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Biomedical subjects

E Stahl

Publications and source records attributed to E Stahl.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Lung manifestation of progressive systemic scleroderma. Computerized tomographic findings].

Progressive systemic scleroderma (PSS) is caused by generalized connective tissue disorder. The most frequent visceral manifestations are pulmonary and oesophageal involvement. Early detection of such visceral manifestations, which are sometimes life-limiting, is of paramount importance in any diagnostic procedures. The sensitivity of the methods differs and depends on the stage of the disease. Modified high-resolution computed tomographic scans (HRCT) were obtained in 28 patients with early forms of PSS and showed pulmonary involvement in 79% and signs of oesophageal involvement in 54%. HRCT is much more sensitive than chest radiography, lung scintigraphy and lung function tests even at an early stage of the disease. Classification of PSS should take account of the clinical type of sclerosis and of immunological and other parameters of prognostic importance.

Adult↗
PubMed1994

In vivo assessment of pulmonary oxidant damage: the role of bronchoalveolar lavage.

Oxidants can cause injury and cell death by modifying and/or disturbing the structure and function of any cellular or non-cellular component. There is overwhelming evidence that a variety of lung disorders are mediated, at least in part, by oxidants causing tissue damage, especially since its location, anatomy, and function makes the lung a primary target for oxidant injury. Bronchoalveolar lavage (BAL) is an excellent tool to evaluate these mechanisms in vivo. BAL allows the repetitive sampling of the cellular and non-cellular components of the fluid lining the epithelium of the lower respiratory tract with minimal risk and discomfort for the patient. The analysis of cell numbers, differential cell counts, cellular functions, and concentrations and functional properties of non-cellular components of BAL fluid continuously improves our understanding of the pathogenesis of lung diseases and of the pathogenetic role of oxidants and antioxidants in particular, by "looking into the living lungs." Further, the ready access of the respiratory epithelial surface by BAL provides opportunities to evaluate and monitor therapeutic strategies directed at reducing the oxidant burden and/or augmenting the antioxidant defense mechanisms in the lower respiratory tract, thereby correcting an oxidant-antioxidant imbalance directly at the site of disease.

Bronchoalveolar Lavage Fluid↗
PubMed1993

Saturable enantioselective first-pass effect for carvedilol after high oral racemate doses in rats.

Carvedilol shows a highly enantioselective first-pass extraction after therapeutic p.o. doses with preferential extraction of the S-enantiomer. To investigate, whether the enantioselective first-pass metabolism is saturable, male Sprague-Dawley rats were administered increasing single doses of R/S-carvedilol (p.o., 5-30 mg/kg; i.v., 5 and 10 mg/kg), and the individual stereopharmacokinetics were studied. Like in humans the plasma concentrations of R-carvedilol exceeded always those of S-carvedilol. As expected, a dose-dependent reduction in oral clearance was observed, while the total clearance after the i.v. doses was constant. Beyond 20 mg/kg an increased plasma half-life was found for both enantiomers, which is due to a reduced plasma clearance.

Administration, Oral↗
PubMed1993

Carvedilol stereopharmacokinetics in rats: affinities to blood constituents and tissues.

Carvedilol, a lipophilic beta-adrenoceptor antagonist with vasodilating activities, is characterized by a high as well as stereoselective metabolic clearance and distribution volume. Tissue distribution of carvedilol enantiomers and their conjugates were determined under steady-state conditions in rats (p.o., 10 mg/kg, repetitive dosage; n = 5) and after single i.v. administration in control rats and rats with surgical portacaval shunt (pcs) (10 mg/kg; n = 3 each group). In addition, in vitro plasma protein binding was evaluated. The plasma protein binding of carvedilol in rats is > 98% for total plasma (tp) and > 96% for rat serum albumin (rsa) solution (4%), with enantioselectivity ratios of 1.53 (tp) and 1.27 (rsa). Significantly higher unbound fractions were observed in pcs rats, in part due to reduced protein concentrations. In contrast to plasma, where a preponderance of the R-enantiomer with an S/R ratio of 0.6 was found, S-carvedilol was predominant in all tissues (heart, liver, kidneys, lung, spleen, muscle, and adipose tissue), with S/R ratios of 1.3-1.4 in most of these tissues and 2.3 in liver. This preferential tissue partitioning of S-carvedilol was in accordance with its higher unbound fraction in plasma. Carvedilol accumulated predominantly in the highly perfused and/or eliminating organs liver, kidneys, and lung (tissue/plasma ratios; lung: S 76, R 34; liver: S 21, R 5; kidney: S 8, R 3). A similarly enantioselective distribution into the heart of control as well as pcs rats was observed, where the S-enantiomer concentrations exceeded the plasma concentrations 7-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

Rats with portacaval shunt as a potential experimental pharmacokinetic model for liver cirrhosis: application to carvedilol stereopharmacokinetics.

