1 Blood cimetidine levels were measured up to 5 h after oral intake of 200 mg cimetidine with breakfast in 13 duodenal, 5 gastric and 15 anastomotic ulcer patients. 2 There were larger inter individual differences in results. The mean peak blood concentrations was 1.14 +/‐ 0.07 microgram/ml (range 0.54‐1.94 microgram/ml), the mean period during which the blood concentration exceeded 0.5 microgram/ml was 141 +/‐ 11 min (range 23‐306 min) and the mean area under the cimetidine blood concentration curve (AUC) was 166 +/‐ 8 microgram ml‐1 min (range 96‐280 microgram ml‐1 min). Coefficient of variation of these parameters was 33%, 43% and 29% respectively. 3 There were no significant differences in these parameters between non‐operated patients and patients with a partial gastrectomy. 4 In 11 patients restudied after 2 to 5 months blood cimetidine levels proved well reproducible; mean coefficient of variation of peak blood levels was 8.5 +/‐ 2.4%, of time during which blood levels exceeded 0.5 microgram/ml 7.6 +/‐ 2.5% and of the AUC 5.0 +/‐ 1.0%. 5 There was no difference in peak blood levels, duration of blood level exceeding 0.5 microgram/ml and blood cimetidine AUC between 24 patients healed after 4 weeks cimetidine therapy and 9 in whom healing took longer. Likewise, there was no evidence of lower blood cimetidine concentrations in 9 patients who relapsed during maintenance cimetidine treatment compared with 24 who did not relapse.

The short-term effects of truncal vagotomy and antrectomy on bombesin-stimulated pancreatic secretion and release of gastrin and pancreatic polypeptide (PP) were studied in 18 anesthetized dogs. Together with an intravenous infusion of secretin (250 ng/kg/hr) bombesin (500 ng/kg/hr) was given before and after truncal vagotomy, antrectomy, and sham operation (N = 6 dogs per group). Peak incremental pancreatic protein output in response to bombesin was about 2-3 times higher before than after the different surgical procedures (tachyphylaxis). Neither truncal vagotomy nor antrectomy significantly altered the pancreatic protein response to bombesin when compared with sham operation. Bombesin produced a mean 1-hr increase over basal of 196 pM for gastrin, which was abolished by antrectomy but not appreciably affected by truncal vagotomy and sham operation. The mean 1-hr increment (207 pM) for PP in response to bombesin was not changed by truncal vagotomy, antrectomy, and sham operation. This study shows in the anesthetized dog that exogenous bombesin stimulates release of PP as well as gastrin; that the release of gastrin by bombesin is not vagally dependent; that neither truncal vagotomy nor antrectomy alter the release of PP by bombesin; and that the action of bombesin on pancreatic protein secretion does not depend on release of gastrin or on intact vagal nerves.

Secretion of pancreatic polypeptide (PP) is regulated mainly by cholinergic mechanisms and we have studied this in patients with chronic renal failure (CRF). Basal serum PP concentrations in 25 patients with CRF (401 +/- 80; 116-2100 pmol/l; mean +/- SEM and range) were significantly higher than in 65 normal subjects (33 +/- 2; 21-120 pmol/l, P less than 0.001). Ingestion of a standard test meal induced significantly larger increases in serum PP in 11 patients with CRF (304 +/- 45; 155-640 pmol/l) than in 11 normal subjects (140 +/- 33; 51-440 pmol/l, P less than 0.005). Insulin-hypoglycaemia (0.1 U/kg i.v.) provoked similar increases in serum PP in five patients with CRF (404 +/- 79; 170-665 pmol/l) as in five normal subjects (449 +/- 92; 180-706 pmol/l). Administration of atropine (1 mg i.v.) did not normalize the elevated basal serum PP concentrations in five patients with CRF. On the other hand, administration of the same dose of atropine 60 min after ingestion of food decreased postprandial serum PP levels to basal values within one hour both in five patients with CRF and in six normal subjects. Sephadex G-50 column chromatography of basal, postprandial and post-atropine sera from three patients with CRF revealed at least three different molecular forms. The PP peak coeluting with the 4200 molecular weight human PP standard comprised more than half of total PP immunoreactivity and was the only peak to be influenced by feeding or atropine. We conclude that in patients with CRF, PP secretion stimulated by cholinergic mechanisms is normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Mean fasting levels of pancreatic polypeptide (PP) in 24 patients with Zollinger-Ellison syndrome (ZES) and in 12 patients with hyperparathyroidism originating from families with multiple endocrine adenomatosis type I (MEAI-HPT) were significantly higher than in 72 normal controls. The overlap between the 3 groups, however, was large. In patients with ZES, increased PP levels were not related to the presence of MEAI or metastases; nor was there a correlation between serum PP and gastrin concentrations. The post-prandial PP release in 10 ZES patients and in 10 patients with MEAI-HPT was lower than in 9 normal controls. The physiological significance of the present findings is unclear.