Inhibition of gastric acid secretion in the gastric brooding frog, Rheobatrachus silus.

The female gastric brooding frog Rheobatrachus silus broods its young in its stomach. A substance that inhibits gastric acid secretion in a toad stomach preparation in vitro appears to be secreted by the developing young. This substance has been identified as prostaglandin E2. Rheobatrachus silus may thus have developed a mechanism whereby prostaglandin secreted by the larvae inhibits acid secretion in the stomach of the female until the larvae have completed development and emerged as juvenile frogs by way of the female's mouth.

Disorders of gastric emptying in humans and the use of radionuclide techniques.

Associated with the development of methods to quantify gastric emptying, there has been an increased understanding of the physiology of gastric emptying in normal subjects and the pathophysiology and pharmacological treatment of gastric emptying disorders. The measurement of gastric emptying, using radionuclide-labeled food markers and a scintillation camera, has widespread clinical and research applications.

Measurement of specific antibodies in human intestinal aspirate: effect of the protease inhibitor phenylmethylsulphonyl fluoride.

Incorporation of the protease inhibitor phenylmethylsulphonyl fluoride in a solid-phase enzyme-linked immunoassay increased the sensitivity of this assay for detecting antibodies to dietary proteins present in human intestinal aspirate. Its effect was due in part to the prevention of antigen degradation.

Determination of vitamin B 12 absorption by a simple whole body counter.

This paper reports the results of estimating vitamin B(12) absorption by whole body counting in patients without known gastrointestinal disorder, and in patients with pernicious anaemia, idiopathic achlorhydria, achlorhydria following gastric operations, and various forms of small intestinal disease. Patients with pernicious anaemia absorbed less than 30% of the test dose; they could be distinguished from patients without gastrointestinal abnormality and from most achlorhydric patients who secreted more than 300 mg units of intrinsic factor in the post-histamine hour. Nevertheless, the wide range of normal absorption and the variable absorption from the normal gastrointestinal tract is emphasized and discussed. There is no relation between histamine-stimulated intrinsic factor production and vitamin B(12) absorption in patients with small intestinal disease.

Correction for tissue attenuation in radionuclide gastric emptying studies: a comparison of a lateral image method and a geometric mean method.

Variation in depth of radionuclide within the stomach may result in a significant error in the measurement of gastric emptying if no attempt is made to correct for gamma-ray attenuation by the patient's tissues. In this study a method of attenuation correction, which uses a single posteriorly located scintillation camera and correction factors derived from a lateral image of the stomach, was compared with a two-camera geometric mean method, both in phantom studies and in five volunteer subjects. A meal of 100 g of ground beef containing 99Tcm-chicken liver, and 150 ml of water, was used in the in vivo studies. In all subjects the geometric mean data showed that solid food emptied in two phases: an initial lag period, followed by a linear emptying phase. Using the geometric mean data as a standard, the anterior camera overestimated the 50% emptying time (T50) by an average of 15% (range 5-18) and the posterior camera underestimated this parameter by 15% (4-22). The posterior data, corrected for attenuation using the lateral image method, underestimated the T50 by 2% (-7 to +7). The difference in the distances of the proximal and distal stomach from the posterior detector was large in all subjects (mean 5.7 cm, range 3.9-7.4). We conclude that attenuation effects may account for large errors in the measurement of gastric emptying with radionuclide methods and that the application of correction factors derived from a lateral image of the stomach reduces these errors.

Cigarette smoking and rate of gastric emptying: effect on alcohol absorption.

