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Biomedical subjects

D J Shearman

Publications and source records attributed to D J Shearman.

At least 55 records · Page 3Linked to original sources

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.

Barium Sulfate↗

Gastric emptying after gastroplasty for morbid obesity.

Gastric emptying was studied in 11 patients who had undergone gastroplasty for morbid obesity 6 to 8 months previously and in 22 normal controls without gastrointestinal disease. A dual isotope technique for measuring solid and liquid emptying was used. Liquid emptying was slower in patients than controls. The emptying of solid was initially faster, but was followed by a prolonged slow rate of emptying indicating retention of solid food in the proximal partitioned pouch. There was no correlation between the weight loss produced by the operation and rates of solid or liquid emptying. Unlike gastric bypass, the changes in gastric emptying produced by gastroplasty were relatively small and gastric emptying rates in patients overlapped considerably with the range of emptying rates found in control subjects. The success of the procedure may depend on the induction of satiety by the filling of the partitioned pouch.

Adult↗

On the possible role of prostaglandin E2 in intestinal stasis in the gastric brooding frog Rheobatrachus silus.

Responses of isolated intestinal preparations from the anurans Bufo marinus and Limnodynastes tasmaniensis to various agents have been studied, as models for the intestinal stasis reported in the rare gastric brooding frog, Rheobatrachus silus. It is inferred from the responses that the preparations possessed excitatory muscarinic and histamine receptors and inhibitory adrenergic receptors, conforming to the typical vertebrate pattern. The circular muscle was unresponsive to prostaglandin E2, whereas longitudinal muscle relaxed to prostaglandin E2. Some of the longitudinal preparations exhibited a biphasic response to arachidonic acid, i.e. contraction followed by relaxation. Indomethacin prevented the relaxation phase, indicating that the intestine synthesised a prostaglandin E-like substance from arachidonic acid. These results draw attention to the possibility that PGE2 may be responsible for the intestinal stasis associated with gastric brooding in the gastric brooding frog.

Animals↗

Changes in gastric emptying rates with age.

A dual isotope technique which measures simultaneously the emptying of solids and liquids by the stomach was used to study gastric emptying in 35 subjects in the age range 21-84 years, who were all fit, mobile volunteers and were not taking any drugs. Solid and liquid emptying were significantly slower in older subjects, but this finding is unlikely to be of clinical significance because the changes were small and emptying rates were usually within the normal range for younger subjects.

Adult↗

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.

Adult↗

The effect of omeprazole on gastric emptying in patients with duodenal ulcer disease.

The effect of a single oral dose of omeprazole (90 mg) on gastric emptying was assessed with a dual isotope scintigraphic technique in eight patients with a history of duodenal ulcer disease. Omeprazole had no significant effect on solid or liquid gastric emptying. The bioavailability (AUC0-2 h) of omeprazole in all patients was greater than that required for total suppression of acid secretion. No adverse clinical or laboratory effects were observed.

Adult↗

In vitro immunoglobulin synthesis by human intestinal lamina propria lymphocytes.

The concentration of IgG and IgA was measured in the supernatants of peripheral blood mononuclear cells and of cells harvested from the intestinal lamina propria, which were cultured in vitro in the presence or absence of mitogens. The lamina propria mononuclear cells were harvested by collagenase digestion of macroscopically normal mucosa from 10 fresh surgical resections for carcinoma. Secretion of IgA in cultures of unstimulated lamina propria mononuclear cells greatly exceeded that of IgG. The addition of pokeweed mitogen increased Ig secretion by cultures of peripheral blood mononuclear cells but decreased Ig secretion by lamina propria mononuclear cells. The addition of concanavalin A suppressed Ig synthesis by pokeweed mitogen stimulated cells more in cultures of peripheral blood mononuclear cells than in lamina propria mononuclear cells. Cycloheximide inhibited Ig secretion by more than 90% in cultures of peripheral blood mononuclear cells, but there was less inhibition in cultures of lamina propria mononuclear cells. In the four unstimulated cultures of lamina propria mononuclear cells examined, over 75% of the Ig was secreted in the first three to four days of culture. The results indicate that lamina propria mononuclear cells are refractory to the inductive and suppressive signals of mitogens, and represent an activated cell population which is committed to Ig secretion before being cultured.

Cells, Cultured↗

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.

Adult↗

Polyclonal B cell activation in alcoholic patients with no evidence of liver dysfunction.

