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Biomedical subjects

D J Shearman

Publications and source records attributed to D J Shearman.

At least 37 records · Page 2Linked to original sources

Olsalazine in the treatment of active ulcerative colitis: a placebo controlled clinical trial and assessment of drug disposition.

The efficacy, safety and disposition of olsalazine was assessed in patients with left-sided ulcerative colitis or proctitis in a double-blind placebo controlled trial. Thirty patients with a mild-to-moderate attack of ulcerative colitis were randomly allocated to olsalazine capsules, 1 g b.d., or placebo for 6 weeks. Good clinical response was found in six patients receiving olsalazine and in two receiving placebo. Improvement in sigmoidoscopic findings and histological appearance of rectal biopsies was also seen more often in olsalazine-treated patients. Plasma concentrations of olsalazine were significantly higher in patients who improved. Olsalazine showed an advantage over placebo which needs to be confirmed by further studies; it was safe in sulphasalazine-sensitive patients but appeared to cause watery diarrhoea in two patients.

Aminosalicylic Acids↗

Gastric and esophageal emptying in dystrophia myotonica. Effect of metoclopramide.

Gastric and esophageal emptying were measured using scintigraphic techniques in 16 patients with dystrophia myotonica and in 22 normal volunteers. Gastric emptying of a solid meal was slower than the normal range (defined as the mean +/- two standard deviations obtained in the normal volunteers) in 15 of the 16 patients, and gastric emptying of the liquid meal was slower than the normal range in 10 of the patients. Esophageal emptying was also markedly delayed in patients, with 15 of 16 patients having an emptying time longer than the normal range. There was no relationship between gastrointestinal symptoms, or the severity of the peripheral (skeletal) muscle weakness, and either gastric or esophageal emptying. Oral administration of metoclopramide resulted in a significant improvement in gastric emptying of the solid meal and a nonsignificant trend toward more rapid liquid emptying, but no change in esophageal emptying. These results indicate that there is a very high prevalence of gastric and esophageal smooth muscle dysfunction in dystrophia myotonica and that gastroparesis is likely to be a treatable cause of morbidity in this disease.

Adult↗

Effect of cisapride on gastric and esophageal emptying in insulin-dependent diabetes mellitus.

The effects of cisapride on gastric emptying, esophageal emptying, gastrointestinal symptoms, and glycemic control were evaluated in 20 insulin-dependent diabetics who had delayed gastric emptying of the solid or liquid component of a meal, or both. A double-isotope technique was used to measure gastric emptying, and esophageal emptying was measured as the time for a bolus of the solid meal to enter the stomach. On 2 days each patient received cisapride (20 mg) or placebo orally, 60 min before an esophageal and gastric emptying test. A third gastric and esophageal emptying test was performed after each patient had orally taken 10 mg of cisapride or placebo q.i.d. for 4 wk. Single-dose cisapride increased esophageal emptying (p less than 0.01) and both solid and liquid gastric emptying (p less than 0.001). The response to cisapride was most marked in patients with the greatest delay in esophageal and gastric emptying (p less than 0.05). After administration of cisapride for 4 wk, gastric emptying of solid and liquid were faster (p less than 0.001), but esophageal emptying was not significantly different from the placebo test. Upper gastrointestinal symptoms were less after cisapride (p less than 0.05), whereas there was no change on placebo (p greater than 0.2). Plasma glucose and glycosylated hemoglobin concentrations were not different after cisapride compared with placebo. These results indicate that single-dose cisapride increases esophageal emptying in insulin-dependent diabetics and that chronic administration of cisapride is effective in the treatment of diabetic gastroparesis.

Adult↗

Effects of cisapride on gastric and esophageal emptying in progressive systemic sclerosis.

The effects of cisapride on gastric emptying, esophageal emptying, and gastrointestinal symptoms were evaluated in 8 patients with progressive systemic sclerosis who had delayed gastric emptying of the solid or liquid component of a meal, or both. A double-isotope technique was used to measure gastric emptying, and esophageal emptying was measured as the time for a bolus of the solid meal to enter the stomach. Gastrointestinal symptoms were assessed by a questionnaire. On 2 days each patient received cisapride (10 mg) or placebo intravenously, 5 min before an esophageal and gastric emptying test. After these 2 days each subject took cisapride (10 mg q.i.d., p.o.) for 1 mo. Cisapride improved solid and liquid gastric emptying (p less than 0.001), but had no significant effect on esophageal emptying (p less than 0.1). Upper gastrointestinal symptoms were reduced after cisapride (p less than 0.001), and no side effects were reported. These results indicate that gastroparesis is a treatable cause of morbidity in progressive systemic sclerosis.

Adult↗

Variation of serum and intestinal gluten antibody specificities in coeliac disease.