OBJECTIVE: To examine the effects of cigarette smoking on alcohol absorption and gastric emptying. DESIGN: Randomised crossover study. SETTING: Research project in departments of medicine and nuclear medicine. SUBJECTS: Eight healthy volunteers aged 19-43 who regularly smoked 20-35 cigarettes a day and drank small amounts of alcohol on social occasions. INTERVENTIONS: Subjects drank 400 ml of a radiolabelled nutrient test meal containing alcohol (0.5 g/kg), then had their rates of gastric emptying measured. Test were carried out (a) with the subjects smoking four cigarettes an hour and (b) with the subjects not smoking, having abstained for seven days or more. The order of the tests was randomised and the tests were conducted two weeks apart. MAIN OUTCOME MEASURES: Peak blood alcohol concentrations, absorption of alcohol at 30 minutes, amount of test meal emptied from the stomach at 30 minutes, and times taken for 50% of the meal to leave the proximal stomach and total stomach. RESULTS: Smoking was associated with reductions in (a) peak blood alcohol concentrations (median values in non-smoking versus smoking periods 13.5 (range 8.7-22.6) mmol/l v 11.1 (4.3-13.5) mmol/l), (b) area under the blood alcohol concentration-time curve at 30 minutes (264 x 10(3) (0-509 x 10(3)) mmol/l/min v 140 x 10(3)) (0-217 x 10(3) mmol/l/min), and (c) amount of test meal emptied from the stomach at 30 minutes (39% (5-86%) v 23% (0-35%)). In addition, smoking slowed both the 50% gastric emptying time (37 (9-83) minutes v 56 (40-280) minutes) and the intragastric distribution of the meal. There was a close correlation between the amount of test meal emptied from the stomach at 30 minutes and the area under the blood alcohol concentration-time curve at 30 minutes (r = 0.91; p less than 0.0001). CONCLUSION: Cigarette smoking slows gastric emptying and as a consequence delays alcohol absorption.

Effect of histamine H2-receptor blockade on gastric emptying and serum gastrin in man.

The effect of orally administered metiamide, a Histamine H2-receptor antagonist, on the rate of gastric emptying was assessed in 24 uncomplicated duodenal ulcer patients given a standard meal containing indium 113m D.T.P.A. chelate. Metiamide produced significant slowing of gastric emptying when compared with control studies performed on the same patients following oral administration of a placebo. In a further study the effect of metiamide on the serum gastrin response to a protein meal was assessed in seven healthy male volunteers. Paired experiments demonstrated that a significantly greater elevation of serum gastrin occurred after metiamide than after placebo. The delay in gastric emptying produced by metiamide may be mediated by an elevation of the serum gastrin concentration.

The treatment of dyspepsia.

Dyspepsia may result from over-indulgence in alcohol and food, or from anxiety and emotional problems. It may also indicate a peptic ulcer, oesophagitis or less commonly, gallstones or gastric cancer. Investigation by endoscopy or barium studies is always indicated when an organic lesion is suspected. Reassurance, tranquillizers and antispasmodics help patients with functional dyspepsia. Antacids given hourly between meals are important in the treatment of all symptomatic peptic ulcers. Cimetidine causes rapid symptomatic relief of duodenal ulcer symptoms, and most ulcers will heal with six weeks' therapy. Gastric ulcer can be treated with carbenoxolone, but this drug is avoided in the elderly and in patients with cardiac failure or hypertension. Anticholinergic drugs are of value in duodenal ulcer, especially for night pain, but they should not be used in patients over the age of 50. Special diets are of no value. For the heartburn of oesophagitis, weight reduction and a regime of regular antacid therapy remain the important measures.

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.

A new form of antihistamine--the H2-receptor antagonist.

A new group of drugs, the histamine2 (H2)-receptor antagonists, act on receptors in the stomach to reduce acid secretion when this is stimulated by histamine, pentagastrin, the vagus nerve or food. The reduction in acid secretion is profound and may approach the degree of reduction brought about by gastric surgery. The H2-receptor antagonist metiamide, administered orally, has been used successfully in the treatment of duodenal ulcer and the Zollinger-Ellison syndrome, but it has been shown to cause agranulocytosis. Trials are in process with an analogue, cimetidine (Tagamet, SKF), which has a different chemical structure from metiamide and has not caused haematological changes in animals or man. These drugs offer the prospect of successful medical management of duodenal ulcer, while a study of their effects on H2-receptors elsewhere in the body may reveal other therapeutic benefits.

Omeprazole inhibition of nocturnal gastric secretion in patients with duodenal ulcer.

We studied the effect of single 08.00 h doses of omeprazole or placebo on gastric acid secretion during the following night, 14 to 23 h after administration, in seven male subjects with duodenal ulcer. The drug was given orally, double-blind, in randomized order. Omeprazole 20 mg, 40 mg and 80 mg reduced mean total overnight acid output by 43%, 73% and 91% respectively and median pH increased from 1.4 with placebo to 1.6, 3.1 and 7.0 respectively. The inhibitory effect was maintained throughout the study period. No clinical side effects or abnormalities of laboratory screening tests were seen. Omeprazole is well tolerated and administration at 08.00 h produces prolonged dose related inhibition of acid output during the following night.

