Do patients with systemic sclerosis have abnormal gallbladder function?

OBJECTIVE: To determine gallbladder motility in patients with systemic sclerosis. DESIGN: Case control study. SETTING: University hospital, out-patient department of rheumatology. PATIENTS: Ten patients with systemic sclerosis according to the criteria of the American Rheumatism Association with documented involvement of the gastrointestinal tract and 10 healthy controls matched for age, sex and body mass index. INTERVENTION: Cephalic vagal cholinergic simulation by modified sham feeding and hormonal stimulation by infusion of cholecystokinin. MEASUREMENTS: Gallbladder volume obtained by ultrasonography and determination of plasma cholecystokinin concentrations. RESULTS: Fasting gallbladder volumes were not significantly different between patients with systemic sclerosis and controls (19.6 +/- 1.9 cm3 and 23.3 +/- 2.9 cm3, respectively, mean plus or minus standard error of the mean). Neither were there significant differences in reduction of gallbladder volume in response to modified sham feeding (35 +/- 4% and 33 +/- 4%, respectively) nor during cholecystokinin infusion (56 +/- 4% and 60 +/- 6%, respectively). The increase in plasma cholecystokinin levels during infusion was not different in the two groups. CONCLUSION: Gallbladder motility in patients with systemic sclerosis is preserved in response to both cholinergic and hormonal stimulation, even when other gastrointestinal motor disturbances are present. These results suggest that patients with systemic sclerosis are not at increased risk for cholelithiasis because of gallbladder dysmotility.

Effect of antrectomy and truncal vagotomy on erythromycin induced pancreatic polypeptide secretion.

Erythromycin, a motilin agonist, enhances gastrointestinal motility but also stimulates endogenous pancreatic polypeptide (PP) secretion. We investigated whether the effect of erythromycin on PP release is dependent on (1) prokinetic activity of erythromycin generated from the antrum and (2) the long vagus nerve since erythromycin acts via cholinergic neurons. Erythromycin induced PP secretion was determined in 14 patients with antrectomy (6 patients with Billroth I type anastomosis, 8 patients with Billroth II type anastomosis), in 6 patients with truncal vagotomy and pyloroplasty but without gastric resection and in 8 healthy controls. Plasma PP levels in response to erythromycin (3 mg/kg i.v.) were determined at regular intervals for 180 min. Erythromycin induced a significant increase in plasma PP in the control subjects from 22 +/- 4 pmol/l (basal) to 49 +/- 4 pmol/l at 10 min. In the patients with truncal vagotomy plasma PP secretion after erythromycin was significantly (P < 0.05) increased (peak increment vs. basal: 98 +/- 10 pmol/l vs. 27 +/- 2 pmol/l) and prolonged compared to controls. In the patients with antrectomy no significant increases in plasma PP over basal were observed after erythromycin infusion. It is concluded that erythromycin stimulates PP secretion in healthy controls. The PP response to erythromycin is exaggerated after truncal vagotomy but absent after antrectomy indicating that the antrum is essential for erythromycin induced PP secretion.

Effect of erythromycin on gallbladder emptying in patients with antrectomy or truncal vagotomy.

OBJECTIVES: Erythromycin, a motilin-like agent, stimulates gallbladder contraction in healthy control subjects. Because the action of erythromycin is cholinergic dependent and possibly related to premature phase III migrating motor complex activity in the antrum, we investigated the effect of erythromycin on gallbladder volume in six patients with truncal vagotomy without gastric resection and 14 patients with antrectomy (6 with Billroth I anastomosis, 8 with Billroth II anastomosis), and we compared the results obtained with those in eight healthy controls. In addition, the effect of meal ingestion on gallbladder volume was studied. METHODS: Gallbladder volumes, measured with ultrasonography, were determined every 15 min for 180 min after erythromycin infusion (3 mg/kg i.v.), as well as 30 and 60 min after meal ingestion. RESULTS: Basal gallbladder volumes were not significantly different among the four groups. Erythromycin induced a significant (p < 0.01-0.05) gallbladder contraction of maximal 46 +/- 6% in the controls, 49 +/- 9% in the patients with truncal vagotomy, and 38 +/- 7% in the patients with antrectomy and Billroth I anastomosis. In the patients with antrectomy and Billroth II anastomosis, no significant reduction in gallbladder volume after erythromycin was observed. Meal-induced gallbladder contraction was normal in all patients, including those with Billroth II anastomosis. CONCLUSIONS: These results indicate that neither the long vagus nerve nor the antrum is essential for erythromycin-induced effects on the gallbladder. Because no significant reduction in gallbladder volume in response to erythromycin was observed in the patients with antrectomy and Billroth II anastomosis, we suggest that duodenojejunal anatomical integrity is essential for erythromycin-induced gallbladder contraction.

