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Biomedical subjects

P Hellstern

Publications and source records attributed to P Hellstern.

At least 55 records · Page 3Linked to original sources
PubMed1987

[Spontaneous thrombocyte aggregation and blood sugar profile in children with diabetes mellitus type I treated with human and porcine insulin].

In a three-year bicentric cross-sectional investigation on type I diabetic children aged between 6 and 18 years, blood sugar profiles and spontaneous thrombocyte aggregation were reported besides anamnestic and clinical data. In the children treated with human insulin, raised spontaneous thrombocyte aggregation was significantly more frequent than in those treated with porcine insulin. At the same time, blood sugar fluctuation from day to day measured between 7 and 9 a.m. tended to be raised in the children treated with human insulin; the fluctuation in the diurnal profile measured over 14 days was indeed very much greater. Since the two groups were comparable as to sex distribution, age, duration of disease, quality of compensation, application and dose of insulin, the greater fluctuation of blood sugar in the children treated with human insulin appears to be the cause for the raised spontaneous thrombocyte aggregation.

Adolescent↗
PubMed1987

High-dose systemic streptokinase and acylated streptokinase-plasminogen complex (BRL 26921) in acute myocardial infarction: alterations of the fibrinolytic system and clearance of fibrinolytic activity.

We report the results of two consecutive studies using intravenous bolus injections of streptokinase (SK) or acylated plasminogen-SK complex (BRL 26921) in patients with acute myocardial infarction (AMI). In the first study, 20 patients received either 750,000 units (U) SK (group IA, n = 10) or 1,500,000 U SK (group IB, n = 10) within 5-10 min intravenously. In the second study 10 consecutive patients received 750,000 U SK within 15 min (group IIA) intravenously. The following 10 consecutive patients received 30 mg BRL 26921 within 2 min (group IIB). Early reperfusion was found in 16 patients in the first study (8 in each group) and in 18 patients in the second study (9 in each group). The decrease of fibrinolytic activity was biphasic with a half-disappearance time of 112.5 min for BRL 26921 and 31 (IA) and 18 (IB) min for SK. alpha 2-Antiplasmin depletion and a decrease of fibrinogen was observed with no differences after bolus injections of SK and of BRL 26921.

Aged↗
PubMed1987

Measurement of factor VIII procoagulant antigen in normal subjects and in hemophilia A patients by an immunoradiometric assay and by an enzyme-linked immunosorbent assay.

Factor VIII coagulant antigen (FVIII:Ag) and FVIII coagulant activity (FVIII:C) were measured in 102 healthy individuals, in 5 hemophilia A carriers and in 21 hemophilia A patients before and after infusion of heat-treated high-purity FVIII concentrates. Factor VIII:Ag was determined by a solid-phase micro enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies and by a conventional solid-phase immunoradiometric assay (IRMA). Factor VIII:C was assessed using a one-stage assay. The micro ELISA was decidedly more precise than the IRMA. There was a close correlation between the results obtained by the three assays in the plasma of healthy subjects and in hemophilia A carriers. After transfusion of FVIII concentrates to hemophilia A patients, the FVIII:Ag recoveries were significantly lower than the FVIII:C recoveries and the biological half-life of FVIII:Ag was significantly shorter than for FVIII:C. The calculated half-life of FVIII:C was longer than in any previous study.

Adolescent↗
PubMed1987

Identification of a defective factor XI cross-reacting material in a factor XI-deficient patient.

A homozygous factor XI-deficient girl, who appeared to be positive for cross-reacting material (CRM+) was studied for clarification. Factor XI antigen (F XI:Ag) was measured by radial immunodiffusion using monospecific, heterologous anti-factor XI antibodies. Factor XI coagulant activity (F XI:C) was determined in a modified activated partial thromboplastin time (APTT) test. The ratio of F XI:C to F XI:Ag was 0.04 for the proposita, as compared with 0.7 to 0.74 in the other family members. In contrast, 12 normal individuals had ratios of F XI:C to F XI:Ag of 1.04 +/- 0.15. F XI esterolytic activity was clearly higher than F XI:C in the proband, but not in her relatives. Immunoblotting studies demonstrated F XI CRM in the patient's plasma. Chromatography on diethylaminoethanol (DEAE)-Sephadex at pH 8.4 led to an almost complete removal of F XI from the plasma. The defective F XI was not bound to a negatively charged kaolin surface due to an abnormal interaction with high-mol-wt kininogen (HMWK).

