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Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 181 records · Page 10Linked to original sources
PubMed1991

Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide.

The role of cholecystokinin (CCK) in the regulation of gastric emptying and pancreatic enzyme secretion was evaluated by infusing the CCK-receptor antagonist loxiglumide. Gastric emptying rates and pancreatic secretory outputs were measured in five healthy volunteers by the double-indicator perfusion technique using a multiple-lumen tube in the duodenum. Placebo or loxiglumide (22 mumol.kg-1.h-1) was infused throughout each experiment. Five hundred-milliliter liquid intragastric meals of (a) fat, protein, and glucose (Ensure; Abbott, Chicago, IL); (b) glucose, 20 g/dL; and (c) guar gum, 1.1 g/dL, were given in random order. In addition, the effect of a physiologic CCK-8 dose (20 pmol.kg-1.h-1) after an intragastric 500-mL saline meal (0.154 mol/L) was tested. Intravenous CCK-8 induced a marked retardation of the gastric emptying rate of the saline solution (P less than 0.05) while stimulating pancreatic secretory outputs; both effects were completely abolished by the infusion of loxiglumide. Loxiglumide markedly accelerated the gastric emptying rates (by approximately 40%) and simultaneously diminished lipase (by approximately 75%) and trypsin (by approximately 50%) outputs of both the mixed meal (P less than 0.01) and the pure glucose meal (P less than 0.05). Additional experiments using gamma camera scintigraphy confirmed the accelerating effect of loxiglumide on gastric emptying of the mixed meal (P less than 0.01). The gastric emptying rate of the guar meal, which did not release CCK, was not influenced by the infusion of loxiglumide. Loxiglumide distinctly augmented plasma CCK levels after the mixed (2.6 times) and the pure glucose (2.1 times) meals while markedly reducing (approximately 76%) pancreatic polypeptide release (P less than 0.02). It is concluded that endogeneous CCK exerts a major role in the regulation of both gastric liquid emptying and pancreatic secretion in humans.

Adult↗
PubMed1991

Interaction of the cholinergic system and cholecystokinin in the regulation of endogenous and exogenous stimulation of pancreatic secretion in humans.

Pancreatic enzyme secretion is regulated in humans by the cholinergic system and by cholecystokinin (CCK). The interaction between both regulatory systems in response to exogenous and endogenous stimulation was analyzed in the present study using the cholinergic antagonist atropine and the CCK antagonist loxiglumide. A dose-dependent stimulation of pancreatic enzyme output was achieved either by duodenal perfusion of graded caloric loads or by IV infusion of increasing doses of cerulein. Prestimulated pancreatic secretion was inhibited by atropine and loxiglumide. Atropine furthermore almost completely blocked meal-stimulated pancreatic secretion, whereas loxiglumide caused 60% inhibition. The enzyme response to graded doses of exogenous CCK was significantly inhibited by atropine and loxiglumide. Plasma levels of CCK were not altered by atropine but increased with infusion of loxiglumide. This study supports the concept that pancreatic enzyme secretion is predominantly dependent on a cholinergic tone and that CCK modulates the enzyme-secretory response.

Adult↗
PubMed1991

Hormonal control of pancreatic secretion by intrajejunal HCl: studies in dogs with an autotransplanted entire jejunoileum.

