J. Hansky

RADIOIMMUNOASSAY OF GASTRIN IN HUMAN SERUM

Abstract Antibodies to human gastrin I have been produced in rabbits and formed the basis of a simple, precise, and specific immunoassay procedure for measuring gastrin concentration in human serum. Amounts as low as 5 pg. per ml. were detected, and fasting gastrin levels in subjects free of gastrointestinal disease ranged from 5 to 290 pg. per ml. with a mean of 113 pg. Patients with duodenal ulcer had a mean gastrin level of 53 pg. per ml., whereas gastric-ulcer patients had a value of 165 pg. per ml. High levels of up to 5000 pg. per ml. were found in patients with Zollinger-Ellison syndrome and pernicious anaemia. In several physiological studies on normal subjects, food and insulin hypoglycaemia were shown to stimulate gastrin secretion, and secretin produced a fall in serum-gastrin levels.

Campylobacter pylori – A Role in Non-Ulcer Dyspepsia?

Non-ulcer dyspepsia (NUD) is a common complaint in which no systematic illness or organic proximal alimentary tract disease can be identified. The pathophysiology of NUD is probably heterogeneous. Eighty-two subjects with NUD were studied in a prospective randomized placebo-controlled study to assess the efficacy of colloidal bismuth subcitrate (CBS) chewable tablets at a dose of four tablets daily for 1 month. The role of Campylobacter pylori and associated histological gastritis was evaluated. Sixty-one percent of NUD patients had C. pylori in the gastric antrum compared with 25% of age-matched controls. C. pylori was associated with acute and chronic inflammation (P less than 0.001) in the antrum. C. pylori was cleared in 59% of CBS-treated subjects compared with only 4% placebo (P less than 0.05). Both acute and chronic inflammation improved in subjects cleared of bacteria. Clearance of C. pylori and histological improvement was associated with a significant decrease in symptoms. In C. pylori negative subjects improvement in symptoms occurred in both the placebo and active treatment groups. This study would suggest that C. pylori and associated histological gastritis may play a role in non-ulcer dyspepsia.

An 8-year prospective experience with balloon tamponade in emergency control of bleeding esophageal varices.

The use of balloon tamponade in the emergency control of bleeding from esophageal varices is controversial. This paper reports a prospective study over an 8-year period in which balloon tamponade has been the sole means employed for the early control of bleeding varices. During 1972–1980 all patients referred to Prince Henrys Hospital with upper gastrointestinal bleeding were admitted to a special unit. Ninety-one had bleeding esophageal varices, and 17 were admitted on one or more occasions for bleeding for a total of 132 admissions. After early endoscopy, balloon tamponade was used during 103 of these admissions with failure to control bleeding on six occasions; five of these patients died from hemorrhage and the sixth recovered after emergency portacaval shunt. Another patient died from rebleeding not treated by tamponade. Reinsertion of the balloon for rebleeding was necessary on 28 occasions with successful control in all cases. Balloon tamponade was not used during 29 admissions because bleeding had ceased or the patient was considered to have terminal liver disease. In this group there were four deaths from severe liver disease and hemorrhage. Balloon tamponade was used in 78% of admissions and controlled bleeding in more than 90% of patients. This suggests that tamponade may be the method of choice for early control of bleeding from esophageal varices.The use of balloon tamponade in the emergency control of bleeding from esophageal varices is controversial. This paper reports a prospective study over an 8-year period in which balloon tamponade has been the sole means employed for the early control of bleeding varices. During 1972–1980 all patients referred to Prince Henrys Hospital with upper gastrointestinal bleeding were admitted to a special unit. Ninety-one had bleeding esophageal varices, and 17 were admitted on one or more occasions for bleeding for a total of 132 admissions. After early endoscopy, balloon tamponade was used during 103 of these admissions with failure to control bleeding on six occasions; five of these patients died from hemorrhage and the sixth recovered after emergency portacaval shunt. Another patient died from rebleeding not treated by tamponade. Reinsertion of the balloon for rebleeding was necessary on 28 occasions with successful control in all cases. Balloon tamponade was not used during 29 admissions because bleeding had ceased or the patient was considered to have terminal liver disease. In this group there were four deaths from severe liver disease and hemorrhage. Balloon tamponade was used in 78% of admissions and controlled bleeding in more than 90% of patients. This suggests that tamponade may be the method of choice for early control of bleeding from esophageal varices.

