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Biomedical subjects

E Kostka-Trabka

Publications and source records attributed to E Kostka-Trabka.

At least 19 recordsLinked to original sources
PubMed2001

Plasma and urine pharmacokinetics of the dopamine agonist alpha-dihydroergocryptine in patients with hepatic dysfunction.

OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic behavior of unchanged alpha-dihydroergocryptine (DHEC, Almirid, Desitin Arzneimittel GmbH, Hamburg, Germany, under licence of Polichem S.A., Luxembourg) and total DHEC (unchanged DHEC and pooled metabolites) in plasma and urine in patients with impaired hepatic function, following administration of single oral doses. METHODS: The study was carried out according to an open, uncontrolled, parallel-group design, investigating two study groups: patients with hepatic dysfunction, i.e. with evidence of stable cirrhosis (n = 10) and age- and sex-matched healthy subjects (n = 8). Each subject received a single dose of 20 mg DHEC. Blood samples were taken at specified intervals up to 72 h after dosing and urine was collected fractionally for 24 h. Concentrations of unchanged DHEC were determined by RIA and concentrations of total DHEC (unchanged and pooled metabolites) by EIA. RESULTS: The plasma and urinary pharmacokinetics of DHEC and its metabolites were characterized by large variability. In patients with impaired hepatic function, the geometric mean Cmax and AUC(0-infinity) values for unchanged DHEC were 571.3 pg/ml (CV: 0.87) and 4038 pg x h/ml (CV: 1.04) and were approximately 2 times (2.04, 95% CI: 0.93 to 4.46 and 2.11, 95% CI: 0.58 to 7.73 for Cmax and AUC(0-infinity), respectively) larger than those measured in age-matched healthy controls. The 24-hour urinary excretion was approximately 3 times (3.41, 95% CI: 0.95 to 12.21) higher in patients with hepatic dysfunction. Similar results were obtained for total DHEC. CONCLUSIONS: The results reflect an increased systemic exposure in patients with impaired hepatic function which is not due to a reduced urinary excretion/elimination or reduced renal clearance. The most likely mechanism involved is a reduction in pre-systemic biotransformation. The observed range of effects on the pharmacokinetics of DHEC in patients with compromized hepatic function does not suggest the need to revise the dosage recommendations, since treatment with DHEC is generally started with low doses and is slowly up-titrated according to the individual response and the occurrence of adverse effects. Nevertheless, lower maintenance doses are likely to be achieved.

Adolescent↗
PubMed2000

[Clinical aspects of drug interactions with selected antiplatelet drugs].

Physiological and pathological knowledge of blood platelets effectively permit to inhibition their adhesion and aggregation processes. Antiplatelet drugs are very important therapeutic groups in prevention of many cardiovascular system diseases. They characterize with high effectiveness tested in many clinical studies and small amount of side effects. However during the interaction with other simultaneously applied drugs one may observe decrease of therapeutic tolerancy, diminishing of its effectiveness and appearing of adverse effects. In this work we considered clinical results of interactions of some antiplatelet drugs (acetylosalicylic acid, ticlopidin, clopidogrel, heparin).

Drug Interactions↗
PubMed1999

[Evaluation of fraxiparine efficacy in the treatment of retinal vein occlusion].

PURPOSE: To evaluate the efficacy of Fraxiparine in the treatment of central retinal vein occlusion and retinal branch vein occlusion. METHODS: 30 patients were treated. Fraxiparine (Sanofi-Pharma) was injected subcutaneously in doses of 7.5 thousand units twice daily for 10 days and once daily for 18 days. In 19 cases central retinal vein occlusion was observed and retinal branch vein occlusion in 11 cases. Mean follow-up was 15 months (range 10-35 months). Ophthalmological examination including fluorescein angiography was performed before and after therapy. RESULTS: Improvement of visual function and condition of retina after therapy was observed in about 50% of cases. In 16 patients laser photocoagulation applied for neovascularisation or retinal edema was necessary.

Adult↗
PubMed1998

Treatment of peripheral vascular disease with misoprostol (Cytotec): a pilot study.

