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Objectives: The objective of this study was to gain insight into the hormonal responses to enteral nutrition in critically ill newborns requiring venoarterial extracorporeal membrane oxygenation (ECMO) by analyzing plasma gut hormone levels of gastrin, cholecystokinin and peptide-YY in relation to enteral nutrition., Methods: In 24 consecutive neonates treated with venoarterial ECMO intestinal hormone secretions were determined by radioimmunoassay at 2-day intervals. Twelve received parenteral nutrition only. In 12 enteral nutrition was introduced later. The findings in these patients were compared with those of 16 measurements in eight non-ECMO treated age-matched controls. Mixed model analysis of variance was used for statistical analysis., Results: Concentrations of gastrin, cholecystokinin and peptide-YY were significantly higher in ECMO patients receiving enteral nutrition compared with ECMO patients who received parenteral nutrition (62, 3.8 and 59.4 pmol/L versus 46, 3.1 and 34.7 pmol/L, respectively). Overall, plasma hormone levels did not differ from those in age-matched controls., Conclusions: Intestinal hormone levels showed normal responses after introduction of enteral feeding, comparable with those in age-matched controls without ECMO. These results do not provide an argument for withholding enteral nutrition even in the most severely ill neonates on venoarterial ECMO.

Background/purpose: Gastrointestinal hormones modulate gut function in response to enteral nutrition. Infants with a congenital intestinal anomaly with loss of bowel length either pre-or postnatal, who are on total parenteral nutrition for prolonged periods after surgery, are especially prone to a disturbed secretion of gut hormones. The aim of this study was to determine whether circulating gut hormones were altered in these patients and to collect baseline data for future studies in short bowel patients using different enteral substrates., Methods: Gastrin, cholecystokinin, and peptide YY were measured in 14 operated neonates who had a congenital intestinal anomaly during starvation and introduction of enteral nutrition. None of the neonates had a short bowel. Fourteen neonates who underwent surgery for other major congenital anomalies served as age-matched controls. Gut hormones were measured with radioimmunoassays., Results: Postprandial gut hormone values were higher than basal gut hormone values within both groups. Compared with the controls, postprandial gastrin and cholecystokinin were significantly higher in the patients., Conclusions: Neonates with a congenital intestinal anomaly in the absence of a short bowel have a similar secretion pattern of gastrointestinal hormones as neonates with a structurally normal intestinal tract, both during starvation and enteral nutrition.

Background: Helicobacter pylori infection affects the concentration of regulatory peptides such as gastrin, somatostatin and cholecystokinin and the concentration and activity of glutathione and glutathione S-transferases in the gastric mucosa., Methods: Literature review., Results: Although some of these peptides have been known since the beginning of this century, their action has changed since the discovery of H. pylori infection in 1983. Chronic infection with H. pylori might lead to an increased risk in developing gastric cancer. Glutathione S-transferases are involved in the cellular detoxification of xenobiotics and other toxic compounds. Since there is a close inverse relationship between the activity of glutathione S-transferase and incidence of malignancies in the gastrointestinal tract, the possible relation between H. pylori infection and activity of glutathione S-transferases in the gastric mucosa is discussed., Conclusion: The effect of H. pylori infection on regulatory peptides and glutathione/glutathione S-transferases might play a role in the development of neoplastic changes of the H. pylori-infected gastric mucosa.

Background/aim: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation., Methods: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls., Results: Fasting levels of plasma cholecystokinin (3.1+/-0.2 vs. 2.4+/-0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4+/-1.4 vs. 8.9+/-0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60-90 min), incremental cholecystokinin (p<0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0-60 min), incremental plasma cholecystokinin (251+/-20 pM.min) and peptide YY (1,146+/-186 pM. min) in patients were almost similar to control values (262+/-22 and 901+/-166 pM. min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying., Conclusion: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying., (Copyright 2000 S. Karger AG, Basel.)

Bile salts modulate postprandial gallbladder emptying and pancreatic enzyme secretion, possibly by interfering with plasma cholecystokinin (CCK) responses. The regulatory role of bile salts in the absence of nutrients from the gut is poorly understood. Therefore, we studied the effect of intraduodenal sodium chenodeoxycholate on bombesin (BBS)- or CCK-stimulated plasma CCK levels, plasma pancreatic polypeptide levels, gallbladder motility, and pancreatic enzyme secretion. In a crossover design, saline without or with chenodeoxycholate was perfused intraduodenally for 3 hours in healthy volunteers. During the last hour, either BBS (n = 9) or CCK (n = 10) was infused intravenously. Chenodeoxycholate inhibited BBS-stimulated gallbladder emptying from 59% +/- 4% to 34% +/- 6% (P <.05) and intraduodenal bilirubin output from 41 +/- 9 to 21 +/- 5 micromol/h (P <.05), but it increased integrated plasma CCK levels from 157 +/- 19 to 184 +/- 19 pmol/L. 60 min (P =.01). Similarly, chenodeoxycholate administration inhibited gallbladder emptying and bilirubin output in response to intravenous CCK. Chenodeoxycholate also tended to reduce pancreatic polypeptide release and intraduodenal amylase output in response to intravenous BBS or CCK. It is concluded that intraduodenal chenodeoxycholate administration inhibits BBS- or CCK-stimulated gallbladder emptying, probably by diminishing target organ sensitivity to circulating CCK.