Effects of somatostatin and loxiglumide on gallbladder motility.

Cholecystokinin (CCK) is the major hormonal stimulus of gallbladder contraction. Both somatostatin and CCK-A receptor antagonists inhibit stimulation of the gallbladder by CCK. The aim of this study was to compare the effect of somatostatin and the CCK-A receptor antagonist loxiglumide (CR 1505) on gallbladder volume at baseline and after feeding. In random order nine healthy subjects received somatostatin (IV loading dose 125 micrograms, followed by IV infusion of 125 micrograms.h-1), loxiglumide (10 mg.kg-1.h-1) and control saline. Gallbladder volumes and plasma CCK levels were measured basally and during stimulation by an intraduodenal infusion of fat using, respectively, ultrasound and a sensitive and specific radioimmunoassay. Mean basal gallbladder volume was similar prior to the saline control (28.5 ml), loxiglumide (28.7 ml) and somatostatin (23.4 ml) experiments. In the control experiment, intraduodenal fat led to a significant increase in plasma CCK from 2.6 to 4.8 pmol.1-1, accompanied by contraction of the gallbladder to 2.0 ml. Loxiglumide induced dilatation of the gallbladder to 40 ml and prevented the any contraction in response to intraduodenal fat. During the somatostatin infusion, gallbladder volume remained the same both basally and during fat stimulation. The plasma CCK response to intraduodenal fat was exaggerated by loxiglumide and was abolished by somatostatin.

Nutrient-specific effects of modified sham feeding on pancreatic polypeptide release.

OBJECTIVE: To study the effect of meal composition on pancreatic polypeptide release during modified sham feeding. DESIGN: In random order and on separate occasions, isocaloric, isothermic, isoosmotic, homogenized meals (1050 kJ; 250 kcal) either rich in fat (walnuts; 64 g fat, 7 g protein, 15 g starch per 100 g), protein (codfish, 1 g fat, 23 g protein per 100 g) or carbohydrates (bananas; 22 g starch, 1 g protein per 100 g) were sham-fed for 30 min by tasting and spitting out the meal. The plasma pancreatic polypeptide response was monitored by radioimmunoassay at 10 min intervals from 20 min before to 120 min after modified sham feeding. SETTING: Department of Gastroenterology and Hepatology of a University Hospital. SUBJECTS: Seven healthy volunteers: 3 male, 4 female; age 45 (range 30-77) years. RESULTS: Integrated plasma pancreatic polypeptide responses to modified sham feeding of codfish (1088 +/- 395 pM*120 min; P < 0.05) and walnuts (1200 +/- 542 pM*120 min) were distinctly higher (P < 0.05) than to modified sham feeding of bananas (-390 +/- 291 pM*120 min). CONCLUSIONS: These results demonstrate that the pancreatic polypeptide response to modified sham feeding is dependent on the composition of the meal.

Gallbladder responses to modified sham feeding: effects of the composition of a meal.

Changes in gallbladder contraction and plasma cholecystokinin release were studied following modified sham feeding of 3 different isocaloric meals rich in either fat, protein or carbohydrates in healthy volunteers, and results were compared with those following real feeding of comparable meals. In contrast to carbohydrate-rich meals (8 +/- 19 ml/120 min), fat- (-412 +/- 46 ml/120 min) and protein-rich meals (-352 +/- 42 ml/120 min) reduced integrated gallbladder volume (P < 0.05) in response to modified sham feeding. Plasma cholecystokinin levels were not significantly influenced by modified sham feeding of fat, protein or carbohydrates. Real feeding of a carbohydrate-rich meal also failed to significantly reduce gallbladder volume and to stimulate cholecystokinin release (-45 +/- 40 ml/120 min and 51 +/- 11 pmol/120 min, respectively), while real feeding of both fat- and protein-rich meals distinctly reduced gallbladder volume (-679 +/- 76 and -564 +/- 53 ml/120 min, respectively; P < 0.05) and increased cholecystokinin release (651 +/- 72 and 504 +/- 43 pmol/120 min, respectively; P < 0.05). This study demonstrates that gallbladder contraction during the cephalic phase of meal stimulation is dependent on the fat, protein and carbohydrate percentages of a meal, and is activated by different mechanisms than the intestinal phase of a meal.