Protein blotting techniques were used to investigate the gluten specificity of IgA and IgG antibodies in sera and intestinal aspirates from patients with coeliac disease and normal controls. Initially, discontinuous SDS polyacrylamide gel electrophoresis was used to separate the flour proteins. All normal and coeliac sera contained antibodies which bound to various of the gliadin proteins. In only a few sera was binding found to the high molecular weight glutenin subunits, while none was detected to the salt-soluble wheat proteins. Polyacrylamide gradient gel electrophoresis was then used to further separate the gliadin proteins. Almost all normal sera examined showed similar gliadin specificity, binding uniformly to all gliadin groups. While approximately a quarter of the coeliac sera showed even binding to all of the gliadin proteins, the majority showed antibody binding intensely to discrete groups of gliadin bands. We were unable to identify any gliadin band(s) which only bound antibodies from coeliac patients in comparison with normal subjects. The specificities of IgG and IgA serum antibodies were identical for each patient examined, but some differences between serum and intestinal IgA specificities were found for certain patients.

Adult↗

Abnormalities of gastric and esophageal emptying in polymyositis and dermatomyositis.

Gastric and esophageal emptying were assessed using scintigraphic techniques in 13 patients with polymyositis or dermatomyositis and in 13 normal volunteers. Esophageal emptying was significantly delayed in patients, with 8 of 13 patients being outside the normal range. Gastric emptying was also markedly slower in patients than in controls, with 8 patients being outside the normal range for solid emptying and 8 patients beyond the normal range for liquid emptying. The 5 patients with dysphagia all had delayed esophageal emptying, but both gastric and esophageal emptying were delayed in some asymptomatic patients. There was a significant correlation between esophageal emptying and both solid and liquid gastric emptying in the patients. Both gastric and esophageal emptying correlated with the severity of the peripheral (skeletal) muscle weakness. These results indicate that profoundly delayed gastric and esophageal emptying are common in polymyositis and dermatomyositis, implying frequent malfunction of the smooth muscle of the upper gastrointestinal tract in this disease.

Adolescent↗

Intestinal and serum antibody in coeliac disease: a comparison using ELISA.

Intestinal and serum antibody to antigens derived from gluten and other food proteins in 16 children with coeliac disease and 15 control subjects was measured using an enzyme-linked immunosorbent assay (ELISA). High concentrations of antibody to gluten antigens were found in children with coeliac disease who were on a diet which contained gluten. This antibody was predominantly in the IgA and IgM classes in intestinal fluid, and in the IgG and IgA classes in serum. When coeliac children transferred to a gluten-free diet for 6 months or more, anti-gluten antibody fell much more rapidly in serum than in intestinal fluid. Although no single measure of antibody, in any immunoglobulin class, to a gluten-derived antigen proved sufficiently discriminating to be suggested as a diagnostic test for coeliac disease, serum antibody, particularly in the IgA class, may be of value in following the progress of patients and in assessing their adherence to a gluten-free diet.

Adolescent↗

Gastric emptying after gastric bypass.

Gastric emptying of two test meals, consisting of ground beef and water and ground beef with 25 percent dextrose was measured with a scintigraphic technique in patients after gastric bypass surgery and in control subjects. Solid emptying was slower and liquid emptying was more rapid after gastric bypass and 25 percent dextrose emptied as rapidly as water. The pattern of gastric emptying after gastric bypass would favour more rapid initial absorption with liquid calories and may also be implicated in the dumping syndromes sometimes seen after gastric bypass.

Adult↗

Effect of increasing the caloric/osmotic content of the liquid component of a mixed solid and liquid meal on gastric emptying in obese subjects.

A dual isotope scintigraphic technique was used to assess the effect of increasing the caloric content of the liquid component of a mixed solid and liquid meal on gastric emptying in control and obese subjects. For the two test meals used gastric emptying of solid was significantly slower in the obese subjects compared to the control subjects. In both obese and control subjects the substitution of 25 per cent dextrose for water as the liquid component of the meal resulted in a significant delay of both solid and liquid emptying. The magnitude of this change was similar in obese and control subjects. The results suggest that the duodenal receptor mechanisms which slow gastric emptying are not defective in obesity.

Adult↗

Disorders of gastric emptying and the application of radionuclide techniques.

There has been a greatly increased understanding of the physiology of gastric emptying in normal subjects, and of the pathophysiology and pharmacological treatment of gastric emptying disorders associated with the development and application of methods to quantify gastric emptying in humans. The non-invasive measurement of gastric emptying by means of radionuclide-labelled food markers has widespread clinical and research applications.

Domperidone↗

Solid and liquid gastric emptying in patients with gastro-oesophageal reflux.

A dual isotope radionuclide technique has been used to assess solid and liquid gastric emptying simultaneously in 72 patients with symptomatic gastro-oesophageal reflux and 22 normal controls. Objective evidence of gastro-oesophageal reflux was obtained from standard acid reflux testing and/or endoscopy in all patients. Solid emptying was delayed in 32 patients (44 per cent), liquid emptying was delayed in 27 patients (37 per cent) and 16 of those two groups had delayed solid and liquid emptying. Thus 29 patients (40 per cent) had normal solid and liquid group (P less than 0.01). There was a significant correlation (P less than 0.01) between the solid and liquid gastric emptying values obtained in patients. No significant correlation was found between gastric emptying and the resting lower oesophageal sphincter pressure or the presence of symptoms of regurgitation and epigastric fullness. In the patients with delayed solid emptying there was a higher incidence of oesophagitis than in patients with normal emptying (P less than 0.05).