Antigens↗
PubMed1986

Factor VIII: C (FVIII: C) recovery and half-life after infusion of steam-treated high purity factor VIII concentrate in severe hemophilia A--comparison of one-stage assay, two-stage assay and a chromogenic substrate assay.

Factor VIII:C recovery and half-life was measured in 16 hemophilia A patients under comprehensively standardized conditions. Each patient received the same lot of a steam-treated high purity FVIII concentrate at a dose of 19-33 U/kg body weight. A comparison was made between the one-stage assay, the two-stage assay and a chromogenic substrate test for FVIII:C determination using a FXa-sensitive chromogenic substrate. Factor VIII:C potency of the administered FVIII concentrate was measured using calibration curves derived from a concentrate standard and FVIII:C plasma levels were read from calibration curves derived from a plasma standard. The chromogenic assay showed a good reproducibility at FVIII:C levels between 0.015 and 0.50 U/ml. The FVIII:C recoveries calculated from the results of the one-stage assay, the two-stage assay and the chromogenic substrate test were 109 +/- 20, 92 +/- 14 and 81 +/- 11% (mean +/- SD), respectively. The elimination half-lives of FVIII:C were calculated by non-linear least square analysis using a modified computerized Gauss-Newton algorithm. The half-lives calculated from the FVIII:C plasma levels measured by the one-stage assay, the two-stage assay and the chromogenic test were 23.8 +/- 6.4, 22.2 +/- 5.7 and 17.1 +/- 4.8 h (mean +/- SD), respectively. No previous study has reported such long half-life values. Our findings indicate that measurements of recoveries and half-lives by the chromogenic FVIII:C assay and by computerized non-linear least square analysis allow the possibility of individualized FVIII replacement therapy.

Adolescent↗
PubMed1986

Dose response relationships of anticoagulant activities after subcutaneous administration of two low molecular weight heparins in healthy individuals.

This study was performed to estimate appropriate dosages of two low molecular weight heparins (LMWH) for clinical trials on subcutaneous perioperative thrombosis prophylaxis. Anticoagulatory activities and platelet function were investigated after single doses of two LMWH and of unfractionated sodium heparin (UFH) in 24 healthy individuals. Twelve subjects received subcutaneous injections of 1000, 1500, and 2500 i.u. (aPTT) of LMHW 1, and the other 12 received LMWH 2 at same dosages. The following parameters were determined before 30 min, 1 h, 90 min, 2 h, 3 h, 4 h, 6 h, 8 h, and 10 h after either LMWH or 5000 i.u. (aPTT) UFH: aPTT, thrombin time, anti-Xa activity (S 2222, Coatest heparin), and anti-IIa activity (Chromozym TH). Bleeding time, platelet count, and adrenalin-, collagen-, and ADP-induced platelet aggregation were assessed before and 3 h after administration. After application of 1500 i.u. LMWH 1 and LMWH 2, the anti-Xa and anti-IIa levels were already significantly higher than after 5000 i.u. UFH. 2500 i.u. LMWH 1 and LMWH 2 evoked significantly greater prolongations of aPTT and thrombin time values than did 5000 i.u. UFH. This was not the case after 1000 and 1500 i.u. LMWH. The half-lives of anticoagulatory effects after LMWH were markedly longer than after UFH. Platelet function was not altered by any of the heparins tested. Our results indicate that LMWH cause anticoagulatory effects in vivo that cannot be predicted by in vitro studies and that the appropriate single dosages of LMWH in subcutaneous perioperative thrombosis prophylaxis have to be estimated by dosage determinations in healthy subjects.

Adult↗
PubMed1986

[Bolus injection of anisoylated plasminogen-streptokinase activator complex (BRL 26921) as an alternative concept of systemic lysis in acute myocardial infarct].