Ventricular, paraventricular and circumventricular structures involved in peptide-induced satiety

Cholecystokinin, bombesin or gastrin (2 microliter of 50 ng/microliter) was injected stereotaxically into the paraventricular nucleus of the hypothalamus, the arcuate/ventromedial area, the subfornical organ, the area postrema and the cerebral aqueduct of Sprague-Dawley rats and the effects of these injections on food and water intake were studied. While the injection of cholecystokinin reduced food intake when it was injected into both hypothalamic loci, food and water intake were most severely affected by the injection of this peptide into the cerebral aqueduct. Bombesin reduced food intake after its injection into all areas except the subfornical organ and reliable reductions in water intake were seen after injection of this peptide into all areas except the paraventricular nucleus. Minor reductions in food intake were seen following gastrin injection into the paraventricular nucleus while increased water consumption was observed after this peptide was injected into the paraventricular nucleus and cerebral aqueduct. In a second study 6-hydroxydopamine injections (2 microliter of 8 micrograms/microliter were made into the five areas studied 10 days before animals were injected with 100 micrograms/kg of cholecystokinin (i.p.). All 6-hydroxydopamine-injected animals reduced their food and water intake in response to the cholecystokinin challenge as did intact controls. These results indicate that while the changes in food and water intake produced by the central injection of cholecystokinin, bombesin or gastrin may involve central catecholamine systems, those occurring after its systemic administration do not. Therefore, if the release of gastrointestinal peptides during natural feeding is part of a homeostatic mechanism regulating hunger and satiety, this mechanism may operate without directly involving central catecholamine systems.

Relapse rate of duodenal ulcer after cessation of long-term cimetidine treatment

Patients with a healed duodenal ulcer and who were symptom-free following 12 months of maintenance treatment with cimetidine 400 mg twice daily were randomized double-blind to a further 6 months therapy with either cimetidine 400 mg twice daily or placebo 2 tablets twice daily. Twenty-six patients received placebo and 15 patients cimetidine. Relapse was defined as symptoms for 3 out of 7 consecutive days and ulcer recurrence was confirmed by independent endoscopy. One of 15 patients on cimetidine relapsed: 20 of 26 patients on placebo relapsed. This relapse rate (77%) is similar to that found in previous studies after only 6 weeks cimetidine therapy (71%). This study suggests that 12 months cimetidine does not change the tendency of duodenal ulcer to recur and that the relapse rate is no greater than after 6 weeks cimetidine.

Long-term cimetidine in duodenal ulcer disease.

Forty patients with chronic duodenal ulcer who had healed endoscopically with a 6-week course of cimetidine were randomized double blind to 1 year of either placebo or cimetidine tablets 400 mg bid (20 patients in each group). Patients were seen at monthly intervals, and endoscopy was performed at clinical relapse or on completion of 1 year. One of 20 patients on active cimetidine relapsed clinically and endoscopically at 3 months; 16 of 20 patients on placebo relapsed clinically and endoscopically within 9 months, the majority within 3 months, and 2 were shown to have asymptomatic chronic ulcers at routine 12-month endoscopy. None of the 19 patients on active cimetidine routinely endoscoped at 12 months showed evidence of ulceration. This study confirms a high relapse rate when short-term cimetidine is ceased and indicates that maintenance treatment with cimetidine prevents relapse.Forty patients with chronic duodenal ulcer who had healed endoscopically with a 6-week course of cimetidine were randomized double blind to 1 year of either placebo or cimetidine tablets 400 mg bid (20 patients in each group). Patients were seen at monthly intervals, and endoscopy was performed at clinical relapse or on completion of 1 year. One of 20 patients on active cimetidine relapsed clinically and endoscopically at 3 months; 16 of 20 patients on placebo relapsed clinically and endoscopically within 9 months, the majority within 3 months, and 2 were shown to have asymptomatic chronic ulcers at routine 12-month endoscopy. None of the 19 patients on active cimetidine routinely endoscoped at 12 months showed evidence of ulceration. This study confirms a high relapse rate when short-term cimetidine is ceased and indicates that maintenance treatment with cimetidine prevents relapse.

Pancreatic polypeptide. Release following surgery for duodenal ulcer disease.

