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Biomedical subjects

J B Jansen

Publications and source records attributed to J B Jansen.

At least 217 records · Page 12Linked to original sources

High doses of ranitidine in patients with reflux oesophagitis.

As in duodenal and gastric ulcer patients, a highly significant correlation between suppression of 24-h intragastric acidity and healing rates in reflux oesophagitis patients was demonstrated by meta-analysis of data obtained from the literature (r = 0.90; p less than 0.001). Furthermore, we have demonstrated in eight patients with reflux oesophagitis that 2-week treatment courses with 300 mg ranitidine twice daily and 300 mg four times daily progressively decreased 24-h intraoesophageal acidity but only moderately elevated basal and meal-stimulated serum gastrin concentrations, significantly below gastrin values obtained after a 2-week treatment course with 20mg omeprazole once daily. Further studies are awaited to demonstrate long-term effects on both healing rates and serum gastrin responses with high doses of histamine H2-receptor antagonists.

Adult↗

Role of cholecystokinin in the regulation of pancreatic enzyme secretion in the rat.

Whereas pancreatic exocrine secretion in the rat varies considerably depending on the condition under which a study is performed, it is of great importance to study pancreatic pathophysiology in vivo, while the rat is conscious. In recent years several studies were performed in the conscious rat with a cannulated pancreatic duct, and much progress was made in delineating the role of cholecystokinin (CCK) in the regulation of pancreatic enzyme secretion in more detail. This progress was mainly due to the development of specific and sensitive radioimmunoassays for CCK and the availability of specific CCK-receptor antagonists. In the rat it was shown that a negative feedback regulation mechanism of pancreatic enzyme and CCK secretion exists in which intraluminal trypsin and, to a lesser extent, bile acids and plasma CCK, plasma secretin, and the cholinergic system play important roles. Probably by interference with this feedback mechanism in the rat, casein is a stronger stimulant of plasma CCK release and pancreatic exocrine secretion than fat. Finally, CCK does not play an important role in bombesin-stimulated pancreatic enzyme secretion in the rat.

Animals↗

Effect of gastrectomy with either Roux-en-Y or Billroth II anastomosis on small-intestinal function.

This prospective study was undertaken in patients scheduled for gastrectomy for peptic ulcer disease to determine the effect of partial gastrectomy with either Roux-en-Y (n = 11) or Billroth II anastomosis (n = 11) on the function of the small intestine. Patients were studied before and at 6 months (blood and small-intestinal function tests) and at 24 months (blood tests) postoperatively. Median postoperative body weights at 6 months (70.5 kg; p less than 0.01) and 12 months (70.3 kg; NS) were lower than preoperatively (73.0 kg). Haemoglobin concentrations at 6 months (8.9 mM; p less than 0.01) and at 24 months (9.1 mM; p less than 0.05) were also significantly reduced compared with the preoperative value (9.5 mM). However, neither at 6 nor at 24 months postoperatively were there significant changes for serum iron, iron saturation, folic acid, vitamin B12, protein, albumin, alkaline phosphatase, and calcium concentrations. Whereas no significant deterioration of the absorption of D-xylose and vitamin B12 or of faecal fat excretion was observed, the orocoecal transit time was significantly shortened from 98 to 50 min (p less than 0.01), the expiratory hydrogen excretion after a 50-g oral glucose load was significantly increased from 8 to 54 ppm (p less than 0.01), as was indicanuria from 257 to 368 mumol/24 h (p less than 0.01). Apart from a lower serum iron concentration and iron saturation index in the Roux-en-Y patients 6 months postoperatively (p less than 0.05), no significant differences between the two types of anastomosis were observed. It is therefore concluded that both in patients with Roux-en-Y and in those with Billroth II anastomosis most abnormalities observed after gastrectomy are secondary to an accelerated small-intestinal transit.

Anastomosis, Roux-en-Y↗

Evaluation of tests of exocrine and endocrine pancreatic function in older patients with cystic fibrosis.