The thrombolytic properties of anisoylated plasminogen streptokinase activator complex (BRL 26921) and clinical results of the treatment were studied in 10 consecutive patients with acute myocardial infarction. Exclusion criteria were general contraindications against thrombolytic therapy and a time interval of more than 4 h between the onset of symptoms and admission to the hospital. All patients received a 250-mg bolus of prednisolone prior to intravenous injection of 30 mg BRL 26921 within 2 min. A continuous infusion of heparin at a dose of 1,000 USPU/h was started 2 h after the injection. Blood pressure was monitored via an arterial line. Arrhythmias and changes in the ST segments were documented by conventional ECG recording and computer-based ECG monitoring. Coronary arteriography and left ventriculography were carried out within 72 h. Besides routine laboratory tests, serial CK and CK-MB activity measurements were carried out. We determined the following hemostaseological parameters before and 15 min, 30 min, 1 h, 4 h, and 12 h after application of BRL 26921: prothrombin time, activated partial thrombosplastin time, thrombin time, thrombin coagulase time, fibrinogen, streptokinaseplasminogen activator activity, plasminogen and alpha-2-antiplasmin. Our results (reperfusion in all patients angiographically and in 7 to 8 of 10 patients from noninvasive criteria) show that BRL 26921 is a highly effective thrombolytic agent in patients with myocardial infarction, when compared with high-dose systemic fibrinolysis. Applied in dosages required for early reperfusion, it does not appear to be selectively thrombolytic and is not free of hypotensive effects in man. The decrease of fibrinolytic activity is biphasic with a half-disappearance time of 112 min.

Adult↗
PubMed1986

Comparative study of intranasal, subcutaneous and intravenous administration of desamino-D-arginine vasopressin (DDAVP).

This study was performed to evaluate the influence of different routes of administration on the efficacy of DDAVP treatment. Ten healthy volunteers received DDAVP intranasally (i.n.), subcutaneously (s.c.) and intravenously (i.v.) in a randomized cross-over trial. Factor XII and high molecular weight (HMW)-kininogen levels increased only slightly after DDAVP administration. The mean increase of factor VIII: C was 3.1 (i.v.), 2.3 (s.c.), and 1.3 (i.n.) - fold over baseline. Ristocetin cofactor (von Willebrand factor antigen) increased 3.1 (2.5), 2.0 (2.3) and 1.2 (1.2) - fold over baseline mean values after i.v., s.c. and i.n. DDAVP, respectively. The half-disappearance time of factor VIII and von Willebrand factor (vWF) after DDAVP ranged from five (factor VIII:C) to eight hours (vWF). The mean increase of fibrinolytic activity was more pronounced after i.v. DDAVP. The antidiuretic effect was moderate with no apparent differences between the routes of application. This study provides further evidence that both i.v. and s.c. DDAVP administration result in an appropriate and reliable stimulation of haemostasis. An additional advantage of s.c. administration is its suitability for home treatment.

Adult↗
PubMed1986

[Thrombolytic therapy with ultra-high doses of streptokinase].

Two pilot studies were carried out in patients suffering from acute myocardial infarction. They received high doses of streptokinase and acylated streptokinase-plasminogen activator complex intravenously as a bolus injection. Furthermore, the possibility of using streptokinase bolus therapy was examined in patients with acute vascular occlusion. Due to the limited number and the heterogenicity of cases the results obtained in patients with acute myocardial infarction are to evaluate with some reservation. In patients with acute vascular occlusion streptokinase bolus therapy at high doses proved to be a promising alternative to the conventional therapy.

Coronary Angiography↗
PubMed1986

[Clinical aspects of acquired antithrombin III deficiency].

