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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A case-control study was undertaken to investigate the effects of smoking, alcohol consumption, use of non-steroidal anti-inflammatory and other analgesic medications and family and medical history on the risk of ulcerative reflux oesophagitis (URO). We recruited 191 cases with URO diagnosed at endoscopy, 162 hospital controls who had also undergone endoscopy and 140 community controls from the Adelaide metropolitan area. From these three groups of subjects, 134 case-community control pairs, Matched on age, sex and postcode of residence and 142 case-hospital control pairs, matched on age, sex, hospital and endoscopist, were formed. Elevated non-significant risks were found in those smoking at least 20 cigarettes per day relative to those who never smoked (relative risk = 1.9, 95% confidence interval: 0.9-3.9 in case-hospital control pairs; relative risk = 1.9, 95% confidence interval: 0.9-3.7 in case-community control pairs). There was no elevation in risk associated with the use of non-steroidal anti-inflammatory drugs, with alcohol consumption, factors related to medical and reproductive history, nor with family history except for paternal history of heartburn (relative risk = 2.5, 95% confidence interval: 1.2-5.4 in case-hospital control pairs; relative risk = 1.9, 95% confidence interval: 1.0-4.0 in case-community control pairs). With the possible exception of smoking, no other risk factors for ulcerative reflux oesophagitis related to lifestyle are apparent.

The aim of this study was to compare recurrence rates of reflux oesophagitis (after endoscopic healing with omeprazole) over a 12 month period of randomised, double blind, maintenance treatment with either daily omeprazole (20 mg every morning; n = 53), weekend omeprazole (20 mg on three consecutive days a week, n = 55) or daily ranitidine (150 mg twice daily, n = 51). Patients were assessed for relapse by endoscopy (with gastric biopsy) at six and 12 months, or in the event of symptomatic recurrence, and serum gastrin was monitored. At 12 months, the estimated proportions of patients in remission (actuarial life table method) were 89% when receiving daily omeprazole compared with 32% when receiving weekend omeprazole (difference 57%, p < 0.001, 95% confidence intervals: 42% to 71%) and 25% when receiving daily ranitidine (difference 64%, p < 0.001, 95% confidence intervals: 50% to 78%). Median gastrin concentrations increased slightly during the healing phase, but remained within the normal range and did not change during maintenance treatment. No significant pathological findings were noted, and no adverse events were attributable to the study treatments. In conclusion, for patients who respond favourably to acute treatment with omeprazole 20 mg every morning, the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months. By contrast, weekend omeprazole and daily ranitidine were ineffective.

Recent manometric and radiological studies suggest that the upper oesophageal sphincter has poor compliance in patients with a pharyngeal (Zenker's) diverticulum. To test the hypothesis that this phenomenon is related to structural changes within the cricopharyngeus muscle we examined, histologically, muscle strips from 14 patients with a Zenker's diverticulum and compared them with control tissue obtained at autopsy from 10 non-dysphagic individuals. The cricopharyngeus muscle from patients and controls differed from inferior constrictor muscle by virtue of type 1 fibre predominance and greater fibre size variability. Ragged red fibres and nemaline bodies are a normal finding in the cricopharyngeus. Marked differences were observed in the cricopharyngeus muscle of Zenker's patients which demonstrated fibro-adipose tissue replacement and fibre degeneration. It is concluded that these structural changes may account for the observed diminished upper oesophageal sphincter opening and dysphagia in patients with Zenker's diverticulum.

Pharyngeal coordination, sphincter opening, and flow pressures during swallowing were investigated in patients with pharyngeal (Zenker's) diverticula. Fourteen patients with diverticula and 9 healthy age-matched controls were studied using simultaneous videoradiography and manometry. Pharyngeal and upper esophageal sphincter pressures were recorded by a perfused side hole/sleeve assembly. Temporal relationships among swallowing events, extent of sphincter opening during swallowing, and intrabolus pressure during bolus passage across the sphincter were measured. The timing among pharyngeal contraction and sphincter relaxation, opening, and closure did not differ between patients and controls. Sphincter opening was significantly reduced in patients compared with controls in sagittal (P = 0.0003) and transverse (P = 0.005) planes. Manometric sphincter relaxation was normal in patients. Intrabolus pressure was significantly greater in patients than in controls (P = 0.001). It is concluded that Zenker's diverticulum is a disorder of diminished upper esophageal sphincter opening that is not caused by pharyngosphincteric incoordination or failed sphincter relaxation. Incomplete sphincter opening is likely to cause dysphagia. Increased hypopharyngeal pressures during swallowing are probably important in the pathogenesis of the diverticulum.

