Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 19 recordsLinked to original sources

PubMed1992

Role of cholecystokinin in mediating GRP-stimulated gastric, biliary and pancreatic functions in man.

To explore the mechanisms of gastrin-releasing peptide (GRP)-induced gut functions in man, we investigated the effect on gallbladder contraction, exocrine pancreatic secretion and gastric acid secretion of a recently developed CCK receptor antagonist, loxiglumide, on GRP-stimulated effects in six healthy human subjects. Intravenous infusion of graded doses of synthetic human GRP (1-27 pmol/kg per h) caused significant and dose-dependent increases in pancreatic enzyme and gastric acid secretions and in gallbladder contraction. Intravenous administration of loxiglumide (10 mg/kg per h) abolished GRP-stimulated gallbladder contraction, augmented gastric acid secretion, but did not affect exocrine pancreatic secretion. The results suggest that endogenously released CCK is (1) responsible for GRP-stimulated gallbladder contraction, and (2) involved in regulating gastric acid secretion. The results further suggest that GRP-stimulated pancreatic secretion is not mediated by CCK, but has a direct response of GRP on the exocrine pancreas.

Adult↗

PubMed1992

[Age- and sex-specific standard values of colonic transit time in healthy subjects].

Use of radiopaque markers with a plain X-ray of the abdomen is a simple technique to measure mean segmental and total colonic transit time. We evaluated 128 healthy volunteers with a mean age of 40 years (range 20-81 years) from three different parts of Switzerland to assess age and sex specific normal transit times. In men and women colonic transit time was not influenced by age. The mean transit time was significantly shorter in men than in women (30 +/- 2 hours versus 41 +/- 3 hours: p less than 0.05). In men the transit time was also influenced by smoking. Non-smoking men had a significantly shorter transit time than smokers (26 +/- 2 hours versus 40 +/- 5 hours: p less than 0.05). In women, neither smoking nor the menstrual cycle influenced transit time. For normal colonic transit time we recommend up to 66 hours for smoking men, up to 44 hours for non-smoking men and up to 70 hours in general for women.

Adult↗

PubMed1992

[Is flexible sigmoidoscopy as preventive measure for colorectal carcinoma in asymptomatic patients over 45 practicable?].

The efficacy of flexible sigmoidoscopy as a screening method for colorectal cancer is still undetermined, and a reduction in mortality due to this cancer by mass screening has not been demonstrated so far. An important precondition for the practicability of screening sigmoidoscopy is its acceptability by the persons to be screened. Acceptability was tested in 294 volunteers without abdominal symptoms from a general medical outpatients clinic. Mean age of participants was 58 years (45-86), 65% were men and 35% women. Sigmoidoscopy was judged harmless by 221 persons (75.1%), painful by 62 (21.1%), very painful by 11 (3.7%), and unacceptable by none. Every participant would have agreed to repeat the examination. In 36 patients 52 polyps were detected, comprising one carcinoma, 18 adenomas (in 15 patients), 32 hyperplastic polyps and one lipoma. We conclude that sigmoidoscopy was well accepted in this study and should be evaluated further as a mass screening method for colorectal cancer.

Aged↗

PubMed1992

Induction of the fed pattern of human exocrine pancreatic secretion by nutrients: role of cholecystokinin and neurotensin.

The aim of the present study was to assess the role of cholecystokinin and neurotensin in converting the cyclical interdigestive pattern of pancreatic secretion into the non-cyclical fed pattern. Six healthy male volunteers were studied on 4 separate days. During each experiment a mixed liquid meal or solutions of individual nutrients were perfused intraduodenally for 180 min at 2 ml/min. The mixed meal contained 4.3 g glucose, 2.0 g fractionated soya oil, and 1.7 g casein hydrolysate per 100 ml, which delivered a caloric load of 0.9 kcal/min into the duodenum. The isocaloric and isotonic solutions of individual nutrients contained 44.5 g glucose, 17.8 g fractionated soya oil, or 44.5 g hydrolysed serum bovine albumin per liter and delivered 0.36 kcal/min into the duodenum. Duodenal aspirates and blood samples were collected at regular intervals for determination of pancreatic enzyme outputs and plasma levels of cholecystokinin and neurotensin, respectively. The mixed meal converted the cyclical interdigestive secretory pattern into the noncyclical fed pattern whereas none of the three individual nutrients abolished the interdigestive pattern. Not only the mixed meal but also lipid and protein perfusion consistently stimulated cholecystokinin release. Integrated incremental cholecystokinin release amounted to 32.3 +/- 9.9 pg/ml x 180 min with the mixed meal, 23.2 +/- 6.5 with lipid perfusion (P < 0.05 versus mixed meal) and 13.4 +/- 3.8 with protein perfusion (P < 0.05 versus mixed meal). The carbohydrate solution did not significantly release cholecystokinin. None of the duodenal perfusates raised neurotensin plasma levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Intracolonic bioavailability of human calcitonin in man.