Misoprostol, the oral analogue of alprostadil, was used to treat 20 patients (aged 40-60 years) with peripheral arterial disease (PAD) according to Fontaine's classification at stages IIa and IIb. All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in clinical improvement in all patients. Elongation of pain-free (before treatment: 129 m +/- 78 m; after treatment: 214 m +/- 109 m) and maximum walking distance (before treatment: 304 m +/- 169 m; after treatment: 471 m +/- 264 m) was observed. At the same time, a shortening of the duration of pain was noted (before treatment: 100 sec +/- 37 sec; after treatment: 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of treatment. Activation of the fibrinolytic system was seen in the course of therapy (shortening of euglobulin clot lysis time (ECLT) and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.

Adult↗
PubMed1998

Thrombolytic and antiplatelet action of xanthinol nicotinate (Sadamin): possible mechanisms.

Here we report on thrombolytic and hypotensive actions of Xanthinol nicotinate (Sadamin) in rats and on its anti-platelet and fibrinolytic effects in patients with peripheral arterial obliterative disease (PAOD). Special consideration was given to a proposal of new mechanisms of anti-platelet and thrombolytic actions of Sadamin. We conclude that the mechanism of anti-platelet and thrombolytic activity of Sadamin partly consists of a simultaneous release of endogenous prostacyclin and nitric oxide by the nicotinate component of Sadamin, whereas the theophylline component is responsible for enhancement of physiological actions of these endothelial mediators at the level of cyclic nucleotides which are their second messengers.

Adult↗
PubMed1997

[The effect of treatment with sulphur water from the spring in Wiesław in Busko-Solec on levels of lipids,the fibrinolytic system and thrombogenic platelet function in patients with arteriosclerosis].

29 patients with arteriosclerosis obliterans and elevated level of cholesterol and/or triglycerides in blood received undiluted sulphur water from the spring Wiesław in Busko-Solec at the dose of 50 ml 3 times a day for 4 weeks. Such a treatment resulted in statistically significant decrease of blood levels of cholesterol, triglycerides and LDL cholesterol. The concentration of HDL cholesterol did not change significantly. Moreover, therapy with sulphur water resulted in decreasing of platelet aggregability evoked by ADP and collagen, spontaneous platelet aggregability and increasing fibrinolytic activity of the blood (elongation of euglobulin clot lysis time). We concluded that orally administered sulphur water from the spring Wiesław in Busko-Solec may be an additional means of treatment of patients with arteriosclerosis obliterans and high levels of cholesterol and/or triglycerides.

Adult↗
PubMed1997

[Misoprostol--oral prostanoid--the first clinical trial for use in patients with peripheral vascular disease].

Misoprostol, the oral analogue of alprostadil was used for the treatment of 20 patients (aged 40-60) with peripheral arterial disease according to Fontaine's classification at stages IIa and IIb (PAD). All patients received 200 micrograms of misoprostol 3 times a day during a month. The therapy with misoprostol resulted in a clinical improvement in all patients. Elongation of pain free (before treatment 129 m +/- 78 m, after treatment 214 m +/- 109 m) and maximum walking distance (before treatment 304 m +/- 169 m, after treatment 471 m +/- 264 m) was observed. At the same time a shortening of the pain duration was noted (before treatment 100 sec +/- 37 sec, after treatment 71 sec +/- 23 sec). The ankle/arm pressure ratio (AAPR) and arterial blood flow increased in both limbs after 4 weeks of the treatment. Activation of the fibrinolytic system was seen in the course of the therapy (shortening of euglobulin clot lysis time-ECLT and increase in t-PA activity). The platelets became less sensitive to ADP and collagen after intake of misoprostol. The results justify administration of misoprostol as a new therapeutic agent for the treatment of patients with PAD.

Administration, Oral↗
PubMed1996

Treatment with L-arginine is likely to stimulate generation of nitric oxide in patients with peripheral arterial obstructive disease.