Leukocyte reactivity to alpha-gliadin in dermatitis herpetiformis and adult coeliac disease.

The leukocyte adherence inhibition test has been used to study leukocyte reactivity to alpha-gliadin in 20 patients with dermatitis herpetiformis and 11 patients with adult coeliac disease. Leukocytes from both groups of patients showed a significant inhibition of leukocyte adherence thus indicating possible cell-mediated reactivity to this fraction of gluten.

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.

A factor present in human milk, but not colostrum, which is cytotoxic for human lymphocytes.

This study reports the presence of a factor in human milk which is cytotoxic to both autologous and heterologous human peripheral blood mononuclear cells (PBMC). The cytotoxic effect was measured by the release of 51Cr from labelled cells or by the inability of PBMC to exclude trypan blue following exposure to milk. The cytotoxic factor was not dialysable or sensitive to heating at 56 degrees C for 30 min, and could not be adsorbed from milk by PBMC. It lysed lymphocytes harvested from colostrum and from autologous or heterologous milk. The cytotoxic factor in the milk was different from the factor found in colostrum which inhibits the proliferation of mitogen stimulated PBMC, but which is not cytotoxic. Testing of serial samples of milk from the same mother indicated that the factor could be detected in the milk after 3-4 days post partum. We conclude that factors cytotoxic for human PBMC appear in human milk early in lactation.

The effect of cyclosporin A in delaying maturation of the small intestine during weaning in the rat.

As maturation of the small intestine has similar features to an immunologically mediated reaction, we studied the effect of the immunosuppressive agent, cyclosporin A (CyA), on the development of the small intestine during weaning in the DA x PVG rat. Intestinal development was measured by villus area, crypt length, crypt cell production rate (CCPR), and disaccharidase activity. Rat pups received either cyclosporin A (7.5 mg/kg daily subcutaneously) or polyethoxylated castor oil (Cremophor, drug vehicle) subcutaneously from 12 days of age. Cremophor- and CyA-treated litters were killed at 18, 20, 22, 24, and 26 days of age. CyA-treated animals had retarded weight gain, lower mesenteric lymph node and spleen weights, fewer intraepithelial lymphocytes, and reduced systemic secretion of rat mucosal mast cell protease II. CyA treatment retarded any increase in villus area, crypt length and CCPR until day 26 of age. Lactase activity was retained longer, and sucrase and maltase induction was delayed. We conclude that CyA retarded normal development of the small intestine, but some maturation still occurred at the end of weaning.

Synthesis of immunoglobulin and secretory component by gastrointestinal mucosa in patients with hypogammaglobulinaemia or IgA deficiency.

Biopsies of intestinal mucosa from patients with adult hypogammaglobulinaemia or selective IgA deficiency have been studied for the ability to synthesize immunoglobulins and secretory component. Tissue fragments were cultured in vitro in medium containing 14C-labelled amino acids and newly snythesized proteins were detected by radioimmunoelectrophoresis. Synthesis of IgA, and in some cases IgG and IgM, was found in intestinal mucosal biopsies from hypogammaglobulinaemics and IgA-deficient subjects. Biopsies from all the patients also synthesized secretory component, but evidence was obtained which indicated that secretory component does not combine normally with IgA. Tissue sections of these biopsies have also been studied by immunofluorescence and immunoglobulin bearing cells have been demonstrated. The present findings demonstrate that immunoglobulin synthesizing cells are present in the intestinal mucosa of immunoglobulin-deficient individuals. Local immunoglobulin synthesis may partially explain why these patients do not often have major problems with intestinal infections.

Measurement of intestinal antibody by radioimmunoassay.

The study of antibody responses in the intestine has been greatly hampered by lack of reproducible sensitive assays. An assay for measuring antibody against bacteria capable of regularly detecting gut antibody in gastroenteritis is described. It is based on absorption of antibody onto bacteria and measurement of the amount of antibody bound using radiolabelled anti-immunoglobulin antibody. Anti-light chain antibody is used to detect all classes of antibody as well as partially degraded antibody which retains the capacity to bind; anti-alpha and anti-gamma antibody is used to measure IgA and IgG antibody. The sensitivity of the assay depends on the use of anti-immunoglobulin antibody purified by affinity chromatography and allows measurement of nanogram amounts of antibody. Its specificity and kinetics are described and the particular advantages it provides in the measurement of antibacterial antibody in the intestine are discussed.