Human calcitonin (hCT) injected into the lumen of the descending colon of normal human subjects was absorbed within minutes and could be recognized intact in plasma as shown by RIA in combination with reverse-phase HPLC. The absorption was low and variable, with bioavailabilities ranging from 0.01% to 2.7% relative to intravenously administered hCT (area under the concentration-time curve). With intravenous hCT serum calcium was lowered and the fractional urinary excretion of calcium, phosphorus, sodium and chloride was significantly stimulated. With the intracolonic hCT, the fractional urinary excretions of calcium, sodium and chloride were also marginally stimulated relative to intracolonic vehicle (placebo). In conclusion, hCT is absorbed intact from the colon, but the bioavailability is low and highly variable.

Adult↗

PubMed1992

Somatostatin 28 and coupling of human interdigestive intestinal motility and pancreatic secretion.

To determine the effects of small increases in somatostatin 28 plasma concentrations on human interdigestive gastrointestinal motility and pancreatic secretion, six fasting volunteers were intubated with gastroduodenal multilumen tubes and motility and pancreatic enzyme secretion were measured. Subjects received intravenous NaCl and somatostatin 28 at 11 and 44 pmol.kg-1.h-1 for 120 minutes or at least one interdigestive cycle. The two doses increased plasma somatostatin 28 levels within the physiological or into the supraphysiological range, respectively. Somatostatin 28 at 11 and 44 pmol.kg-1.h-1 decreased the length of the interdigestive motility cycle by 50% and 67% compared with controls, respectively (both P less than 0.002). Propagation velocity of the migrating motor complex (P less than 0.01) and plasma motilin were decreased (P less than 0.01). The smaller and larger dose decreased pancreatic enzyme outputs by 50% and 65%, respectively (P less than 0.005), but with the smaller dose, phase III-associated enzyme outputs were greater than phase I outputs. These findings suggest that small changes in somatostatin 28 plasma concentrations modulate human interdigestive motility and pancreatic enzyme output while coupling of motor and secretory events is preserved.

Adult↗

PubMed1992

Cephalic stimulation of gastrointestinal secretory and motor responses in humans.

The present study was designed (a) to investigate the cephalic phase of gastropancreatic secretion, antroduodenal motility, and regulatory peptide release in six healthy young men and (b) to assess its regulation by the cholinergic system and endogenous cholecystokinin. Sham feeding performed for 15 minutes induced a concurrent stimulation of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release that lasted for 30 minutes. Reappearance of interdigestive phases III was retarded in the post-sham-fed state. Atropine abolished secretory, motor, and pancreatic polypeptide responses to sham feeding and enhanced gastrin release. The cholecystokinin receptor antagonist loxiglumide did not attenuate pancreatic enzyme response but diminished antral motor response by 72% (P less than 0.05) and release of pancreatic polypeptide by 91% (P less than 0.05); it enhanced gastrin release and abolished retardation of reappearance of phase III with sham feeding. It is concluded that (a) there is a distinct cephalic phase of gastropancreatic secretion, antroduodenal motility, and pancreatic polypeptide release in humans that is primarily under cholinergic control and that (b) endogenous cholecystokinin is involved in antral motor, gastrin, and pancreatic polypeptide responses to sham feeding.

Adult↗

PubMed1992

A physiological role for cholecystokinin as a regulator of gastrin secretion.

