Biomedical subjects

J B Jansen

Publications and source records attributed to J B Jansen.

At least 199 records · Page 11Linked to original sources

PubMed1990

Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans.

The present study was undertaken to investigate the gastric and intestinal phase of stimulation of postprandial gallbladder contraction and endogenous cholecystokinin secretion in patients with truncal vagotomy and pyloroplasty. Gallbladder emptying, measured by cholescintigraphy, and endogenous cholecystokinin secretion, measured by radioimmunoassay, were studied after both intragastric and intraduodenal administration of corn oil. In addition, the gallbladder responsiveness to cholecystokinin was investigated by infusion of stepwise increasing doses of exogenous cholecystokinin. In the 6 patients with truncal vagotomy, plasma CCK and gallbladder responses to intraduodenal fat were significantly delayed compared to normal subjects. In contrast, the onset of the plasma cholecystokinin increase and gallbladder emptying after intragastric fat was significantly earlier in the vagotomized patients compared with the normal subjects. In the normal subjects, plasma cholecystokinin and gallbladder responses to intragastric fat were significantly lower during the first 25 min after stimulation compared with the results after intraduodenal fat, whereas in the patients with truncal vagotomy and pyloroplasty, no differences in plasma cholecystokinin and gallbladder responses were found according to the site of fat stimulation. The gallbladder-emptying response to exogenous cholecystokinin increased significantly in patients who had undergone truncal vagotomy. It is concluded (a) that truncal vagotomy with pyloroplasty influences the timing but not the magnitude of fat-stimulated gallbladder contraction and endogenous cholecystokinin secretion; and (b) that the sensitivity of the gallbladder to endogenous and exogenous cholecystokinin is significantly increased in patients with truncal vagotomy.

Adult↗

PubMed1990

Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis.

Twenty-nine nongastrectomized and three partially gastrectomized patients with chronic reflux esophagitis resistant to 12 weeks' treatment with histamine H2-receptor antagonists were treated with a daily oral dose of 20-40 mg of omeprazole for 12-30 months. Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals. Serum gastrin levels significantly (P less than 0.01) increased threefold to fourfold during the first 1-2 months of the study when all patients ingested 40 mg of omeprazole daily. Dose reduction to 20 mg did not significantly decrease gastrin levels. Serum gastrin levels showed a trend to further increase after the first 3 months of treatment, reaching statistically significant differences for values from the 3-12-month period (P less than 0.05) and from the 3-24-month period (P less than 0.005). Women and patients with high basal serum gastrin levels before omeprazole treatment were more likely to achieve higher serum gastrin levels during omeprazole treatment. Serum pepsinogen A and C levels were significantly (P less than 0.01) increased at all time intervals during long-term treatment with omeprazole. No significant tendency toward higher serum pepsinogen C levels in time was observed. However, serum pepsinogen A levels and the ratio of pepsinogen A to pepsinogen C further increased significantly (P less than or equal to 0.05) during the initial 3-12-month period. However, this trend was not observed anymore afterward. Antrectomized patients did not show increases in serum gastrin and serum pepsinogen A and C levels, suggesting that hypergastrinemia may be involved in the observed hyperpepsinogenemia.

Aged↗

PubMed1990

Effects of ursodeoxycholic acid on gallbladder contraction and cholecystokinin release in gallstone patients and normal subjects.

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.

Adult↗

PubMed1990

Comparison of the effect of lorglumide on pancreatic growth stimulated by camostate in rat and hamster.

We conducted a 14 day experiment in which we administered camostate (a trypsin inhibitor) and cholecystokinin alone or in combination with lorglumide, a cholecystokinin receptor antagonist, to both rats and hamsters. Plasma cholecystokinin levels were 21.7 +/- 3.2 pM and 19.6 +/- 2.5 pM with camostate, 16.3 +/- 2.4 pM and 14.8 +/- 2.2 pM with exogenous cholecystokinin, and 3.7 +/- 0.4 pM and 4.2 +/- 1.0 pM in control experiments in rats and hamsters, respectively. Both cholecystokinin and camostate were found to promote pancreatic growth in rats (18 +/- 4 and 111 +/- 7%, respectively) and hamsters (76 +/- 18 and 61 +/- 12%, respectively). Although lorglumide caused a decrease of this effect of camostate in both rats (78 +/- 5%) and hamsters (25 +/- 10%), it only became significant in rats. We therefore conclude that there are important interspecies differences in the role cholecystokinin plays in mediating the trophic effects of trypsin inhibitors on the pancreas.