In order to determine the value of noninvasive tests in the analysis of pancreatic function in cystic fibrosis, 14 older cystic fibrosis patients were studied by a set of noninvasive tests of exocrine and endocrine pancreatic function. The tests, comprising trypsin, total amylase, pancreatic isoamylase, lipase, pancreatic polypeptide (PP), glucose and insulin in fasting serum, PP, glucose and insulin in postprandial serum, and p-aminobenzoic acid (PABA) excretion in urine, were compared to fecal fat excretion after discontinuation of pancreatic enzyme supplementation. Eleven of the 14 patients were found to have a fecal fat excretion of more than 7 g/day. Serum levels of trypsin, pancreatic isoamylase and lipase, and the urinary excretion of PABA showed significant negative correlations with fecal fat excretion. Endocrine pancreatic function was abnormal in the majority of patients with fibrocystic disease. Although serum trypsin, postprandial PP, and urinary PABA excretion were the most sensitive tests for severe exocrine pancreatic insufficiency, the differences in sensitivity were rather modest. Therefore, the type of test to be selected for clinical use is mainly dependent upon factors as accessibility, simplicity, patient's acceptability, and costs.

4-Aminobenzoic Acid↗

Ambulatory 24-hour pH-metry in the diagnosis of gastroesophageal reflux disease. Determination of criteria and relation to endoscopy.

The results of ambulatory 24-h esophageal pH monitoring in 67 patients with gastroesophageal reflux symptoms (endoscopic esophagitis, n = 44; normal endoscopy, n = 23) were compared with those of 27 normal subjects without reflux symptoms. Patients with reflux symptoms had significantly increased gastroesophageal reflux compared with normal subjects. Acid reflux time was significantly (p less than 0.001) correlated with the severity of endoscopic esophagitis. Linear discriminant analysis was used to differentiate, for each reflux variable, between patients and controls. When the percentage of overall time at pH below 4 was used as a single determinant of gastroesophageal reflux, the sensitivity and specificity were 81% and 85%, respectively, with 4% as upper limit of normal. Pathologic reflux was found in 61% of the patients with negative endoscopy. Long-term ambulatory pH-metry is of clinical value in detecting pathologic reflux in symptomatic patients with negative endoscopy.

Acids↗

Feedback regulation of human pancreatic secretion. Effects of protease inhibition on duodenal delivery and small intestinal transit of pancreatic enzymes.

To determine the effects of luminal protease inhibition on duodenal delivery and the intraluminal fate of pancreatic enzymes, six healthy subjects were intubated with an oro-ileal multilumen tube assembly. By using nonabsorbable markers, cumulative trypsin, chymotrypsin, lipase, and amylase activities were measured as delivered to duodenum, midjejunum, and distal ileum, with or without simultaneous duodenal perfusion of the protease inhibitor camostat at graded doses. Compared with saline, camostat (a) inhibited trypsin activity in the entire small intestinal lumen by up to 99%, and significantly reduced chymotrypsin activity by up to 89%; (b) significantly increased duodenal deliveries of lipase activity, amylase activity and volume; (c) did not influence plasma cholecystokinin concentrations; and (d) significantly increased jejunal and ileal deliveries of lipase but not amylase activity. Small intestinal transit and motility were not affected by camostat. In additional in vitro studies, camostat significantly reduced the spontaneous decline in lipase activity in fresh human duodenal juice incubated at 37 degrees C. These findings demonstrate that duodenal deliveries of lipase and amylase activities increase when intraluminal protease activity is decreased; they suggest that this increase is not caused by slower proteolytic destruction of enzyme protein but by stimulation of pancreatic secretion. Thus, luminal protease-mediated feedback regulation of pancreatic secretion may be operative in humans. Because plasma cholecystokinin concentrations were not affected, these effects may in part be independent of cholecystokinin. The data further suggest that proteolytic digestion plays a major role in the rapid loss of luminal lipase activity on small intestinal transit.

Adult↗

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.

Adult↗

Role of cholecystokinin in regulation of gastrointestinal motor functions.