To explore the role of cholecystokinin (CCK) in regulating gastrin secretion in humans, the effect of a CCK antagonist (loxiglumide) on meal-stimulated hormone responses was investigated. Subjects received 500 mL of a liquid test meal in the presence and absence of loxiglumide (22 mumol.kg-1.h-1). In the control experiments, both plasma gastrin and CCK levels increased postprandially. In loxiglumide-treated subjects there was a marked elevation in gastrin (area under the curve, 11,042 +/- 1493/120 min vs. 2156 +/- 281 pg/120 min) and CCK levels compared with the control experiment. These observations were confirmed in experiments with modified sham feeding and gastrin-releasing peptide stimulation in which loxiglumide pretreatment also caused a significant increase in gastrin release compared with saline (P less than 0.05). Further studies with intravenous infusion of gastrin, CCK-8, and CCK-33 with and without loxiglumide showed that the increases in CCK and gastrin during loxiglumide application cannot be explained by alterations in clearance rates. The findings of this study show that postprandial gastrin secretion is influenced by CCK and support the concept of a negative feedback control of gastrin secretion by CCK.

Adult↗

PubMed1992

Evidence for hormonal inhibition of exocrine pancreatic function by somatostatin 28 in humans.

Somatostatin 28 (S-28), originating in gastrointestinal cells, is secreted into the circulation and increases in humans after ingestion of a mixed meal. To evaluate the possibility that the increased levels of S-28 post cibum might modulate the release of enzymes and bicarbonate from the exocrine pancreas, S-28 was infused intravenously into healthy volunteers to levels seen after food intake. During S-28 infusion, the output of lipase, trypsin, amylase, and bicarbonate stimulated by either exogenous cholecystokinin octapeptide or endogenous signals from intraduodenal administration of tryptophan or a mixture of amino acids was significantly reduced. It is concluded that S-28 released from the gut during food intake modulates pancreatic exocrine function in humans.

Adult↗

PubMed1992

Role of circulating cholecystokinin in control of fat-induced inhibition of food intake in humans.

Cholecystokinin (CCK) has been proposed to serve as a satiety signal in animals and humans. To further explore the role of CCK in humans, the effect on satiety and eating behavior of a specific CCK-receptor antagonist, loxiglumide, that preferentially inhibits peripheral (CCK-A) receptors was investigated. In a randomized, blind, four-period latin square design, 10 subjects received intravenous saline (placebo) or loxiglumide (10 mg/kg per hour) with concomitant intrajejunal perfusions of isotonic saline or fat (containing 50% corn oil and 3% albumin). Food intake and plasma CCK concentrations were assessed, and subjects scored their feelings of hunger and fullness in paired experiments. In placebo-treated subjects, the duration of the meal was shorter during fat perfusion (30 +/- 2 minutes vs. 35 +/- 2 minutes; P less than 0.01; mean +/- SEM). The amount of food intake was reduced (361 +/- 31 g vs. 454 +/- 35 g; P less than 0.05), and fluid ingestion was inhibited (490 +/- 31 mL vs. 625 +/- 38 mL; P less than 0.01). Loxiglumide did not affect any parameter and did not change the pattern of responses. In loxiglumide-treated subjects there was a 4-5-fold elevation in plasma CCK levels. These results confirm that jejunal infusion of lipid reduces the size of the meal and stimulates early satiety. The data imply that these effects are not mediated through peripheral endogenous CCK under these conditions.

Adult↗

PubMed1992

Tolerability and absorption enhancement of intranasally administered octreotide by sodium taurodihydrofusidate in healthy subjects.

Nasal sprays containing different concentrations of the somatostatin analogue octreotide and sodium tauro-24,25-dihydrofusidate (STDHF) as an absorption promoter were evaluated in two consecutive pharmacokinetic studies in healthy volunteers to characterize their bioavailability and local tolerability. The concentrations of STDHF were selected on the basis of a phase diagram generated by a dynamic laser light-scattering technique to ensure that the mixture was above the critical micellar concentrations. Compared to a 50-micrograms subcutaneous injection, the nasal spray formulation without STDHF had a mean relative bioavailability of 17.9%. For nasal formulations containing 3 and 1.65% (w/v) of STDHF, the bioavailability increased to 29.0 and 25.7%, respectively. The enhancement of nasal absorption was dependent on the STDHF concentrations as shown by decreasing the amounts to 1.2 and 0.8% (w/v) for tolerability reasons; the bioavailability was reduced to 15.3 and 20.5% in these cases, respectively. The local tolerability of all STDHF-containing sprays was poor, leading to stinging sensations and lacrimation. The poor local tolerability of the octreotide nasal spray containing different concentrations of STDHF required for effective nasal absorption enhancement appears to be impractical for further clinical development. These findings clearly stress the necessity to investigate tolerability and safety issues of new drug delivery systems in early developmental phases.

Administration, Intranasal↗

PubMed1992

The absorption site of cyclosporin in the human gastrointestinal tract.