To elucidate the role of hormones in the control of pancreatic secretion, we developed, in seven dogs, a model of total extrinsic denervation of the jejunoileum by autotransplanting this segment of bowel. A Thomas-like cannula was placed into the stomach, the duodenum (to collect pure pancreatic juice), and the proximal part of the jejunum. Thus, intestinal stimulants could only stimulate the pancreas via release of humoral (= hormonal) mediators. Seven control dogs received only the three fistulas. After recovery, dose-response curves of pancreatic bicarbonate and protein response to perfusion of the extrinsically denervated or innervated jejunoileum with HCl (1.5 to 48 mmol h-1) were performed with and without atropine (14 nmol kg-1 h-1 i.v.). Plasma levels of secretin were determined by radioimmunoassay. The maximal bicarbonate output occurred in response to 24 mmol h-1 of HCl and was significantly (p less than 0.05) higher in intact as compared to denervated animals. Atropine only significantly depressed the bicarbonate response to HCl in dogs with a denervated jejunoileum. HCl caused a dose-dependent increase in plasma levels of secretin, which was not altered by denervation and/or atropine. Irrespective of the innervation of the small bowel, pancreatic protein output was only significantly stimulated above basal when high loads (12-48 mmol h-1) of HCl were given. Atropine significantly reduced these responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Helicobacter pylori infection in healthy people: a dynamic process?

Epidemiological studies using serological tests have shown that a large proportion of healthy people have antibodies against Helicobacter pylori (anti-Hp). It is uncertain whether the presence of anti-Hp indicates active infection or only past exposure to the micro-organism. In this study we determined anti-Hp with a specific enzyme linked immunosorbent assay in 100 healthy volunteers who were at the same time investigated for active H pylori infection by means of the 13C-urea breath test. Forty nine per cent had a high anti-Hp titre, but only 24% had active H pylori infection. Our study suggests that a considerable number of healthy people previously infected with H pylori have spontaneously eliminated this microorganism. We suggest that the inability of ulcer patients to eliminate H pylori may be important in the pathogenesis of peptic ulcer disease.

Adult↗
PubMed1991

Regulation of postprandial mesenteric blood flow in humans: evidence for a cholinergic nervous reflex.

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to determine the physiological importance of postprandial blood concentrations of cholecystokinin octapeptide (CCK8), gastrin 17, secretin, and glucagon and to study whether a nervous cholinergic reflex mechanism has a role in the postprandial mesenteric blood flow response. Duplex parameters of vessel diameter, mean velocity, and flow volume were determined serially in the basal state and after stimulation. Changes were compared with baseline values. Superior mesenteric artery parameters were significantly increased over baseline values after a liquid test meal, but ingestion of saline did not cause any changes. Hormones infused simultaneously at postprandial concentrations did not change mesenteric blood flow. When they were infused at pharmacological doses, however, a significant increase in flow parameters was observed. Pretreatment with atropine significantly (p less than 0.05) reduced the mesenteric blood flow response to meal stimulation (57%). These data suggest that the four hormones tested are not of quantitative importance in regulating postprandial superior mesenteric artery blood flow. A cholinergic nervous reflex, however, participates in the control of food induced mesenteric artery flow changes.

Adult↗
PubMed1991

Effect of a cholecystokinin antagonist on meal-stimulated insulin and pancreatic polypeptide release in humans.

A cholecystokinin (CCK) receptor antagonist, loxiglumide, was used to investigate the potential regulating role of CCK in the entero-insular axis in humans. Ingestion of a mixed liquid meal stimulated plasma CCK, insulin, and pancreatic polypeptide (PP) release in the control experiment. With iv loxiglumide (22 mumol/kg.h), mean plasma insulin and glucose levels did not differ between placebo and loxiglumide treatment. The area under the plasma concentration for PP was reduced to 6,060 +/- 1,706 (P less than 0.05) compared to that during placebo treatment (12,266 +/- 4,748). Administration of loxiglumide failed to change insulin secretion in response to perfusion of the same meal or perfusion of a 10-amino acid solution into the duodenum. However, PP secretion in response to the intraduodenal meal or amino acid mixture was abolished after loxiglumide (P less than 0.05). Intravenous administration of the 10-amino acid mixture stimulated insulin from a mean basal level of 7 +/- 3 microU/mL to a peak level of 16 +/- 4 microU/mL. Infusion of a CCK octapeptide (CCK-8) at 8.6 pmol/kg.h, which produced a plasma concentration of 3.3 pmol/L, which is within the postprandial range, augmented amino acid-stimulated insulin and PP output (P less than 0.05). When CCK-8 was infused with loxiglumide, the insulin and PP responses were similar to the values found with loxiglumide alone. We conclude that CCK receptor blockade with iv loxiglumide does not affect postprandial insulin secretion. CCK is, therefore, not a major incretin. However, it is involved in the postprandial PP response, especially during the intestinal phase stimulation. These data suggest that CCK has a role in the human enteroinsular axis.