Animals↗

PubMed1990

Effects of lorglumide on gastrin- and peptone-stimulated gastric acid secretion in rats.

This study in rats demonstrates that gastric acid secretion stimulated by infusion of gastrin 17-I yielding plasma concentrations in the physiological range is almost abolished by the cholecystokinin-receptor antagonist lorglumide. Furthermore, lorglumide also inhibited intragastric peptone stimulated gastric acid secretion by 43%. When compared to peptone stimulation with a saline background infusion, lorglumide infusion inhibited peptone stimulated gastric acid secretion only significantly in the late (20 to 30 minutes) part of stimulation, while the initial part (0 to 10 and 10 to 20 minutes) was not significantly inhibited by lorglumide. Both peptone stimulation and gastrin infusion significantly augmented serum gastrin concentrations, which were not significantly influenced by lorglumide. The serum gastrin concentrations achieved during gastrin infusion were higher than during peptone stimulation, however the differences were not statistically significant. It is concluded that lorglumide abolishes gastrin stimulated gastric acid secretion in rats, but only partly (43%) inhibits peptone-meal stimulated gastric acid secretion. In contrast to the gastrin infusion experiments, where lorglumide abolishes acid secretion during the entire study period, the compound inhibits gastric acid secretion more effectively towards the end of peptone stimulation than in the beginning.

Animals↗

PubMed1990

Coffee stimulation of cholecystokinin release and gallbladder contraction in humans.

We studied the effect of the ingestion of 400 mL regular coffee on plasma cholecystokinin (CCK) concentrations and of 165 mL regular and decaffeinated coffee on plasma CCK and gallbladder contraction in six healthy regular coffee drinkers. Plasma CCK concentrations rose 3.3 +/- 0.4 pmol/L after 400 mL and 2.8 +/- 0.9 pmol/L after 165 mL regular coffee compared with 1.8 +/- 0.6 pmol/L after 165 mL decaffeinated coffee. These plasma CCK increments were greater than those after 400 and 165 mL of an isosmotic and isothermic sodium chloride solution (0.6 +/- 0.2 and 0.4 +/- 0.1 pmol/L, respectively). An average gallbladder contraction of 33 +/- 7% was observed after 165 mL regular coffee and 29 +/- 10% after 165 mL decaffeinated coffee, whereas after 165 mL sodium chloride the contraction was only 10 +/- 12%. We conclude that both regular coffee and decaffeinated coffee give rise to increments in plasma CCK and contractions of the gallbladder.

Adult↗

PubMed1990

Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters.

Cholecystokinin (CCK) has been shown to promote pancreatic growth and azaserine-induced pancreatic carcinogenesis in rats. The present study was carried out to determine effects of CCK on pancreatic growth and carcinogenesis in the N-nitrosobis(2-oxopropyl)amine (BOP) hamster model. One hundred male Syrian golden hamsters were injected s.c. once weekly with 20 mg BOP/kg body wt at 6, 7 and 8 weeks of age, and divided into four groups of 25 animals each, which received one of the following treatments (once daily, 3 days/week for 16 weeks): gelatin; CR-1409, a potent CCK-receptor antagonist; CCK-8, 2.5 micrograms/kg body wt; or CCK-8 in combination with CR-1409 (30 min before CCK treatment). The animals were killed after 19 weeks. The growth of the pancreas but not the incidence of pancreatic (pre)neoplastic lesions was enhanced by CCK-8. CR-1409 did not influence the effect of CCK on pancreatic growth.

Animals↗

PubMed1990

Effect of various triglycerides on plasma cholecystokinin levels in rats.