Adult↗

Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy.

Gastric emptying was studied with a double radioisotopic method in 12 patients with insulin-dependent diabetes mellitus complicated by autonomic neuropathy and in 22 control subjects. In the diabetics, the acute and chronic effects of oral domperidone on gastric emptying, symptoms of gastroparesis, and glycemic control were assessed. Gastric emptying of solid and liquid was slower in diabetics than controls (P less than 0.001). Acute administration of domperidone increased the rate of both solid and liquid emptying (P less than 0.005). Domperidone was most effective in those patients with the greatest delay in gastric emptying. After chronic administration (35-51 days), domperidone had no significant effect on solid emptying (P greater than 0.05), but was still effective in increasing liquid emptying (P less than 0.025). Symptoms of gastroparesis were less after domperidone (P less than 0.001).

Adult↗

Gastric acid secretion in the toad Bufo marinus with the description of a new technique for in vivo monitoring.

A technique for the implantation of a pH electrode into the stomach of the toad, Bufo marinus, is described. The technique permits continuous monitoring of gastric pH for extended periods. Results from continuous monitoring and from acute measurements of gastric pH are compared in fasting and fed toads. Prostaglandin E, given orally with food, caused a dose-related delay in the fall of gastric pH which followed feeding.

Animals↗

Gastric emptying and intestinal transit in Bufo marinus and the actions of E prostaglandins.

Gastric emptying and intestinal transit have been studied in the anuran Bufo marinus using Tc99-labelled chicken liver as the test meal. Gastric emptying was measured as the proportion of the test meal remaining in the stomach after 3 or 6 h. Intestinal transit was calculated by the geometric centre method at the same time intervals. There was a high degree of variability in these parameters between individual animals, in both control and treated groups. Both SC29333 (Searle), a synthetic E prostaglandin, and prostaglandin E2 given orally delayed gastric emptying. These results complement the finding that prostaglandin E2 causes relaxation of anuran longitudinal muscle in vitro, and lend further support to the suggestion that prostaglandin E2 may be responsible for the gut stasis associated with gastric brooding in the gastric brooding frog Rheobatrachus silus.

Animals↗

The effect of diet on systemic immune responses to wheat gliadin.

These studies examined the influence of gluten ingestion on the murine immune response to this cereal antigen. The results demonstrated that the level of specific antibody in the serum of mice immunised with gliadin is markedly reduced when gluten is present in the diet on which the animals were raised. Serum antibody concentrations in the gluten-free (G-F) mice were between 10- and 50-fold greater than those in the standard (STD) mice. The suppression of the antibody response to gliadin in the gluten-fed mice appeared to be antigen-specific, as STD mice responded normally to unrelated antigens such as sheep red blood cells (SRBC). This hyporesponsiveness towards gliadin develops very early in the animals' life. We suggest that this may occur through the transfer of small immunogenic fragments from mothers to their offspring either in utero or post-natally in the milk.

Animals↗

Vaso-active intestinal peptide: a neurotransmitter which reduces human NK cell activity and increases Ig synthesis.

The effect of vaso-active intestinal peptide (VIP) on natural killer (NK) cell activity and immunoglobulin synthesis in vitro has been studied. At a concentration of 10(-6)M, VIP significantly inhibited the NK cell activity of normal human peripheral blood mononuclear cells (PBMC) on K562 target cells. The concentration of IgG, IgA and IgM in the supernatants of pokeweed mitogen-stimulated PBMC was increased when VIP was added at the beginning of the culture period. It is possible that VIP may influence immune responses in the intestinal tract, where it is a neurotransmitter and is found in high concentrations.

Cells, Cultured↗

Fenfluramine delays gastric emptying of solid food.

The effect of a single dose of (+/-)-fenfluramine hydrochloride (40 mg) on gastric emptying of a mixed solid and liquid meal was assessed with a dual isotope scintigraphic technique in eight obese patients. Fenfluramine significantly delayed gastric emptying of solid food (approximately a 15% reduction in the solid linear emptying rate), but had no effect on gastric emptying of liquid.

Adult↗

The normal menstrual cycle has no effect on gastric emptying.

Recent studies have demonstrated that orocaecal transit time is prolonged both in the luteal phase of the ovulatory cycle in normal women and during pregnancy, but have made no attempt to differentiate between the individual effects of gastric emptying and small intestinal transit. We have assessed the effect of the normal menstrual cycle on gastric emptying of solids and liquids in 10 women, using a dual isotope scintigraphic technique. In each subject gastric emptying was measured on 2 days: first during the follicular phase (day 8-10) and then during the luteal phase (day 18-20) of one ovulatory menstrual cycle (where day 1 was the first day of menstrual bleeding). Measures of solid and liquid gastric emptying did not change significantly between the follicular and luteal phases indicating that the normal menstrual cycle has no effect on gastric emptying.

Adult↗