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Biomedical subjects

C Leithner

Publications and source records attributed to C Leithner.

At least 37 records · Page 2Linked to original sources

Parathyroid hormone does not inhibit platelet aggregation.

The suggestion that parathyroid hormone (PTH) is a major uraemic toxin was examined by testing the effects of synthetic human PTH fragments and synthetic bovine PTH on ADP-induced and collagen-induced platelet aggregation. Whereas the bovine parathyroid-gland extracts inhibited platelet aggregation in a dose-dependent manner, none of the synthetic compounds was effective even at high concentrations. It is suggested that the inhibition of platelet aggregation by extracts of bovine parathyroid glands is not caused by PTH fragments and is probably an effect of other constituents contained in the extract. These findings argue against a role of PTH in the pathogenesis of platelet dysfunction and bleeding tendency in uraemia and were supported by platelet-aggregation studies in 6 patients with primary hyperparathyroidism. Platelet aggregation was normal before and unchanged after surgery of the parathyroid glands.

Adenosine Diphosphate

[Efficacy and tolerance of hepatitis B vaccination in medical personnel and hemodialysis patients].

The efficacy and safety of a hepatitis B vaccine (Pasteur Institute) has been evaluated in 93 healthy members of the medical staff and in 28 patients undergoing chronic haemodialysis. Following 3 injections of vaccine (each 5 micrograms) at monthly intervals, 94% of the healthy subjects and 61% of the patients were already successfully immunized 4 months after commencement of the vaccination course. Those who did not respond initially received an additional dose at 6 months, which induced seroconversion in several more cases, resulting in the successful immunization of 98% of healthy subjects and 75% of haemodialysis patients. Immune response was sex- and age-dependent. Peak anti-HBs concentrations in responders at 6 months were 643, 325, and 194 mU/ml in healthy women, healthy men, and in patients, respectively. None of the staff members developed clinical or biochemical signs of hepatitis or of any other disease. Markers of hepatitis B virus infection were detected in 3 healthy subjects and in 6 dialysis patients.

Antibody Formation

[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

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

[Prostacyclin therapy in EPH gestosis (preliminary report)].

EPH-gestosis is still today one of the most dangerous complications of pregnancy, threatening both, maternal and fetal life. Until now only symptomatic treatment was possible. A new mode of treatment of EPH-gestosis may evolve from the use of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation. We tried prostacyclin therapy in three patients with severe gestosis. The results of prostacyclin infusion on this condition, the pregnancy, the fetus, the placenta and the morphology of the umbilical artery are discussed.

Adult

Radiolabelled platelets and prostacyclin in diagnosis and treatment of transplant rejection.

The trapping of 111Indium-oxine labelled autologous platelets by the transplant was recorded by means of a computerised gamma camera and expressed as platelet uptake index (PUI). Eighty-five patients were studied. The PUI increased in acute rejection from 1.13 +/- 0.11 to 1.74 +/- 0.17, and decreased again when rejection was reversed. In chronic rejection PUI was significantly lower than in acute rejection, but still higher than in long term stable grafts. Prostacyclin infusions were given to six cases of acute rejection and 12 of chronic rejection. In the majority of patients an improvement in transplant function and a decrease in platelet trapping could be demonstrated.

Adolescent

[Age dependency of platelet half life].

In the last few years many reports have been published concerning shortened platelet half-life in different diseases such as atherosclerosis and hematological disorders. Up to the present moment, however, there is no information available concerning age and sex dependency in healthy people. Therefore, we evaluated platelet half-life in 106 patients, who had been examined because of a suspected atherosclerotic or hematological disorder having been excluded in the sequel. In all the patients we found negative bicycle ergometry and negative sonography of the carotid arteries and the legs. Platelets were labelled with 100 muCi of 111Indium-oxine-sulfate at 37 degrees C for 5 minutes. The mean labelling efficiency was 90%, the recovery about 70% after two hours. We found a statistically significant correlation (r = -0,5395; p less than 0,001 between age and platelet half-life. In male patients we observed a trend towards shortened platelet half-life, however, the differences were not significant.

Adult

[Prostacyclin synthesis-stimulating plasma factor in different age groups].

The vascular synthesis of prostacyclin (PGI2), the most powerful endogenous inhibitor of platelet aggregation and vasodilator, plays a central role in prevention of vascular damages by uncontrolled platelet aggregation. PGI2 seems to be an important defense mechanism of vascular system against, among others, the development of atherosclerosis. The PGI2-production of blood vessels is stimulated and thereby decisively influenced by a plasma factor (PF). This PF participates in the pathogenesis of several diseases. This activity of PF is for instance increased in renal insufficiency, which explains partly the haemorrhagic diathesis occurring in this illness. On the other hand there seems to be a hereditary lack of PF in patients suffering from thrombotic-thrombocytopenic purpura or haemolytic-uraemic syndrome. The PF was estimated in 62 healthy subjects collected in 8 age groups by means of bioassays and RIA-determination of 6-oxo-PGF1 alpha, the stable PGI2-metabolite, in tissue cultures. No differences of PF in the different age groups could be demonstrated. These findings support the view, that the PF as an important regulator of vascular PGI2-synthesis is functioning absolutely normal in older age.