By means of loxiglumide, a potent and highly specific antagonist for cholecystokinin (CCK), the effects of blocking CCK receptors on gastrointestinal motility were investigated in a placebo-controlled study in healthy young men (aged 21-39, mean 24 years). Gallbladder contraction stimulated by ingestion of a liquid test meal was completely abolished by oral administration of loxiglumide 30 min before the test meal. Gastric emptying of radio-opaque markers ingested with the test meal was significantly accelerated by loxiglumide (area under the curve [markers x h] 33.3 [SEM 3.8] vs 17.9 [2.7] after placebo). No effect of loxiglumide was found on small-bowel transit time, but 7 days' treatment with oral loxiglumide (800 mg three times daily) significantly shortened colonic transit time (29.4 [4.1] h after placebo, 15.0 [3.4] h after loxiglumide). It is concluded that CCK is an important mediator of meal-induced gallbladder contraction and is involved in the regulation of gastrointestinal motility in man.

4-Aminobenzoic Acid↗

Modulation by CR-1409 (lorglumide), a cholecystokinin receptor antagonist, of trypsin inhibitor-enhanced growth of azaserine-induced putative preneoplastic lesions in rat pancreas.

Feeding of raw soya flour or other trypsin inhibitors such as camostate is a well-established method for promoting growth of (pre)neoplastic foci induced in the exocrine pancreas of rats by azaserine. The effect of trypsin inhibitors is thought to be mediated through an increased release of cholecystokinin. Using the specific cholecystokinin receptor antagonist lorglumide (CR-1409), we performed a 16-wk study to investigate the potential of this drug in inhibiting growth of putative preneoplastic foci and to determine whether and to what extent cholecystokinin is responsible for the effect of trypsin inhibitors on pancreatic growth. After initiation with 30 mg/kg of azaserine at 19 days of age, six groups of 15 rats each received one of the following treatments: camostate, cholecystokinin-8, or gelatin control, either or not in combination with CR-1409, once daily, 3 days wk for 16 wk. Plasma cholecystokinin levels, measured 30 min after the stimulus, were similar after camostate and cholecystokinin octapeptide administration. After 16 wk the pancreata were removed, weighted, and quantitatively analyzed for the number and size of putative preneoplastic foci by light microscopy. Both camostate and cholecystokinin octapeptide stimulated pancreatic growth and development of acidophilic putative preneoplastic foci, whereas growth of basophilic putative preneoplastic foci was inhibited by camostate but stimulated by cholecystokinin. CR-1409 almost completely abolished the effect of cholecystokinin and was found to cause a significant decrease in the effects of camostate. It is concluded that (a) cholecystokinin plays a significant role in camostate-stimulated growth of acidophilic putative preneoplastic foci in rat pancreas and (b) CR-1409 inhibits growth of putative preneoplastic foci induced in rat pancreas by azaserine and hence may be of potential value for the treatment of pancreatic cancer in humans.

Animals↗

Study into the role of cholecystokinin in bombesin-stimulated pancreatic growth in rats and hamsters.

The effects of cholecystokinin and bombesin on growth of the exocrine pancreas have been studied extensively in rats but not in hamsters. Since hamsters are frequently used for studying pancreatic carcinogenesis it seems highly relevant to determine the effects of these peptides on growth of the hamster pancreas as well. In order to determine whether or not bombesin stimulates pancreatic growth in hamsters and to investigate the role of cholecystokinin in mediating this effect, we conducted a 2-week experiment in which cholecystokinin and bombesin were administered to both rats and hamsters, either with or without lorglumide (CR-1409; a specific cholecystokinin receptor antagonist). Rats were included in the study for comparison. Cholecystokinin and bombesin were found to stimulate pancreatic growth and DNA synthesis in both species. Lorglumide did not significantly influence the effect of bombesin on pancreatic weight but did significantly inhibit DNA synthesis in both species. The effect of cholecystokinin on pancreatic weight was greater in hamsters than in rats. This effect was significantly inhibited by lorglumide in hamsters but not in rats, whereas a significant decrease in DNA content was attained in both species. Thus, this study shows marked differences between rats and hamsters in the pancreatic growth response to cholecystokinin and bombesin.

