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Biomedical subjects

H Sinzinger

Publications and source records attributed to H Sinzinger.

At least 271 records · Page 15Linked to original sources
PubMed1990

Platelet kinetics in patients with atherosclerosis.

In 12 patients (8 males, 4 females; 59.4 +/- 6.2 years) with clinically manifest atherosclerosis (peripheral vascular disease stage II according to Fontaine and coronary heart disease) without any risk factor and 6 controls (4 males, 2 females; 58.5 +/- 7.06 years) autologous platelets were labelled using 100 microCi 111-In-oxine. In parallel, serum- and plasma-thromboxane (TX) B2 and conversion of exogenous radiolabelled arachidonic acid towards TXB2 were determined. No difference in labelling efficiency and recovery was noted. Platelet half-life was significantly (p less than 0.01) shortened in the atherosclerotics. Gamma-camera images were obtained during the first 64 minutes after reinjection as well as 2, 6, 18, 24 and daily up to 1 week after reinjection of autologous radiolabelled platelets. No difference between the patients suffering from atherosclerosis--having either visible atherosclerotic lesions or not--could be discovered. Serum-TXB2 was comparable, whereas plasma-TXB2 showed a trend towards an increase and the conversion from exogenous 14C-AA to 14C-TXB2 was increased in atherosclerosis.

Arachidonic Acid↗
PubMed1990

[Defects in the prostaglandin system. IX. Lipoxygenase defect of thrombocytes in a patient with polycythemia vera].

Patients with the myeloproliferative syndrome (MPS) often show morphological and functional platelet abnormalities and an increased incidence of lowered cyclooxygenase- and/or lipoxygenase activity. We present the case history of a 68-year-old male patient with polycythaemia vera in whom an absolute absence of platelet lipoxygenase activity has been detected for the first time in the literature.

Aged↗
PubMed1990

Prevalence of a shortened prostacyclin half-life in plasma in healthy adults: results of a screening investigation.

Out of a total of 1,981 adults (956 males, 1,025 females; aged 16-71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half-life in these three screenings was shorter than 60 sec and persisted during several follow-up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half-life of PG12 in 1,978 people amounted to 10.71 +/- 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons.

Adolescent↗
PubMed1990

Effects of taprostene, a stable prostacyclin analogue, on haemodynamics, platelet function and arachidonate metabolism in healthy volunteers.

In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng.kg-1.min-1 was given for 6 h. During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min. During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI2 and PGE1 was increased. Plasma and serum thromboxane B2, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, beta-thromboglobulin, malondialdehyde and the PGI2-synthesis stimulating plasma factor did not show any clear drug-related alteration. It is concluded that infusion of taprostene 25 ng.kg-1.min-1 caused measurable inhibition of platelet function ex vivo.

Adult↗
PubMed1990

Nuclear medicine and atherosclerosis.

Although the pathomechanisms of atherosclerosis are well known, their radioisotopic monitoring is still in its early childhood. The current radioisotope techniques are of only limited value for contributing to the clinical diagnosis of atherosclerosis. The limited reaction time of cellular blood constituents (platelets, monocytes) with the vascular surface at the injury site makes it very difficult to catch the point of injury. Lipoproteins excellently allow receptor imaging, while vascular monitoring is only of scientific interest at present. Labelling and subsequent imaging of components of the coagulation cascade have not succeeded so far, nor have attempts using unspecific labels such as porphyrin, polyclonal IgG and Fc fragments, for example. Preliminary evidence indicates that radioisotopic techniques may be of great benefit in the future in elucidating functional aspects of the disease, while they do not contribute to examining the stage and extent of atherosclerosis.

Arteriosclerosis↗
PubMed1990

A double blind placebo controlled trial of intravenous prostacyclin (PGI2) in 108 patients with ischaemic peripheral vascular disease.

108 patients with ischemic peripheral vascular disease were randomly allocated to receive infusion of either PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days) or placebo in a double-blind manner. All patients had Stage II disease (Fontaine classification). One month after infusion the absolute and relative walking times were significantly (p less than 0.05) longer in the PGI2- than in the placebo-treated group. Patients were further classified as treatment responders or non-responders on the basis of increase of absolute and relative walking times. After one month 44% (24 out of 54) of the PGI2- and 15% (8 out of 54) of the placebo-treated patients were positive treatment-responders (p less than 0.01).