The significance of acquired antithrombin III (AT III) deficiency must be interpreted in close relation to the underlying disease process. In patients with acute or chronic liver impairment, the AT III activity is related to a decrease of procoagulatory factors, whereas, in protein loss syndromes such as nephrotic syndrome, the AT III indicates an increased risk of thromboembolic events. The effect of oral contraceptives (OC) on AT III levels in young healthy females (n = 30) was determined prospectively. AT III decreases during OC usage could not be related to the estrogen content of the examined oral contraceptives, and there was no parallel decrease of AT III activity and concentration in each type of OC. In a prospective study, the extent of AT III decrease was determined in patients undergoing cardiopulmonary bypass operations (CPB) receiving different anticoagulant schedules during extracorporeal circulation (n = 49). There was no significant influence on the effectiveness of anticoagulation by the observed AT III decreases. AT III deficiency during CPB was primarily the result of hemodilution. However, the AT III kinetics were significantly influenced by the different protamin dosages and were not affected by the different heparin dosages. Correction of diminished AT III levels by substitution of AT III concentrates is beneficial in cases, in which an interruption of an enhanced coagulatory process such as disseminated intravascular coagulation is necessary or in patients requiring high dosage heparinization as in deep vein thrombosis. In those cases the quality of AT III correction correlates to the course of the disease. However, the potency of concentrates as well as the individual AT III recovery and half-life must be considered for an appropriate treatment with AT III substitution.

Adult↗
PubMed1986

[Fibrinolytic treatment of deep vein thrombosis and lung embolism].

Selective evaluation prior to determining the indication for thrombolytic therapy is just as important for therapeutic success as choosing the appropriate fibrinolytic agent. During this initial stage, the localization, age, extension, and possible consequences of the thrombosis must be determined with suitable as well as specific methods. Selection of the fibrinolytic agent and careful monitoring of the thrombolysis should ensure a maximum therapeutic effect with a minimum of bleeding complications.

Fibrinolysis↗
PubMed1985

[Successful treatment of superior mesenteric artery thrombosis with local high-dose urokinase therapy].

A 56 year old man presented with increasing abdominal pain. He suffered from arterial occlusive disease with occlusion of the right A. iliaca communis. Angiography revealed partial thrombotic occlusion of the superior mesenteric artery. Urokinase (UK) at a dose of 150 IU/kg X minutes and heparin (1,000 U/h) was infused through the 7F angiographic catheter for 180 minutes. After 70 min of treatment, angiography showed improvement, and after 120 min the thrombus was nearly completely lysed. A stenosis of approximately 50% was still present after 180 min. Two hours after treatment the patient was pain free without analgesics. Laboratory studies showed systemic fibrinogenolysis, but fibrinogen was still within the upper normal range. Only slight systemic fibrinolytic activity (less than 5 IU UK/ml) could be determined. However, alpha 2-antiplasmin was depleted. The catheter was drawn 15 h after thrombolysis without bleeding. While under concurrent heparin and phenprocoumon therapy, the patient developed an infected gluteal hematoma as a result of i.m. injections prior to this treatment. A repeat angiography approximately one month after thrombolysis revealed further improvement and patency. The patient is well and free of abdominal angina and under oral anticoagulant therapy.

Drug Therapy, Combination↗
PubMed1985

The use of heat-treated Factor VIII-concentrates in von Willebrand's disease.

In vitro investigations have demonstrated a high F VIII:Rcof potency and a high F VIII:Rcof/F VIII R:Ag ratio of two heat-treated F VIII concentrates. We therefore studied the in vivo effectiveness of these preparations (F VIII HSR, Behringwerke Marburg and F VIII HTR, Travenol) in five patients with von Willebrand's disease (vWd). In the steady state in vivo recoveries of F VIII:Rcof ranged from 73-153% after transfusion of F VIII HSR and from 11.5-17% after F VIII HTR respectively. The gain of F VIII-complex after F VIII HS was comparable to cryopecipitate (KryobulinR SP, Immuno AG Wien). All three products shortened the bleeding-time. Three of our five patients underwent surgery (Billroth I, papillotomy, laparatomy, open heart surgery) under F VIII HS cover without bleeding complications. The dose applied ranged from 20 to 40 U/kg at 8 or 12 h intervals for a period of approx. 14 days. Serum-transaminase elevations were observed in two of four patients after F VIII HT treatment. Although the risk of hepatitis of heat-treated F VIII concentrates remains to be determined, these products proved to be effective in vWd. The major advantages of these preparations are stability, rapid solubility, a low content of contaminating proteins, and a rapid, general availability.

Chemical and Drug Induced Liver Injury↗