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Biomedical subjects

H Bleyl

Publications and source records attributed to H Bleyl.

At least 19 recordsLinked to original sources

Apoprotein-based synthetic surfactants inhibit plasmic cleavage of fibrinogen in vitro.

Fibrinogen (Fbg) leakage and intra-alveolar fibrin accumulation are commonly noticed in adult respiratory distress syndrome and interstitial lung diseases. Activation of the extrinsic coagulation pathway and elevation of antiplasmin- and plasminogen-activator inhibitor levels are assumed to favor alveolar clot formation and to inhibit fibrinolysis under these conditions. We investigated the influence of synthetic surfactants on the plasmic cleavage of fibrinogen in vitro. Fibrinogenolysis was quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with densitometric evaluation and fragment E enzyme-linked immunosorbent assay. A synthetic phospholipid mixture (PLM) (dipalmitoyl-DL-alpha-phosphatidylcholine:L-alpha-phosphatidyl-DL-gly cer ol: palmitic acid 68.5:22.5:9) caused a dose-dependent inhibition of fibrinogenolysis in a concentration range between 0.1 and 2 mg/ml. This inhibitory capacity was markedly amplified upon reconstitution of PLM with natural and recombinant surfactant protein (SP)-C as well as natural SP-B. Natural SP-A and recombinant SP-A were far less effective in this respect. In the absence of phospholipids, the hydrophobic apoproteins revealed only moderate plasmin inhibitory capacity (recombinant SP-C > natural SP-C and SP-B). Natural calf lung surfactant extract displayed comparable inhibitory capacity on plasmic Fbg cleavage as PLM. We conclude that hydrophobic surfactant material may suppress plasmin activity and thus may contribute to the finding of delayed alveolar fibrin clearance in inflammatory lung diseases with Fbg leakage.

Animals↗

Factor IXi-antithrombin (IXiAT) and thrombin-antithrombin (TAT) complexes in lung cancer patients.

Coagulation activation frequently occurs in cancer patients, resulting in thromboembolic complications and/or intravascular coagulation activation. The mechanisms leading to these alterations still are poorly understood. One explanation for the coagulation activation in malignant diseases is the presence of a direct factor X-activating cancer procoagulant. Coagulation activation in lung cancer patients develops at earlier stages than factor X activation; we demonstrated increased factor IXiAT complexes in addition to elevated TAT complexes. The increases of factor IXiAT complexes were not dependent upon the stage of the disease. In contrast, TAT complexes were higher in patients suffering from advanced pulmonary non-small cell carcinoma than in patients with limited disease. In conclusion, coagulation activation in pulmonary cancer patients occurs at earlier steps in the coagulation cascade than factor X activation. While this activation is not dependent upon the stage of the disease, the observation that TAT complexes showed higher elevations in patients with advanced than in those with limited pulmonary non-small cell carcinoma could be an indication of a cancer procoagulant that directly activates factor X.

Aged↗

Coagulation activation in liver diseases.

In liver disorders alterations of the coagulation system are mainly due to a reduced synthesis of coagulation proteins. In addition, an enhanced intravascular consumption of coagulation factors is discussed controversely in liver diseases. By measuring factor IXiAT- and TAT-complexes we tried to find out, whether coagulation activation in liver patients leads to activation of the complete coagulation cascade followed by DIC or whether in some diseases a futile partial coagulation activation develops. In all liver diseases examined, elevated factor IXiAT-complexes were demonstrated, while TAT-complexes were only elevated in chronic active hepatitis, metabolic decompensated liver cirrhosis and in patients suffering from end stage liver disease. We conclude that all liver diseases examined lead to an activation of the coagulation cascade. A complete activation followed by DIC only occurs in patients with very severe liver disorders.

Antithrombin III↗

Evaluation of an amidolytic test for comparative calibration of HMW- and LMW-heparins.

Amidolytic chromogenic substrate assays are frequently used to determine the anticoagulant activities of various commercial heparins. With the help of a combined assay method heparin characterization is made possible using the TAT/XAT quotient under consideration of the simultaneous inhibition of the two serine proteases thrombin and factor Xa by antithrombin III. The test is primarily designed for qualitative characterization where a numerical value can be assigned to every heparin. However, quantitative aspects may also be evaluated.

Amides↗

Search for optimizing dialysis therapy. I. Acute effects of hemodiafiltration with a highly permeable membrane and a large dose of convection and diffusion.