Effect of duodenal juice on bombesin-stimulated cholecystokinin release during loxiglumide administration in man.

Stimulation of cholecystokinin release by bombesin in augmented by cholecystokinin receptor blockade with loxiglumide. We hypothesize that this augmented cholecystokinin release results from inhibition of the pancreatico-biliary response to bombesin during cholecystokinin receptor blockade. To test this hypothesis, we infused bombesin for 180 min in six healthy subjects Three bombesin-infusion experiments were performed in each subject in random order on different days. In two of these experiments loxiglumide was co-infused with bombesin, while in the third experiment saline was co-infused with bombesin. In one of the loxiglumide experiments, duodenal juice, collected on the previous day during infusion of cholecystokinin-GIH, was reperfused intraduodenally during the second hour of bombesin infusion. In the saline experiment, the integrated cholecystokinin response during the first hour of bombesin-infusion (262 +/- 63 pmol 60 min-1) was significantly (P < 0.01) higher than during the second (88 +/- 26 pmol 60 min-1) and third (87 +/- 31 pmol 60 min-1) hour of bombesin-infusion. Loxiglumide augmented bombesin-stimulated cholecystokinin secretion from 262 +/- 63 pmol 60 min-1 to 453 +/- 63 pmol 60 min-1 in the first hour of bombesin infusion (P < 0.01). Integrated cholecystokinin values in the second (489 +/- 90 pmol 60 min-1) and third (450 +/- 74 pmol 60 min-1) hour of the loxiglumide experiment, were significantly (P < 0.01) higher than in the saline experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of acute hyperglycaemia on gall bladder contraction induced by cholecystokinin in humans.

This study examined the effect of acute hyperglycaemia, induced by intravenous glucose, on gall bladder motility. Six healthy volunteers were studied in random order on three occasions during normoglycaemia and hyperglycaemia with blood glucose concentrations stabilised at 8 and 15 mmol/l. Gall bladder volumes, measured with ultrasonography, were studied before and during infusion of stepwise increasing doses of cholecystokinin (CCK-33; 0.25, 0.5, and 1.0 IDU.kg-1.h-1). Each dose was given for 30 minutes. Pancreatic polypeptide (PP) secretion was determined as an indirect measure of cholinergic tone. Infusion of CCK-33 resulted in significant dose dependent reductions in gall bladder volume in all three experiments. Compared with normoglycaemia the gall bladder contraction was significantly (p < 0.05) reduced during infusion of 0.25 and 0.5 IDU kg-1.h-1 CCK-33 in the 8 mmol/l hyperglycaemic experiment, and during infusion of 0.25, 0.5, and 1.0 IDU kg-1.h-1 CCK-33 in the 15 mmol hyperglycaemic experiment. During hyperglycaemia basal plasma PP concentrations and PP secretion in response to CCK-33 were significantly (p < 0.05) reduced. It is concluded that blood glucose concentrations affect gall bladder motility, that an acute hyperglycaemia at 8 and 15 mmol/l reduces the gall bladder responsiveness to CCK-33 in a dose dependent manner, and that hyperglycaemia reduces basal and CCK-33 stimulated plasma PP concentrations, suggesting impaired cholinergic activity during hyperglycaemia.

Effect of loxiglumide on basal and gastrin- and bombesin-stimulated gastric acid and serum gastrin levels.

