confirm their diagnoses. Nineteen had been diagnosed in adult life (ACD) and nine in childhood (CCD). Patients were assessed on jejunal, morphological, and symptomatic parameters. Eighteen patients with ACD relapsed within seven weeks. Nine patients with CCD relapsed at variable times but five took longer than seven weeks, the longest period beint 10 months. Seven patients had no symptoms despite morphological deterioration during challenge and one patient, with ACD, did not relapse and was HLA B8 negative. This patient with ACD had subtotal villous atrophy on two jejunal biopsies and later showed morphological improvement on a gluten free diet. There was no correlation between the relapse time and time spent on a gluten free diet.
Three patients with coincident coeliac disease and inflammatory bowel disease are described. In 2 patients with known coeliac disease the recurrence of diarrhoea was not due to dietary deviation but to an additional large bowel pathology.
Five of 33 patients with dermatitis herpetiformis (DH) were found to have gastric parietal cell antibody in their sera, whereas it was not found in 30 healthy controls of comparable age distribution. Fifteen of the patients with DH underwent further studies to investigate the histological and functional state of their gastric mucosa. Atrophic gastritis was found in all five patients whose sera contained gastric parietal cell antibody and in three of 11 patients with no antibody in their sera. In addition, there was marked impairment of acid secretion in the DH group as a whole, but, apart from one patient with overt pernicious anaemia (PA), there was no evidence of malabsorption of B12.
The proportional and absolute numbers of circulating thymus dependent lymphocytes (T cells) were reduced in untreated patients with coeliac disease but were normal after treatment with a gluten free diet. There was an inverse correlation between circulating T cell numbers and jejunal intraepithelial lymphocytes. This evidence suggests a possible role for T cells in the pathogenesis of coeliac disease and is a further example of disturbed cell mediated immunity in this condition.
Jejunal lamina propria plasma cells and eosinophils and intraepithelial lymphocytes were raised in coeliac children on gluten-containing diets, but only intraepithelial lymphocytes were increased in patients on gluten-free diets. In contrast, lamina propria lymphocytes were reduced in children with coeliad disease on gluten-containing diets but were normal in paitents on gluten-free diets. In children with coeliac disease who were studied serially, lamina propria plasma cells and eosinophils and intraepithelial lymphocytes increased, and lamina propria lymphocytes decreased, within three months of the reintroduction of gluten to the diet. These observations are essentially similar to those made in the adult form of the disease and suggest that more than one type of immunological reaction is involved in the pathogenesis of the jejunal lesion.
Jejunal mucosal immunoglobulin-containing cells of all three major classes (IgA, IgM, IgG) were increased in coeliac children on gluten-containing diets but only IgM cell numbers were raised in those on gluten-free diets. Patients with subtotal villous atrophy had greater numbers of immunoglobulin-containing cells than patients with normal mucosa. In previously treated patients studied before and after three months on a gluten-containing diet ther was an increase in all three classes of cell, IgM containing cells showing the greatest proportional rise. Basement membrane staining with anti-IgA serum occurred in coeliacs and was most intense in untreated patients. Apart from one patient with very low levels of serum IgA, serum immunoglobulins did not differ from normal. However, after reintroduction of gluten to the diet a significant fall in serum IgM concentrations occurred compared with levels in the same patients while on gluten-free diets. It seems probable that both IgA and IgM systems are important in the immunopathogenesis of the small intestinal lesion of childhood coeliac disease.
Serum antibodies to a variety of dietary proteins were investigated in 26 patients with adult coeliac disease (ACD, 14 untreated and 17 treated with a gluten-free diet) and 38 patients with dermatitis herpetiformis (DH) with varying small bowel abnormalities. The incidence of one or more positive tests was highest in untreated ACD (73.4%) and DH with subtotal villous atrophy (57.4%). This incidence fell with morphological improvement, being 56.4% in treated ACD patients with partial villous atrophy (PVA), and 33.4% in DH with PVA, and 0% in DH with normal biopsies. The height of the serum antibody titre also fell with morphological improvement. These results show that there is an abnormally high incidence of dietary antibodies in patients with DH, and this correlates with the degree of small bowel damage.