Clinical Trials as Topic↗
PubMed1990

Successful therapy of the prostaglandin defect "Wien-Hietzing" (lack of platelet high-affinity binding sites for prostaglandin I2).

Some years ago we detected a lack of platelet high-affinity PGI2 binding sites in a 10 year-old girl who presented to the outpatient unit with clinical symptoms and signs of acute popliteal artery occlusion. We named this new defect in the prostaglandin system "Wien-Hietzing". Acute surgery was successful. On the basis of earlier findings that aspirin is able to sensitize platelets to the action of PGI2 and produce beneficial changes in platelet sensitivity, we decided to treat this girl with a daily dosage of 20 mg aspirin orally. Repeated control examinations during the total follow-up period of about 6 years revealed normalized platelet sensitivity and normalized receptor behaviour. The girl is symptom-free to date. It is concluded that this prostaglandin defect may be successfully treated with long-term, low-dose aspirin administration.

Arterial Occlusive Diseases↗
PubMed1990

Impaired conversion of exogenous arachidonic acid by platelets to thromboxane B2 and correction of that deficiency by interferon-alpha.

In the course of an investigation of cyclooxygenase and 12-lipoxygenase activity in platelets of patients with myeloproliferative syndrome receiving treatment with interferon-alpha 2 patients showed unusual results which have not been reported so far. Both patients had thrombocytosis, in one case associated with polycythaemia. In platelets of both patients, a reduced conversion of exogenous 14C arachidonic acid to TXB2 was observed accompanied by a shift in conversion to PGE2 and 12-HETE in one patient and to 12-HETE alone in the other before therapy. These findings were paradoxically associated with evidence of enhanced platelet activation in vivo. Treatment of both patients with interferon-alpha resulted in reversal of the biochemical abnormalities and in clinical remission.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1990

Local benefit of prostaglandin E2 in radiochemotherapy-induced oral mucositis.

In 15 patients suffering from maxillofacial cancer with radiochemotherapy-induced oral mucositis the local application of prostaglandin E2 (PGE2) tablets, 0.5 mg four times a day at a 4-h interval was performed. Plasma determination of the bicyclo-prostaglandin E2 metabolite showed no significant amount of the locally applied substance in the circulation. It is claimed that for this particular indication, PGE2 is a potent locally acting compound without affecting circulating levels.

Aged↗
PubMed1990

Defects in the prostaglandin-system--heredity, prevalence and vascular risk analysis.

2180 healthy adults, 620 patients (90% with cardiovascular disease, 10% others), 143 newborns and 351 relatives of persons in whom any abnormality of the prostaglandin (PG)-system had been discovered were involved in the Viennese Initiative for Prostaglandin (VIP)-Screening from 1984 through May 1989. The defects discovered were either inborn or acquired ones and were either familial or non-familial. The highest number of defects (54.8% of the total) identified were associated with PGI2. They indicated a lack of the PGI2-synthesis stimulating plasma factor (PF)-activity (n = 17) and PGI2-stabilizing capacity in plasma (defect 'Vienna-Döbling', n = 4, 12.9% of total), absence of high-affinity PGI2-binding sites on platelet membranes and lack of response of platelets to PGI2 (defect 'Vienna-Hietzing', n = 2, 6.5% of total). Furthermore, a lack of cyclooxygenase (n = 2, 6.5% of total), 12-lipoxygenase (defect 'Vienna-Penzing', n = 3, 9.7% of total) and thromboxane synthetase (n = 3, 9.7% of total) activities were diagnosed. In newborn screening, the PF-absence amounted to 2.8% (4/143), the lack of PGI2-stabilizing capacity to 0.7% (1/143). In adults, the prevalence is difficult to assess. Nevertheless, our findings indicate a frequency of 0.93% (26/2800) of defects in the PG-system among the adult Viennese population. The lack of PF-activity seems to be by far the most frequent one (0.46%, 13/2800). Other defects are much less common. It is not clear whether the incidence in healthy subjects or in patients with cardiovascular disease is different from each other. Further, it remains to be assessed whether there is a causative relation to vascular events or just an association. More intensive screening activities should validate the diagnostic, pathogenetic and therapeutic impact of the various defects in the PG-system.

