Larry C. Watson

Correlation between Release of Cholecystokinin and Contraction of the Gallbladder in Patients with Gallstones

The role of endogenously released cholecystokinin (CCK) in mediating gallblader (GB) contraction was evaluated in 12 normal volunteers and 24 patients with gallstones (11 additional gallstone patients were excluded because of failure of adequate ultrasonographic visualization). CCK concentrations before and after oral administration of fat (Lipomul®) were measured by a specific radioimmunoassay. CCK release was correlated with changes in GB volume determined simultaneously by ultrasonography. On the basis of gallbladder contraction and operative findings, gallstone patients were divided into “contractors” (14), “noncontractors” (6), and “hydrops” (4). Lipomul caused prompt release of CCK in normal volunteers and all groups of gallstone patients. The changes (basal to peak) in plasma CCK (pg/ml) for the different groups were as follows: normal volunteers (108 ± 9 to 200 ± 16), contractors (77 ± 10 to 128 ± 13), noncontractors (59 ± 7 to 159 ± 38), and hydrops (43 ± 5 to 113 ± 47). The total integrated output of CCK (0–60 min) was greater in normal volunteers (3975 ± 762 pg-min/ml) than in contractors (1530 ± 567 pg-min/ml). Lipomul caused similar GB contraction in normal volunteers and contractors (from basal volumes to maximal contraction); these changes were from 19.5 ± 2.3 ml to 5.6 ± 1.0 ml in normal volunteers, and from 19.6 ± 3.2 to 5.2 ± 1.0 in contractors. Plasma concentrations of CCK and GB volume were highly correlated in the 12 normal volunteers (r = −0.89, p < 0.01) and in the 14 contractors (r = −0.99, p < 0.01)), but the GB was significantly (p < 0.01) more sensitive to changes in plasma CCK in the gallstone contractors than in the normal volunteers. The authors suggest that there may be two groups of gallstone patients, noncontractors and contractors. Stasis may be important in the pathogenesis of gallstones in the noncontractors, whereas in contractors, the authors speculate that an abnormality in the CCK-gallbladder relationship (characterized by diminished CCK release and increased GB sensitivity to CCK) may be involved in the evolution of the disease.

Infusion of Pure Cholecystokinin in Humans: Correlation Between Plasma Concentrations of Cholecystokinin and Gallbladder Size

This study was undertaken to correlate changes in the plasma concentration of cholecystokinin with changes in gallbladder volume, during and after infusion of cholecystokinin in humans. Cholecystokinin-33, 99% pure, was administered intravenously for 1 h at the rate of 0.58 μg/kg · h to 5 fasting adult men. Plasma for radioimmunoassay of cholecystokinin was collected before and during the cholecystokinin infusion, and for 40 additional minutes. Gallbladder volumes were determined from sonograms obtained from a phased-array real-time ultrasound scanner. The mean basal concentration of cholecystokinin in plasma was 88.5±3.9 pglml. Mean peak cholecystokinin concentration of 366.2±32.0 pg/ml was achieved 8 min after the start of the infusion. The mean resting gallbladder volume was 23.0±2.9 cm3. Maximal gallbladder contraction was achieved at 10 min, at which time the mean gallbladder volume was 3.4±0.5 cm3. After the cessation of cholecystokinin infusion, plasma cholecystokinin returned to basal concentrations after 12 min and the gallbladder refilled within 40 min. The correlation coefficients between plasma cholecystokinin and gallbladder size, determined by linear regression analysis, were −0.7649 (p

Emergency diagnosis of upper gastrointestinal bleeding by fiberoptic endoscopy.

Emergency esophagogastroduodenoscopy has been performed in 192 consecutive patients admitted with massive gastrointestinal bleeding. Accurate endoscopic diagnosis was made in 184 or 96%; 58 patients underwent emergency operations to control bleeding with an overall operative mortality of 26%. Excluding 16 patients who underwent emergency portacaval shunting, the operative mortality was 7%. In 6 patients, the bleeding was controlled by endoscopic electrocoagulation. There were no complications. Emergency endoscopy should be done routinely as the primary diagnostic approach in the diagnosis of upper gastrointestinal bleeding.

The effects on gastrin and gastric secretion of five current operations for duodenal ulcer.

We have measured serum gastrin and gastric acid secretion in 66 duodenal ulcer patients before and after vagotomy and pyloroplasty (V + P—15 patients), selective proximal vagotomy without drainage (SPV – D—11 patients) and with drainage (SPV + D—19 patients), and vagotomy, antrectomy, and either gastroduodenostomy (V + BI—15 patients) or gastrojejunostomy (V + BII—6 patients). Basal and peak postprandial gastrin levels were increased in postoperative V + P, SPV – D, and SPV + D patients. Basal and peak postprandial levels of gastrin were unchanged after V + BII, indicative of duodenal release of gastrin. Gastrin response to food was abolished in V + BII patients. Acid output was reliably reduced after all five operations; reduction was greatest in patients after antrectomy and least in patients after SPV. No beneficial results were found with drainage in SPV patients. Acid secretion increased with time in SPV patients, especially those with drainage.