Adolescent

Increased deposition of 111Indium labelled platelets in chronically rejected kidney transplants.

Increased deposition of 111In-oxine labelled autologous platelets in chronically rejected kidney transplants was demonstrated using a gamma-camera and by measurement of a platelet uptake index (PUI). In this group of patients the PUI correlated indirectly with the platelet half-life and was statistically different from the PUI found in stable transplant patients who acted as controls. It is therefore suggested that platelets may play a key role in chronic rejection by the release of a mitogenic factor which promotes the development of obliterative arterial lesions in the transplant.

Adult

[The use of labeled thrombocytes in the monitoring of patients after kidney transplantation].

Indium 111 (111In) labelled autologous platelets were used in the diagnostic observation of patients after renal transplantation. 75 patients were collected in 3 groups of 25 cases each. The first group consisted of patients who were examined during the first 4 weeks after transplantation. Group 2 were patients suffering from histologically proved chronic graft rejection. The 3rd group included cases with good and stable transplant function tested at least 9 months after transplantation. By means of a computerized static study the transplants were examined under the gamma-camera concerning a platelet trapping. Thereby a platelet-uptake-index (PUI) was calculated and compared with the platelet half-life-time (t1/2). This diagnostic method turned out to be suitable for early diagnosis of acute graft rejection. Hereby the PUI increased from 1.13 +/- 0.11 to 1.74 +/- 0.17. The further course of rejection episode manifested itself in corresponding changes of PUI. In irreversible rejections the PUI stayed in the high range or increased further. On the other hand reversible graft rejections showed a reduction of PUI, however, in the most cases not to the original basic level. The platelet t1/2 exhibited a strong negative correlation with PUI. Cases suffering from chronic transplant rejection revealed significantly higher platelet trapping by the graft than patients with good and stable transplant function.

Adolescent

[The value of sonography in the follow-up of patients with transplanted kidneys].

42 cases with transplanted kidneys were examined by ultrasound. The results were compared critically with clinical and histological data. The ultrasound findings are identical with the other findings in 86%. Ultrasound therefore together with clinical laboratory and nuclear medical findings can in a very high percentage replace other high risk examinations like retrograde pyelography or angiography.

Acute Disease

[Determination of immune complexes in renal diseases (author's transl)].

The concentration of circulating immune complexes were determined by Clq solid phase assay in 30 patients with systemic lupus erythematosus (n = 15), glomerulonephritis (n = 5), and after kidney transplantation (n = 10). Elevated immune complex concentrations were found in glomerulonephritis and systemic lupus erythematosus correlating with disease activity. In the posttransplant period the level of immune complexes was increased after antilymphocyte globulin therapy. The function of the transplanted kidney or rejection crises showed no effect on immune complex formation. The presence of circulating immune complexes indicates a high activity of disease in cases of glomerulonephritis and systemic lupus erythematosus.

Antigen-Antibody Complex

Enhanced 6-oxo-PGF1 alpha levels in plasma during hemodialysis.

The activation of platelets due to foreign surface interaction is a well known fact. Earlier, we found an increase of circulating platelet microaggregates (method of Wu and Hoak) during hemodialysis. Since this phenomenon might cause a PGI2-release by lung and/or vascular tissue, we studied the plasma 6-oxo-PGF 1 alpha-levels in 6 patients during hemodialysis. We found an initial increase of plasma 6-oxo-PGF 1 alpha. Coincidently, hypoxemia, fall in platelet and lekocyte count and a decrease in platelet count ratio were observed. An effect of heparin was excluded in a control group. The findings support the hypothesis that PGI2 acts as a defense mechanism against platelet deposition on vascular wall by a temporary increased synthesis which could be monitored by a temporarily enhanced plasma 6-oxo-PGF 1 alpha-level during the initial phase of hemodialysis.

6-Ketoprostaglandin F1 alpha

[Age dependence of vascular prostacyclin formation in man (author's transl)].

The synthesis of prostacyclin (PGI2), the most potent known inhibitor of platelet aggregation, varies with age. After 30 years the production decreases, but increases again in the 6th and 7th decade. Contrary to these physiological variations patients suffering from juvenile onset diabetes or peripheral angiopathy show a markedly decreased prostacyclin synthesis. Since the prostacyclin system in thought to be an important blood vessel protector, the pathological low level of PGI2-synthesis could be a key position in development or progression of vascular complications.

Adult