Impaired postprandial gallbladder emptying in celiac disease has been attributed to an absence of appropriate cholecystokinin release. To determine if a flat jejunal mucosa in celiac patients is related to a reduced cholecystokinin-secreting capacity, increasing doses of bombesin were infused into six patients with celiac disease and a flat jejunal mucosa (group A), in seven celiac patients with a normal jejunal mucosa while on a gluten-free diet (group B), and in seven healthy controls (group C). Bombesin induced significant (P < 0.05) increments of plasma CCK to a maximum value of 1.0 +/- 0.3 pM in group A, to 1.5 +/- 0.3 pM in group B, and to 1.2 +/- 0.3 pM in group C (NS between groups), that were accompanied by significant (P < 0.05) gallbladder emptying responses of 70 +/- 4% in group A, 47 +/- 10% in group B and 65 +/- 5% in group C. Dose-response relationships were not different between groups. We conclude that there is no major impairment of gallbladder responsiveness to bombesin or of cholecystokinin-secreting capacity in patients with a flat jejunal mucosa due to celiac disease.

Background: Cholestyramine enhances gallbladder emptying and plasma cholecystokinin responses to oral ingestion of a mixed meal. It is not known whether this effect occurs independently of alterations in gastric emptying or maldigestion of nutrients., Methods: We perfused 15 g of an amino acid meal intraduodenally for 60 min in seven healthy volunteers, once with and once without cholestyramine. Intraduodenal perfusion of saline with or without cholestyramine (6 g/h) was started 60 min before the amino acid meal and continued for 2 h., Results: Cholestyramine markedly enhanced the incremental plasma cholecystokinin response to the meal from 36 +/- 12 to 139 +/- 25 pmol/l x 60 min (P < 0.005), incremental amylase output from 2.4 +/- 0.7 to 5.7 +/- 0.7 kU/h (P < 0.05), and incremental integrated gallbladder contraction from 1948 +/- 235 to 2840 +/- 189% x 60 min (P < 0.05)., Conclusion: The enhancing effect of cholestyramine on postprandial gallbladder contraction, pancreatic enzyme secretion, and plasma cholecystokinin release is not dependent on gastric emptying rates or appropriate digestion of nutrients.

Replacement of dietary fat by sucrose polyester reduces fat intake. However, little is known about the effects of sucrose polyester on gastrointestinal function. To investigate the effect on gastric acid secretion and on release of cholecystokinin into plasma, we perfused eight healthy male volunteers intraduodenally with sucrose polyester, digestible fat, or saline on separate days in random order. Intraduodenal perfusion of sucrose polyester did not suppress gastrin-stimulated gastric acid secretion (-1.8 +/- 6.8%) whereas digestible fat suppressed gastric acid secretion by 64 +/- 9% (P = 0.001) compared with saline. Sucrose polyester did not affect plasma cholecystokinin concentrations (-12.8 +/- 9.3 pmol.30 min/L) whereas perfusion with digestible fat resulted in a significant increase (31.7 +/- 9.3 pmol.30 min/L, P = 0.017) compared with saline. We conclude that sucrose polyester, in contrast with digestible fat, does not inhibit gastrin-stimulated gastric acid secretion or stimulate release of cholecystokinin.

Background & Aims: The role of small intestinal proteolytic activity in the regulation of upper gastrointestinal function in humans is poorly understood. The aim of this study was to determine the importance of proteolytic activity for protein- or amino acid-induced cholecystokinin release and pancreaticobiliary secretion., Methods: In 9 healthy subjects, saline was perfused intraduodenally for 3 hours either with or without the synthetic protease inhibitor camostate. During the last hour, albumin or amino acids in the same molecular composition as albumin were also perfused., Results: Perfusion with camostate, in concentrations that abolished intraduodenal proteolytic activity, had no effect on unstimulated plasma cholecystokinin concentrations or gallbladder emptying, but markedly (P < 0.05) increased unstimulated pancreatic enzyme output. Perfusion with protein distinctly stimulated cholecystokinin release, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Perfusion with camostate resulted in significantly lower protein-stimulated plasma cholecystokinin, gallbladder, and pancreatic enzyme responses (P < 0.05). Perfusion with amino acids also stimulated plasma cholecystokinin, gallbladder emptying, and pancreatic enzyme output (P < 0.05). Camostate did not inhibit these values., Conclusions: This study shows that appropriate digestion of protein is required to stimulate plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion in humans.

Background: The colon and rectum contain regulatory peptides in mucosal endocrine cells, which suggests a hormonal role. In animal studies colectomy leads to increased plasma levels of cholecystokinin. Little is known about the effects of proctocolectomy with ileal pouch-anal anastomosis on the release of cholecystokinin in human beings. Therefore we studied the effects of this procedure on fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels and gallbladder volumes., Methods: Ten patients who had undergone proctocolectomy with ileal pouch-anal anastomosis and 12 healthy volunteers participated in the study. Fasting and postprandial plasma cholecystokinin levels and gallbladder volumes were studied for 3 hours at 15-minute intervals. In a second experiment plasma cholecystokinin levels were measured before and during intravenous administration of bombesin in six patients with ileal pouch and five healthy volunteers., Results: Fasting plasma cholecystokinin levels were higher (p < 0.05) in patients with ileal pouch-anal anastomosis (2.6 +/- 0.3 pmol/L) compared with controls (1.7 +/- 0.2 pmol/L). Integrated postprandial plasma cholecystokinin levels were also distinctly higher (p < 0.01) in patients (978 +/- 126 pmol/L.180 min) than in controls (588 +/- 60 pmol/L.180 min). Mean fasting gallbladder volume was significantly (p < 0.01) decreased in patients with ileal pouch-anal anastomosis (18 +/- 2 ml) compared with controls (28 +/- 2 ml). Postprandial gallbladder emptying as measured by percentage change was similar in both groups. After infusion of bombesin, integrated plasma cholecystokinin responses were higher (p < 0.05) in patients (161 +/- 20 pmol/L.20 min) than in controls (90 +/- 12 pmol/L.20 min)., Conclusions: Fasting, postprandial, and bombesin-stimulated plasma cholecystokinin levels are elevated in patients with ileal pouch-anal anastomosis compared with controls. Fasting gallbladder volume is decreased after ileal pouch-anal anastomosis. These findings suggest that the colon contains a factor that inhibits the release of cholecystokinin.