Adult↗
PubMed1990

Cholecystokinin is a regulator of intestinal phase-stimulated PP release.

The purpose of this study was to determine the role of CCK during the intestinal phase of pancreatic polypeptide (PP) release in man. We first compared the PP response to exogenous caerulein infusion in the presence or absence of either loxiglumide (a specific CCK antagonist) or atropine in six healthy subjects. In the second part of the study, a meal was perfused to the duodenum with and without either loxiglumide or atropine. Both loxiglumide and atropine completely abolished the PP response to exogenous or endogenous stimulation (P less than 0.05). We conclude that CCK participates in the intestinal phase of PP secretion.

Adult↗
PubMed1990

[A year experience with extracorporeal shockwave lithotripsy of gallstones].

43 patients with symptomatic gallbladder stones were treated by extracorporeal shockwave lithotripsy and oral bile acids. In all patients the stones were successfully fragmented during the first lithotripsy session. 33 patients underwent 2-4 treatment sessions. In 16 out of 43 patients the stones disappeared within 7.9 months. The rate of stone dissolution was dependent on the number and size of stones. 3 patients required surgery because of frequent colic in one case, cholecystitis in one case and lack of cooperation in one case. No important side effects were noted except mild pancreatitis 3 weeks after lithotripsy in one patient. Results at this center of extracorporeal shockwave lithotripsy combined with oral bile acids indicate that this treatment may become an alternative to cholecystectomy in patients with a small number (less than 3) of stones not exceeding 30 mm in diameter.

Adult↗
PubMed1990

Calcitonin gene-related peptide (CGRP) causes redistribution of blood flow in humans.

In normal human subjects (n = 6), blood flow in the common carotid artery, assessed with an ultrasonic duplex-scanning unit, was increased up to 152% of basal levels by 60-min infusions of human calcitonin gene-related peptide I (alpha CGRP) 80 pmol.kg-1.h-1, but it was not affected by 20 pmol.kg-1.h-1 CGRP or 88 pmol.kg-1.h-1 human calcitonin. In the superior mesenteric artery, on the other hand, blood flow was reduced by 80 pmol.kg-1.h-1 CGRP to 58% of the basal level, but not by 20 pmol.kg-1.h-1 CGRP or with 88 pmol.kg-1.h-1 calcitonin. Blood flow in the abdominal aorta remained largely unchanged under the same conditions. Skin blood flow, assessed by a laser Doppler unit, was increased up to 682% of the basal level by 80 pmol.kg-1.h-1 CGRP, but not by 20 pmol.kg-1.h-1 CGRP or calcitonin. Thus CGRP increased regional blood flow to the brain and the skin at the expense of the gastrointestinal tract.

Adult↗
PubMed1990

Effect of loxiglumide, a cholecystokinin antagonist, on pancreatic polypeptide release in humans.

The purpose of this study was to determine the role of cholecystokinin in the regulation of postprandial pancreatic polypeptide secretion in humans. The pancreatic polypeptide responses to modified sham feeding and gastric instillation of a test meal were first compared with the response to oral ingestion of the same meal. The experiments were repeated under cholinergic (atropine) and cholecystokinin (loxiglumide) blockade. Atropine completely abolished the pancreatic polypeptide response to sham feeding and caused significant reductions after gastric and oral food intake. Loxiglumide, on the other hand, significantly reduced pancreatic polypeptide release to oral food (51% inhibition) without affecting the response to sham feeding. In separate experiments using a duodenal perfusion system, the effects of atropine and loxiglumide on intestinal phase-stimulated pancreatic polypeptide release were examined, and both cholinergic and cholecystokinin blockade induced complete suppression. It was concluded (a) that cholecystokinin is involved in postprandial pancreatic polypeptide response, especially during the intestinal phase stimulation, and (b) that the cholinergic system is crucial and superimposed on cholecystokinin in stimulating pancreatic polypeptide release.