The effect of the specific cholecystokinin-receptor antagonist loxiglumide on basal and bombesin-, and gastrin 17-I-stimulated gastric acid secretion and serum gastrin levels was studied in 12 healthy subjects. Loxiglumide (10 mg.kg-1.h-1) significantly augmented basal gastric acid output from 1.8 +/- 0.3 to 3.9 +/- 0.6 mmol H+/h (P less than 0.005) but did not significantly influence integrated basal serum gastrin concentrations (2 +/- 21 vs. 32 +/- 21 pmol L-1.h-1). Both gastric acid secretion and integrated serum gastrin concentrations stimulated by bombesin infusion (92.6 pmol.kg-1.h-1) were significantly augmented by loxiglumide [from 4.0 +/- 0.3 to 10.0 +/- 1.3 mmol H+/h (P less than 0.005) and from 1251 +/- 93 to 2558 +/- 206 pmol.L-1.h-1 (P less than 0.005), respectively]. Gastric acid output and serum gastrin concentrations during infusion of 5 pmol.kg-1.h-1 of synthetic human gastrin 17-I (9.6 +/- 2.9 mmol H+/h and 1045 +/- 177 pmol.L-1.h-1) and during infusion of 15 pmol.kg-1.h-1 of gastrin 17-I (14.5 +/- 3.1 mmol H+/h and 2412 +/- 312 pmol.L-1.h-1) were not significantly influenced by loxiglumide (10.3 +/- 2.3 mmol H+/h and 1291 +/- 257 pmol.L-1.h-1 for the 5-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide and 13.6 +/- 3.4 mmol H+/h and 2611 +/- 305 pmol.L-1.h-1 for the 15-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide). These data indicate that endogenous cholecystokinin inhibits gastric acid secretion under basal conditions and gastrin release and gastric acid secretion during infusion of bombesin in humans and suggest that the augmented effect of loxiglumide on bombesin-stimulated gastric acid secretion may be explained largely by enhanced gastrin release.

Effect of loxiglumide and atropine on erythromycin-induced reduction in gallbladder volume in human subjects.

This study was undertaken to investigate the effect of erythromycin, a motilin agonist with prokinetic activity, on fasting gallbladder volume. To evaluate the mechanism of action of erythromycin on gallbladder motility, erythromycin (3.5 mg/kg.20 min, intravenously) was infused on three separate occasions: during cholinergic blockage with atropine (0.005 mg/kg.hr), during cholecystokinin receptor blockade with loxiglumide (10 mg/kg.hr) and during saline solution infusion (control). Atropine, loxiglumide and saline solution infusions were started 3 hr before administration of erythromycin and were continued for 3 hr thereafter. Gallbladder volumes (measured by ultrasonography), plasma cholecystokinin levels (radioimmunoassay) and plasma pancreatic polypeptide levels (radioimmunoassay) were determined at regular intervals for 6 hr in six healthy volunteers. During the 3-hr infusion before administration of erythromycin, both loxiglumide and atropine significantly increased gallbladder volumes--from 18 +/- 2 to 37 +/- 3 cm3 (p less than 0.05) and from 17 +/- 3 to 24 +/- 2 cm3 (p less than 0.05), respectively--whereas saline solution did not significantly affect gallbladder volume. During control saline solution infusion, erythromycin induced prolonged gallbladder contraction that was significant (p less than 0.05) between 60 and 180 min and reached a maximum of 45% +/- 8% at 150 min. Plasma cholecystokinin levels were not affected by erythromycin. Erythromycin induced a significant (p less than 0.05) increase in plasma pancreatic polypeptide levels, from 12 +/- 1 pmol/L to 34 +/- 3 pmol/L. Loxiglumide did not prevent the erythromycin-induced reduction in gallbladder volume. Atropine markedly reduced the effect of erythromycin, causing slight but significant (p less than 0.05) gallbladder volume reductions (18% +/- 4%) between 150 and 180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Gallbladder disease in cystic fibrosis.

Among the various gastrointestinal manifestations observed in patients with cystic fibrosis (CF), gallbladder abnormalities occur frequently. These include a high prevalence of nonfunctioning gallbladders (30%), micro-gallbladders (8-30%), and gallstones (4-30%). The underlying pathophysiology for this increased prevalence in patients with CF is not completely understood, due to contradictory findings. These findings concern: (1) abnormalities in bile acid metabolism resulting in bile that is supersaturated with cholesterol, (2) an impaired nucleation time, and (3) biliary stasis, due to bile duct abnormalities and/or impaired gallbladder motility. The diagnosis of gallbladder disease in CF may be obscured by other common gastrointestinal complications, resulting in a long delay between onset of symptoms and the diagnosis. Cholecystectomy in CF is the treatment of choice, provided they are carefully managed in the pre- and perioperative period. The operative morbidity and mortality, even with intensive management of pulmonary disease, amounted to 10% and 5%, respectively. Therefore, alternative options, like laparoscopic cholecystectomy are of interest and require further investigation, especially for CF patients with severe pulmonary disease.

Evidence against autocrine feedback regulation of cholecystokinin secretion in man.