Cholecystokinin (CCK) release and gall bladder emptying in response to a fatty meal are completely abolished in coeliac disease. To determine the effect of lipid digestion on CCK release and gall bladder motility, six patients with untreated coeliac disease and a flat jejunal mucosa were studied on two separate days. After an overnight fast, the plasma CCK concentration and gall bladder volume were measured before and at regular intervals after the intraduodenal instillation of 60 ml corn oil (triglycerides) incubated with 40 ml saline or with 40 ml bile and pancreatic juice. The mean (SEM) concentration of free fatty acids in the aqueous phase of corn oil after incubation with bile and pancreatic juice (predigested corn oil) was 78 (35) mM compared with 0.1 (0.1) mM in the aqueous phase of corn oil incubated with saline (undigested corn oil). Integrated plasma CCK in response to predigested corn oil was significantly greater than that in response to undigested corn oil (101 (18) pM. 80 min v-2 (9) pM.80 min; p < 0.005). Similarly, integrated gall bladder contraction in response to predigested corn oil was significantly larger than that after undigested corn oil (817 (210) ml. 80 min v-225 (243) ml. 80 min; p < 0.05). In contrast to undigested corn oil, corn oil that has been predigested with bile and pancreatic juice induces plasma CCK secretion and gall bladder contraction in patients with untreated coeliac disease, presumably by generating and rendering soluble lipolytic products.

Background/aims: Bombesin-stimulated plasma cholecystokinin levels decrease after an initial increase despite continuous infusion of bombesin. The aim of this study was to determine if a feedback mechanism, mediated by bile salts or proteolytic enzymes, is responsible for this decline., Methods: Bombesin (1.0 ng.kg-1.min-1) was infused into volunteers for 180 minutes on separate occasions. Cholestyramine, colestipol, camostate, or saline were perfused intraduodenally during the second hour of the tests. Cholestyramine was also administered without infusion of bombesin., Results: Colestipol and cholestyramine, dependent on their bile salt-binding capacity, markedly enhanced (P < 0.05) bombesin-stimulated plasma cholecystokinin from 2.1 +/- 0.5 pmol/L to 6.4 +/- 2.2 pmol/L and 12.1 +/- 3.3 pmol/L (P < 0.05 vs. colestipol), respectively, and further decreased gallbladder volume (P < 0.05) from 9.4 +/- 1.6 mL to 2.0 +/- 0.4 mL and 2.2 +/- 0.5 mL, respectively. The protease inhibitor camostate had no effect. Bile salt precipitation also enhanced plasma pancreatic polypeptide responses (P < 0.01) but did not alter gastrin responses. Plasma cholecystokinin responses to cholestyramine without bombesin infusion varied considerably, but increments were highly correlated to decreases in gallbladder volume (r = 0.91; P < 0.005)., Conclusions: Bile salt sequestration but not protease inactivation enhances plasma cholecystokinin and gallbladder responses to bombesin infusion in humans.

In vitro studies have demonstrated that cholecystokinin releases somatostatin from the gastric mucosa. To date, there is no information about the in vivo significance of this finding in man. Therefore, we have studied the effect of infusion of cholecystokinin resulting in plasma concentrations within the range found after meal-stimulation, on somatostatin release and on gastric acid secretion. In addition we have studied these functions during infusion of the type A cholecystokinin receptor antagonist loxiglumide. In eight healthy subjects, basal gastric acid secretion was distinctly stimulated by cholecystokinin. The effect of cholecystokinin on gastric acid secretion was markedly enhanced by loxiglumide. Cholecystokinin also significantly stimulated somatostatin output into the gastric lumen, but not into the systemic circulation. Somatostatin output into the gastric lumen during infusion of cholecystokinin was abolished by loxiglumide. The data indicate that on the one hand circulating cholecystokinin, like gastrin, stimulates gastric acid secretion probably by binding to less specific type B receptors on parietal cells that are not blocked by loxiglumide, but on the other hand that cholecystokinin, in contrast to gastrin, also inhibits gastric acid secretion probably by binding to specific type A receptors present on somatostatin producing D-cells in the gastric mucosa, that are blocked by loxiglumide.

The effect of intragastric dextrose on albumin-stimulated cholecystokinin (CCK) release was studied in five healthy subjects and was related to gastric emptying and pancreatobiliary secretions. When combined with low concentrations of dextrose (4 g/100 ml), a 500-ml solution of albumin (7 g/100 ml) was rapidly emptied from the stomach into the duodenum (T1/2: 35 min). This rapid gastric emptying resulted in an only transient stimulation of pancreatobiliary secretion and an integrated CCK release of 278 +/- 45 pM x 180 min. When the concentration of dextrose in the albumin solution was increased from 4 g/100 ml to 21 g/100 ml, gastric emptying rate was distinctly slower (T1/2: 78 min; P < 0.01) and pancreatobiliary secretions became sustained (P < 0.01). CCK release was markedly higher (900 +/- 421 pM x 180 min; P < 0.05) after ingestion of the solution containing a high dextrose concentration. Intraduodenal infusion of 21 g/100 ml dextrose (3.1 ml/min) failed to significantly stimulate plasma CCK levels (119 +/- 38 pM x 120 min). We suggest that the higher CCK release in response to intragastrically administered albumin solution containing high concentrations of dextrose may have been induced by augmented peptic digestion of albumin due to delayed gastric emptying and by increased enteral digestion of albumin due to increased pancreatobiliary outputs.