Based on the concept that an optimisation of dialysis therapy might be achieved by increasing the removal of small metabolic substances as well as low molecular weight proteins, hemodialfiltration (HDF) was modified. In 9 ESRD patients, HDF was performed acutely for 4 h, where 60 liters of substitution fluid were infused per patient. Two polysulphone F60 membranes in line were used as hemodialfilters. As compared to conventional hemodialysis (HD), performed with a cuprophane dialyser, HDF resulted in higher extraction indices for small solutes assessed by HPLC. Due to the large amount of convection applied, HDF was followed by significant decreases of low molecular weight proteins ranging from 9.5 kdaltons (iPTH, p less than 0.01) to 17 kdaltons (myoglobin, p less than 0.01). Analysis of the protein pattern of the serum revealed a nonlinear function in the decrease of plasma proteins after HDF. It is concluded that even though the detoxification efficacy of the described HDF method is by far superior to conventional HD in quality and quantity, the efficacy is still far from that of excretory renal function. Thus, to further improve efficacy with respect to the catabolic renal function for low molecular weight proteins, membranes for HDF or hemofiltration barriers but should surpass the sieving properties of the glomerulus in the low molecular protein range.

Adult↗

Early detection of amatoxins in human mushroom poisoning.

Amatoxins were detected radioimmunologically as early as 90-120 min after ingestion in the gastric fluid and urine of a 15-year-old boy who tried to commit suicide by ingestion of wild mushrooms. This early detection of amatoxins in the urine is proof of rapid absorption from the intestinal tract and subsequent excretion by the kidneys in man.

Adolescent↗

High dosage desferrioxamine therapy in a female patient with acquired aplastic anaemia and transfusion siderosis.

A 32 year old woman with severe aplastic anaemia required frequent transfusions and consequently developed hyperferrioxaemia (54 microMol/l) and hyperferritinaemia (1,700 ng/ml). For the treatment of transfusion siderosis she was given 18 high dose courses each comprising 35 g of desferrioxamine. Because of pre-existing thrombocytopenia (platelet count 5 X 10(9)/l) the iron chelating agent was given by continuous intravenous infusion over 3 1/2 days. High dose desferrioxamine had to be abandoned because of severe bone pain. The desferrioxamine infusions achieved a negative iron balance, iron loss after each infusion being 100 to 200 mg in the urine and 400 mg in the faeces. Serum iron and ferritin concentrations fell almost to normal. This report shows that faecal iron excretion must be taken into account in assessing the balance of iron input and output during desferrioxamine treatment.

Adult↗

[Insulin and C-peptide in chronic liver diseases during oral glucose tolerance testing].

Insulin and C-peptide in venous blood were determined during oral glucose tolerance testing in 59 non-manifest diabetics with histologically established chronic liver disease (fatty degeneration, chronic aggressive hepatitis, cirrhosis). Glucose tolerance was pathologic in 60-80% of patients. When compared to a control group patients with chronic liver disease showed significantly increased values of blood glucose (after glucose intake), of insulin and of C-peptide (fasting and after glucose intake). The C-peptide/insulin ratio, a measure of hepatic insulin degradation, was significantly decreased after glucose uptake. There were no significant differences of blood sugar, insulin and C-peptide among the various liver diseases. In chronic aggressive hepatitis and in cirrhosis the C-peptide/insulin ratio was partly significantly lower than in fatty degeneration. From the increased C-peptide values increased insulin secretion in chronic liver diseases can be deducted. In addition, the decreased C-peptide/insulin ratios show an impairment of insulin degradation in liver cirrhosis and other chronic hepatic diseases. However, in fatty liver degeneration this is clearly less pronounced than in more serious liver diseases.

C-Peptide↗

Assessment of definitive residual pituitary-adrenal function and of hydrocortisone replacement therapy 10 to 14 days after microsurgery for pituitary adenomas.

Anterior pituitary function was evaluated by a combined stimulation test 10-14 days and again 6-8 months after micro-surgery for pituitary tumors. It was found that definite residual pituitary-adrenal function could accurately be assessed already 10-14 days after operation, as judged by the subsequent testing. By this means, hydrocortisone replacement therapy necessary one year after operation could be predicted.

Adenoma↗

Systemic short-term fibrinolysis with high-dose streptokinase in acute myocardial infarction: time course of biochemical parameters.