1. An emulsion preparation of cyclosporin was administered locally to different parts of the small and large intestine by gavage: to the duodenum (opposite to the papilla of Vater), jejunum (150 cm distal to the teeth), ileum (300 cm distal to the teeth), and to the colon descendens (30 cm proximal to the anus). 2. The bioavailability of cyclosporin after these instillations was compared with that after oral administration of a hard gelatine capsule formulation. 3. Cyclosporin was found to be absorbed predominantly in the small intestine. This may have implications for dosage in patients with reduced absorptive surface area.

Adult↗

PubMed1992

Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man.

To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.

Adult↗

PubMed1992

Enteral absorption of octreotide.

1. The somatostatin octapeptide-analogue, octreotide, is absorbed as intact peptide from the gastrointestinal (GI) tract. 2. In situ absorption experiments in rats confirmed our recent intubation studies in human volunteers demonstrating that the peptide has preferential absorption sites in the small intestine. Absorption of octreotide was higher in the jejunum than in the duodenum or the ileum. 3. Experiments with bile-duct cannulated rats demonstrated that the absorption of octreotide decreased in the presence of bile, reflecting a negative influence of biliary components on the absorption of the peptide. 4. Uptake experiments using rat jejunal brush border membranes were performed to analyse the absorption mechanisms. The transport of octreotide into jejunal brush border membranes was significantly higher than the uptake into membrane vesicles isolated from rat ileum. When initial uptake (0-15s) rates into the membrane vesicles were calculated as a function of the peptide concentration, a saturable component could be observed, indicative of transport mechanisms different from simple diffusion.

Animals↗

PubMed1992

Intestinal phase of superior mesenteric artery blood flow in man.

Duplex ultrasound was used to investigate superior mesenteric artery haemodynamics in humans in order to study the contribution of the small intestine to the postprandial splanchnic hyperaemia, and to determine the relative potencies of the major food components in the postprandial mesenteric flow response. Duplex parameters of vessel diameter, mean velocity, and volume flow were determined serially in the basal state and after stimulation. Flow parameters were significantly (p less than 0.05) increased after liquid and solid oral meals. Modified sham feeding did not alter mesenteric blood flow. Intestinal perfusion of an isocaloric liquid test meal induced flow increases comparable with oral intake. Superior mesenteric artery blood flow also significantly (p less than 0.05) increased after isocaloric and iso-osmolar loads of intraduodenal carbohydrate, fat, and protein meals. Responses were similar after the test meal, fat, and protein, but were significantly (p less than 0.05) less for carbohydrates. Different osmolar loads of saline did not affect flow responses. We conclude that the intestinal phase is the major regulator of the postprandial mesenteric blood flow response in healthy humans and that the chemical nature of food determines the mesenteric response pattern.

Adult↗

PubMed1992

Non-invasive assessment of gastrointestinal motility disorders in diabetic patients with and without cardiovascular signs of autonomic neuropathy.

Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.

Adult↗

PubMed1992

Relevant aspects of physiology in chronic pancreatitis.

Specific points of physiology which are relevant for the understanding and management of chronic pancreatitis are focussed on. First, the regulatory factors of exocrine pancreatic secretion are described, discussing the role of the cholinergic system and of the classical gut hormones cholecystokinin and secretin. The association of upper gastrointestinal dysfunctions with a disturbed exocrine pancreatic response is also dealt with. Lastly, these changes are related to clinical consequences such as maldigestion or malabsorption.

Chronic Disease↗

PubMed1992

Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy.

The purpose of this study was to evaluate the method of obtaining aspirated fluid for culture from the small intestine through a fiberoptic gastrointestinal endoscope for diagnosing small-bowel overgrowth. The study population consisted of 10 healthy volunteers and 26 patients with various gastrointestinal problems referred for routine endoscopic examination. The material to be cultured was obtained under direct visualization approximately 25 to 30 cm distal to the pylorus or from the afferent loop (in Billroth-II patients) with a sterilized sheathed wash pipe passed through the suction channel of the endoscope. Cultures were considered positive for bacterial overgrowth if total counts of organisms were 10(5)/ml or more. All healthy volunteers and 16 of 21 unoperated patients had sterile or insignificant growth, whereas all 5 patients who had Billroth-II operations had positive overgrowth. The endoscopic method for collection of proximal gastrointestinal fluid for culture is simple and can be performed during routine endoscopy.

Adult↗