Correlation Between Gallbladder Size and Release of Cholecystokinin After Oral Magnesium Sulfate in Man

In order to determine the effect of oral magnesium sulfate on gallbladder contraction and release of cholecystokinin (CCK) in man, magnesium sulfate (25 g in 100 ml distilled water) was given by mouth to five fasting adult male volunteers. Plasma samples were collected for measurement of CCK by a specific radioimmunoassay. Gallbladder volumes were determined from sonograms obtained from a phased-array real-time ultrasound scanner. Basal concentrations of CCK (82.2 +/- 10.1 pg/ml) increased significantly at 20 minutes after oral magnesium sulfate (113.8 +/- 7.1 pg/ml), and reached a maximal value at 50 minutes (150.0 +/- 42.0 pg/ml). The mean basal volume of the gallbladder was 30.8 +/- 5.3 cm(3) and maximum reduction of gallbladder volume (to one third of original) was achieved at 50 minutes after ingestion of magnesium sulfate. Linear regression analysis showed a close correlation (r = -0.9337) between plasma concentrations of CCK and gallbladder size in response to magnesium sulfate. Oral magnesium sulfate also caused a significant increase in serum gastrin (from basal of 51.4 +/- 9.9 pg/ml to 69.8 +/- 15.5 pg/ml at 5 min); there was no significant correlation between gastrin release and gallbladder contraction. This study provides direct evidence that the mechanism of magnesium sulfate-stimulated gallbladder contraction occurs through the release of CCK, and shows a close correlation between CCK release and contraction of the gallbladder.

Removal of Circulating Gastrin and Cholecystokinin into the Lumen of the Small Intestine

This study was undertaken to investigate the mechanism by which the small intestine removes circulating gastrin and cholecystokinin (CCK). A 100-cm (acute study, 10 dogs) or a 50-cm (chronic study, 5 dogs) segment of midjejunum was excluded in all 15 dogs. The excluded loop was perfused with 0.1 M phosphate buffer (pH 7.4), which was constantly recirculated by a peristaltic pump. It the acute control study (5 dogs), gastrin concentrations in the intestinal perfusate were increased gradually to a level of 320 +/- 49 pg/ml at 90 min (i.e., 7.6 +/- 0.9 times higher than serum gastrin levels). In the antrectomy group (5 dogs), perfusate gastrin concentrations were greatly decreased after antrectomy, in consonance with the decrease in serum gastrin concentrations. In the chronic study (5 dogs), perfusate gastrin concentrations were significantly increased after food stimulation, in consonance with the increase in serum gastrin concentrations. CCK was also released into the bowel lumen in considerable amounts basally and after endogenous release. Although one cannot exclude the possibility that a considerable amount of gastrin or CCK in the lumen may originate from the bowel segment, this study shows that the small bowel removes gastrin and CCK from the circulation by their secretion into the bowel lumen. Loss of this mechanism might partially explain the rise in gastrin levels that is observed in some patients after extensive small bowel resections.

Effect of colectomy on cholecystokinin and gastrin release.

Studies were conducted to determine the effect of resection of the colon on the release of cholecystokinin (CCK) and gastrin. A standard food stimulation test was performed in five dogs. Peripheral blood samples were collected for future measurement of CCK and gastrin by specific radipimmunoassay. Each dog underwent subtotal colectomy with side-to-end ileoproctostomy. The food stimulation test was repeated at approximately weekly intervals for eight weeks after colectomy. Basal plasma CCK levels of 139 ± 21 pg/ml before colectomy did not change after colectomy. Total amount of CCK released after food was increased significantly at both four (5.94 ± 0.78 ng min/ml) and eight (13.00 ± 2.72 ng min/ml) weeks after colectomy in comparison with that observed prior to colectomy (2.94 ± 0.54 ng min/ml). Basal serum gastrin levels of 28 ± 9 pg/ml did not change significantly after colectomy. Total amount of gastrin released after food was increased significantly at both two (8651 ± 2294 pg min/ml) and three (6940 ± 1426 pg min/ml) weeks after operation, but at none of the later weeks. The precolectomy output, used for comparison, was 5608 ± 1346 pg min/ml. It was concluded that resection of the colon leads to an increase in release of CCK and gastrin after food stimulation. This finding provides further evidence that the colon contains a factor that inhibits the release of CCK and gastrin, and that the colon functions as an endocrine organ.