We describe a reliable and sensitive semiautomated spectrophotometric assay of aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activity in erythrocytes. The hemolysate can be stabilized with sucrose, and the technique involves only microliters of hemolysate on a centrifugal analyzer. The use of microcolumns to remove interfering hemoglobin is avoided, and reproducibility of the assay has been improved by manipulating the inherent lactate dehydrogenase activity of erythrocytes by adding lactate and oxalate to the reaction mixture. These modifications have decreased the analytical imprecision of the assay, allowing a better appraisal of aldehyde dehydrogenase activity in erythrocytes as a biological marker of excess alcohol consumption. Erythrocytic ALDH activity was significantly less in 40 alcoholics than in 145 teetotallers (median activity 128 vs 219 mU/g of hemoglobin, respectively; P = 0.0001), indicating the potential of this assay as a useful marker of excess alcohol consumption.

The effects of parenteral administration of a killed typhoid vaccine on the intestinal immune response to live orally administered Salmonella typhi Ty21a in human subjects was evaluated. Priming with parenteral vaccination neither enhanced nor suppressed the subsequent specific serum and intestinal immunoglobulin A (IgA) immune responses to a booster course of live oral vaccine. Neither a single oral dose of live vaccine nor a single dose of parenteral vaccine had any measurable booster effect on the observed primary intestinal IgA response to the live oral vaccine. Two booster doses of subcutaneously administered killed typhoid vaccine did result in a significant increase in the specific intestinal IgA antibody in those subjects primed with the oral live vaccine. This response was comparable in magnitude to the primary intestinal response. No evidence of this response could be found in serum IgA, although nonsignificant rises in serum IgG were evident. Previous parenteral priming had no effect on secondary immune responses to a live oral vaccine in humans. Serum immune responses were generally found to be of little value as indicators of local intestinal immunity. This study confirmed that parenteral vaccination was only able to induce an intestinal immune response following priming with live, orally administered organisms and that multiple parenteral booster doses were necessary to induce a measurable effect on intestinal immune responses.

Specific antibody responses in the lower respiratory tract of human subjects to orally administered Salmonella typhi Ty21a are reported. These responses, predominantly of the immunoglobulin G class, were determined to be a transudate from serum. These results were supported by the similarity in responses to parenteral administration of heat-killed typhoid vaccine. Specific immunoglobulin A antibody was a poor contributor to the respiratory antibody response to either vaccine.

The short-term kinetics and the effects of different dose regimens and formulations on the humoral immune response induced in human subjects by the live attenuated typhoid vaccine Salmonella typhi Ty21a were examined. Antibody responses in jejunal fluid and serum and by specific antibody production in vitro by peripheral blood lymphocytes to S. typhi lipopolysaccharide were determined. A short vaccination schedule of three doses of 10(11) live organisms over 5 days induced significantly greater intestinal IgA antityphoid antibody responses than did two comparable doses 21 days apart. The humoral immune response was dose dependent with 10(10) and 10(11) live organisms stimulating greater intestinal immune responses than did 10(11) killed organisms. No responses were evident with either 10(9) viable organisms or with an enteric-coated preparation. In the continued development and assessment of oral typhoid vaccines, the effects of different doses and formulations and the timing of sampling on the humoral immune response should be considered.

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.

In 87 randomly selected diabetic patients (67 type 1, 20 type 2) and 25 control subjects, gastric emptying of digestible solid and liquid meals and oesophageal transit of a solid bolus were measured with scintigraphic techniques. Gastrointestinal symptoms, autonomic nerve function and glycaemic control were evaluated in the diabetic patients. Gastric emptying and oesophageal transit were slower (P less than 0.001) in the diabetic patients compared with the control subjects, and each was delayed in about 40% of them. There was a relatively weak (r = 0.32; P less than 0.01) relationship between solid and liquid gastric emptying, and no significant correlation (r = 0.11, NS) between oesophageal transit and gastric emptying of the solid meal. Scores for upper gastrointestinal symptoms and autonomic nerve function correlated weakly (r = 0.21; P less than 0.05) with both oesophageal transit and gastric emptying. Gastric emptying of the liquid meal was slower (P less than 0.05) in patients with blood glucose concentrations greater than 15 mmol/l. These results indicate that gastric emptying in patients with diabetes mellitus should be assessed by liquid as well as by solid test meals and that oesophageal transit should not be used as a predictor of generalised diabetic gastroenteropathy.

