A cholecystokinin (CCK) receptor antagonist, loxiglumide, was used to investigate the potential regulating role of CCK in the entero-insular axis in humans. Ingestion of a mixed liquid meal stimulated plasma CCK, insulin, and pancreatic polypeptide (PP) release in the control experiment. With iv loxiglumide (22 mumol/kg.h), mean plasma insulin and glucose levels did not differ between placebo and loxiglumide treatment. The area under the plasma concentration for PP was reduced to 6,060 +/- 1,706 (P less than 0.05) compared to that during placebo treatment (12,266 +/- 4,748). Administration of loxiglumide failed to change insulin secretion in response to perfusion of the same meal or perfusion of a 10-amino acid solution into the duodenum. However, PP secretion in response to the intraduodenal meal or amino acid mixture was abolished after loxiglumide (P less than 0.05). Intravenous administration of the 10-amino acid mixture stimulated insulin from a mean basal level of 7 +/- 3 microU/mL to a peak level of 16 +/- 4 microU/mL. Infusion of a CCK octapeptide (CCK-8) at 8.6 pmol/kg.h, which produced a plasma concentration of 3.3 pmol/L, which is within the postprandial range, augmented amino acid-stimulated insulin and PP output (P less than 0.05). When CCK-8 was infused with loxiglumide, the insulin and PP responses were similar to the values found with loxiglumide alone. We conclude that CCK receptor blockade with iv loxiglumide does not affect postprandial insulin secretion. CCK is, therefore, not a major incretin. However, it is involved in the postprandial PP response, especially during the intestinal phase stimulation. These data suggest that CCK has a role in the human enteroinsular axis.

An attack of gallstone ileus observed in a 60-year-old female patient is reported. In this patient who previously had been cholecystectomized, instant extraction of giant residual gallstones was unsuccessful despite a large endoscopic sphincterotomy. Three days later, she developed colicky abdominal pain and vomiting. At laparotomy nine days after the endoscopic procedure an impacted gallstone measuring 3.5 cm in diameter was removed from the the jejunum, some 50 cm below the ligament of Treitz. This observation demonstrates an unusual complication of endoscopic sphincterotomy and clearly outlines that very large stones can, after an initial delay, pass into the duodenum despite an apparently "unsuccessful" sphincterotomy.

The gastric secretory response to impromidine (SKF 92676), a potent selective histamine H₂ agonist, has been studied in 40 patients with peptic ulcer disease or ulcer-like dyspepsia. Peak acid output following the intravenous infusion of impromidine, 10 μg kg^-1·h^-1, or pentagastrin, 6 μg kg^-1h^-1, was not significantly different. This was also the case when the two drugs were administered subcutaneously at the same dose. Impromidine was well tolerated with only minor effects on the cardiovascular system both in 10 younger patients and in 20 subjects over the age of 55 years with mild to moderate cardiovascular disease. Impromidine can be considered an important tool for further investigation of the role of histamine at the H₂-receptor site in man.

In view of the conflicting results on whether pentagastrin sensitivity is genuinely increased in duodenal ulcer (DU) patients, the pentagastrin-gastric acid relationship was restudied in 17 normal subjects and 15 DU patients. In a reproducibility study performed on nine healthy subjects the mean pentagastrin responses obtained on 2 different study days, using a step technique (range, 0.025-6.4 micrograms kg-1h-1), were congruent at each of the five measuring points. Analysis of variance revealed no significant overall differences. However, ED50 values showed a large within- and between-subject variation and failed to correlate significantly, this because a plateau response was not regularly obtained with the top dose. Consequently, ED50 values in normal subjects and DU patients showed a large scatter and were not significantly different, although the potency ratio calculated from the linear parts of the respective dose-response curves was significantly different (2.6; 95% confidence limits, 1.8-3.9). This study thus supplies further evidence that the parietal cell of DU patients has a higher sensitivity to pentagastrin and demonstrates that the reliability of individual ED50 estimations obtained in pentagastrin dose-response studied should not be overrated.

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