The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6-32 months with 200-300 micrograms octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-micrograms subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (-125 +/- 194 cm3/120 min) and integrated PP secretion (-0.1 +/- 0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P < 0.05) when measured 8 hr (1376 +/- 322 cm3/120 min and 3.0 +/- 1.0 nmol/liter/120 min) and two weeks (1437 +/- 263 cm3/120 min and 10.6 +/- 1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P < 0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13 +/- 0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15 +/- 0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P < 0.05 vs 45 min and 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Since abnormal gallbladder emptying may be a contributing factor in the development of gallstone disease, we determined fasting gallbladder volume and postprandial contraction in 20 gallstone patients and 20 normal subjects with the aid of ultrasonography. Moreover, basal plasma cholecystokinin levels and postprandial cholecystokinin (CCK) release were determined. Gallstone patients were divided into strong contractors (13 pts) and weak contractors (below 95% confidence interval for AUC contraction in % during 90 min: 7 pts). Strong contractor patients had significantly larger mean fasting volumes than normal subjects (mean +/- S.E.: 34.9 +/- 6.1 ml and 18.9 +/- 1.6 ml, respectively). This was not true for weak contractor patients (mean fasting volume 23.2 +/- 3.2 ml). Both strong contractor and weak contractor patients had significantly higher mean residual volumes than normal subjects (17.0 +/- 4.1 ml, 18.0 +/- 2.9 ml, and 8.8 +/- 1.1 ml, respectively). Absolute gallbladder emptying was significantly higher for strong contractor patients than for normal subjects, but relative emptying was the same. Opposite patterns of CCK release occurred in gallstone patients and normal subjects. In normal subjects, more CCK release was associated with stronger gallbladder emptying. In contrast, weak contractor gallstone patients had significantly higher CCK release than strong contractor patients. (AUC CCK: 304 +/- 89 pmol/l x 90 min and 106 +/- 29 pmol/l x 90 min, respectively). The present study indicates that strong contractor gallstone patients may have large residual gallbladder volumes due to large starting volumes, whereas weak contractor patients may have large residual volumes due to impaired contraction. Subjects with large fasting and residual volumes may be at increased risk for gallstone disease.(ABSTRACT TRUNCATED AT 250 WORDS)

The radioimmunologic determination of cholecystokinin (CCK) has proved to be notoriously difficult. This is due to the specificity of antibodies, preparation of radiolabeled CCK and low CCK concentrations in human plasma. About 10 years ago we succeeded in developing two highly sensitive region-specific radioimmunoassays for CCK. Antibody T204 binds to the sulfated tyrosine region of CCK, while antibody 1703 reacts with biologically active molecular forms of CCK containing at least 14 amino acid residues. Both antibodies are devoid of significant cross-reaction with gastrin. By means of these two radio-immunoassays CCK concentrations were measured in both tissue and plasma of various species, including man. In addition, the molecular forms of CCK in tissue and plasma were characterized. These CCK assays were used to study the mechanism of CCK secretion. It appeared that digested rather than intact protein and fat stimulated CCK release from the small intestine. The physiologic and pathophysiologic role of CCK in humans was studied using CCK radioimmunoassays and specific CCK-receptor antagonists. CCK was found to play an important role in pancreatic enzyme secretion, gallbladder contraction, and gastrointestinal motility but possibly also in pancreatic carcinogenesis and regulation of satiety and satiation.

1. In patients with cystic fibrosis, abnormalities in plasma cholecystokinin level and gall-bladder emptying may contribute to the development of maldigestion and gall-stones. 2. Therefore, we have measured plasma cholecystokinin levels and gall-bladder volumes before and after ingestion of a standard breakfast in eight adult patients with cystic fibrosis and in eight normal control subjects. 3. In the patients with cystic fibrosis basal (2.8 +/- 0.4 pmol/l; P less than 0.05, t-test) and maximum post-prandial (5.7 +/- 0.5 pmol/l; P less than 0.05, t-test) plasma cholecystokinin levels were significantly higher than those in the control subjects (1.9 +/- 0.1 pmol/l, and 4.5 +/- 0.2 pmol/l, respectively). On the other hand, integrated plasma cholecystokinin secretion in response to the meal was similar (t-test, P = 0.4 versus control subjects). The increased plasma cholecystokinin levels in the patients with cystic fibrosis were accompanied by reduced gallbladder volumes in both the basal (7.8 +/- 2.1 cm3 versus 20.9 +/- 2.3 cm3 in control subjects; P less than 0.005, t-test) and the post-prandial state (2.2 +/- 1.0 cm3 versus 4.8 +/- 0.8 cm3 in control subjects; P = 0.06, t-test). Gall-bladder emptying in the patients with cystic fibrosis was well preserved (70 +/- 7% versus 78 +/- 9% in control subjects; P = 0.4, t-test). 4. In comparison with normal control subjects, patients with cystic fibrosis have an increased basal plasma cholecystokinin level and a reduced gall-bladder volume, whereas post-prandial gall-bladder emptying and plasma cholecystokinin secretion are not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

In the present article we report transitory severely impaired postprandial gallbladder emptying preceding biliary colic in a cholesterol gallstone patient. Gallbladder emptying 1 wk before and 3 wk after the biliary colic was normal. Treatment with ursodeoxycholic acid led to increased fasting gallbladder volumes, but the postprandial residual volume did not change. Postprandial cholecystokinin release appeared not to change during ursodeoxycholic acid treatment or during biliary colic.