Secretory component (SC) binding assays which detect polymeric IgA (pIgA) in serum were used to measure serum antigliadin pIgA and total pIgA in patients with coeliac disease. Total IgA antigliadin antibody in serum and intestinal fluid was measured by enzyme linked immunosorbent assay (ELISA). The relationship of pIgA antibody to dietary gluten and the antigliadin IgA antibody in intestinal fluid was examined. Twenty-nine serum samples were assayed, twelve from patients ingesting gluten and seventeen from patients who had excluded gluten from their diet for 6 months. Eight of these were paired samples from 4 adults on and off gluten. In addition, paired samples of both intestinal fluid and serum were obtained from 7 children on and off gluten. Polymeric IgA antibody to gliadin was detected in 11 of 12 subjects on gluten but in only 3 of 17 who had excluded gluten. Three of the four adults from whom paired serum samples were obtained had pIgA antigliadin, but only while on gluten. Three of the seven children in whom intestinal and serum antibody were assayed had pIgA to gliadin, which could not be detected after exclusion of gluten, although their intestinal antibody level remained elevated. There was no change in total pIgA levels with diet although the levels were higher than those seen in normal subjects. We conclude that pIgA antibody to gliadin is frequently found in the serum of coeliac patients ingesting gluten. It disappears with gluten elimination at a time when the IgA antigliadin antibody in intestinal fluid has not altered.

The specific immune responses to the live vaccine Salmonella typhi Ty21a following rectal administration were determined in serum, peripheral blood lymphocytes, saliva and in jejunal fluid of adult human subjects. Following vaccination, all seven subjects had a detectable anti-typhoid IgA antibody response using their peripheral blood lymphocytes (p = 0.009). Significant rises in postvaccination anti-typhoid IgA antibody were observed in the jejunal fluid (p = 0.033), serum (p = 0.010) and saliva (p = 0.050) of these subjects. This study confirms that the normal rectal mucosa is an efficient route of entry to the systemic immune system for microbial agents, and therefore may provide a further possible route of immunization with attenuated bacterial vaccines.

A quantitative histological study was performed on small intestinal biopsies from eight ambulatory patients with HIV infection (AIDS/AIDS-related complex, ARC) and compared with those from 16 normal subjects. Enteropathy was assessed by measurement of villus area, crypt length and mitotic count, as well as duodenal counts of intraepithelial lymphocytes, mucosal mast cells and goblet cells. Enteropathy in subjects with AIDS/ARC was shown by reduced mean villus area of 0.363 (SD 0.081) compared with 0.500 (SD 0.064) mm2 in control subjects (p less than 0.0001), while intestinal crypts were of similar length with 239 (SD 36) compared with 225 (SD 28 microns, but mitotic count was increased to 3.8 (SD 1.2) compared with 2.4 (SD 0.8) (p = 0.01) in the same control subjects. These results indicate villous atrophy with impaired crypt hyperplasia. Duodenal cell counts showed similar numbers of mucosal mast cells, intraepithelial lymphocytes and goblet cells in AIDS/ARC patients and fifteen control subjects.

The relationship between the IgA antibody response in serum (total and polymeric IgA) and intestinal secretions was examined in volunteers subjected to oral and parenteral typhoid vaccination. After oral vaccination (three doses of 10(11) live Ty21a vaccine given at 48-hr intervals), serum pIgA antibody to typhoid lipopolysaccharide (LPS) was detected in seven of the 14 subjects (46.4 +/- 59 U/100 microliters, mean +/- SD). However, all 14 showed a significant intestinal IgA response (993 +/- 2516 and 9349 +/- 6754 U/mg pre- and post-vaccine; t = 5.25, P = 0.0002). The level of pIgA antibody declined rapidly, whereas intestinal IgA antibody levels remained elevated. Serum pIgA antibody was also found after parenteral immunization (two doses of 5 X 10(8) heat-killed bacteria given 14 days apart to six subjects), but an intestinal IgA antibody response was detected in these individuals only after a subsequent course of the oral vaccine given 1 month after initial parenteral immunization. Changes in serum pIgA antibody followed those of total serum IgA antibody rather than those of intestinal antibody. The results indicate that a serum pIgA response can be induced by an antigenic stimulus delivered either orally or parenterally, whereas an intestinal IgA response is induced only by a local antigen stimulus. The regulation of serum pIgA and intestinal IgA appear to be independent.

