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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 469 records · Page 26Linked to original sources

[111-Indium-labeled thrombocytes in the diagnosis of acute kidney transplant rejections and in monitoring the therapy of rejection reactions with prostacyclin].

33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment.

Acute Disease↗

[Technic of radioactive labeling of autologous human thrombocytes using 111-indium-oxine and 111-indium-oxine-sulfate and their clinical use].

Using 111indium oxine and 111indium oxine sulphate as platelet labels, maximal labelling efficiency can be achieved already after 3 minutes at an incubation temperature of 37 degrees C. Mean labelling efficiency values of about 90% are reached at a platelet count of greater than 10(9) platelets/ml, but the labelling efficiency is satisfactory also at a rather low platelet count of about 10(6) platelets/ml (71% on average). Platelet labelling with these tracers allows the calculation of platelet half-life in vivo, and gamma-camera imaging of platelet aggregates in thrombosis and renal transplant rejection as well. In the present study, the platelet half-life is significantly shortened in patients with coronary heart disease (n = 15), peripheral vascular disease (n = 13) and primary hyperlipoproteinaemia (n = 32) in comparison with 106 controls. No age dependence of platelet half-life was found in the different groups of patients whereas in the control group, a significant negative correlation between age and platelet half-life was observed.

Adult↗

[In vitro and in vivo studies using 111 indium oxine, 111 indium oxine sulfate and 99m Tc oxine in erythrocyte labeling].

The optimal conditions for red blood cell labelling using 111indium oxine, 111indium oxine sulphate and 99mTc oxine were established both in vitro as well as in vivo. The coagulant had no effect on labelling efficiency. Other variables such as the incubation time, temperature, duration, cell number and concentration of the complex exert a significant influence on labelling efficiency. Labelling efficiency of red blood cells is very high also under non-optimum conditions as compared with other cells (leucocytes, platelets).

Erythrocytes↗

A simple and safe technique for sterile autologous platelet labelling using "Monovette" vials.

A simple technique of autologous platelet labelling is described, which allows labelling within 40 min, and has the advantage of low costs, as no laminar air flow is required. Blood (16 ml) was withdrawn into 4 ml ACD, 500 ng prostacyclin was added. After 10 min sedimentation the vials were centrifuged for 5 min at 150 g. The plateletrich plasma in the supernatant was centrifuged at 500 g for 10 min to obtain a platelet pellet. The platelet-poor plasma was preserved in a sterile syringe and the platelet pellet was resuspended in 1 ml tyrode buffer. The cell suspension was labelled at 37 degrees C for 5 min with 100 muCi 111In-oxine sulphate and reinjected after dilution with the plasma. Mean labelling efficiency was 90% +/- 3%, mean recovery 2 h after reinjection 76% +/- 3% (mean +/- SD).

Blood Platelets↗

Plasma concentration of 13,14-dihydro-15-keto-PGE2 (PGEM) after various ways of cervix ripening with PGE2.

PGEM concentration was determined radioimmunologically in a non-pregnant woman, in whom PGE2 was infused intravenously at increasing rates and in women, in whom labor was induced by various methods for local application of PGE2. There was excellent correlation between the amount of PGE2 infused intravenously and the levels of PGEM determined in the peripheral plasma. The following methods of local application of PGE2 were included in the study: 0.4 mg PGE2 gel placed retroamnially by means of a balloon catheter, 0.4 and 0.5 mg PGE2 applied endocervically and 3 mg PGE2 placed intravaginally in form of a single vaginal tablet; also included was a control-group, where only vaginal examination was performed. Bloods were drawn before, 30 minutes, 1, 2 and 3 hours after PGE2 administration. Mean levels of PGEM in the maternal peripheral plasma did not change neither within nor between the various groups. It is concluded from the present study, that local application of doses currently used to soften the cervix and/or induce labor at term do not lead to the same PGEM-concentration in the maternal blood as after intravenous infusion of PGE2 in doses normally used to induce labor.

Cervix Uteri↗

The intrainfusion platelet rebound during and following PGE1-infusion is faster and more intensive than that with PGI2.

During continuous long-term prostacyclin infusion an intra- and post-infusion rebound of platelets has been reported. During the present study 8 patients suffering from peripheral vascular disease in stage IIb according to Fontaine have been infused intravenously at a constant rate of 5 ng/kg/minute for seven days. Throughout this time the platelet function parameters were followed daily in the morning. An intrainfusion platelet rebound occurs using PGE1 as well. In comparison to the data for PGI2 published earlier it is noteworthy that the rebound for PGE1 occurs faster and more intensive. We conclude that for both the antiaggregatory prostaglandins PGE1 and PGI2, an intermittent treatment scheme seems to be optimal at the moment.

Alprostadil↗

Prostacyclin-synthesis-stimulating plasma factor in patients with different stages of hepatic coma.

In patients with acute hepatic coma the prostacyclin synthesis stimulating plasma factor is significantly enhanced. This increased activity has been verified by using various test systems. However, there is no correlation between the actual plasma factor activity and the coma stage, respectively. The increase of plasma factor activity in these patients might account at least in part for the increased bleeding tendency seen in these patients.

Adolescent↗

Effect on nitroglycerin and other organic nitrates on the in-vitro biosynthesis of arachidonic acid-metabolites in washed human platelets.