Animals↗

Effect of short-term omeprazole administration on serum pepsinogens in relation to fasting serum gastrin and gastric acid secretion.

A study has been done in 10 male healthy volunteers of the effect of oral omeprazole 20 mg daily for 3 days on the serum concentrations of Pepsinogens A and C in relation to changes in fasting serum gastrin and basal and pentagastrin stimulated gastric acid output. The concentrations of Pepsinogens A and C showed concomitant and variable but significant increases, and the Pepsinogen A, C ratio did not change during the 3-day course of omeprazole. The increments were also significantly correlated with the increase in fasting serum gastrin and with the reduction in pentagastrin stimulated acid output. The correlations were mainly due to the marked inhibition of gastric acid secretion and the corresponding increases in serum gastrin and Pepsinogens A and C in two subjects, as in the other 8 subjects the changes were only modest. There appears to be a relationship, therefore, between the degree of inhibition of acid by omeprazole and the parallel increases in both serum pepsinogens and fasting gastrin.

Adult↗

Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients.

Impaired gallbladder emptying is one of the various factors suggested to be involved in the pathogenesis of gallstones. The present study was undertaken to determine whether gallbladder emptying, endogenous cholecystokinin (CCK) secretion, or their interrelation is altered in patients with gallstones. After intraduodenal administration of 60 ml corn oil, plasma CCK concentration was measured by a sensitive and specific radioimmunoassay and gallbladder emptying by cholescintigraphy. Patients with gallstones (N = 20) produced significantly less endogenous CCK (105 +/- 17 pmol/liter 60 min; P less than 0.001) than control subjects (191 +/- 11 pmol/liter 60 min, N = 20); gallbladder emptying in the patients was significantly decreased at 5, 10, 40, 45, and 50 min but the reduction in gallbladder emptying did not reach statistical significance at 60 min (patients 44 +/- 8%, control subjects 60 +/- 4%). In addition, the gallbladder responsiveness to intravenous infusion of the synthetic CCK analog cerulein was investigated. Based on the results of gallbladder emptying in response to endogenous and exogenous CCK, four subgroups of gallstone patients were identified: (1) a group (N = 7) with normal gallbladder sensitivity to CCK, (2) a group (N = 6) with significantly increased gallbladder sensitivity to CCK, (3) a group (N = 6) with impaired gallbladder emptying after corn oil due to a significantly reduced endogenous CCK secretion but with normal gallbladder sensitivity to CCK, and (4) one patient whose gallbladder was unresponsive to CCK and was found to have chronic cholecystitis at surgery.

Ceruletide↗

Pancreatobiliary responses to an intragastric amino acid meal: comparison to albumin, dextrose, and a maximal cholecystokinin stimulus.

Little is known about how gastric and pancreatobiliary responses differ after intake of elemental diets from responses to polymeric food. We therefore compared pancreatic and biliary secretions after gastric instillation of albumin (7 g%, with dextrose 21 g%) with an elemental diet in 6 healthy volunteers. The elemental diet contained amino acids (7 g%, with dextrose 21 g%) in the same molar composition as the albumin. Furthermore, we studied the effect of a pure intragastric dextrose solution (21 g%) on pancreatobiliary secretions, as glucose constitutes a major component of elemental diet formulas. The various pancreatobiliary responses were tested against a maximal i.v. cholecystokinin stimulus. The dextrose, amino acid, and albumin meals emptied at similar rates, and gastric emptying was completed within 3 h. Similar pancreatobiliary responses were observed after the albumin and amino acid meals, but response to both the amino acid and albumin meals was smaller than to the intravenous cholecystokinin stimulus. The glucose meal caused a marked and sustained stimulation of pancreatobiliary outputs, which did not differ significantly from the other test meals. However, lower cholecystokinin levels were observed after the glucose meal compared with distinct cholecystokinin release after the albumin and amino acid meals. We conclude first that there are no major differences in secretory responses between elemental (amino acid) and polymeric (protein) meals and second, that intragastric pure glucose meals strongly stimulate pancreatobiliary secretions. The marked pancreatic and biliary responses to intragastric dextrose cannot be fully explained on the basis of cholecystokinin release, suggesting that this response is probably mediated by neural mechanisms.