Rheobatrachus silus is a rare aquatic frog of eastern Australia. The female ingests the eggs after fertilization and broods them in the stomach until fully formed. "Gastric brooding" takes place in the fundus and proximal part of the body of the stomach, which dilates to accommodate the growing young. The surface epithelium becomes attenuated and the cells contain fewer mucus droplets. The acini of the glands are less numerous because of stretching, and they contain oxyntic cells that show evidence of profound suppression or regression. Morphometric studies on the limited number of samples show that the oxyntic cells are attenuated with few surface projections, sparse tubulovesicular reticulum, and a few pepsinogen granules and mitochondria. Eight days after ejection of the young, and 4 days after feeding commences, the lining shows a return of gastric pits and glands. The oxyntic cells show many surface projections and a proliferation of the tubulovesicular reticulum and mitochondria. These findings suggest that the eggs, tadpoles, and juvenile frogs release a substance, or substances, that inhibit acid secretion immediately after the eggs are ingested and that persist throughout brooding.

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.

Gastric emptying of a digestible solid and liquid meal and oesophageal emptying of a solid bolus were measured with scintigraphic techniques in 20 randomly selected Type 2 (non-insulin-dependent) diabetic patients receiving oral hypoglycaemic therapy and 20 control subjects. In the diabetic patients, the relationships between oesophageal emptying, gastric emptying, gastrointestinal symptoms, autonomic nerve function and glycaemic control were examined. The percentage of the solid meal remaining in the stomach at 100 min (p less than 0.001), the 50% gastric emptying time for the liquid meal (p less than 0.05) and oesophageal emptying (p less than 0.05) were slower in the diabetic patients compared to the control subjects. Scores for upper gastrointestinal symptoms and autonomic nerve dysfunction did not correlate significantly (p greater than 0.05) with oesophageal, or gastric emptying. The 50% gastric emptying time for the liquid meal was positively related (r = 0.58, p less than 0.01) to the plasma glucose concentration at the time of the performance of the gastric emptying test and the lag period, before any solid food emptied from the stomach, was longer (p less than 0.05) in subjects with plasma glucose concentrations during the gastric emptying measurement greater than the median, compared to those with glucose concentrations below the median. These results indicate that delayed gastric and oesophageal emptying occur frequently in Type 2 diabetes mellitus and that delayed gastric emptying relates, at least in part, to plasma glucose concentrations.

A sequential scintiscanning method was used to study gastric emptying in a total of 46 patients given a meal of cornflakes, sugar and milk containing radioactive markers of the solid and liquid components. In control and duodenal ulcer patients, liquid emptying was faster than solid emptying and could be represented as a monoexponential process, but solid emptying followed a different pattern, better represented as linear emptying with time. However, in patients who had undergone Billroth II gastrectomy there was no evidence of differential emptying of the two markers. In addition, rapid emptying of both markers occurred in the gastrectomy patients during the first 10 min after meal ingestion but did not occur in control or duodenal ulcer patients. The observations illustrate the limitations of using liquid meals to identify the effects of gastric surgery on emptying. Measurements of early emptying and of solid-liquid differentiation are necessary for full definition of gastric emptying after ingestion of a mixed solid and liquid meal.

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.

Forty-eight patients with chronic duodenal ulcers which were healed with cimetidine were allocated at random into two equal groups to assess different ways of using cimetidine during one year of treatment. Twenty-four patients received intermittent six-week courses of cimetidine for each relapse, and 24 patients were treated with maintenance administration of cimetidine (400 mg twice a day) continuously. Only one patient in the group receiving continuous therapy suffered clinical recurrence, but asymptomatic ulceration was found in four others. The group of patients who were receiving intermittent therapy suffered a total of 36 clinical recurrences. Three of these patients required prolonged treatment to heal their ulcers, and seven developed asymptomatic ulcer. The number of relapses varied from none to five. No way of predicting the individual prognosis was found. Intermittent treatment was an acceptable alternative in approximately half of the patients treated in this way, and was a failure in one-quarter of the group.

