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Biomedical subjects

H Ostermann

Publications and source records attributed to H Ostermann.

54 records · Page 3Linked to original sources
PubMed1993

Comparison of 5 vs 10 micrograms/kg per day of GM-CSF following dose-intensified chemotherapy with cisplatin, etoposide, and ifosfamide in patients with advanced testicular cancer.

Despite the increasing use of granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of chemotherapy-induced neutropenia, few studies have focused on the activity and toxicity of the different clinically used dosages of GM-CSF. Forty-four patients with "poor-risk" (advanced disease, according to the Indiana University classification) testicular cancer were treated with a dose-intensified chemotherapy regimen of cisplatin (30 mg/m2), etoposide (200 mg/m2), and ifosfamide (1.6 g/m2), given on days 1-5 for a total of four cycles at planned intervals of 21 days. Patients (pts) received GM-CSF, either 10 (22 pts; 70 cycles evaluable) or 5 micrograms/kg body wt. daily s.c. (22 pts; 72 cycles evaluable), starting the first day after chemotherapy for 10 consecutive days. Overall, 34 patients (78%) achieved a favorable response (CR or PR with negative tumor markers), six patients (14%) failed this chemotherapy regimen, and four patients (9%) died of therapy-related complications. The durations of both neutropenia and thrombocytopenia increased with the number of treatment cycles given. The duration of granulocytopenia after the fourth PEI cycle was significantly shorter for patients receiving 10 micrograms/kg than for those with 5 micrograms/kg per day of GM-CSF (9 vs 13 days; p < 0.05). The median duration of thrombocytopenia < 20,000/microliters after the fourth cycle of PEI was also significantly reduced in favor of patients receiving 10 micrograms/kg of GM-CSF (4 vs 9 days; p < 0.02). However, there were no differences in the frequency of severe infections or in the achieved dose intensity. Five patients (11%) discontinued GM-CSF due to side effects (three anaphylactoid-type reactions, one myalgia and fever, one cutaneous toxicity). No difference in the frequency of side effects was seen between patients receiving 5 and those receiving 10 micrograms/kg per day of GM-CSF. The dose of 5 micrograms/kg per day of GM-CSF may be sufficient to ameliorate neutropenia following standard-dose chemotherapy, while higher dosages of GM-CSF may be advantageous in patients receiving repetitive cycles of dose-intensified chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

The influence of different procedures of general anaesthesia on platelet function, coagulation and the fibrinolytic system.

We investigated whether different procedures during general anaesthesia alter platelet activation in vivo and/or activate coagulation and fibrinolysis. Forty-one healthy adult patients, scheduled for elective ophthalmic surgery under general anaesthesia, were studied with regard to changes of plasma beta-thromboglobulin (beta TG, index of platelet activation), thrombin-antithrombin III-complex (TAT, index of activation of coagulation) and d-dimer (index of fibrinolysis) during anaesthesia. The patients underwent either inhalation anaesthesia with enflurane and nitrous oxide or balanced anaesthesia with enflurane (0.5% end-tidal concentration) and alfentanil. Ten minutes after intubation the beta TG level was significantly reduced compared to the preoperative value in both general anaesthesia groups. Balanced anaesthesia caused a moderate but significant increase of TAT values at 10 min after extubation. No significant change in d-dimer levels was seen. Presuming a minimal effect of the surgical procedure on the determined variables, we conclude that none of the anaesthetic procedures induces platelet activation and fibrinolysis. The clinical relevance of the moderate coagulation activation during balanced anaesthesia remains to be investigated.

Adolescent↗
PubMed1993

Complete bilateral oculomotor palsy: the only clinical sign of subarachnoid hemorrhage in leukemia.

We report the original case of a patient with acute myelogenous leukemia who presented with a painless, complete bilateral oculomotor palsy during induction chemotherapy. Headache, signs of meningeal irritation or further neurological symptoms were absent throughout the course of illness. The CT revealed a subarachnoid hemorrhage (SAH). Within a day of the onset of symptoms, the oculomotor palsy subsided completely with no residual damage. To our knowledge, this is the first described case of SAH in leukemia with complete bilateral oculomotor palsy being the only clinical symptom. Furthermore, the spontaneous remission of this pathological condition is an extremely rare event.

Aged↗
PubMed1993

[Blood coagulation and fibrinolysis].

