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Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 55 records · Page 3Linked to original sources

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

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

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

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

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

[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

[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

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

[Pain-free piezoelectric extracorporeal shock wave lithotripsy in gallbladder stones. Initial experiences].

Efficacy and side effects of lithotripsy of gallbladder stones with a piezoelectric lithotriptor are assessed. 16 treatments were performed in 8 patients (1-3 per patient). Patients required no premedication, analgesia, infusion or monitoring. Gallstone fragmentation was achieved with all treatments. Laboratory findings remained unchanged after treatment, with the exception of one patient with mild pancreatitis. With adjuvant oral bile acid treatment, 6 of the 8 patients were stone-free within 3 days to 3 months. Extracorporeal shockwave lithotripsy with piezoelectric shock waves provides painless and efficient gallstone fragmentation. Repeated treatments may speed complete fragment dissolution.

Adult

[Percutaneous endoscopic gastrostomy. Personal experiences with Russell's method].

Feeding with nasally placed enteral feeding tubes is a method frequently used for long-term nutrition of patients with neurologically or mechanically induced swallowing disorders. Feeding tubes, however, may be unsatisfactory due to either esthetic considerations or complications such as esophagitis, bleeding or pulmonary aspiration. Recently, endoscopic techniques for placing of feeding gastrostomies without laparotomy have been introduced. We report on our experience with 46 endoscopically controlled percutaneous gastrostomies in 38 patients according to the method described by Russell. Cerebrovascular diseases and malignancies of the oropharynx were the 2 most common indications for creation of the gastrostomy. Endoscopically assisted gastrostomy was successful in 38 of 40 patients referred. One serious and two minor complications were encountered. Gastrostomy was in use for a median time span of 3 months (range 1-83 weeks). We conclude that endoscopically assisted percutaneous gastrostomy is a simple, safe, and effective means of providing enteral nutrition in patients requiring tube feeding.

Adolescent

Physical characteristics of indigestible solids affect emptying from the fasting human stomach.

Gastric emptying of indigestible solids depends on their size. It is not clear whether physical characteristics other than particle size affect emptying of indigestible solids from the fasting human stomach. We studied gastric emptying of three differently shaped particles, (cubes, spheres, rods) of either hard or soft consistency during the fasting state in human volunteers. The shape of indigestible particles did not affect their emptying. The area under the gastric emptying curve (AUC: particles x hour) was for hard cubes 24.7 (2.2), for hard spheres 27.9 (1.6), for hard rods 26.9 (2.7). All soft particles emptied faster than their identically shaped hard counterparts, but there was no difference among the three shapes (AUC for soft cubes: 29.2 (3.0), for soft spheres 32.0 (1.8), for soft rods 34.1 (1.2). If gastric emptying of hard and soft particles was compared independently of their shape, soft particles emptied significantly faster than hard ones: AUC 31.8 (1.2) v 26.5 (1.3) (p less than 0.01). In conclusion, the consistency but not the shape significantly affects gastric emptying. Specific physical characteristics other than size and shape may affect gastric emptying of indigestible particles which may be of importance in the design of drugs.

Adult

A physiologic role for somatostatin 28 as a regulator of insulin secretion.

Somatostatin 28 (S-28) is a peptide produced in the intestinal tract which rises in the circulation during nutrient absorption. We tested the hypothesis that S-28 regulates B-cell function by (a) studying the effects on insulin secretion of "physiologic" infusions of S-28 and (b) measuring insulin responses during elevated nutrient-stimulated endogenous S-28 levels. (a) Synthetic S-28 was infused on separate days into six healthy men at rates of 25 and 50 ng/kg per h which mimicked postprandial levels. Subjects were given a bolus of glucose (0.1 g/kg) after 120 min. Insulin responses during S-28 infusions were compared to a control study using a saline infusion in the same individuals. Glucose-stimulated insulin secretion was inhibited during the infusion of 50 ng/kg per h S-28 when compared to control (P less than 0.05). (b) Insulin secretion during elevations of endogenous S-28 was studied in healthy men who received a bolus of 2.5 g arginine (n = 14) or 25 U of secretin (n = 8) 120 min after swallowing 50 g fat, or, on a separate day, an equivalent volume of water. S-28 levels rose significantly after fat ingestion but did not change after water. Arginine and secretin-stimulated insulin secretion was inhibited following ingestion of fat compared with intake of water (P less than 0.05). Arginine-enhanced glucagon secretion was not changed by fat ingestion. We conclude that elevations in plasma S-28 levels, occurring during the postprandial state, attenuate B-cell secretion and this peptide may be a physiologic modulator of nutrient-stimulated insulin release.

Administration, Oral

To extract or not to extract in secretin radioimmunoassay?

The importance of an ethanol extraction procedure in the radioimmunoassay of plasma secretin was investigated. The extraction step led to a higher assay sensitivity of 0.35 fmol/ml, compared to 5.93 fmol/ml using unextracted samples. The rise of plasma secretin after infusion of a low dose of secretin (1 pmol.kg-1.h-1) in 10 healthy humans was only detected after sample extraction. Higher doses (3 and 9 pmol.kg-1.h-1) resulted in increments of plasma IRS (immunoreactive secretin), which could be recorded both with and without sample extraction. After a steak meal 7 of 10 subjects showed a significant increase of plasma secretin assaying extracted plasma samples. The secretin release occurred in spikes. The mean increase of plasma IRS in this group was 0.6 fmol/ml, the mean maximal secretin release above basal was 2.3 fmol/ml. Without sample extraction, plasma secretin was not significantly changed. We conclude that plasma samples should be extracted in order to detect physiological postprandial secretin release.

Animals

Calcitonin gene-related peptides I and II and calcitonin: distinct effects on gastric acid secretion in humans.

The human calcitonin gene-related peptides I and II (CGRP I and CGRP II) are two neuropeptides that have been recognized throughout the gastrointestinal system including the stomach. The present study was undertaken to compare in healthy volunteers the effects of intravenous infusions of CGRP I and CGRP II (79 pmol/kg.h) on pentagastrin-stimulated acid secretion to those of calcitonin (88 pmol/kg.h). Calcitonin gene-related peptide I did not inhibit basal or pentagastrin-stimulated acid secretion. However, CGRP II and calcitonin inhibited pentagastrin-stimulated acid responses by 20% and 28%, respectively (p less than 0.05 and p less than 0.01), whereas basal acid output was only reduced with calcitonin (p less than 0.05). These effects were recognized with low doses of pentagastrin, and absent with high doses suggesting competitive inhibition. Furthermore, step-doses of CGRP I and CGRP II (79-320 pmol/kg.h) were given intravenously on continuous pentagastrin stimulation and compared with calcitonin (88-352 pmol/kg.h). Calcitonin gene-related peptide II and calcitonin induced a dose-dependent decrease of acid output, whereas CGRP I was ineffective. The inhibitory effects of CGRP II and calcitonin are not due to increased gastric alkaline secretion or to somatostatin release, as neither peptide stimulated gastric bicarbonate secretion or induced an increase in circulating somatostatin. In conclusion, CGRP II, unlike CGRP I, inhibits gastric acid secretion in humans. Inhibitory effects of CGRP II and of calcitonin were comparable. The results imply that CGRP I and II, at the level of the stomach, have distinct biological properties in humans.

Adult