The pancreatic polypeptide (PP) response to food has been measured by radioimmunoassay in patients with duodenal ulcer and 3 months following proximal gastric vagotomy (PGV), 18 and 49 months following truncal vagotomy and pyloroplasty (TV), 35 months following Billroth II gastrectomy (BII), and 35 months following truncal vagotomy and antrectomy (TV&A). Basal PP levels and those in response to food were similar in DU and PGV, but these values were significantly higher than those 18 months or 49 months after TV, or after BII and TV&A. The responses in the latter four groups were similar and in particular, the levels 18 and 49 months after TV were the same. These results indicate that the release of PP by food in unoperated patients consists of two phases, a primary phase which requires both intact vagi and an intact stomach and a secondary phase which also depends on vagal innervation and normal gastric anatomy. Disturbances in vagal innervation or gastric integrity lead to profound changes in PP release which may be due to interruption of neural arcs or loss of gastric hormones. Unlike others, we have been unable to document a return of PP secretion towards normality with time after TV.The pancreatic polypeptide (PP) response to food has been measured by radioimmunoassay in patients with duodenal ulcer and 3 months following proximal gastric vagotomy (PGV), 18 and 49 months following truncal vagotomy and pyloroplasty (TV), 35 months following Billroth II gastrectomy (BII), and 35 months following truncal vagotomy and antrectomy (TV&A). Basal PP levels and those in response to food were similar in DU and PGV, but these values were significantly higher than those 18 months or 49 months after TV, or after BII and TV&A. The responses in the latter four groups were similar and in particular, the levels 18 and 49 months after TV were the same. These results indicate that the release of PP by food in unoperated patients consists of two phases, a primary phase which requires both intact vagi and an intact stomach and a secondary phase which also depends on vagal innervation and normal gastric anatomy. Disturbances in vagal innervation or gastric integrity lead to profound changes in PP release which may be due to interruption of neural arcs or loss of gastric hormones. Unlike others, we have been unable to document a return of PP secretion towards normality with time after TV.

Paradoxical Effect of Secretin on Serum Immunoreactive Gastrin in the Zollinger-Ellison Syndrome

Serum gastrin has been measured by radioimmunoassay following intravenous secretin in 86 control subjects, 9 patients with pernicious anaemia and 9 patients with Zollinger-Ellison syndrome. In 55 cont

The role of some central catecholamine systems in cholecystokinin-induced satiety

Cholecystokinin (CCK), bombesin and gastrin were stereotaxically injected into catecholamine (CA) innervated areas of the lateral hypothalamus (LH), the nucleus caudatus putamen (NP) and the olfactory tubercle (OT) in male Sprague Dawley rats. Bilateral injections of 100 ng of CCK in 2 microliters of vehicle into the LH produced a slight but significant decrease in food intake during the first hour of a 4 hour eating test. The other peptides when injected into any of the brain areas did not significantly alter food intake. Water intake was affected by the injection of all three hormones although differentially in all 3 sites. The observed changes in drinking were not related to the prandial characteristics of drinking typically seen in rodents. Denervation of the CA innervation of the OT, LH or NP with 6-hydroxydopamine did not change the satiety response to peripherally administered CCK displayed by intact animals. These results suggest that the satiety which occurs after the central and peripheral administration of CCK may be mediated by different mechanisms and that central CA systems may not be necessary for CCK-induced satiety to occur during natural feeding.

Ranitidine in duodenal ulcer

The effect of ranitidine, a new H2-receptor antagonist, on the healing of duodenal ulcer has been assessed in a double-blind study. Fifty patients with endoscopically proven duodenal ulcer were randomly assigned to ranitidine 150 mg twice daily or placebo for 4 weeks. Endoscopic examination at this time showed that 20 of 25 patients (80%) on ranitidine healed compared to 4 of 25 patients (16%) on placebo (P<0.01). Smoking adversely affected the incidence of healing: 70% of nonsmokers healed compared to 30% of smokers (P<0.03). There were no side effects noted on ranitidine. Review at 6 months after cessation of therapy showed relapse of duodenal ulcer in 10 of 20 patients (50%) healed with ranitidine and 1 of 4 patients (20%) healed with placebo. Thus, ranitidine (300 mg/day) produces similar healing rates to those reported for cimetidine (1000 mg/day); also like cimetidine, the incidence of healing on ranitidine is adversely influenced by smoking and the relapse rate on cessation of therapy is high.The effect of ranitidine, a new H2-receptor antagonist, on the healing of duodenal ulcer has been assessed in a double-blind study. Fifty patients with endoscopically proven duodenal ulcer were randomly assigned to ranitidine 150 mg twice daily or placebo for 4 weeks. Endoscopic examination at this time showed that 20 of 25 patients (80%) on ranitidine healed compared to 4 of 25 patients (16%) on placebo (P<0.01). Smoking adversely affected the incidence of healing: 70% of nonsmokers healed compared to 30% of smokers (P<0.03). There were no side effects noted on ranitidine. Review at 6 months after cessation of therapy showed relapse of duodenal ulcer in 10 of 20 patients (50%) healed with ranitidine and 1 of 4 patients (20%) healed with placebo. Thus, ranitidine (300 mg/day) produces similar healing rates to those reported for cimetidine (1000 mg/day); also like cimetidine, the incidence of healing on ranitidine is adversely influenced by smoking and the relapse rate on cessation of therapy is high.