A detailed understanding of the hemostatic process and the pathogenesis of thrombosis provides the basis for the development of more selective and potentially more efficient antithrombotic agents. These may allow to tailor antithrombotic treatment strategies for specific disease entities according to relative risk and prevailing pathogenetic mechanisms. Conversely, the use of selective pharmacological inhibitors has become an indispensable tool in experimental hemostasis and thrombosis research. Recent advances in the field have prompted profound reappraisal of concepts and hypotheses related to blood coagulation, thrombogenesis and the biologic role of the plasminogen activator-plasmin system. The present article will focus on the various mediator functions of thrombin, on the key role of tissue factor in the initiation of blood coagulation, and on the potential relevance of the tissue factor pathway inhibitor (TFPI).

Blood Coagulation↗
PubMed1992

Enhancement of spontaneous fibrinolytic activity in diabetic retinopathy.

The fibrinolytic system was studied in 96 patients with type I diabetes mellitus. Patients were grouped according to their degree of retinopathy; 38 patients with no evidence of retinopathy, 28 patients with background retinopathy and 30 patients with proliferative retinopathy. Thirty healthy individuals served as controls. The basal fibrinolytic activity as measured by clot lysis time and t-PA activity was increased in diabetic patients. This was associated with low levels of plasminogen activator inhibitor. Increased levels of D-dimer in diabetic patients further indicate enhanced in vivo fibrinolysis. The increase in fibrinolytic activity was highest in diabetics without retinopathy, and decreased with increasing retinopathy. Endothelial release of t-PA after venous occlusion was not different between controls and all diabetic groups. These findings suggest that in type I diabetics the fibrinolytic system is in an activated state. With worsening of retinopathy this increase in fibrinolytic activity diminishes.

Adolescent↗
PubMed1992

Contralateral early blink reflex in patients with facial nerve palsy: indication for synaptic reorganization in the facial nucleus during regeneration.

Fifty patients with Bell's palsy and 30 patients with etiologically different symptomatic peripheral facial nerve palsy were studied by means of electrically evoked blink reflexes 1-23 days after onset of paresis. Their results were compared with a normal control group of 30 healthy subjects. In a significant number of patients (64% in Bell's palsy and 53% in symptomatic facial nerve palsy) a contralateral early blink reflex response (R1) could be elicited upon stimulation of the normal side as compared to 13% in the control group. It is suggested that this result may be explained by synaptic reorganization of the facial nucleus leading to functional unmasking of pre-existing crossed trigemino-facial reflex pathways during regeneration. This view is in line with previous experimental data in animals on the time course of structural changes in the facial nucleus after lesioning of the ipsilateral facial nerve.

Adolescent↗
PubMed1992

Rate of fibrinogen breakdown related to coronary patency and bleeding complications in patients with thrombolysis in acute myocardial infarction--results from the PRIMI trial.

Four hundred and one patients with acute myocardial infarction of less than 4 h duration were randomized to receive intravenous thrombolytic treatment with either 80 mg of full length unglycosylated single-chain-urokinase plasminogen activator (INN saruplase) or 1.5 million IU of streptokinase delivered over a 60 min period. Angiographic patency rates were higher at 60 min in saruplase treated patients (71.8% vs 48%; P less than 0.001), but did not differ significantly at 90 min (71.2% vs 63.9%; P = 0.15). Fibrinogen levels dropped markedly in both groups, the decrease being delayed and less pronounced with saruplase. Total fibrin and fibrinogen degradation products and D-dimer values rose earlier and to higher peak values in streptokinase treated patients. In both groups marked plasminogen and alpha 2-antiplasmin consumption was observed. Lower fibrinogen levels, and in particular the faster rate of fibrinogen breakdown, were associated with higher patency rates at 90 min (P less than 0.05). Patients with bleeding complications had lower 'lowest points' and a more rapid decrease in fibrinogen (P less than 0.05). These findings were not related to the drug used. Increased heparin levels at 6 to 12 h were correlated to bleeding complications in streptokinase treated patients. It is concluded that the rate of fibrinogen breakdown during and following thrombolytic treatment for acute myocardial infarction is related to early vessel patency and bleeding complications.

Blood Coagulation Tests↗
PubMed1991

Cisplatin/etoposide/ifosfamide stepwise dose escalation with concomitant granulocyte/macrophage-colony-stimulating factor for patients with far-advanced testicular carcinoma.

In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120-150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died of Clostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/microliters and a thrombocyte nadir of 47,000/microliters. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 micrograms/kg on days 6-15. Acute toxicity was severe with a white blood cell nadir of 300/microliters and thrombocyte nadir of 11,000/microliters. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure and Aspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GM-CSF 10 micrograms kg-1 day-1 on days 6-15 s.c.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

What's new in the causes of hemorrhage in acute myelogenous leukemia?