Adult↗

Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas.

Both cholecystokinin and bombesin have been shown to promote pancreatic carcinogenesis in the azaserine-rat model. The present study was undertaken to discriminate between the effects of cholecystokinin and bombesin and to establish the modulating properties of the specific cholecystokinin receptor antagonist CR-1409 on pancreatic carcinogenesis. After initiation with 30 mg/kg of azaserine, six groups of 15 Wistar rats were treated for 16 wk with cholecystokinin, bombesin, or gelatin (control), some in combination with CR-1409. Doses of cholecystokinin (2.5 micrograms/kg) and bombesin (10 micrograms/kg) were chosen that rendered approximately equal plasma cholecystokinin levels. Both cholecystokinin and bombesin were found to stimulate pancreatic growth, whereas CR-1409 only inhibited the growth-promoting effect of cholecystokinin significantly. Furthermore, both peptides stimulated the development of putative preneoplastic lesions, whereas CR-1409 only inhibited the effect of cholecystokinin significantly. It is concluded that (a) CR-1409 inhibits the promoting effect of cholecystokinin on pancreatic growth and azaserine-induced early pancreatic lesions and (b) the effects of bombesin cannot be fully ascribed to stimulation of the secretion of endogenous cholecystokinin.

Animals↗

Effect of immunoneutralisation of cholecystokinin on bombesin-stimulated pancreatic enzyme secretion in the rat.

Infusion of bombesin stimulates plasma cholecystokinin (CCK) and pancreatic enzyme secretion in various species, including the rat. This study was undertaken in two groups of four conscious rats with a cannulated pancreatic duct to determine the role of endogenously released CCK in mediating the effect of bombesin on pancreatic enzyme secretion. Infusion of 2 ml CCK antiserum or normal rabbit serum for 40 min was followed 10 min later by infusion of 18 pmol/kg bombesin for 30 min and after an interval of 90 min by infusion of 24 pmol/kg CCK for 30 min. After administration of control rabbit serum, pancreatic protein secretion increased by 3.2 +/- 1.0 mg/30 min during bombesin and 4.0 +/- 1.5 mg/30 min during CCK, while the plasma CCK increments were 1.7 +/- 0.5 pM and 7.0 +/- 0.9 pM for the bombesin and CCK infusions, respectively. Immunoneutralisation with the CCK antiserum did not significantly affect bombesin-stimulated pancreatic protein secretion (3.6 +/- 1.3 mg/30 min), but almost abolished the pancreatic protein response to CCK (0.5 +/- 0.2 mg/30 min). It is therefore concluded that CCK is not an important mediator of the stimulatory effect of bombesin on the pancreas in the rat.

Animals↗

The cholecystokinin receptor antagonist CR1409 increases plasma cholecystokinin in rats.

This study was undertaken to determine whether plasma cholecystokinin (CCK) levels are affected by the administration of the CCK-receptor antagonist CR1409 to rats. Infusion of 0.19, 0.94 and 4.75 mg/kg.h CR1409 for 30 min each into 6 conscious rats increased (P less than 0.05) plasma CCK from 1.3 +/- 0.5 to 6.0 +/- 1.2, 5.4 +/- 1.2, and 5.4 +/- 1.0 pM, respectively. In a subsequent study infusion of stepwise increasing lower doses of 0.3, 1.5, 7.5, 37.5 and 187.5 micrograms/kg.h CR1409 for 30 min each into 6 other rats dose-dependently increased (P less than 0.05) plasma CCK from 1.4 +/- 0.3 to 3.1 +/- 0.6, 4.1 +/- 0.8, 5.4 +/- 1.0, 5.9 +/- 0.8 and 7.1 +/- 1.1 pM, while infusion of saline did not affect plasma CCK concentrations. We therefore conclude that the CCK-receptor antagonist CR1409 increases plasma CCK in the rat.

Animals↗