To determine whether exogenous cholecystokinin (CCK) inhibits endogenous CCK release, cholecystokinin-8S (CCK-8S) was infused intravenously during continuous intraduodenal stimulation of endogenous CCK by a meal. CCK was measured in plasma by 2 region-specific radioimmunoassays employing antibodies T204 and 1703. AB T204 binds to carboxy-terminal CCK peptides containing the sulphated tyrosyl region, including CCK-8S, and AB 1703 to carboxy-terminal CCK peptides containing at least 14 amino acid residues. Meal-stimulated plasma CCK concentrations remained elevated during the entire infusion period. CCK-8S infusion further increased meal-stimulated plasma CCK concentrations, when measured with AB T204, while meal-stimulated plasma CCK concentrations were not suppressed by CCK-8S infusion, when measured with AB 1703. It is concluded that meal-stimulated endogenous CCK release is not affected by the effects of intravenously administered CCK-8S. These data suggest that autocrine feedback regulation of CCK release is not operative in man.

Effect of intravenous fat on cholecystokinin secretion and gallbladder motility in man.

During total parenteral nutrition (TPN) gallbladder bile stasis and hypomotility have been well documented. Little is known, however, about the effect of the separate components of TPN on gallbladder motor function. Inasmuch as fat, administered intraduodenally, is a potent stimulus of cholecystokinin (CCK) secretion and gallbladder contraction we have investigated whether intravenous (IV) fat affects gallbladder motility. Six healthy volunteers were studied on two separate occasions, during infusion of Intralipid 10%, 200 mL/h or saline infusion (control) for 3 hours, to evaluate the effect of IV infusion of fat on (1) plasma CCK concentration and gallbladder volume and (2) CCK-induced gallbladder emptying. Intravenous infusion of Intralipid resulted in significant increases in serum triglycerides from 0.9 +/- 0.1 to 5.1 +/- 1.3 mmol/L (at 90 min). During fat infusion no significant changes in plasma CCK and gallbladder volume were noted when compared with basal values or to the control experiment. During IV fat, concomitant infusion of 0.25, 0.5, and 1.0 Ivy dog unit (IDU) per kilogram per hour of CCK-33 resulted in a significant reduction in gallbladder volume from 26 +/- 6 cm3 (basal) to 15 +/- 4 cm3 (p less than .05), 6 +/- 2 cm3 (p less than .05) and 2.5 +/- 1 cm3 (p less than .05), respectively. No significant differences in CCK-induced gallbladder emptying were observed between IV fat and saline infusion (control). It is concluded that, in contrast to intraduodenal fat, IV infusion of fat does not affect (1) basal plasma CCK and gallbladder volume and (2) CCK-induced gallbladder contraction.

Effect of the specific cholecystokinin-receptor antagonist loxiglumide on bombesin stimulated pancreatic enzyme secretion in man.

We have investigated the effects of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on basal and bombesin stimulated pancreatic enzyme secretion, bilirubin output and plasma CCK release in six healthy subjects. The data were compared with those obtained in control experiments where saline was infused instead of loxiglumide. Basal amylase output (4.7 +/- 0.8 kU/45 min), trypsin output (2.9 +/- 0.8 kU/45 min) and bilirubin output (7.7 +/- 2.8 mmol/45 min) gradually declined during infusion of loxiglumide to values of 1.3 +/- 0.3 kU/45 min, 0.5 +/- 0.1 kU/45 min and 0.4 +/- 0.0 mmol/45 min, respectively, reaching statistical significance (P less than 0.05) in the 30 to 45-min period after the start of the loxiglumide infusion. In the control experiments saline infusion failed to influence basal amylase, trypsin and bilirubin output, while bombesin stimulated amylase output from 4.7 +/- 0.8 kU/45 min to 25.1 +/- 5.1 kU/45 min (P less than 0.05), trypsin output from 2.9 +/- 0.8 kU/45 min to 11.6 +/- 2.0 kU/45 min (P less than 0.05) and bilirubin output from 7.7 +/- 2.8 mmol/45 min to 68.0 +/- 16.0 mmol/45 min (P less than 0.05). Loxiglumide failed to significantly influence bombesin stimulated amylase output (36.7 +/- 9.0 kU/45 min) and trypsin output (8.3 +/- 2.9 kU/45 min), but almost abolished bilirubin output (9.7 +/- 3.6 mmol/45 min) (P less than 0.05). Basal plasma CCK (2.4 +/- 0.1 pM) was not significantly influenced by loxiglumide (2.4 +/- 0.2 pM).(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of effect of the specific cholecystokinin receptor antagonist loxiglumide on cholecystokinin clearance from plasma in man.

