Ranitidine maintenance therapy in the prevention of duodenal ulceration; a comparison of 150 mg at night with 300 mg at night.

BACKGROUND: The purpose of this study was to investigate if the use of a higher night time dose of ranitidine (300 mg) could keep significantly more duodenal ulcer patients in remission than the usual maintenance dose (150 mg). METHODS: Double-blind, multi-centre, parallel group study of patients with proven healed duodenal ulcer randomized to ranitidine 150 mg or 300 mg daily for 1 year. The primary study end-point was symptomatic, endoscopically proven ulcer relapse. RESULTS: A total of 489 patients were recruited into the study. The endoscopically proven relapse rates were 6.1% of ranitidine 150 mg daily (n = 250) and 6.9% on 300 mg daily (n = 239). These differences were not statistically significant. CONCLUSION: This study provides further evidence that maintenance therapy with ranitidine 150 mg daily is highly effective at preventing duodenal ulcer relapse. The use of the higher dose of 300 mg daily does not appear to keep significantly more patients in remission.

Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers.

In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable.

Leukaemoid reaction and ulcerative colitis.

We describe a patient who presented with a pronounced neutrophil leucocytosis and leukaemoid reaction in association with toxic dilatation of the colon secondary to ulcerative colitis. Although the patient had been previously investigated, the significance of bowel disturbance had not been recognised. Once the inflammatory bowel disease was treated the haematological abnormality subsided.

Influence of drug treatment on the irritable bowel syndrome and its interaction with psychoneurotic morbidity.

Sixty per cent of the patients referred to two gastroenterological clinics and diagnosed as suffering from the irritable bowel syndrome (IBS), were found to have significant psychoneurotic morbidity on the basis of the General Health Questionnaire. A double-blind, completely randomised, placebo controlled comparison of treatment with a combined anxiolytic/antidepressant (Motipress) found a significantly better effect of Motipress than placebo on diarrhoea and abdominal pain. Detailed analysis of the results suggests that there is no direct relationship between psychoneurotic illness and IBS, but the presence of the former has an adverse effect on the short-term outcome of the bowel disorder.

Immunoglobulins in the jejunal mucosa in adult coeliac disease and dermatitis herpetiformis after the reintroduction of dietary gluten.

Cells containing immunoglobulin (IgA, IgG, IgM) have been measured and the distribution of extracellular and epithelial cell immunoglobulin assessed in treated patients with adult coeliac disease (ACD) and dermatitis herpetiformis (DH) before and after gluten was reintroduced to the diet. Patients with ACD and DH frequently had IgM and IgG cells above the normal range even before re-exposure to gluten, although the range of IgA cells was normal. In both diseases IgA and IgM cells increased after gluten with a proportionally greater rise in the latter, so that numbers of IgM cells, but not of IgA, exceeded the control range in all but one patient. There were increased quantities of IgA and IgM extracellularly in the lamina propria and in epithelial cells after challenge with gluten. Third component of complement was also found in some biopsies after re-exposure to gluten. These findings support the suggestion that gluten induces a humoral immunological response within the small intestinal mucosa and that both IgA and IgM systems are involved.

Cellular infiltrate of the jejunum after re-introduction of dietary gluten in children with treated coeliac disease.

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.

Immunological phenomena in the jejunum and serum after reintroduction of dietary gluten in children with treated coeliac disease.

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.

T cell depletion in untreated adult coeliac disease.

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.

Gastric lesion in dermatitis herpetiformis.

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.

Food antibodies in patients with dermatitis herpetiformis and adult coeliac disease - relationship to jejunal morphology.

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.

The cellular infiltrate of the jejunum in adult coeliac disease and dermatitis herpetiformis following the reintroduction of dietary gluten.

The cellular infiltrate of the jejunal mucosa has been studied in patients with both treated and untreated adult coeliac disease and dermatitis herpetiformis and serially in treated patients before and after the reintroduction of gluten to the diet. In adult coeliac disease and dermatitis herpetiformis the jejunal mucosa showed similar abnormalities of the cellular infiltrate which was characterized by an increase in intraepithelial lymphocytes and lamina propria plasma cells and eosinophils, with the greatest numbers of cells occurring in untreated patients. At 24-48 hours following a single 25-g gluten challenge there was an increase in lamina propria plasma cells, lymphocytes and eosinophils and intraepithelial lymphocytes. This rise was sustained after seven days on a gluten-containing diet for all of these cell groups except lamina propria lymphocytes. These responses were essentially similar in both adult coeliac disease and in those dermatitis herpetiformis patients who had jejunal lesions before treatment. In dermatitis herpetiformis patients with normal jejunal morphology on a normal diet there was an upward trend in lamina propria plasma cells and intraepithelial lymphocytes within one to three weeks of taking extra dietary gluten. These results are compatible with the view that more than one immunological mechanism may be responsible for the pathogenesis of the jejunal lesion of coeliac disease and dermatitis herpetiformis.

A double-blind controlled trial of 'Gaviscon' in patients with symptomatic gastro-oesophageal reflux.

In a double-blind trial in 26 patients with symptomatic gastro-oesophageal reflux, the alginate/effervescent/antacid compound 'Gaviscon' was compared with antacid containing placebo similarly formulated. Retrosternal pain after meals and at night was significantly reduced whilst patients were taking 'Gaviscon' and the beneficial effects lasted for many weeks after discontinuation of the active preparation.

Antireticulin antibodies in dermatitis herpetiformis and adult coeliac disease. Their relationship to a gluten free diet and jejunal histology.

Antireticulin antibody was present in 17% of sera from thirty-five patients with dermatitis herpetiformis, 45% from twenty-eight patients with adult coeliac disease and none of thirty healthy controls. There was a higher incidence of antireticulin antibody(a) in patients on normal diets than in those on gluten free diets, and (b) in patients with subtotal villous atrophy than in those with partial villous atrophy. Two patterns of tissue staining were demonstrated, one of which was almost invariably associated with jejunal subtotal villous atrophy. The Ig class of the antibody was IgG in all instances but in 64% antibody of the IgA class was also present.

Jejunal mucosal immunoglobulin-containing cells and jejunal fluid immunoglobulins in adult coeliac disease and dermatitis herpetiformis.

Immunoglobulin-containing plasma cell densities in the jejunal mucosa and serum and jejunal fluid immunoglobulins have been measured in patients with adult coeliac disease and dermatitis herpetiformis with and without jejunal mucosal abnormality. Studies were performed in patients before and after treatment of the jejunal lesion.Total immunofluorescent plasma cells were increased in untreated adult coeliac disease and dermatitis herpetiformis patients with jejunal lesions, but in general the normal predominance of IgA > IgM > IgG was found. There was no difference from controls in IgA-containing cells in the two conditions before or after treatment. The numbers of IgM-containing cells were significantly increased both before and after treatment in groups of patients with adult coeliac disease and dermatitis herpetiformis who had jejunal lesions. IgG-containing cells were significantly raised in only the before-treatment groups. Patients with dermatitis herpetiformis without jejunal lesions, even whilst on gluten-containing diets, had normal numbers of immunoglobulin-containing cells. IgA and IgM jejunal fluid immunoglobulins were significantly raised in dermatitis herpetiformis and adult coeliac disease.It is concluded that patients with dermatitis herpetiformis with jejunal morphological abnormality have a comparable immunological disturbance of the jejunal mucosa to that found in adult coeliac disease.