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.

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.

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.

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.

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.

The relationship between maturation of the small intestine and change in mucosal immune activity was examined in the DA rat during the weaning period from 12 to 30 days. Two stages of jejunal maturation were observed: an initial stage of morphological development and crypt proliferation (days 12 to 22), followed by a period of stabilisation (days 24 to 30). By day 22 of the initial phase, villi increased principally in width but not in length, crypt length increased, and crypt cell production rate increased from 0.5 (day 12) to 11.1 (day 22) cells/crypt/hour. Various measures of mucosal immune activity showed a biphasic response. Up to days 20 to 22, the weight of the mesenteric lymph node increased seven-fold (p less than 0.0001), counts of jejunal eosinophils and goblet cells increased 3- (p less than 0.0001) and 19-fold (p less than 0.0001) respectively, and mean serum rat mucosal mast cell protease II, released from mucosal mast cells, increased from 24 (day 12) to 313 (day 22) ng/ml (p less than 0.0001). After day 22, mesenteric lymph node weight stabilised, eosinophil count stabilised and goblet cells decreased, serum rat mucosal mast cell protease II decreased three-fold (p less than 0.0001), and mean jejunal count of intraepithelial lymphocytes increased from 26 (day 22) to 54 (day 24) cells per mm of muscularis mucosae (p less than 0.0001), before stabilising. These results demonstrated a close association between maturation of the small intestine and change in activity of the mucosal immune system.

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.

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.

To assess the influence of ethnic origin on the incidence of HLA antigens in duodenal ulcer, we typed 160 white Australian patients (including 22 born in Greece or Italy) and 320 blood donor controls for the HLA-A and -B loci. 5 of the 22 (22.7%) southern European patients, but only 19 of the 138 (13.8%) of the remaining duodenal ulcer patients were found to have antigen B5 compared with 27 (8.4%) of the controls. HLA-B12 was found in 55 (34.4%) duodenal ulcer patients (including 6 of the 22 southern European patients) and 117 (36.6%) controls. No significant association of duodenal ulcer with HLA-B5 or HLA-B12 was found when differences in racial origin of patients were taken into account.

Thirty-nine persons with selective IgA deficiency were studied. These comprised 27 subjects found by population screening and 12 by other means. Low molecular weight (LMW) serum IgM was sought in 28 of the 39 persons. Nine of the 28 (32%) had LMW IgM detectable by a sensitive gel filtration technique. Of 17 patients discovered by screening, five (29%) had LMW IgM. In the nine positive persons, LMW IgM constituted up to 17% of the total serum IgM concentration. Eight of the nine IgA deficient persons with LMW IgM, had clinical disease while associated disease in the entire IgA deficient population was less frequent. Serum immune complexes were demonstrated in five of seven subjects with LMW IgM using a C1q-dependent radioimmunoassay; four of these had immune complex associated disorders, three with polyarthritis and one with glomerulonephritis. Because circulating immune complexes are frequently detected in IgA deficient persons without disease, it is proposed that the presence of LMW serum IgM in IgA deficiency may be associated with disease due to the formation of specific pathogenic immune complexes.

The antibody response in serum and intestinal fluid in eight patients 1 year after their recovery from salmonella gastroenteritis was measured by solid phase radioimmunoassay and compared to the immune response within a few weeks of infection, reported previously in these and other patients. High concentrations of intestinal antibody were found in six patients compared to the concentrations found in 10 control subjects. By contrast the serum antibody concentration in the patients was only marginally higher than in the controls. The use of IgA and IgG specific antisera in the assay confirmed the presence of IgA antibody in the absence of IgG antibody in the gastrointestinal secretions, and the predominance of IgG antibody in the serum. The prolonged immune response in the gut after acute bacterial gastroenteritis supports the possibility of effective immunization against diseases entering via the gut.

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.

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.

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.

Cimetidine infusion (100 mg h-1) reduced the acid secretory response to insulin infusion (0.03 units Kg-1h-1) when compared to paired control tests in 6 healthy volunteers. There was no significant difference between cimetidine and control tests in terms of pepsin output or serum gastrin concentrations. Cimetidine also reduced the acid secretory response when administered after 90 minutes of insulin had established a secretory response in extended tests in 3 additional volunteers. Cimetidine may have therapeutic potential in the peptic ulcer diathesis.