Adult↗
PubMed1990

Effects of bopindolol on platelet function in hypertension at rest and during exercise.

The effects of bopindolol, a new nonselective beta-blocking agent, on platelet function have been studied in 10 male hypertensive patients given the drug (1 mg/day) in turn for eight weeks. Bopindolol significantly (p less than 0.01) decreased the bicycle exercise- (1.5 W/kg body weight for 6 minutes) induced increase in platelet aggregation. During bopindolol-treatment both the slope and the height of the platelet aggregation response curve were moderately decreased at rest before exercise and significantly (p less than 0.05) decreased at rest after exercise. During exercise the slope amounted to 75.4 +/- 44 degrees before and to 70.8 +/- 5.3 degrees after therapy (p less than 0.01), the height to 64.0 +/- 11.9% before and to 58.1 +/- 14.7% (p less than 0.05) after therapy. Furthermore, bopindolol significantly increased the exercise-induced decrease in platelet sensitivity to PGI2 (p less than 0.05; IC-50-value: 2.10 +/- 0.47 vs 1.88 +/- 0.31 ng/ml) and PGD2 (p less than 0.05; IC-50-value: (19.88 +/- 2.10 vs 18.57 +/- 1.63 ng/ml). Bopindolol also significantly (p less than 0.05) decreased the exercise-induced elevation in serum-TXB2 (244.9 +/- 35.2 vs 237.3 +/- 27.2 ng/ml) and plasma-TXB2 (15.7 +/- 6.3 vs 13.1 +/- 3.7 pg/ml). The platelet count, the plasma levels of 6-oxo-PGF1 alpha, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were not affected by bopindolol. It is concluded that bopindolol favourably affects platelet function, in that it lowers exercise-induced platelet aggregation and TXB2-formation in therapeutical doses and increases platelet sensitivity to antiaggregatory prostaglandins.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Additive benefit of PGI2 and PGE1 (via different mechanisms?) on inhibition of activation of human vascular smooth muscle cells?

It seems likely that the antiplatelet action of antiaggregatory prostaglandins (PGE1, PGI2) is not the pivotal mechanism of action involved in clinical improvement of peripheral vascular disease. Based upon earlier results that both of these agents may have a certain effect on proliferation of vascular smooth muscle cells, we approached that question of an "optimal therapeutic regimen" going one step further. Patients having to undergo amputation were given a randomized "last choice" therapy with either PGI2 (once or twice a day, 6 h, 5 ng/kg/min i.v.), PGE1 (once or twice a day, 1 ng/kg/min i.a.) or a combination of both with a 6 h interval in between for 5 consecutive days. The ones who underwent surgery had a pathomorphological examination of vascular segments removed during amputation. The counting of activated smooth muscle cells indicates a significant drop induced by both of the PG's alone. A second infusion a day with the same compound, however, did not induce a further decrease in the activation state. In contrast administering the complimentary PG caused a comparable, significant decrease (p less than 0.01) in activation of smooth muscle cells in the intima and the media as well. It thus seems, that different mechanisms may be involved inducing additive therapeutic benefit. PGI2 is hypothesised to act predominantly by blocking PDGF-release and interference with PDGF, whereas PGE1 may have a more direct vascular action. From these findings, as well as the beneficial clinical results to be reported elsewhere, a combined therapy by the infusion scheme used may be the optimal one for a PG-therapy at the moment, based upon platelet and smooth muscle cell action.

Age Factors↗
PubMed1990

Decreased hepatic function in patients with hepatoma or liver metastasis monitored by a hepatocyte specific galactosylated radioligand.