It has been previously suggested that treatment with ursodeoxycholic acid leads to decreased gallbladder emptying. The proposed mechanism is decreased release of cholecystokinin through negative feedback control by an increased amount of intraduodenal bile acids. In the present study we examined cholecystokinin release and gallbladder contraction after oral administration of a commercial fatty meal (Sorbitract; Dagra, Diemen, The Netherlands) using ultrasonography in eight normal subjects and eight gallstone patients before and after 1 and 4 weeks of treatment with ursodeoxycholic acid (10 mg kg-1.day-1). Fasting gallbladder volume increased in 15 of 16 subjects during treatment (P less than 0.01). Minimal volume did not change. Therefore, both absolute and relative gallbladder emptying increased during therapy. Maximal decrement of gallbladder volume in milliliters and percentage as well as integrated gallbladder contraction during 90 minutes in milliliters and percentage were significantly increased after 1 and 4 weeks of treatment with ursodeoxycholic acid when compared with data before therapy. Gallstone patients tended to have larger fasting and residual gallbladder volumes than normal subjects, whereas parameters for the amount of bile expelled (maximal decrement of gallbladder volume and integrated gallbladder contraction in milliliters and percentage) did not differ. Release of cholecystokinin did not change during treatment and did not differ significantly between patients and normal subjects. Mean relative percentage of ursodeoxycholic acid in bile during treatment in 13 subjects consenting to have duodenal intubation was 47% (range 31%-60%). Changes of fasting gallbladder volume after institution of bile acid treatment correlated significantly (r = 0.74, P less than 0.01) with changes of cholesterol saturation index but not with relative percentage of ursodeoxycholic acid in bile. This study indicates that gallbladder emptying does not decrease during treatment with ursodeoxycholic acid. Moreover, there is no evidence of decreased cholecystokinin release.

This prospective study was undertaken to determine the effect of partial gastrectomy without vagotomy on postprandial gallbladder contraction and secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP) in 22 peptic ulcer patients randomly assigned to either Billroth II (N = 11) or Roux-en-Y (N = 11) anastomosis. The patients were studied within two weeks before surgery and at six months postoperatively. After surgery basal gallbladder volumes were larger than preoperatively (P less than 0.02). Integrated postprandial gallbladder contraction was not significantly affected by gastrectomy, either in the patients with Billroth II anastomosis (2276 +/- 268 vs 1985 +/- 362%/60 min) or in those with Roux-en-Y anastomosis (2045 +/- 327 vs 2445 +/- 352%/60 min) when studied pre- and postoperatively, respectively. Similarly, integrated postprandial plasma CCK secretion was not significantly changed by either Billroth II gastrectomy (200 +/- 31 vs 166 +/- 21 pM/60 min) or Roux-en-Y gastrectomy (146 +/- 26 vs 147 +/- 12 pM/60 min). However, integrated postprandial PP secretion was significantly (P less than 0.05) lower after Billroth II gastrectomy (6.8 +/- 2.4 vs 2.2 +/- 1.0 nM/60 min), while the reduction in plasma PP after Roux-en-Y gastrectomy just failed to reach statistical significance (6.0 +/- 1.5 vs 3.4 +/- 0.9 nM/60 min). Similarly, the PP response, but not the gallbladder response, to an intravenous bolus injection of 1 IDU CCK/kg body weight was significantly decreased after gastrectomy independent of the type of anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the role of cholecystokinin and the cholinergic system in intestinal stimulation of gallbladder contraction, we studied the effects of atropine on plasma cholecystokinin and gallbladder contraction in six healthy volunteers (four men and two women aged 20 to 27 yr). Effects were noted after intraduodenal fat instillation and after dosage with exogenous cholecystokinin inducing plasma cholecystokinin concentrations similar to those after intraduodenal fat instillation. At regular intervals before and after administration of each stimulus, plasma cholecystokinin concentrations and gallbladder volumes were measured by radioimmunoassay and real-time ultrasonography, respectively. Intraduodenal infusion of 250 ml 20% Intralipid induced a peak plasma cholecystokinin increment of 10.2 +/- 1.6 pmol/L compared with 10.7 +/- 0.7 pmol/L during infusion of 1 Ivy dog unit per kilogram per hour of cholecystokinin. The increases in plasma cholecystokinin after fat and exogenous cholecystokinin administration were accompanied by similar decreases in gallbladder volume. Integrated gallbladder contraction after fat instillation was 3,939% +/- 288%.min compared with 3,301% +/- 359%.min during cholecystokinin infusion (NS). Atropine (0.015 mg/kg as bolus followed by 0.005 mg/kg/hr) did not change plasma cholecystokinin concentrations but induced similar inhibition of gallbladder contraction to 2,296% +/- 511%.min (p less than 0.05) after intraduodenal fat instillation and to 1,756% +/- 456%.min (p less than 0.05) during cholecystokinin infusion. We conclude that cholecystokinin is of major importance in intestinal stimulation of gallbladder contraction. Atropine inhibits the gallbladder response to intraduodenal fat. This inhibition is not due to a reduction in cholecystokinin secretion but to a diminished gallbladder response to cholecystokinin.