In the rat model, polyunsaturated vegetable oil has been shown to stimulate pancreatic secretion and promote pancreatic carcinogenesis, whereas dietary fish oil has been found to protect against carcinogenesis. Because cholecystokinin (CCK), a hormonal polypeptide secreted from the upper small intestine after food stimulation, is the most important known humoral stimulus of pancreatic secretion and also because this gut hormone has been shown to promote pancreatic carcinogenesis in the rat, we decided to study the effects of various triglycerides on CCK secretion in this species. Small amounts (2.5 mL) of corn oil, beef tallow, fish oil, medium-chain triglyceride (MCT) oil or saline (control) were administered to groups of five fasted rats. Plasma CCK levels were measured using a specific and sensitive radioimmunoassay. The maximal CCK increments for corn oil, beef tallow, fish oil and MCT oil were 3.0 +/- 0.5, 2.1 +/- 0.6 and 7.2 +/- 0.4 pmol/L, respectively. All the increments were significantly greater (p less than 0.05) than the change found after saline administration (-0.8 +/- 0.3 pmol/L). In another experiment, plasma CCK levels after intragastric administration of MCT oil reached a peak increment of 6.4 +/- 0.4 pmol/L after 240 min and continued to be significantly increased for the entire 480-min study period. It was concluded that all four triglycerides caused a significant CCK release in the rat and that the MCT oil was the most powerful stimulator of CCK secretion among the triglycerides studied.

Analysis of Variance↗

PubMed1990

Role of cholecystokinin in bombesin-stimulated pancreatic enzyme secretion in conscious rats.

Since bombesin is a potent stimulus of cholecystokinin (CCK) secretion, it is assumed that the stimulatory effect of bombesin on pancreatic protein secretion is mediated by CCK. This study was undertaken to determine in the conscious rat with a cannulated pancreatic duct the role of CCK in the stimulation of pancreatic protein secretion by bombesin. Infusion of 18 pmol/kg/30 min of bombesin into rats stimulated pancreatic protein secretion from 6.7 +/- 1.1 to 9.9 +/- 0.4 mg/30 min (p less than 0.05). This stimulation of pancreatic protein secretion was accompanied by a significant increase in plasma CCK, measured by a specific and sensitive radioimmunoassay, from 3.2 +/- 0.2 to 4.7 +/- 0.2 pM (p less than 0.01). When a similar plasma CCK increment as during infusion of bombesin (1.5 +/- 0.2 pM) was achieved by infusion of 6 pmol/kg/30 min of exogenous CCK (1.6 +/- 0.3 pM), pancreatic protein secretion increased only from 6.9 +/- 0.7 to 7.6 +/- 0.7 mg/30 min (p less than 0.05). To achieve a pancreatic protein secretion similar to that during bombesin, large doses of exogenous CCK (24 pmol/kg/30 min) were needed, resulting in considerably higher plasma CCK concentrations of 10.9 +/- 0.7 pM. It is concluded that CCK is unlikely to play a significant role in the stimulation of pancreatic protein secretion by bombesin in the rat.

Animals↗

PubMed1990

Effect of increasing oral doses of loperamide on gallbladder motility in man.

1. Loperamide, a peripherally acting opiate receptor agonist with antidiarrhoeal action, inhibits ileal and colonic motor function. To determine the effect of loperamide on gallbladder motility, we have pretreated five healthy volunteers with 2 mg oral loperamide 24 h, 20, 12 and 2.5 h before; six healthy volunteers with 16 mg oral loperamide 2.5 h before; and eight healthy volunteers with 16 mg oral loperamide 12 and 2.5 h before intravenous infusion of a 'physiological dose' of 12.5 pmol kg-1 cholecystokinin (CCK) for 1 h to stimulate gallbladder contraction. All subjects served as their own controls. Gallbladder volume was measured by ultrasonography and plasma CCK by radioimmunoassay until 90 min after start of the CCK infusion. 2. Infusion of CCK resulted in plasma CCK concentrations similar to those after intraduodenal fat. Integrated gallbladder contraction after 4 X 2 mg loperamide (4600 +/- 891% min) was similar to that without pretreatment (5270 +/- 1037% min; NS). Integrated gallbladder contraction after 1 X 16 mg loperamide diminished from 5458 +/- 412% min without to 2632 +/- 816% min with loperamide (P less than 0.05), and was completely abolished to -596 +/- 762% min (P less than 0.0005 vs without loperamide) after 2 X 16 mg loperamide. 3. It is concluded that loperamide inhibits gallbladder contraction in response to a physiological dose of cholecystokinin in a dose-dependent manner.

Adult↗

PubMed1990

Effect of intermittent administration of omeprazole on serum pepsinogens in duodenal ulcer patients and healthy volunteers.

1. Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K(+)-APT-ase, was administered orally at a dose of 20 mg in the morning of 3 consecutive days, followed by a period of 4 days without medication, and this intermittent dosage regimen was continued for 4 weeks. 2. During intermittent administration of omeprazole to 10 patients with duodenal ulcer disease and 10 healthy volunteers concentrations of serum pepsinogen A and serum pepsinogen C were monitored by sensitive and specific radioimmunoassays to study whether the effect of this treatment on serum pepsinogens is different between patients and normal subjects and to evaluate whether serum pepsinogen levels can be used to assess compliance with therapy. 3. Administration of omeprazole for 3 days induced significant increases in pepsinogen A and pepsinogen C serum concentrations, which rapidly fell after stopping the omeprazole intake. The pattern of serum pepsinogens after stopping the drug was different for duodenal ulcer patients and normal subjects. Both pepsinogens were intra-individually related in both patients and healthy subjects when compared during the first and last 3-day course with omeprazole, but in duodenal ulcer patients both pepsinogens tended to be higher in the last treatment course, while the opposite was found in the normal subjects. 4. The present study confirms that serum pepsinogen concentrations are higher in duodenal ulcer patients than in normal subjects, but also shows for the first time that serum pepsinogens in the patients respond differently upon stimulation with omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

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.

Adult↗

PubMed1990

Postprandial exocrine pancreatic function during long-term treatment with the somatostatin analogue SMS 201-995 in acromegalic patients.

Long-term treatment with the somatostatin analogue SMS 201-995 (SMS) might impair exocrine pancreatic function, secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP), and pancreatic size. In five acromegalics on chronic treatment with SMS, we investigated postprandial 6-h urinary excretion of p-aminobenzoic acid (PABA) and p-aminosalicylic acid (PAS) after s.c. injection of 100 micrograms SMS or placebo and after ingestion of 2 mmol nBT-PABA and 2 mmol PAS. In the acromegalics, urinary PABA/PAS ratio (reflecting exocrine pancreatic function) after SMS was similar to that after placebo (P greater than 0.10) and higher than in healthy volunteers (n = 8, P = 0.05). The initial inhibition of plasma CCK secretion by SMS was cancelled during the 3rd h after the meal, whereas PP release remained completely abolished. Pancreatic size as measured by ultrasonography, was not reduced in seven acromegalics compared with 14 healthy volunteers. It is concluded that despite a blunted release of the trophic hormone CCK, long-term treatment with SMS 201-995 neither induces an abnormally small pancreas nor deterioration of postprandial exocrine pancreatic function in patients with acromegaly.

4-Aminobenzoic Acid↗

PubMed1990

Pancreatic exocrine and gallbladder function during long-term treatment with octreotide (SMS 201-995).

Since octreotide (SMS 201-995, Sandostatin; Sandoz Pharmaceuticals) is a potent inhibitor of pancreatic exocrine secretion and gallbladder contraction, long-term treatment with this drug may theoretically result in impaired pancreatic function and gallstones. However, we observed excellent pancreatic exocrine function--as assessed by the PABA/PAS test--in acromegalics who received octreotide treatment for more than 6 months. Plasma cholecystokinin showed a significant, although blunted, postprandial response, which exceeded the threshold for gallbladder contraction in healthy controls. Remarkably, postprandial gallbladder contraction was completely abolished for at least 2 h during octreotide treatment. In contrast to other studies, none of 16 acromegalic patients on long-term octreotide treatment developed gallstones. Although the incidence of gallstones in patients on long-term octreotide treatment may be increased, the risk seems to be variable.

4-Aminobenzoic Acid↗

PubMed1990

Postprandial release of cholecystokinin after duodenum-preserving total pancreatectomy is independent of intraluminal pancreatic protease activity in dogs.

