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Biomedical subjects

E Stahl

Publications and source records attributed to E Stahl.

At least 19 recordsLinked to original sources
PubMed1992

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans.

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P less than 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P less than 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 +/- 0.2 to 4.1 +/- 0.3 compared with 4.5 +/- 0.3 to 5.0 +/- 0.4 after placebo (P less than 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 +/- 7.7 vs. 140.0 +/- 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 +/- 1.3 vs. 4.0 +/- 0.5 pmol/L after placebo (P less than 0.001), and the integrated response exceeded the control value by 175% (P less than 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

Adult↗
PubMed1990

Barefoot in the OR.

In 1988 Dr. Sylvia Uhthoff Munro, an Ottawa general practitioner, and her husband Martin Munro, a professional engineer, spent a year at a small hospital in Ialibu, in the Southern Highlands of Papua New Guinea. The way medicine is practised there may be primitive by Canadian standards, she learned, but the country also proved to be a valuable classroom, one where the lessons came very quickly.

Health Services↗
PubMed1990

In vitro activity of biosynthetic human diarginylinsulin.

In diarginylinsulin two arginine residues are located at the C-terminal end of the B-chain (ArgB31 and ArgB32). This accounts for a shift of the isoelectric point from pH 5.4 in native insulin to pH 7.0 in diarginylinsulin leading to pharmacodynamic characteristics of an intermediate acting insulin when administered s.c. as pH 4.0-5.0 solution. We have investigated insulin receptor binding and biological activity of biosynthetic human diarginylinsulin in human adipocytes and compared to native insulin and proinsulin. Association- and dissociation studies of insulin receptor binding revealed no differences for diarginylinsulin and native insulin. In competition studies under steady-state binding conditions, half-maximal displacement of tracer occurred at 352 +/- 33 pmol/l, 337 +/- 32 pmol/l and 3640 +/- 480 pmol/l for diarginylinsulin, insulin and proinsulin, respectively. The biologic potency of human diarginylinsulin was evaluated by the ability to stimulate D-glucose transport and by the assessment of the antilipolytic activity. Activation of D-glucose transport was half-maximal at 49.6 +/- 5.4 pmol/l (diarginylinsulin), 44.8 +/- 5.8 pmol/l (insulin) and at 476.7 +/- 134.3 pmol/l (proinsulin). Half-maximal inhibition of lipolysis occurred at 13.9 +/- 3.4 pmol/l, 15.4 +/- 2.9 pmol/l and 138.4 +/- 38.6 pmol/l, respectively. In conclusion, diarginylinsulin has almost identical insulin receptor binding characteristics and full biological activity in vitro compared to native insulin. This pharmacodynamically intermediate acting insulin preparation is therefore of potential therapeutical value.

Adipose Tissue↗
PubMed1988

Tolerability and pharmacokinetics of L-648,051. A leukotriene D4-receptor antagonist, in healthy volunteers.

Two formulations of L-648,051 (L) were studied [intravenous (i.v.) and aerosol (A)] in two separate trials. Study I (i.v.) involved 4 normal male subjects in a single blind dose ranging study where good systemic tolerability and safety was shown. However, dose dependent local irritation at the injection site was observed at all dose levels (35, 52.5 and 70 mg/5 min infusion). L has a high systemic clearance rate (1.2 1/min), a small volume of distribution (4.41) and a short plasma half-life (2.4 min). Study II (A) involved 16 normal male volunteers who received incremental aerosolized doses of L from 0.1 to 1.6 mg in a double-blind, placebo controlled, dose ranging study. Complaints of mild local irritation or discomfort in the upper respiratory tract were the only significant findings. No dose relationship of these complaints could be shown. In conclusion, L is a safe and well tolerated drug when administered by aerosol. It causes dose related local, but not systemic, adverse experiences when administered i.v. In view of this tolerability and of its demonstrated activity against LTD4-challenge in animals, clinical efficacy studies with the aerosol formulation are warranted.

Adult↗
PubMed1988

[ Aneurysma spurium of the pancreaticoduodenal artery].

A predominantly cystic process of the upper abdominal region of a 61 year old female patient was punctured via the fine-needle technique. The clinical assumption had been a lymphoma. Bright red blood was aspirated. The Doppler sonographic measurement revealed an arterial pulsating aneurysmatic process, and this was subsequently proved by selective angiography and, finally, by surgical treatment.

Aneurysm↗
PubMed1979

[Morphological and clinical liver changes after taking oral contraceptives].

In 155 women of the age group 16-45 years after intake of oral contraceptives in 68.4% (106 cases) histologically provable liver changes were found. Sinusoidal ectasias of different size and drug-conditioned hepatitides most frequently occurred. An isolated intrahepatic cholestase only rarely existed. Increases of transaminase are the most frequent reference to a lesion of the liver parenchyma after intake of oral contraceptives. The author adopts a definite attitude to the differential diagnosis and its difficulties between a drug-conditioned hepatitis and the usual virus hepatitis.

Adolescent↗
PubMed1978

[Urinary hydroxyproline excretion in liver cirrhosis].

In 50 patients with a laparoscopically ascertained liver cirrhosis the hydroxyproline excretion was estimated in the 24-hour-urine. There could not be found any significant differences between hydroxyprolinuria in normal persons and in patients with liver cirrhosis. The increased hydroxyproline excretion is an unspecific symptom and thus cannot contribute to the diagnosis and the observation of the course of a liver cirrhosis.

Adult↗
PubMed1978

[Studies on the biotransformation of fominoben-HCl in man (author's transl)].

The biotransformation of 3'-chloro-2'-(N-methyl-N-[(morpholino-carbonyl)methyl]aminomethyl)benzanilide hydrochloride (fominoben-HCl, PB 89 Cl, Noleptan) was investigated in man. The most substantial metabolites were quantified. The metabolite patterns of fominoben in urine and plasma are compared. Fominoben, is rapidly and extensively metabolized to many metabolites. At the time of the maximum plasma level. 2 h after an oral dose of 160 mg of 14C-PB 89 Cl, only 1.5% of the plasma radioactivity can be measured as the unchanged initial compound. No parent compound can be found in the urine, only in the stool some traces of fominoben can be detected. The biotransformation can be characterized by four main pathways: 1. cleavage reactions, 2. hydroxylations, 3. cyclisations, 4. conjugations. The reactions 1--3 proceed as well simultaneously as successively.

Adult↗
PubMed1977

Irreversible shock in rats after injection of microspheres into the renal artery.

After injection of microspheres into both renal arteries of rats, an irreversible shock syndrome develops, resulting in death within 4-12 h. Ligation of both renal pedicles after injection of microspheres prevents the shock. It is presumed that kininogenases released from the kidneys participate in the pathogenesis of the shock syndrome.

Animals↗