Adult↗
PubMed1990

Pancreatic secretory responses to long-term infusions of secretin and cerulein in humans.

We measured pancreatic enzyme and bicarbonate responses to graded doses of intravenous secretin or cerulein alone or together in healthy human subjects. Bicarbonate responses were steady and well maintained during the last 3.5 h of the 4 h of infusions of secretagogues, giving evidence for a constant pancreatic flow rate. Potentiation (more-than-additive response) was observed between secretin and cerulein for bicarbonate secretion, but not for enzyme secretion. Secretin stimulated pancreatic enzyme secretion. The effect was most pronounced with amylase secretion and less prominent with lipase, trypsin, and chymotrypsin secretion. Changes in the proportion of enzymes were seen over time, with trypsin and chymotrypsin output declining towards the end of cerulein infusion. We conclude that in humans the effects of secretin on pancreatic enzyme secretion are complex and include time-dependent changes in the enzyme mixture, but potentiation between secretin and cerulein does not occur for enzyme output.

Adult↗
PubMed1990

Hormones as regulators of pancreatic secretion in man.

At the beginning of the century, Pavlov suggested that the pancreas was exclusively controlled by the nervous reflex mechanisms. In 1902, Bayliss & Starling published their experiments on secretin and claimed that the nervous regulation is 'superfluous and improbable'. In the following decades, especially after the discovery of CCK, it was generally held that exocrine pancreatic secretion is regulated mainly by hormones. The present summary clearly demonstrates the importance of the cholinergic system in regulating exocrine pancreatic secretion and the complexity of neurohormonal interactions. The question is no longer hormones or nerves, but rather a very complicated coordination of neural, hormonal and possible paracrine effects, resulting in the control of exocrine pancreatic activity. In this complex regulatory system, the cholinergic control is central with hormones such as CCK or secretion modulating the response.

Cholinergic Fibers↗
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

[Current perspectives in ulcer disease].

1. Helicobacter pylori has been associated with chronic type-B gastritis, which in turn is always present in duodenal ulcer patients; therefore, it is likely that Helicobacter pylori is an important cofactor in the pathogenesis of peptic ulcer disease. An eradication of Helicobacter pylori is associated with the reduced ulcer relapse rate, but an effective therapy for eradication is not yet available and should be restricted to experimental protocols. 2. Omeprazole is an antagonist of the proton pump of the acid-producing cell of the human stomach. With once-daily omeprazole treatment it is possible to almost abolish 24-hour intragastric acidity in the majority of duodenal ulcer patients; therefore, omeprazole allows alternative treatment of different causes of peptic disease.

Anti-Bacterial Agents↗
PubMed1990

[Value of extracorporeal piezoelectric lithotripsy in treatment of gallstone disease].

Alternative techniques were introduced in the last 20 years for the treatment of gallstones. Among these the extracorporeal shock wave lithotripsy followed by a systemic litholytic therapy represents undoubtedly the most attractive one. A group of two surgeons and two gastroenterologists has started to evaluate this treatment in April 1988, using a piezoceramic lithotryptic system (Piezolith 2300). From April 1988 to May 1989 we have treated 32 patients who fulfilled the selection criteria-symptomatic gallstone disease, 1-3 radiolucent concrements of less than 30 mm of diameter, functioning gallbladder. We noted only one pancreatitis as a complication of this treatment. The overall stonefree rate is 16% after two months, 32% after four months and 56% after six months, depending on the size and number of stones. A definitive evaluation and final conclusion will only be possible when the rate of late recurrences after this treatment will be known.

Adult↗