The course of plasma catalytic activities of total creatine kinase, creatine kinase isoenzyme MB, total, cytoplasmatic and mitochondrial aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, glutamate dehydrogenase and concentrations of myoglobin, urea, acidic alpha 1-glycoprotein and creatinine were followed in 33 patients suffering from acute myocardial infarction. All patients were randomized in a double-blind, prospective study. One group (18 patients) was infused with streptokinase 1.5 X 10(6) units/90 minutes; the control group received routine continuous i.v. heparin treatment (1000 units/h). Ten hours after completion of the study protocol, treatment of both groups of patients was continued with heparin, 1000 units/h and Aspisol, 1 g/day2). Streptokinase treatment induced earlier wash-out and therefore earlier peak levels of several enzymes: total creatine kinase (11 hours), creatine kinase isoenzyme MB (6 hours), total and cytoplasmatic aspartate aminotransferase (6 hours) and lactate dehydrogenase (9 hours). Total creatine kinase peak catalytic activity and myoglobin peak concentration were higher in the group receiving thrombolytic therapy. A significantly different course of catalytic activity between both treatment groups was found for total creatine kinase and creatine kinase isoenzyme MB, total and cytosolic aspartate aminotransferase, lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase. The course of mitochondrial aspartate aminotransferase catalytic activity was different only 12 hours after the beginning of treatment. The shift of several catalytic activities to an earlier peak level in plasma may indicate reperfusion of ischaemic myocardium due to thrombolytic therapy.

Adult↗

Hyperinsulinemia in hepatic steatosis.

Blood glucose, serum insulin, C-peptide, free fatty acids and growth hormone were evaluated in 45 patients with histologically established hepatic steatosis after an oral glucose load (100 g). Glucose tolerance was impaired in 59 per cent of the patients. Significantly increased levels were found for blood glucose (fasting and after 60 and 120 min), insulin (after 60, 120 and 180 min), C-peptide (fasting and after 60, 120 and 180 min), and free fatty acids (fasting and after 60 and 120 min). Human growth hormone levels were not altered. After glucose administration the C-peptide/insulin ratio was significantly reduced in hepatic steatosis compared to controls. In patients with hepatic steatosis there were no differences between subjects with normal body weight or overweight nor between stadium I and stadium II ('alcoholic hepatic steatosis') concerning glucose, insulin, C-peptide, HGH and FFA levels in blood. We conclude, that hepatic steatosis is associated with relative insulin resistance to which elevated FFA may contribute. In addition, the decreased C-peptide/insulin ratios suggest an impaired hepatic insulin degradation as it was already described for more serious liver diseases.

Adult↗

[Hyperinsulinaemia and impaired glucose tolerance in chronic inflammatory liver disease (author's disease)].

In 64 patients suffering from chronic inflammatory liver disease (alcoholic hepatitis, chronic active hepatitis, chronic persistent hepatitis) significantly increased values of blood glucose and insulin, free fatty acids and C-peptide were observed during a 100 g oral glucose load. Fasting values of blood glucose, free fatty acids and C-peptide were also increased, while serum growth hormone remained unchanged. In patients with chronic active hepatitis the C-peptide/insulin-ratio, a measure for hepatic insulin degradation, was significantly lowered after glucose uptake. During oral load there were no discernible differences between the different types of chronic inflammatory liver disease concerning blood glucose, serum insulin and free fatty acids. In normal weight and in overweight patients suffering from liver disease blood glucose and serum insulin values were increased to the same extent. As it is known from the liver cirrhosis chronic inflammatory liver disease lead to an insulin resistance, to which elevated free fatty acid levels contribute. Increased body weight has no influence on the insulin resistance observed in chronic liver inflammation. From the changes of the C-peptide and the C-peptide/insulin-ratio it can be deduced, that the hyperinsulinism in patients with chronic inflammatory liver disease is due to both insulin hypersecretion and diminished hepatic insulin degradation.

Adult↗

[Pharmacokinetic analysis of the fluctuation in digitalis bloodlevels during oral therapy with beta-methyldigoxin in children with heart insufficiency (author's transl)].

In five children with insufficiency of the heart the blood digitalis-digoxin level was monitored by drawing blood 5 times daily over a period of 7 days, starting from the first day of digitalisation. The dosage aimed at a mid-rate attainment of the plateau concentration in the blood. Digitalis blood levels were determined by a commercial radioimmunoassay. The blood level curves were simultaneously adjusted over the whole period, with the aid of a self-developed programme for tablecacultators, so that the considerable fluctuations of blood levels could be exhibited. The so adjusted curves were also pharmacokinetically analysed. Our data are in good agreement with the literature. The total clearance was significantly below that of adults. The total amount of digoxin in the whole organism, as calculated and represented graphically, changed less significantly, but was clearly higher in the first days of the mid-rate digitalisation than during the steady state.

Administration, Oral↗