The impairment of endothelial function in hypercholesterolaemic animals and humans is known to be reversed by intravenous infusions of L-arginine (L-ARG), the precursor of NO. 22 patients with peripheral arterial obstructive disease (PAOD) received L-ARG (60 mmol) as intravenous infusions, each lasting three hours, daily for seven consecutive days. This treatment resulted in elongation of the painfree and maximum walking distances, as well as shortening of the period of time required for pain relief after walking the maximum distance. A rise in the ankle/arm pressure ratio (AAPR) was associated with an increase of arterial blood flow in both calves. The transcutaneous oxygen tension (tcpO2) in the ischaemic foot was also increased. After the 1st and the 7th infusion of L-ARG the spontaneous (PAR) as well as the ADP- and collagen-induced platelet aggregation were suppressed, the euglobulin clot lysis time (ECLT) shortened, plasma levels of platelet activator inhibitor (PAI) decreased, and cGMP levels increased. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with PAOD. We presume that in these patients high doses of exogenous L-ARG can be partially converted to NO.

Adult↗
PubMed1996

L-arginine--substrate for no synthesis--its beneficial effects in therapy of patients with peripheral arterial disease: comparison with placebo-preliminary results.

Intravenous infusions of L-arginine (L-ARG) and placebo (saline) resulted in improvement of clinical assessments, statistically significant after L-ARG but not after saline. Results of laboratory estimations for platelet and fibrynolysis changed significantly following L-ARG infusions but not after infusions of placebo. These data indicate beneficial effects of L-ARG as a therapeutic agent in patients with peripheral arterial obliterative disease (PAOD). In these patients exogenous L-ARG can be converted to NO.

Adult↗
PubMed1994

Lack of beneficial effects of L-arginine infusion in primary pulmonary hypertension.

The aim of this study was to assess the effects of L-arginine in primary pulmonary hypertension (PPH). Diagnostic cardiac catheterization was performed in 4 patients (pts) (1 man and 3 women, aged 18-47 years) with suspected PPH. In all of them diagnosis of PPH was confirmed; mean pulmonary artery pressure (PAP) ranged from 46 to 83 mmHg. Then 61/min oxygen was administered for 10 min through the oxygen mask (first oxygen test). After another 15 min, L-arginine was infused into an antecubital vein at a dose of 12.63g of L-arginine hydrochloride in 300 ml of 0.9% NaCl over 90 min. 15 min before the planned termination of the infusion the second oxygen test was performed in the same way as the first one. Hemodynamic data were collected by means of two catheters placed in the main pulmonary artery and in the aortic root. Cardiac output (CO) was estimated by the thermodilution technique. Blood samples were drawn from both catheters to estimate oxygen tension and cyclic GMP (cGMP) levels. In pts 1 and 2 differences between baseline values and following L-arginine did not exceed 9% for mean PAP (mPAP), total pulmonary resistance (TPR), mean aortic pressure (mAP), systemic resistance (SR), CO and HR. In patient 3 mAP and SR dropped by about 30%. In patient 4 after 15 min of the infusion mAP and SR fell by about 50%, whereupon we stopped L-arginine administration. Thus, for ethical reasons, we decided not to recruit new subjects for the study. In pts 1-3 aortic oxygen tension diminished by 10-15% on L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Prostacyclin and molsidomine synergise in their fibrinolytic and anti-platelet actions in patients with peripheral arterial disease.

In vitro prostacyclin (PGI2) and nitric oxide (NO) synergise in their anti-aggregatory actions on blood platelets. Presently, we have studied an interaction of molsidomine (ML--pro-drug for the NO-donor SIN-1) and PGI2 in 20 patients with peripheral arterial disease (PAD) on the plasma fibrinolytic system and platelet aggregability. A synergism of these drugs in their fibrinolytic action as measured by shortening of euglobulin clot lysis time (ECLT) and in their anti-platelet action as measured by an increase in the ratio of free platelets to platelet aggregates was observed. It seems that PGI2 and ML activated the fibrinolytic system by two independent mechanisms i.e. by a PGI2-induced direct release of pro-fibrinolytic t-PA from endothelial cells and by a ML-induced suppression of the release of anti-fibrinolytic PAI-1 from platelets. This may constitute a basis for the synergism. A synergism between PGI2 and ML in their anti-platelet action seems to be rooted in the potentiation by cyclic-GMP on the anti-aggregatory action of cyclic-AMP in platelets. On the other hand, no synergism between PGI2 and ML was observed in their hypotensive effects as measured by systolic and diastolic arterial blood pressure. It may well be that the synergism in fibrinolytic and anti-platelet actions between stimulators of adenylate and guanylate cyclases accompanied by a lack of synergism in their hypotensive actions may allow reduction of the therapeutic doses of either stimulator, thus avoiding hazards of their hypotensive side effects.