Organic nitrates exert well known vasodilating effects in coronary arteries, although the exact mechanism of action is not fully understood. In this study the influence of these drugs on the biosynthesis of eicosanoids from labelled exogenous arachidonic acid (AA) in isolated platelets was examined. Platelet malondialdehyde (MDA)-formation in the presence of the substances tested in this system was studied too. The vasodilating drugs were found to reduce the conversion rate to TxB2, hydroxy-5,8,10-heptadecatrienoic acid (HHT) and MDA in platelets dose-dependently. Isosorbid-5-mononitrate (ISMN), nitroglycerin (NG) and SIN 1, the active metabolite of molsidomin, showed their inhibitory effects at concentrations of about 1mM, isosorbid-dinitrate (ISDN) had a much weaker effect on platelet-biosynthesis - a concentration of about 3mM was necessary to inhibit TxB2-formation significantly.

Arachidonic Acid↗

Plasma factor and platelet sensitivity to prostacyclin in patients with peripheral vascular disease before and after treatment with a combination of a cyclooxygenase and a phosphodiesterase inhibitor.

According to a pathogenetic concept originally presented by Moncada in 1977 a therapeutic combination of a low-dose cyclooxygenase inhibitor with a phosphodiesterase inhibitor might help in restoring a disturbed hemostatic balance, as thromboxane synthesis in the platelets should be inhibited to a greater extent than the prostacyclin synthesis of the endothelium. Therefore, we evaluated the influence of a therapeutic combination of cyclooxygenase inhibitors in different dosages (sulfinpyrazone, acetylsalicylic acid) with a phosphodiesterase inhibitor (dipyridamole) on platelet sensitivity and plasma factor in comparison to placebo treatment. We examined 76 males with peripheral vascular disease (PVD) stage IIa according to Fontaine in a double-blind randomized study over a 3 months period. Patients were divided into 4 groups and the different drugs were randomized as follows: I. 75 mg sulfinpyrazone and 75 mg dipyridamole, II. 150 mg ASA and 75 mg dipyridamole, III. 330 mg ASA and 75 mg dipyridamole, IV. placebo. Clinical symptoms as well as the plasma factor and the diminished platelet sensitivity to prostacyclin in patients with PVD remained unchanged throughout the whole observation period. Our findings suggest that no improvement in hemostatic dysregulation can be obtained by this combined treatment.

Aspirin↗

The cyclo-oxygenase and lipoxygenase pathways in human oral cancer tissue.

This paper reports on the synthesis of prostaglandins in oral squamous epithelial carcinomas. Using radio-thin-layer chromatography, we observed the conversion of 14C-labelled arachidonic acid into the prostaglandins PGE2, PGF2 alpha, PGI2 and PGD2. We also observed an approximately equal production of hydroxy fatty acids. The role of the above-mentioned substances in the growth of malignant tumours and the process of metastasis is discussed.

Adult↗

Concentration of 13,14-dihydro-15-keto-prostaglandin E2 in the maternal peripheral plasma during labour of spontaneous onset.

The concentration of 13,14-dihydro-15-keto-PGE2 (PGEM) was measured by radioimmunoassay in pregnant women in the third trimester, in women at term but not in labour and during labour of spontaneous onset. The plasma concentration of PGEM in pregnant women was elevated above that in a non-pregnant control group. Before the onset of labour no increase of PGEM concentration could be identified. Women in labour had higher PGEM plasma concentrations than before the onset of labour, although there was no progressive increase. Immediately after delivery PGEM levels reached a maximum, which decreased significantly to pre-labour values within 30 min. Artificial rupture of the membranes had no influence on plasma PGEM levels. It is concluded that labour is associated with an increased synthesis of PGE2 and that PGE2 may be involved in the mechanism of placental separation. The rapid disappearance of high PGEM levels after labour confirms that PGE2 is probably synthesized mainly in the fetal compartment.

Dinoprostone↗

Pulmonary and antiaggregatory effects of prostacyclin after inhalation and intravenous infusion.

Prostacyclin (PGI2) was administered by inhalation (50 micrograms/min) and intravenous infusion (15 ng/kg/min) in 5 healthy male volunteers. Irrespective of the route of administration this substance was shown to have no effects on respiratory indices studied, whereas a significant inhibition of ADP-induced platelet aggregation and a fall in vascular resistance could be demonstrated. Mainly because of the latter action it is suggested that PGI2, or a stable synthetic analogue, might become a potent drug in various pathological conditions, in which hypertension of various causes is a problem.

Adult↗

Long-lasting depression of rabbit aortic prostacyclin formation by single-dose irradiation.

Male rabbits were exposed to a single irradiation dose of 1000-5000 rad when 12, 15, 16, and 17 months old and were killed when 18 months old (i.e., 1, 2, 3, and 6 months after irradiation). Even after this long interval after irradiation, abdominal aortic prostacyclin formation was significantly depressed, whereas the nonirradiated thoracic aortic segment exhibited no significant alteration in vascular PGI2 generation. The data show that the severe decrease in PGI2 synthesis was not caused by deendothelialization induced by irradiation alone. The data support the view that a deterioration in the prostaglandin system regulating hemostatic balance is an important determinant in the development of radiation-induced vasculopathy.

Animals↗

Prostacyclin synthesis stimulating plasma factor in pregnancy and puerperium.

Prostacyclin is assumed to play a key role in maintaining a sufficient blood flow in maternal and fetal circulation. Recent reports pointed out that the prostacyclin synthesis is regulated by a so-called plasma factor. The activity of this plasma factor was tested during pregnancy, labor, and puerperium. During the first and second trimesters, increased values could be observed, whereas in the third trimester and at the onset of labor, the values decreased. After delivery, there was again a moderate increase in plasma factor activity. A feedback mechanism is discussed between prostacyclin or 6-oxo-prostaglandin F1 alpha and the plasma factor, but hormones, such as 17 beta-estradiol, may possibly influence prostacyclin synthesis in pregnancy.

Animals↗