The effect of meal stimulation, with and without the intraduodenal presence of pancreatic enzymes, on plasma cholecystokinin (CCK) release was studied in order to investigate the role of CCK in the putative feedback mechanism between intraduodenal pancreatic proteases and pancreatic enzyme secretion. Plasma CCK concentrations in response to a semiliquid meal, with and without the supplementation of exocrine pancreatic enzymes, were measured in 8 dogs after duodenum preserving pancreatectomy. With a well-balanced endocrine and exocrine substitution regimen all dogs were kept in good clinical condition, without steatorrhea or significant weight loss, and fasting plasma glucose levels within the normal range. Exocrine supplementation was stopped at least 3 days prior to tests. Basal plasma CCK levels after 3 days without exocrine supplementation (2.5 +/- 0.3 pM) did not significantly differ from the results with supplementation (3.0 +/- 0.5 pM) nor from the preoperative levels (2.3 +/- 0.3 pM). In addition, integrated plasma CCK responses to the meal without exocrine supplementation (330 +/- 37 pM.90 min) were not significantly different from the responses to the meal with exocrine supplementation (303 +/- 49 pM.90 min), or from the postprandial CCK response in the dogs with an intact pancreas preoperatively (390 +/- 100 pM.90 min). It is concluded that the release of CCK in dogs after total pancreatectomy is independent of intraluminal protease activity. It is therefore not likely that CCK mediates the putative feedback mechanism between intraluminal protease activity and pancreatic enzyme secretion in dogs.

Animals↗

PubMed1990

The effect of intravenous amino acids on intragastric pH during continuous intragastric pH-monitoring.

The present study was undertaken to determine the onset and duration of gastric acid stimulation by amino acids measured by continuous intragastric pH-monitoring. A 3-hour intravenous infusion of 250 ml of an amino acid solution (Vamin 18) was given to 20 healthy volunteers. The results were compared with data obtained during basal conditions and during a 3-hour intravenous infusion of a 5% glucose solution. One hour after starting the amino acid infusion the decrease in intragastric pH-levels reached statistical significance (p less than 0.02). This increased intragastric acidity lasted for one hour after stopping the amino acid infusion. Serum gastrin levels remained unchanged. These results indicate that continuous intragastric pH-monitoring is capable of demonstrating stimulation of gastric acidity during and for one hour after an amino acid infusion. These findings may be important for patients on parenteral nutrition.

Adult↗

PubMed1990

Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man.

The present study was designed (a) to characterize the activity of loxiglumide as a peripheral cholecystokinin (CCK) antagonist in healthy human subjects, and (b) to determine whether CCK is a physiologic regulator of the intestinal phase of meal-stimulated exocrine pancreatic and biliary secretions in man. Intravenous loxiglumide (22 mumol/kg per h) was highly potent in antagonizing CCK8-induced pancreatic enzyme and bile acid secretion as well as pancreatic polypeptide release. The potency and selectivity of loxiglumide as an antagonist of CCK provides the tool for evaluating the role of CCK as a physiological mediator of meal-induced pancreatic and biliary responses in humans. Infusion of a liquid test meal into the duodenum evoked an immediate response of pancreatic enzyme and bilirubin outputs, respectively. Intravenous loxiglumide significantly inhibited the meal-induced pancreatic amylase output by 63% (P less than 0.05), lipase output by 43% (P less than 0.05), and bilirubin output by 59% (P less than 0.05). These data suggest that CCK is a physiological mediator of the intestinal phase of meal-stimulated pancreatic and biliary responses.

Adult↗

PubMed1990

Temporary cessation of long-term maintenance treatment with omeprazole in patients with H2-receptor-antagonist-resistant reflux oesophagitis. Effects on symptoms, endoscopy, serum gastrin, and gastric acid output.

To study the effects of sudden withdrawal of long-term maintenance therapy with omeprazole for up to 4 years, 14 patients with resistant reflux oesophagitis were asked to stop their treatment temporarily. Ten days after withdrawal median basal acid output had increased significantly (p = 0.01) from 0 (range, 0-1.18) on day 1 to 1.95 (range, 0-8.45) mmol/h on day 10. Median serum gastrin levels were raised during treatment with omeprazole but decreased significantly from 166 to 42 ng/l within the 10 days of the study (p = 0.01). The median integrated gastrin response after meal stimulation decreased significantly (p less than 0.001) from 758.6 ng/l on day 1 to 267.9 ng/l on day 10. On day 10 after withdrawal of omeprazole all patients had endoscopic and symptomatic evidence of recurrent oesophagitis. Reflux patients receiving maintenance treatment with omeprazole for up to 4 years showed prompt normalization of serum gastrin levels and return of gastric acid production within 10 days after stopping the treatment. Consequently, there was a fast recurrence of aggravation of reflux symptoms and oesophagitis.

Adult↗