It has been claimed that plasma cholecystokinin (CCK) concentrations are raised in patients with pancreatic insufficiency. We have measured plasma CCK concentrations in 32 patients with pancreatic insufficiency (22 alcoholic pancreatitis and 10 cystic fibrosis) and in 30 normal subjects by radioimmunoassays using antibodies with different specificities. Antibody 1703 binds to COOH-terminal forms of CCK containing at least 14 amino acid residues and does not cross-react with gastrins. Antibody T204 binds to all CCK-peptides containing the sulfated tyrosyl region and shows low cross-reactivity with sulfated gastrins but no binding to nonsulfated gastrins. Antibody 5135 binds to all COOH-terminal CCK-peptides and shows full cross-reactivity with gastrins. In patients with pancreatic insufficiency, plasma CCK concentrations (1.2 +/- 0.1 pmol/liter, antibody 1703; 2.0 +/- 0.2 pmol/liter, antibody T204; 12.5 +/- 1.4 pmol/liter, antibody 5135) were not significantly different from those in normal subjects (1.1 +/- 0.1 pmol/liter, antibody 1703; 2.2 +/- 0.3 pmol/liter, antibody T204; 10.5 +/- 0.9 pmol/liter, antibody 5135). Furthermore, plasma CCK concentrations in patients with pancreatic insufficiency due to alcoholic pancreatitis (1.2 +/- 0.1 pmol/liter, antibody 1703; 1.9 +/- 0.2 pmol/liter, antibody T204; 14.0 +/- 1.9 pmol/liter, antibody 5135) were not significantly different from those in patients with cystic fibrosis (1.2 +/- 0.2 pmol/liter, antibody 1703; 2.4 +/- 0.4 pmol/liter, antibody T204, 9.1 +/- 1.0 pmol/liter, antibody 5135). Cross-reactivity with gastrin accounted for almost all CCK-like-immunoreactivity measured with antibody 5135.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the role of cholecystokinin and the cholinergic system in cephalic stimulation of gallbladder contraction and to compare the degree of gallbladder contraction by cephalic stimulation with postprandial gallbladder contraction, 8 healthy volunteers (4 males, 4 females, 20-65 years) underwent the following studies: sham feeding of an appetizing meal, sham feeding with intravenous atropine, and ingestion of the same meal. Gallbladder volume was measured by real-time ultrasonography and plasma cholecystokinin by a sensitive and specific radioimmunoassay using antibody T204. Gallbladder contraction in response to sham feeding, 30 +/- 4% (p = 0.0001 vs. basal), amounted to half of that seen after real feeding, 69 +/- 5% (p less than 0.0001 vs. basal). Significant dissociation between gallbladder response to sham feeding and real feeding was seen from 40 min (p less than 0.005-p = 0.0001). Atropine did not affect basal gallbladder volume but completely abolished gallbladder contraction in response to sham feeding. Neither sham feeding without nor sham feeding with atropine significantly affected plasma cholecystokinin levels. On the other hand, real feeding induced significant increases in plasma cholecystokinin from a basal level of 2.3 +/- 0.1 pM to a peak value of 5.9 +/- 0.4 pM at 40 min. It is concluded that an important cephalic phase of postprandial gallbladder contraction exists which is cholecystokinin-independent but dependent on a cholinergic mechanism.

This study was undertaken to determine in healthy humans the effect of graded physiologic doses of cholecystokinin (CCK) on gallbladder size as assessed by ultrasonography and to analyze the relations between the doses of CCK infused, the plasma CCK increments, the decreases in gallbladder volume, and the cumulative intraduodenal bilirubin output. Infusion of stepwise-increasing doses of CCK, ranging from 0.2 to 6.4 pmol/kg X h, induced dose-related increases in plasma CCK (r = 0.99; p less than 0.001), decreases in gallbladder volume (r = 0.99; p less than 0.001), and increases in intraduodenal bilirubin output (r = 0.96; p less than 0.01). There was a highly significant correlation between the decreases in gallbladder volume and the cumulative intraduodenal bilirubin outputs (r = 0.98; p less than 0.001). Infusion of 0.8 pmol/kg X h of CCK, resulting in an increase in plasma CCK of 1.3 +/- 0.5 pmol/L, was the threshold for stimulating gallbladder contraction as assessed by both ultrasonography and measurement of intraduodenal bilirubin output. It is concluded that ultrasonography is a sensitive method for the quantitation of gallbladder contraction and that physiologic plasma CCK concentrations do stimulate gallbladder contraction.

The effect of ingestion of 50 g fat, 50 g protein, and 50 g starch on plasma cholecystokinin (CCK) concentrations was studied in eight healthy volunteers. Plasma CCK concentrations were measured by radioimmunoassay with Bolton-Hunter-labelled CCK 33, CCK 33 standard, and antibody T204. Antibody T204 was directed to the sulphated tyrosine region of CCK. Ingestion of fat and protein induced significant increases in plasma CCK, whereas ingestion of starch did not significantly influence plasma CCK levels. Peak increments in plasma CCK after fat (4.8 +/- 0.9 pmol/l) and protein (3.4 +/- 0.5 pmol/l) were significantly greater than that after starch (0.9 +/- 0.3 pmol/l). Similarly, the integrated plasma CCK secretion after fat (213 +/- 49 pmol/l X 120 min) and after protein (178 +/- 53 pmol/l X 120 min) was significantly greater than that found after ingestion of starch (9 +/- 23 pmol/l X 120 min). It is concluded that, in contrast to starch, fat and protein are potent stimuli for the release of CCK.

The present study was undertaken to determine whether atropine inhibits the plasma cholecystokinin (CCK) response to intraduodenal fat. Plasma CCK concentrations were measured by radioimmunoassay using two sequence-specific antibodies. Antibody 1703 bound to all COOH-terminal CCK peptides containing at least 14 amino acid residues, while antibody T204 was specific for the sulphated tyrosine region of CCK. Intraduodenal instillation of 60 ml corn oil in 6 normal subjects induced significant increases in plasma CCK. Intravenous administration of atropine (0.015 mg/kg as bolus followed by 0.005 mg/kg X h over 3 h) resulted in significant inhibition of plasma CCK concentrations at 10, 20 and 30 min (antibody 1703) and at 20 and 30 min (antibody T204 ) after instillation of fat. However, the peak increments in plasma CCK during atropine (8.6 +/- 1.9 pmol/l, antibody 1703; 5.4 +/- 1.1 pmol/l, antibody T204 ) were not different from those found without atropine (6.3 +/- 0.8 pmol/l, antibody 1703; 3.9 +/- 0.9 pmol/l, antibody T204 ). Similarly, the integrated plasma CCK secretion after intraduodenal fat was not significantly different when measured during atropine (461 +/- 119 pmol/l X 3 h, antibody 1703; 269 +/- 97 pmol/l X 3 h, antibody T204 ) and without atropine (428 +/- 62 pmol/l X 3 h, antibody 1703; 188 +/- 66 pmol/l X 3 h). It is concluded that administration of atropine delays but does not inhibit the CCK response to intraduodenal corn oil in man.