As an experimental model for reduced liver function rats with surgical portacaval shunts (pcs) may be used. Carvedilol, a nonselective beta-adrenoceptor antagonist with vasodilating activity, is extensively metabolised by phase I as well as phase II pathways. In order to study the stereoselective pharmacokinetics of carvedilol in liver disease, pcs and control rats were given rac-carvedilol intravenously and p.o. The carvedilol enantiomers and their conjugates were assayed in plasma, urine, and bile. Carvedilol was highly bound to plasma proteins; binding was reduced by pcs. In all groups, the plasma concentrations of (R)-carvedilol exceeded those of (S)-carvedilol significantly. In comparison to the control group the plasma concentrations of both enantiomers increased after pcs, while the difference between the stereoisomers decreased. The total clearance decreased proportionally to the decrease in liver weight (30%). Both the apparent oral clearance, as well as its stereoselectivity were reduced, by up to 90 and 43%, respectively. The biliary clearance of the parent drug after i.v. dosage increased in rats with pcs due to the reduced hepatic metabolism.

Adrenergic beta-Antagonists↗
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↗
PubMed1986

Effect of Clinoril (sulindac, MSD), piroxicam and placebo on the hypotensive effect of propranolol in patients with mild to moderate essential hypertension.

One hundred ten patients of both sexes with mild to moderate essential hypertension were studied in this double-blind, multicenter study. In the double-blind portion of this study, which covered weeks 11 to 14, 71 patients were evaluated to determine the effect of Clinoril (sulindac, MSD), piroxicam, and placebo on the hypotensive effect of propranolol. All 110 patients were considered for safety evaluation. Patients treated with propranolol alone were distributed randomly into three groups (Clinoril, piroxicam and placebo) and compared in a 15-week study with four periods (I through IV). Having fulfilled the criteria for hypertension (I) and having been successfully controlled with propranolol alone (II), patients were entered into a double-blind period (III) comparing the three drug treatments during four weeks followed by one week of propranolol alone (IV). During period III, patients treated with piroxicam had significantly greater (p less than 0.05) increases in supine and standing diastolic blood pressure than patients treated with Clinoril. No clinical difference was shown between patients treated with Clinoril and placebo. At the end of period IV patients treated with piroxicam maintained the increase in their diastolic blood pressure, in contrast to Clinoril and placebo where no clinical difference was noted. Significantly more patients treated with piroxicam than Clinoril had a 10 mmHg or greater increase of their supine diastolic blood pressure. These results show that Clinoril does not blunt the antihypertensive effect of propranolol in patients with mild to moderate hypertension in contrast to piroxicam. This is an extension of a report previously published in Advances in Therapy, Vol. 2, No. 4, July/August 1985.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1980

[Diabetic gastroparesis].

It is reported on a 61-year-old patient in whom since 1959 has been existing a diabetes mellitus in need of insulin. 1973 in the endoscopic control of roentgenological findings of a stomach suspect to tumour by means of the Wolf-Schindler gastroscope the suspicion to a gastric carcinoma was expressed. In May 1975 he was again admitted to hospital on account of a hypoglycemic shock. Roentgenologically large filling defects in the stomach were found, gastroscopically macroscopically no clearly explained whitish yellow masses (Histology: remains of food, chronic superficial gastritis, extended settlement of fungi). Only after several days of food carency and daily gastric lavages gastroscopically normal findings could be made. Together with the roentgenological findings of the stomach the diagnosis gastroparesis diabeticorum was made. Therapeutically an optimum stopping of diabetes is recommended and the application of metoclopramide. A surgical intervention is not advisable.

Diabetes Complications↗