Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 145 records · Page 8Linked to original sources

PubMed1994

Circulating somatostatin-28 is not a physiologic regulator of gastric acid production in man.

Studies were designed to establish the acid inhibitory potency and plasma kinetics of somatostatin-28 (S-28) in humans and to determine whether the amount of S-28 released into the circulation after a meal is sufficient to regulate gastric acid secretion. A liquid meal induced a significant increase of S-28 (P < 0.01) whereas S-14 levels did not change. Postprandial S-28 concentrations were then mimicked by exogenous infusions and tested on basal and pentagastrin-stimulated gastric acid secretion. Expressed in terms of circulating plasma concentrations measured by specific radioimmunoassays, S-14 was 10 times more potent than S-28 in inhibiting gastric acid production. The plasma half-life of S-28 (1.86 min) was longer than that of S-14 (1.00 min) due to a slower plasma clearance rate. S-28 did neither affect basal and stimulated gastric acid secretion nor postprandial intragastric acidity. These studies suggest that postprandial plasma concentrations of S-28 are unlikely to regulate gastric acid secretion in man. They also show that S-28 is several times less potent than S-14 with respect to inhibition of gastric acid output.

Adult↗

PubMed1994

Cholecystokinin is a physiological regulator of gastric acid secretion in man.

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.

Adult↗

PubMed1994

[Breath tests--a clarification of the topic].

Breath tests represent a new class of diagnostic tests to be used in gastroenterologic diagnostics. The breath tests depend basically on the quantification of either hydrogen gas or labeled carbon dioxide in the expired air. The main indications are presented and the limitations of the tests are discussed.

Breath Tests↗

PubMed1993

[Portal venous thrombosis following splenectomy in portal hypertension: risks and management].

Splenectomy intended to treat hypersplenism can, in the presence of portal hypertension (PTH), lead to extrahepatic portal and mesenteric vein thrombosis. The management of possible variceal bleeding in patients with extrahepatic portal vein occlusion following splenectomy in portal hypertension is a problematic and challenging undertaking. We report on the management of variceal bleeding in 2 noncirrhotic patients with PTH who developed portal vein thrombosis following ill-advised splenectomy. It must be stressed again that splenectomy alone intended to control hypersplenism in portal hypertension is to be avoided at all costs. Options for the treatment of portal and mesenteric vein thrombosis and variceal bleeding are proposed.

Adult↗

PubMed1993

Low-dose octreotide treatment is not effective in patients with advanced pancreatic cancer.

Octreotide (SMS 201-995), a long-acting somatostatin analogue, has been shown to decelerate growth of human pancreatic cancer in vitro and in vivo. We analyzed the efficacy of octreotide treatment in 22 patients (14 men, 8 women) with histologically verified ductal pancreatic cancer. All patients had advanced tumor stages (stage III: 13 patients; stage IV: 9 patients). Octreotide was given by self-administered subcutaneous injection (3 x 100 micrograms/day). When there was evidence of tumor progression, the dose of octreotide was increased to 3 x 200 micrograms/day. A monthly follow-up, including clinical status, CT scan or ultrasonography, and tumor marker carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 determination was carried out. There were no severe side effects apart from slight burning sensation at the injection site. No partial or complete remission was seen. Eighteen patients showed tumor progression with a median survival time of 17 weeks (range 3-42 weeks). In three patients a "no change" evaluation with a median survival time of 46 weeks (range 40-68 weeks) was registered. In these three patients the serum tumor markers CA 19-9 and CEA did not show an increase to more than twice the baseline value during this time. One patient discontinued the octreotide treatment because of tumor progression. The results of the analysis indicate that low-dose octreotide treatment is not effective in patient suffering from advanced tumor stages of pancreatic cancer.

Adenocarcinoma↗

PubMed1993

Enteral absorption of octreotide: absorption enhancement by polyoxyethylene-24-cholesterol ether.

1. The somatostatin octapeptide-analogue octreotide was absorbed as an intact peptide from the gastro-intestinal tract with an absolute bioavailability of about 0.3% in rats. Administration of octreotide in the presence of polyoxyethylene (24)-cholesterol-ether (POECE) resulted in an about 23 fold increase of bioavailability. 2. In vitro studies with Caco-2 cells showed a dose-dependent increase in octreotide permeation with increasing doses of coadministered POECE. The use of [3H]-polyethyleneglycol (PEG) 4000 as an extracellular marker also indicated that higher doses of POECE may partly enhance paracellular transport of macromolecules. 3. By means of fluorescence microscopy it was shown that transepithelial transport of the fluorescent octreotide analogue (4-nitrobenzo-2-oxa-1,3-diazol [NBD] labelled octreotide) was enhanced by the addition of POECE. Besides an increased enterocyte uptake, there was evidence of enhanced partition of NBD-octreotide into the intercellular space between enterocytes after co-administration of POECE. In addition, there appeared to be changes in the hepatic topographic disposition of NBD-octreotide when it was given together with POECE compared with its administration alone. 4. In a study in healthy volunteers, 16 mg POECE significantly enhanced by 8 fold the absorption of octreotide after oral administration.