The present study was undertaken to determine whether bypassing the duodenum in patients with Billroth II gastrectomy affects plasma cholecystokinin (CCK) release in response to ingestion of fat. Plasma CCK concentrations were measured by radioimmunoassay using two antibodies; antibody 1703 binds to all carboxyl-terminal CCK-peptides containing at least 14 amino acid residues, while antibody T204 is specific for the sulphated tyrosine region of CCK. There were no significant differences among fasting plasma CCK concentrations in seven patients with Billroth II gastrectomy (1.3 +/- 0.4 fmol/ml, antibody 1703; 2.6 +/- 0.4 fmol/ml, antibody T204), six patients with Billroth I gastrectomy (0.6 +/- 0.3 fmol/ml, antibody 1703; 2.9 +/- 0.5 fmol/ml, antibody T204), and nine normal subjects (0.7 +/- 0.1 fmol/ml, antibody 1703; 1.9 +/- 0.3 fmol/ml, antibody T204). Ingestion of 250 ml 20% Intralipid induced similar increases in plasma CCK in patients with Billroth II gastrectomy (11.2 +/- 2.0 fmol/ml, antibody 1703; 10.1 +/- 2.4 fmol/ml, antibody T204) as in patients with Billroth I gastrectomy (11.8 +/- 2.0 fmol/ml, antibody 1703; 8.4 +/- 1.1 fmol/ml, antibody T204). However, the increments in plasma CCK in patients with gastrectomy (11.5 +/- 1.4 fmol/ml, antibody 1703; 9.3 +/- 1.4 fmol/ml, antibody T204) were significantly (p less than 0.01) greater than those in normal subjects (4.7 +/- 0.8 fmol/ml, antibody 1703; 4.1 +/- 0.7 fmol/ml). Similarly, the integrated plasma CCK secretion in patients with Billroth II gastrectomy (510 +/- 58 fmol/ml X 120 min, antibody 1703; 458 +/- 69 fmol/ml X 120 min, antibody T204) and in patients with Billroth I gastrectomy (457 +/- 143 fmol/ml X 120 min, antibody 1703; 365 +/- 61 fmol/ml X 120 min, antibody T204) were significantly (p less than 0.05) greater than in normal subjects (230 +/- 49 fmol/ml X 120 min, antibody 1703; 162 +/- 24 fmol/ml X 120 min, antibody T204). It is concluded that the plasma CCK response to oral fat is significantly greater in patients with partial gastrectomy than in normal subjects, and that patients with Billroth I and Billroth II gastrectomy have similar increases in plasma CCK after ingestion of fat.

Gallbladder contraction and hormone release were measured in six healthy volunteers after their ingestion of two commercially available fatty meals (Biloptin Fatty Meal and Sorbitract) and intravenous bolus injection of 1 Ivy Dog Unit/kg body weight cholecystokinin (CCK) to compare the effectiveness of fatty meals to CCK. Differences in gallbladder volumes, rate constants of emptying, and times of maximal contractions, as measured by real-time sonography, were not statistically significant. Peak levels of CCK, a potent stimulant of gallbladder contraction, and of pancreatic polypeptide, an inhibitor of gallbladder contraction, were significantly higher (P less than .05-P less than .005) after administration of CCK than after ingestion of each fatty meal, but this did not significantly affect emptying rate or maximal contraction. We conclude that the use of intravenous CCK does not offer any advantage over the ingestion of fatty meals in radiographic studies of gallbladder involving induced contractions.

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.

This study was undertaken to investigate the effect of ingestion of 80 g Vivonex on gallbladder volume, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) in eight healthy volunteers and to compare the results with those obtained after ingestion of 60 ml corn oil. Gallbladder volumes were measured by ultrasonography. Plasma CCK was determined by radioimmunoassay using region-specific antibodies; antibody 1703 binds to COOH-terminal CCK-peptides containing at least 14 amino acid residues, while antibody T204 binds to COOH-terminal CCK-peptides containing the sulfated tyrosine region. Plasma PP was also measured by radioimmunoassay. Ingestion of Vivonex induced significant increases in plasma CCK (0.6 +/- 0.1 to 4.6 +/- 0.6 pM, antibody 1703; 1.8 +/- 0.3 to 5.9 +/- 0.5 pM, antibody (T204; P less than or equal to 0.0005) and decreases in gallbladder volume (21.4 +/- 2.8 to 11.2 +/- 2.3 cm3; P = 0.0001). Integrated plasma CCK secretion and gallbladder contraction after Vivonex were not significantly different from the results found after corn oil. Both Vivonex and corn oil-induced small increases in plasma PP. We conclude that Vivonex is a potent stimulus for the secretion of CCK and contraction of the gallbladder.