99mTc-galactosylated neoglycoalbumin (99mTc-NGA) is a hepatocyte-specific tracer that, after injection into the blood stream, delivers radioactivity selectively to the liver. This is based upon chemical recognition and binding by the hepatic binding protein (HBP), a receptor specific for galactosylated glycoproteins. Liver tissue samples were obtained intraoperatively from patients undergoing surgery for various cancers. The concentration of specific HBP receptors in the liver (normal liver, hepatoma, liver metastasis) was calculated from the in vitro binding of 99mTc-NGA. One week after surgery, the in vivo HBP density was also measured in some of these patients after injection of 3.5 mg (50 nmol per patient) 99mTc-NGA (150-200 MBq) for simulation of 99mTc-NGA kinetics. Comparison of in vitro and in vivo HBP concentration in the liver showed values in the same concentration range. In patients with hepatoma or liver metastasis a significantly (P less than 0.01) decreased global HBP density was found in vivo compared to controls. The values obtained for in vivo HBP concentration in the liver amounted to 0.38 +/- 0.05 mumol l-1 liver for patients with hepatoma, to 0.4 +/- 0.1 mumol l-1 in patients with liver metastasis and to 94 +/- 0.05 mumol l-1 liver in cancer patients without liver malignancy. In vitro investigation of HBP density revealed the malignant liver tissue to have a significantly (P less than 0.0001) decreased or almost (completely) absent HBP receptor density compared to the normal tissue apart from the cancer area. It is concluded that determination of HBP density in vivo via a specific tracer is a new, simple and reliable approach for the determination of remaining hepatic function in patients with primary or secondary liver cancer.

Aged↗
PubMed1990

99mTc-neoglycoalbumin (NGA)-binding to human hepatic binding protein (HBP) in vitro.

1 Neoglycoalbumin (NGA) was synthesised by covalent coupling of 2-imino-2-methoxyethyl-1-thio-beta-D-galactopyranoside (IME-thiogalactose) to the primary amino groups of human serum albumin (HSA). NGA was purified by ultrafiltration and size exclusion h.p.l.c. (SEC). 99mTc-labelling was performed with and without SEC purification. 2 Estimation of 99mTc-NGA-binding to human hepatic binding protein (HBP) revealed a complex behaviour indicating saturable high- and low-affinity sites. The high-affinity binding capacity was 1.1 +/- 0.4 pmol mg-1 human liver plasma membrane protein, the low-affinity binding capacity was 6.2 +/- 1.8 pmol mg-1 liver plasma membrane protein. The apparent equilibrium dissociation constants were 2.4 +/- 1.2 and 18.4 +/- 4.8 nM, respectively. 3 Specific binding of 99mTc-NGA to human HBP in the presence of 100 microM unlabelled NGA, Ca++ and Mg++ at pH 7.5 and 37 degrees C reached 85 +/- 5% at equilibrium. The amount of ligand specifically bound increased with the amount of human liver membrane protein added. The concentration of unlabelled agonist necessary to displace 50% of ligand bound amounted to 100 nM.

Albumins↗
PubMed1990

Esophageal prostaglandins in guinea pigs and rats.

The synthesis of prostaglandins (PGs) in the mucosa of the esophagus is studied in 20 albinotic adult guinea pigs and rats using the radioimmunoassay method. Both species investigated synthesize five PGs. The PG synthesis activity in the guinea pig's esophagus is higher than that in the rat's. PGE2 and PGF2 alpha might be involved in the regulation of lower esophagus sphincter pressure.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Platelet scintigraphy and survival in juvenile stroke patients.

In the present study the prevalence of active atherosclerotic lesion sites in the carotid and femoral arteries as well as the platelet survival in a selected group of 33 patients (8 males, 25 females) below the age of 50 after juvenile stroke has been examined. In the patients studied a high frequency (80%) of positive (visible) carotid artery lesions with a platelet uptake ratio (PUR) ranging from 1.07-1.79 as well as an extremely shortened platelet survival were monitored. In-vitro platelet function tests, however, did not show significant abnormalities. No correlation between PUR, platelet survival, platelet function and the clinical situation could be assessed. These findings indicate that in this highly selected group of patients in-vivo haemostatic balancing seems to be severely impaired.

Adult↗