Saline or loxiglumide (2.5 mg kg-1 in 10 min, followed by 5 mg kg-1 h-1 for 200 min) was administered intravenously in random order to six healthy subjects. After 60 min cholecystokinin (CCK-33) was infused (0.5 i.d.u. kg-1 h-1 for 1 h then 1.0 i.d.u. kg-1 h-1 for 1 h). Loxiglumide did not change basal levels of CCK and did not augment plasma CCK-immunoreactivity during CCK-33 infusion. After cessation of the CCK-infusion, plasma CCK concentrations decreased rapidly to basal values within 12 min, and the elimination half-life during loxiglumide infusion (4.8 +/- 0.8 min) was not significantly different from that during saline infusion (4.2 +/- 1.0 min). These results suggest that loxiglumide does not interfere with the distribution and metabolism of CCK.

Effect of loxiglumide (CR-1505) on bombesin- and meal-stimulated plasma cholecystokinin in man.

Cholecystokinin (CCK)-receptor antagonists have been reported to inhibit the effects of the hormone on the gastrointestinal tract. Their effect on plasma CCK levels in man has not been described. The present study in 5 normal subjects demonstrated that i.v. infusion of the potent, specific CCK-receptor antagonist loxiglumide (CR 1505) significantly augmented plasma CCK levels during infusion of bombesin (402 pM per 30 min) and after administration of a meal (1390 pM per 300 min) when compared to the bombesin- (192 pM per 30 min) and meal- (886 pM per 300 min) stimulated CCK responses during infusion of saline. The basal plasma CCK during saline infusion (0.1 pM per 40 min) was not significantly influenced by CR 1505 (-1.8 pM per 40 min). Thus, both enteral (meal) and parenteral (bombesin) stimulation of CCK secretion are augmented by CCK-receptor blockade.

The effect of loxiglumide (CR-1505) on basal and bombesin-stimulated gallbladder volume in man.

This study was undertaken in 5 normal subjects to determine the role of cholecystokinin (CCK) in the regulation of basal gallbladder volume and gallbladder contraction stimulated by infusion of bombesin. Administration of the CCK-receptor antagonist, loxiglumide (CR-1505), led to doubling of the gallbladder volume (increase 104 +/- 26%; P less than 0.05) and reduced the bombesin-stimulated gallbladder contraction from 69 +/- 17 to 19 +/- 17% (P less than 0.05). The findings provide evidence suggesting that CCK plays an important role in the regulation of basal gallbladder tone and in mediating the gallbladder contraction induced by the administration of bombesin.

Effect of pancreatic enzyme supplementation on postprandial plasma cholecystokinin secretion in patients with pancreatic insufficiency.

To test the hypothesis, based on studies in healthy man and dog, that patients with impaired digestion due to severe pancreatic insufficiency have impaired postprandial cholecystokinin (CCK) secretion that can be improved by the addition of pancreatic enzymes, we have studied plasma CCK responses to a test meal with and without addition of pancreatic enzymes in 10 patients with pancreatic insufficiency and steatorrhea, in 8 patients with chronic pancreatitis without steatorrhea, and in 6 healthy subjects. The patients with steatorrhea had a significantly (P less than 0.001) lower integrated plasma CCK response to the meal (177 +/- 23 pM.150 min) than the healthy subjects (468 +/- 41 pM.150 min), while patients with chronic pancreatitis without steatorrhea had an intermediate integrated postprandial CCK secretion (327 +/- 101 pM.150 min). Addition of pancreatic enzymes to the meal significantly augmented the integrated CCK response in both the patients with steatorrhea to 483 +/- 72 pM.150 min (P less than 0.01) and in those without steatorrhea to 480 +/- 85 pM.150 min (P less than 0.05). These values were not significantly different from those in the healthy subjects (521 +/- 86 pM.150 min). Integrated CCK secretion in the three groups during bombesin infusion was similar (patients with steatorrhea 134 +/- 23 pM.20 min, patients without steatorrhea 131 +/- 33 pM.20 min, and healthy subjects 146 +/- 28 pM.20 min), indicating a normal capacity to secrete CCK in response to a humoral stimulus. These data are in agreement with the suggestions from previous studies that digestion of nutrients by pancreatic enzymes plays an important role in the regulation of plasma CCK secretion after feeding.