Aged↗
PubMed1992

[Evaluation of the effectiveness of prostacyclin in the treatment of thrombosis of the central retinal vein using a double-blind method].

The patients were divided by chance into 2 groups: the first one (15 persons) was given a natrium salt of prostacyclin (Epoprostenol Wellcome or Chinoin) in a dose of 5 mg/kg/min. intravenously by an infusion pump in 5 infusions; the control group (15 persons) received instead of prostacyclin a placebo (0.1 M glycine buffer of pH 10.5). Besides all the patients were given Doxium or Calcium dobesilate, Rutinoscorbin, Vitamin C, and Polopyrin S (Soluble Aspirin). Immediately after the completion of the treatment the authors did not find any essential differences between the examined groups. In prolonged observations however one demonstrated a significantly smaller frequency of the development of neovascularization in the eyes of persons treated by prostacyclin in comparison with the control group.

Adult↗
PubMed1990

Effect of heparin and prostacyclin/heparin infusion on platelet aggregation in hemodialyzed patients.

The number of circulating platelet aggregates determined according to the method of Wu and Hoak and the platelet morphology revealed by scanning electron microscopy were investigated in 10 patients (8 males, 2 females) age 28-58 years) with end-stage renal failure treated by repeated hemodialysis. The examination was carried out twice: during a 4-hour hemodialysis session with the use of heparin alone and 1 week later during the course of another dialysis in the presence of both heparin and prostacyclin. During each dialysis session the platelet system was examined three times: prior to, after 90 min, and at the end of the procedure. As compared with the situation prior to dialysis, the number of platelet aggregates assessed after 90 min of dialysis and after its termination insignificantly rose following the treatment with heparin, but significantly fell after the use of the prostacyclin/heparin combination. The differences were also significant when the effects of both treatment types were compared. As revealed by scanning electron microscopy, during the course of hemodialysis with the use of heparin alone, the platelets showed signs of activation manifested by increases in number and length of cytoplasmic processes and by a tendency to aggregate. When both prostacyclin and heparin were used during dialysis, platelet activation was minimal or absent. Thus, the combined treatment with prostacyclin and heparin protects platelets from activation induced by their contact with artificial surfaces and may lower the risk of microthrombosis, making thereby hemodialysis safer and more effective.

Adult↗
PubMed1989

[Effectiveness of etofibrate in arteriosclerosis obliterans. Pilot study in hyperlipidemic patients with arteriosclerosis obliterans].

In a pilot study the therapeutic effect of 2 x 500 mg etofibrate (Lipo Merz retard) on lipids and lipoproteins, fibrinolytic activity and clinical parameters was studied for four weeks in hyperlipidemic patients suffering from arteriosclerosis obliterans (Fontaine stage II/III). The study parameters were evaluated prior to and after the four weeks of treatment. Administration of etofibrate resulted in a significant decrease in serum cholesterol and triglyceride levels, the decrease in LDL-/HDL-cholesterol-ratio due mainly to an elevation of the HDL-cholesterol fraction, an increase in plasma fibrinolytic activity, an increased peripheral blood flow in the ischemic leg, and an increase in the pain-free walking distance. Thus, etofibrate applied twice daily might be recommended for the treatment of hyperlipidemic patients with signs of arteriosclerosis obliterans, Fontaine stage II/III.

Adult↗