Since bombesin is a potent stimulus of the release of cholecystokinin (CCK), it has been suggested that the stimulatory effect of bombesin on pancreatic enzyme secretion is mediated by CCK. The present study was undertaken to determine the role of CCK in the bombesin-induced stimulation of plasma immunoreactive trypsin. Plasma CCK was measured by radioimmunoassay using the antibody T204, which binds to all biologically active sulfated COOH-terminal CCK-peptides. Plasma trypsin was also measured by radioimmunoassay. Infusion of 5 ng/kg/min bombesin in 6 healthy volunteers increased plasma CCK from 1.2 +/- 0.2-8.9 +/- 0.7 pM (p less than 0.0001). The peak increment in plasma CCK during bombesin (9.3 +/- 0.6 pM) was accompanied by a significant rise in plasma trypsin from 206 +/- 21-334 +/- 44 ng/ml (p less than 0.01). However, when similar increases in plasma CCK were achieved by infusion of 0.018 CU/kg/min CCK-33 (9.9 +/- 0.8 pM) or by intraduodenal instillation of 250 ml 20% Intralipid (9.7 +/- 1.9 pM), no significant changes in plasma trypsin were observed. It is therefore concluded that the stimulatory effect of bombesin on plasma immunoreactive trypsin is not mediated by CCK.

Since previous studies have suggested that in patients with truncal vagotomy (TV) the plasma cholecystokinin (CCK) secretion in response to nutrients is impaired, we have measured the plasma CCK response to a liquid fat meal (250 ml 20% Intralipid) in six patients with TV and pyloroplasty. We have compared the results with those obtained in eight normal subjects, six patients with duodenal ulcer, and eight patients with highly selective vagotomy (HSV). Plasma CCK concentrations were measured by a sensitive and specific radioimmunoassay employing antibody T204 directed against the sulphated tyrosine region of CCK. Basal plasma CCK concentrations were not significantly different among the four groups studied (2.1 +/- 0.4 pmol/l in normal subjects, 2.8 +/- 0.5 pmol/l in duodenal ulcer patients, 3.1 +/- 0.5 pmol/l in patients with TV, and 2.7 +/- 0.5 pmol/l in patients with HSV). The increments in plasma CCK after ingestion of the fat meal in patients with TV (15.7 +/- 3.1 pmol/l) and HSV (14.9 +/- 1.6 pmol/l) were significantly higher (p less than 0.01) than those in normal subjects (4.8 +/- 0.9 pmol/l) and in patients with duodenal ulcer (5.5 +/- 0.6 pmol/l). Similarly, the integrated plasma CCK secretions in patients with TV (554 +/- 139 pmol/l, 120 min) and in patients with HSV (876 +/- 132 pmol/l, 120 min) were significantly increased (p less than 0.05) compared to those in normal subjects (187 +/- 29 pmol/l, 120 min) and in patients with duodenal ulcer (264 +/- 35 pmol/l, 120 min). It is concluded that patients with TV and HSV show an increased plasma CCK secretion in response to a liquid test meal.

The present study was undertaken to compare the effects of equimolar amounts of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) on plasma cholecystokinin (CCK) concentrations and gallbladder contraction in man. On separate mornings and in random order six healthy volunteers ingested either 60 mmol LCT or 60 mmol MCT. Plasma CCK concentrations were measured by a sensitive and specific radioimmunoassay and gallbladder contraction by ultrasonography. Ingestion of LCT induced significant increases in plasma CCK from 2.8 +/- 0.5 to 6.5 +/- 0.7 pmol/l (p less than 0.005) and decreases in gallbladder volume from 33.4 +/- 5.9 to 13.2 +/- 4.2 cm3 (p less than 0.005). On the other hand, no significant changes in plasma CCK and gallbladder volume were found after MCT. Ingestion of MCT was followed by abdominal cramps and diarrhea, while LCT were without side effects. It is concluded that, in contrast to LCT, MCT do not induce CCK release and gallbladder contraction.

The distal gut hormone peptide YY (PYY) mediates feedback inhibition of gastric acid secretion, gastrointestinal motility, and pancreatic enzyme output. To investigate the influence of maldigestion on PYY, we determined plasma PYY levels in patients with celiac disease under basal conditions and in response to intraduodenal fat. Basal PYY was increased in untreated celiac patients (N = 13) compared to patients on a gluten free diet (N = 9) [15.6 (11.8-27.0) pM vs 12.2 (10.1-13.1) pM; P < 0.05] and compared to control subjects (N = 15) [9.5 (8.3-10.4) pM; P < 0.001]. Integrated PYY in response to intraduodenally infused predigested fat (1071+/-293 pM 80 min) was significantly (P < 0.05) greater than in response to undigested fat (322+/-223 pM 80 min) in six untreated celiacs. Plasma concentrations of PYY and cholecystokinin were strongly correlated (r = 0.79; P < 0.001). We conclude that basal PYY levels in untreated celiac disease are elevated, that predigestion of fat enhances PYY release in these patients, and that PYY secretion is correlated with CCK release. [ABSTRACT FROM AUTHOR]

Background: To further establish its role in the ileal brake mechanism, we determined the effect of the distal gut hormone peptide YY (PYY) on gallbladder motility and plasma gut hormones during the cephalic phase of meal stimulation. Methods: Eight healthy volunteers were studied in a randomized crossover design, with or without intravenous infusion of a physiological dose of PYY. On each occasion, subjects underwent modified sham feeding followed by real feeding. Results: PYY reduced gallbladder emptying in response to modified sham feeding from 23 ± 5% to 5 ± 7% (P < 0.01) and integrated plasma pancreatic polypeptide from 2337 ± 397 pmol/L × 90 min to 903 ± 232 pmol/L × 90 min (P < 0.01). PYY enhanced plasma cholecystokinin in response to real feeding from 53 ± 9 pmol/L × 90 min to 82 ± 17 pmol/L × 90 min (P < 0.05), but did not significantly affect maximum gallbladder emptying and tended to decrease plasma pancreatic polypeptide. Conclusion: Circulating PYY suppresses the cephalic phase of postprandial gallbladder emptying, but not meal stimulated maximum emptying. The results support the hypothesis that the effect of PYY on gallbladder emptying is mediated by vagal-dependent rather than cholecystokinin-dependent pathways. [ABSTRACT FROM AUTHOR]