Unstimulated and pokeweed mitogen (PWM) stimulated immunoglobulin (Ig) synthesis by peripheral blood mononuclear cells (PBMC) in vitro and plasma Ig concentrations were measured in three groups of alcoholic patients: (i) with clinical or biochemical signs of liver disease, (ii) with evidence of an alcohol related disease but no overt signs of liver damage and (iii) with no evidence of any alcohol related disease. The concentrations of IgG and IgA were significantly raised in the supernatants of unstimulated cultures of PBMC from the patients, while the stimulation of Ig synthesis by PWM, measured as a stimulation index, was significantly reduced. The ratio of the concentration of IgG to IgA was reduced in the unstimulated cultures of PBMC from the alcoholics, indicating a greater relative increase in IgA synthesis compared to IgG synthesis. Comparing the alcoholics to the controls, it was found that the concentration of IgA in the plasma of the alcoholics was increased, but that the concentration of IgG was not altered. Comparing the different groups of patients, it was found that the concentration of IgG in the plasma was higher in the alcoholics with evidence of liver damage compared to alcoholics with alcohol related disease but no evidence of liver damage, and that the concentration of IgA in the plasma was higher in alcoholics with liver damage than those without. Otherwise there were no differences between the alcoholics with respect to the synthesis of IgG or IgA or the plasma Ig concentrations. These results indicate that IgG synthesis by PBMC in vitro, and serum Ig concentration in vivo, are abnormal in all alcoholics, not just those with overt clinical or biochemical signs of liver damage.

Alcoholism↗

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.

Cell Survival↗

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.

Animals↗

Inhibition by colostrum of the responses of peripheral blood mononuclear cells to mitogens.

This study investigated the inhibition by colostrum of the uptake of tritiated thymidine by both autologous and heterologous peripheral blood mononuclear cells (PBMC) stimulated with the mitogens phytohaemagglutinin (PHA), pokeweed mitogen (PWM) or Concanavalin A (Con A). This inhibition was not the result of an alteration in the dose response or kinetics of mitogenesis by the colostrum. The inhibitory factor in the colostrum was neither dialysable nor lymphocytotoxic. Lymphocytes which were briefly pre-treated with colostrum, then washed and cultured, also incorporated much less labelled thymidine than control cells. The inhibitory factor was not adsorbed from colostrum by mononuclear cells. We conclude that colostrum contains a cytostatic factor which inhibits mitogenesis in PBMC.

Colostrum↗

The influence of smoking on the healing of duodenal ulcer treated with oxmetidine or cimetidine.

The influence of smoking on duodenal ulcer healing was examined during a double blind study of 83 patients randomly allocated to oxmetidine or cimetidine treatment. Smoking habits were recorded but patients were not advised to change these. Smokers and nonsmokers were similar clinically and did not differ in compliance with medication. Both H2-receptor antagonists were equally effective and after four weeks of treatment ulcers were healed in 76% of patients. Ulcer healing occurred significantly less frequently in smokers (69%) than nonsmokers (89%). Smokers with healed ulcers consumed fewer cigarettes per day (mean +/- SE: 15.8 +/- 1.4) than those whose ulcers did not heal (22.2 +/- 2.7). When smokers were grouped according to daily cigarette consumption, a direct relationship was found between increasing cigarette consumption and decreasing frequency of ulcer healing. No reduction in ulcer healing was apparent in patients who smoked nine cigarettes a day, or less.

Cimetidine↗

Gastric emptying in normal subjects--a reproducible technique using a single scintillation camera and computer system.

The gastric emptying of a mixed solid and liquid meal was assessed in 24 normal subjects using a single camera/computer system which allowed continuous monitoring of both solids and liquids. It was shown that variation in tissue attenuation caused by the changing depth of radionuclide within the stomach accounted for large errors in the measurement of gastric emptying (alteration in 50% emptying time of up to 65%). A technique for the correction of attenuation is described which used factors derived from a lateral image of the stomach. In all subjects, solid emptying was slower than liquid emptying and was characterised by a delay (lag period) which was followed by linear emptying. Liquid emptying usually followed a single exponential pattern. The effect of physiological changes induced by increasing the calorie content of the liquid component of the meal was assessed by giving either water, 10% dextrose or 25% dextrose. Liquid emptying was slowed and the lag period of solid was prolonged as the calorie content increased. Reproducibility was assessed in 19 subjects. For the three groups studied (water, 10% dextrose, 25% dextrose) the day-to-day variation in gastric emptying was not significant for any measured parameter, while statistically significant differences were present in solid and liquid emptying between subjects and groups.

Adult↗

Abnormalities of gastric emptying in obese patients.

The pattern of gastric emptying in 15 obese patients and 11 control subjects has been assessed using a double isotope technique for measuring solid and liquid emptying with a scintillation camera. In all studies solid emptying was characterized by a lag period (before food enters the duodenum) followed by linear emptying. Liquid emptying was faster than solid and was non-linear. In obese patients solid emptying was delayed due to prolongation of the lag period, and the duration of the lag period correlated with excess body weight. There was no significant change in liquid emptying in obese patients. In control subjects no relationship between gastric emptying rates and body weight was apparent.

Adult↗