Cholecystokinin and gallbladder contraction: effect of CCK infusion.

Cholecystokinin octapeptide (CCK-8) was infused intravenously in five normal subjects. Plasma levels of CCK-8 and infusion concentrations were measured by a specific radioimmunoassay and gallbladder volumes wee monitored using ultrasound. Calculated CCK-8 infusion rates were 16.4, 32.8, and 65.6 pmol.kg(-1) hr(-1). During infusion of the lowest dose plasma concentrations rose from 8 +/- S.E. 5 to 18 +/- 4 pmol.1(-1) equivalent to normal postprandial concentrations of CCK and were accompanied by a 76 +/- 7% reduction in gallbladder volume. Infusion at the two higher rates resulted in 87 +/- 3% and 88 +/- 3% reduction of initial gallbladder volumes returned to 73 +/- 26% of initial volumes within 30 minutes. These studies are consistent with the hypothesis that CCK is the main postprandial stimulus for gall-bladder contraction.

Radioimmunoassay of cholecystokinin in human plasma.

A sensitive radioimmunoassay for cholecystokinin (CCK) has been developed. Porcine CCK-33 was labelled by conjugation with 125I-hydroxyphenyl-propionic acid succinimide ester. Antibodies were raised against porcine CCK-33 covalently coupled to egg albumin. Plasma samples were extracted with 96% ethanol prior to assay. Free and bound hormone were separated by dextran-coated charcoal. The antibodies bound CCK-8 and CCK-33 with equimolar potency. The assay detection limit was 1 pmol/l plasma. Within and between assay coefficients of variation were +/- 12.7 and 13.0% at mean plasma CCK concentrations of 13.2 and 13.6 pmol/l. The concentration of CCK in 47 normal fasting subjects ranged from undetectable to 22 pmol/l. Ingestion of a mixed meal in 9 normal subjects increased the plasma concentration from 8.3 +/- 2.5 S.E. to 24.4 +/- 6.5 pmol/l.

Radioimmunoassay of secretin in plasma.

A sensitive, specific and reproducible radioimmunoassay for secretin is described. Antibodies were readily produced against low microgram quantities of synthetic secretin. The secretin antibodies did not cross-react with the structurally similar G.I.P., V.I.P., or glucagon. Synthetic secretin was iodinated using Chloramine "T" and purified by a two-state procedure incorporating gel filtration and radient elution from a cation exchange column. Plasma samples were found to produce variable interference in the assay necessitating the incorporation of secretin-free "blands" for each patient's plasma. Production of secretin-free plasma was by incubation of plasma samples at 37 degrees C for 96 hours. The sensitivity of the assay was 12.5-25 pg/ml. Normal fasting secretin levels were 21 +/- S.E. 7 pg/ml. A mean rise in plasma secretin to 220 pg/ml was observed after intraduodenal acidification.

The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients.

1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid "normosecretors" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.

Postoperative recurrent peptic ulcer: the significance of the Zollinger-Ellison syndrome.

Twenty-four patients with postoperative recurrent peptic ulcer, presenting to a teaching hospital over a six-year period, are reviewed. The diagnosis was confirmed by endoscopy or surgery in all cases. Four patients (16-7%) were shown to have the Zollinger-Ellison syndrome and were treated successfully by total gastrectomy. This is a significantly higher incidence of Zollinger-Ellison syndrome than in previous reports. Six patients were treated medically, with one death. In the remainder, an inadequate initial operation was considered to be the cause of recurrence. Reoperation, usually involving complete vagotomy and antrectomy, was performed. There was no mortality in this group, and no patients have had further recurrence. The importance of serum gastrin studies in all patients with recurrent peptic ulcer is emphasized.

Acute, severe hepatitis due to Coxiella burneti infection.

An unusual case of Coxiella burneti infection is described in which the patient presented with an "acute abdomen" and marked clinical icterus. This case emphasizes that Q-fever may appear as acute hepatitis and illustrates its "characteristic" histopathological lesions which have been recognized only recently.

Is reduced release of gastrin the mechanism of ulcer healing after gastroenterostomy?

Until recently in this unit gastroenterostomy was the operation of choice for patients with duodenal ulcer whose maximal acid output (MAO) is less than 30 mmol/hr. Ulceration (jejunal) has recurred in only 2.1%. Unlike partial gastrectomy, which has a peak incidence of ulcer recurrence in the first two years, the incidence of ulcer recurrence remains constant throughout the years after gastroenterostomy. In looking for the explanation of this low recurrence rate we have studied the effect of the operation upon serum gastrin responses to standardized test meals 3 weeks and 26 weeks after operation in 9 patients. Nine normal subjects acted as controls. Six months after operation the responses were significantly lowered, a fall in the serum levels of gastrin at 30, 45, 60 and 90 min after means suggesting that gastroenterostomy reduces both the gastric and intestinal phases of acid secretion. The mean integrated gastrin response (IGR) throughout the postprandial 90 min is also significantly lower 6 months after surgery. The overall mean reduction was 31.1%.