4-Chloro-7-nitrobenzofurazan↗

PubMed1993

Influence of Helicobacter pylori, sex, and age on serum gastrin and pepsinogen concentrations in subjects without symptoms and patients with duodenal ulcers.

The relation between Helicobacter pylori (H pylori) infection and fasting gastrin and pepsinogen-I and -II concentrations was evaluated in 278 volunteers without symptoms and the results were compared with the values obtained in 35 patients with duodenal ulcers. H pylori infection was determined with the 13C-urea breath test in subjects without symptoms and with endoscopy, biopsy (histology and culture), and quick urease test (CLO-test) in patients with duodenal ulcers. Gastrin and pepsinogen-I and -II concentrations were assayed with specific radioimmunoassay systems. The results clearly indicate that fasting gastrin and pepsinogen-I and -II concentrations were significantly higher in H pylori positive compared with H pylori negative subjects. Neither age nor sex affected basal gastrin and pepsinogen concentrations in H pylori negative subjects. Fasting gastrin, pepsinogen-I and -II concentrations in serum samples were similar in H pylori positive persons with no symptoms and those with duodenal ulcers suggesting that similar mechanisms are involved in increasing plasma concentrations of these variables in both populations. Hypergastrinaemia and hyperpepsinogenaemia are therefore probably secondary to active H pylori infection.

Adult↗

PubMed1993

[Assessment of gastric emptying].

In the absence of overt mucosal lesions, abnormalities of gastroduodenal motorfunction are considered to be important in the pathogenesis of many upper abdominal symptoms. These may be idiopathic, occur following gastric surgery, or in association with diseases such as diabetes mellitus. A variety of investigations have been developed to examine the motility of the stomach and duodenum. To date the most reliable and useful techniques are those which assess gastric transit either radiologically or scintigraphically. Assessment of the expulsion of radio-opaque gastric markers with a single abdominal x-ray can be performed as a simple outpatient screening procedure. More precise radioisotopic definition of delayed gastric emptying, however, requires access to a Nuclear Medicine Department. A number of other approaches are currently under investigation as potential diagnostic tests. The future role of these techniques is unclear, although 13C breath testing may soon permit rapid and simple screening of gastric emptying abnormalities without exposure to ionizing radiation. At present, other techniques such as ultrasound, antropyloroduodenal manometry, and magnetic resonance imaging have application only in research centers.

Barium Sulfate↗

PubMed1993

[Colonic motility].

Colonic motility is provided by contraction of intramural smooth muscle under the control of the enteric and the extrinsic nervous system and humoral connections. In vivo measurement of colonic motility remains difficult because of the complexity of these interactions and anatomical considerations. The possibility that symptoms are due to colonic dysmotility should be considered in patients with normal barium enema and colonoscopy. Examples of this are patients with chronic constipation, irritable bowel syndrome or colonic symptoms associated with diabetes mellitus or diseases of the nervous system. A number of techniques have been developed to assess colonic motility. The simplest is to assess colonic transient with a single abdominal x-ray following ingestion of radio-opaque markers. This is cheap, reproducible and easy to perform. Normal values for age and sex are available. Colonic transit of both liquid and solid can be determined by scintigraphic measurement. This technique provides information about regional variations in colonic function; it is however relatively demanding and requires access to a gamma camera. Manometry provides a more direct assessment of colonic motor activity. Changes in the electrical potential of the colonic smooth muscle can be determined by electromyography. Both techniques are however difficult to perform, and are currently only used for research purposes. It is likely that the combination of techniques that examine transit with more direct measurement of motor function will provide further insights into the mechanisms responsible for colonic dysmotility.

Barium Sulfate↗

PubMed1993

[Surgery for bleeding peptic ulcer: short- and long-term results].

Thirty-one patients operated on for bleeding peptic ulcer were reviewed. The basic concept was to make an early decision to operate and proceed as soon as the patient was haemodynamically stable. In addition to haemostasis, a definitive operation was performed. The procedure was a proximal gastric vagotomy (PGV) for duodenal ulcers (DU), combined with an antrectomy for pre-pyloric ulcers, and either a PGV with ulcer excision or a Billroth I for gastric (GU) or combined (GU + DU) ulcers. Twenty-four patients (77%) were operated on within the first 24 hours. Nine patients could not be operated according to the basic protocol because of anatomical reason, additional ulcer complication or severe co-existing systemic disease. During the hospital stay, 2 deaths (6%) occurred and 4 patients (13%) rebled postoperatively, all of them were reoperated. During a mean follow-up of 44 months, 12 deaths unrelated to peptic disease and one recurrent bleeding occurred. PGV for DU could be used in 70% of cases without any hospital mortality; one patient rebled after the operation and another during the long-term follow-up. These results support the views that early surgery has a low hospital mortality and that PGV gives good results when performed as an emergency procedure.

Adolescent↗

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↗