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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

Plasma levels of atrial natriuretic peptide (ANP) in volume expanded patients: response to fluid removal by continuous pump driven hemofiltration.

Circulating amounts of human atrial natriuretic peptide (hANP) are elevated in congestive heart failure and renal failure. Stretching of cardiac atria, due to volume expansion associated with these diseases, is widely accepted to be the predominant stimulus for release of the hormone. Measurements of hemodynamic parameters as well as plasma concentrations of ANP in the right cardiac atrium, pulmonary artery, radial artery and vena cava superior, before and after continuous veno-venous hemofiltration (CVVH) of critically ill volume expanded patients, proved that ANP might be a useful indicator of fluid balance in these patients.

Atrial Natriuretic Factor↗

The role of alpha-atrial natriuretic peptide in fluid retention during mechanical ventilation with positive end-expiratory pressure.

Although controlled mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP) has a central place in the treatment of acute respiratory failure (ARF), several side effects of this technique have to be faced. CMV with PEEP may induce pulmonary barotrauma, disturbance of cardiac performance, impairment of renal function and fluid retention. Atrial natriuretic peptides (ANP) are released from the atria upon stretching and play a major role in the control of sodium and fluid balance. Therefore it was logical to determine plasma levels of alpha-ANP in CMV. A study performed in 7 patients suffering from ARF suggested that alpha-ANP plasma levels were depressed during PEEP at 15 cm H2O in comparison with PEEP at 0 cm H2O (ZEEP). The decrease in plasma levels of alpha-ANP was evident in samples taken from superior vena cava, right atrium, pulmonary artery and radial artery as well. The decrease in alpha-ANP was associated with a decline in cardiac index, creatinine clearance, urinary output and urinary sodium excretion. Experiments in volume- expanded healthy volunteers also suggest that CMV with PEEP is able to depress plasma levels of alpha-ANP. The reasons behind the decline in release of alpha-ANP may be atrial compression by the distended lungs and the well-known reduction of venous return to the heart. Other possible factors promoting fluid retention during CMV with PEEP are the decrease in cardiac index and glomerular filtration rate, changes in intrarenal distribution of blood flow, and a stimulation of release of antidiuretic hormone via stretch receptors in the left atrium and baroreceptors in aorta and carotid arteries.

Animals↗

Limited value of 111-indium platelet scintigraphy in renal transplant patients receiving cyclosporine.

Since the differential diagnosis between cyclosporine (CyA) nephrotoxicity and acute graft rejection is still a problem in clinical routine, we studied retrospectively the value of 111-indium (In) platelet scintigraphy in 53 patients immunosuppressed with CyA and prednisolone. Autologous platelets were labeled once per week. After daily gamma camera imaging, the platelet deposition in the graft was expressed as platelet-uptake ratio (PUR). The patients were monitored during the first 4-6 weeks after surgery. PUR values measured during an episode of graft dysfunction were compared to the histological diagnosis. The PUR of well-functioning and stable grafts measured 1.07 +/- 0.11 (mean +/- SD). The 111-In platelet scintigraphy failed to register acute interstitial rejection. The PUR values in episodes of chronic vascular rejection, of acute tubular necrosis due to prolonged ischemia times, of tubular CyA nephrotoxicity and of cytomegalovirus (CMV) infection did not differ from the PUR of well-functioning and stable grafts as well. The PUR was significantly increased to 1.48 +/- 0.26 because of a marked platelet deposition in the graft in episodes of acute vascular rejection. In 4 cases of microvascular CyA nephrotoxicity the same phenomenon of significantly increased PUR (1.33 +/- 0.18), could be encountered, too. Two of these 4 cases resembled the hemolytic uremic syndrome (HUS). The value of PUR measurement for diagnosis of acute vascular rejection and microvascular CyA nephrotoxicity together, was: sensitivity 0.62, specificity 0.95, predictive value of positive result 0.64, predictive value of negative result 0.94.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Possibilities and pitfalls of indium-111 platelet scintigraphy in the monitoring of renal transplant recipients.

During the last four years, we have performed two studies on the clinical application of 111In-platelet scintigraphy after renal transplantation. In the first study, we collected 75 patients who were treated with prednisolone and azathioprine. The platelet deposition in the graft was expressed as a platelet-uptake index (PUI). The results suggested that the platelet scan was a valuable tool for early detection of acute graft rejection, which was indicated by an increase in PUI. Quite different results were obtained in 50 patients immunosuppressed with cyclosporin A (CSA) and prednisolone. Acute interstitial rejection escaped detection by this diagnostic procedure. Significant elevations of PUI were observed in acute vascular rejection and microvascular CSA nephrotoxicity, resembling the haemolytic uraemic syndrome (HUS) only. Therefore, platelet deposition in the graft can be regarded as a non-specific phenomenon, occurring in two entities which require completely different therapeutic approaches. In spite of the monitoring by means of the platelet scan, percutaneous biopsy is still necessary for differential diagnosis of graft dysfunction.

Adult↗

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↗