Motilin and migrating myoelectric complexes in the pig and the dog.

Associations between migrating myoelectric complexes (m.m.c.s) and peak plasma motilin concentrations were confirmed in the dog fasted 18 h and shown not to be present in pigs fasted 3-4 h. Infusions of both natural porcine and synthetic 13-Nle-motilin failed to induce m.m.c.s in the pig. It was confirmed that motilin infusions stimulated the premature appearance of m.m.c.s in the dog whether motilin remained within, or exceeded, its normal plasma values. Immunoneutralization by intravenous administration of rabbit antimotilin serum was without effect on naturally occurring m.m.c.s in the dog and the pig. In the dog, antimotilin serum blocked production of m.m.c.s by exogenous motilin for 7-10 d post-immunoneutralization. It is suggested that there are both: (i) species differences in associations of m.m.c.s and plasma motilin concentration, and (ii) an independence of m.m.c.s from plasma motilin even in the dog in which normally exogenous motilin can produce m.m.c.s.

Release of secretin--plasma levels reproduced by exogenous infusion.

Infusion of 0.1 M HCl (0.5 mmol/kg/hr over 20 minutes) into the duodenum of each of seven normal subjects led to a significant rise (P less than 0.05) in mean plasma secretion levels from 3.0 +/- 2.2 (SE) to 15 +/- 4.0 pmol/l. Intravenous infusion of secretin at a rate of 6.6 pmol/kg/hr (0.08 clinical units/kg/hr) reproduced the peak plasma levels of secretin observed during duodenal acidification. However, there was no detectable (2.5 pmol/l) change in plasma secretin after oral protein or glucose.

Resolution of amyloidosis (AA type) complicating chronic ulcerative colitis.

A 36-yr-old woman was admitted for the investigation of diarrhea, fever, weight loss, and a recurrent painful, red eruption on her forearms. She was found to have total colonic involvement with a nonspecific ulcerative colitis. Vascular and extravascular amyloid (AA type) was present in biopsy specimens of the colon, duodenum, and stomach. There was clinical and radiographic evidence of splenic and hepatic amyloidosis. Moreover, the presence of extravascular colonic amyloid, the absence of renal involvement, the relatively early detection of amyloid, and the resolution of amyloid after treatment make this case unique.

Successful removal of retained bile duct stones by endoscopic sphincterotomy.

Two cases are reported in which endoscopic sphincterotomy was successful in allowing passage of stones retained in the common bile duct after cholecystectomy, performed in one case three weeks and in the other 14 years before.

Serum gastrin in patients with peptic ulceration.

The fasting serum level of gastrin was determined by radioimmunoassay in 41 normal subjects, 27 patients with duodenal ulceration, 12 patients with gastric ulceration, and 8 patients following "complete" vagotomy. The patients with duodenal ulceration had significantly higher serum levels of gastrin (1.3 +/- S.D. 0.7 ng./ml.) than normal subjects (0.4 +/- S.D. 0.3 ng./ml.), patients with gastric ulceration (0.4 +/- S.D. 0.4 ng./ml.), or post-vagotomy patients (0.15 +/- S.D. 0.2 ng./ml.).The gastrin secretion in both normal subjects and patients with duodenal ulceration was responsive to protein ingestion, but a larger incremental secretion of gastrin occurred in the latter group. Hyperglycaemia significantly suppressed the serum level of gastrin in both groups. The patients with gastric ulceration had fasting and postprandial serum gastrin levels not significantly different from normal subjects.

Is pancreatic polypeptide estimation of value in diagnosing gastrinomas (Zollinger-Ellison syndrome)?

Serum levels of pancreatic polypeptide (PP) were determined in 32 normal subjects, 18 patients with gastrinoma, 19 patients with pituitary adenoma and 11 patients with duodenal ulceration. Mean serum levels of PP in patients with gastrinomas (67 +/- 31 pmol/l (SD)) were significantly (P less than 0.01) higher than in the normal subjects (47 +/- 15 pmol/l). However, only five of 18 of the patients with gastrinomas had PP levels above the upper limit of normal and elevations of similar magnitude were observed in patients with other disease processes. It is therefore concluded that serum PP estimations are not of value in the diagnosis of gastrinomas.

Cimetidine and acute upper gastrointestinal bleeding: a double-blind controlled trial.

Patients presenting with acute upper gastrointestinal bleeding from a variety of lesions were admitted to a prospective double-blind controlled trial to determine if cimetidine reduces the severity of bleeding and/or the incidence of rebleeding. During the first 48 hours, the patients received intravenous cimetidine (200 mg four-hourly) or placebo, and for the following ten days, oral cimetidine (1 g/24 hr) or placebo. Eight-eight patients entered the trial of whom 45 (51%) were in the cimetidine-treated group. Six of the seven patients requiring surgery for life-threatening bleeding and four of the six patients who rebled were in the cimetidine-treated group. This study failed to demonstrate any advantage of using cimetidine routinely in the treatment of acute upper gastrointestinal bleeding.