Hemorrhages in AML are still a major problem, although not the most important and different factors are involved in its genesis. The causes that predispose an AML patient to bleed will be reviewed, the hypotheses concerning the coagulation disorder specially found in the FAB M3 type will be discussed and the increasingly recognized role of plasminogen activators and enzymes released from blasts will be emphasized.

Hemorrhage↗
PubMed1990

Evidence for abnormal platelet glycoprotein expression in diabetes mellitus.

In 41 diabetics (27 type I, 14 type II) and in 23 healthy controls the number of glycoprotein (GP) GPIB and GPIIB/IIIA molecules were determined on resting, peripheral platelets by means of flowcytometry after immunostaining with monoclonal antibodies which bind independently from the state of activation. The average number of both glycoproteins per platelet was significantly elevated (GPIB: 54,100 x 1.27 +/- 1 vs. 39,100 x 1.3 +/- 1 GPIIB/IIIA: 77,500 x 1.3 +/- 1 vs. 62,700 x 1.3 +/- 1, in diabetic patients. Platelet volume was significantly correlated with the number of GPIB molecules on normal and diabetic platelets (r (normal) = 0.52 +/- 0.07; r (diabetic) = 0.46 +/- 0.1). Additionally, von Willebrand factor-related antigen (vWF: AG) was increased to 129% x 1.3 +/- 1 in diabetics vs. 111% x 1.4 in controls. The increase of vWF: AG was significantly correlated with HbA1 (r = 0.38*) and seemed to depend on chronic hyperglycaemia. Since platelet glycoprotein receptor status is regulated by the bone-marrow megakaryocyto- thrombopoiesis, our observations support the hypothesis that platelet hyperactivity in the diabetic state may be due to primarily altered production of platelets with an increased number of functional glycoproteins. This may be paralleled by increased plasma levels of cytoadhesive proteins like vWF: AG, which interact with the studied glycoproteins and thereby potentiate the risk of disturbed microhaemorrheology.

Adult↗
PubMed1990

Elevated platelet activation in type I diabetics with chronic complications under long-term near-normoglycemic control.

A prethrombotic state with altered, hyperactive platelets may contribute to the development of diabetic late complications. Whether increased platelet 'in vivo' activation can be reduced by tight metabolic control is controversial. We studied plasma markers of platelet activation in 64 long-term, microangiopathic type I diabetics after at least 18 months of intensive treatment for near-normoglycemia. Both platelet factor 4 and beta-thromboglobulin proved to be significantly (p less than or equal to 0.05) elevated in comparison with healthy controls: 15.8 (sdf 2)/77.6 (sdf 1.9) vs. 8.9 (sdf 1.6)/45.1 (sdf 2) ng/ml (sdf = standard deviation factor). We found no significant correlations with any metabolic parameter (actual blood glucose, mean blood glucose, HbA1, triglycerides, cholesterol) or with the duration of intensive treatment. It is therefore concluded, that platelet 'in vivo' activation takes place in type I diabetics even after long-term near-normoglycemic control. This deviation could be regarded as indicator of an additional risk for the development of vascular complications.

Adolescent↗
PubMed1989

[Anti-phospholipid antibody with recurrent venous thromboembolism and severe autoimmune thrombocytopenia].

A 51 year-old man with a history of deep venous thromboses and recurrent pulmonary embolism on long-term anticoagulant treatment was admitted to our department because of insidious onset thrombocytopenia. He had neither a history nor clinical signs of abnormal bleeding. On admission, the platelet count was reduced to 21 x 10(9)/l, platelet associated IgG was increased, and bone marrow specimens showed megakaryocytic hyperplasia. Platelet survival was slightly shortened with enhanced platelet sequestration in a normal size spleen. Laboratory evaluation after discontinuation of anticoagulant treatment revealed persisting prolongation of both the prothrombin time and the activated partial thromboplastin time which could be attributed to the presence of a lupus-type circulating anticoagulant. Further relevant laboratory findings included an elevated titer of IgG anti-cardiolipin antibodies and a reduced euglobulin clot lysis activity after venous occlusion due to increased plasminogen activator inhibitor activity. In recent years, it has become apparent that a striking correlation exists between the presence of antibodies to phospholipids and thromboembolic disease and immune thrombocytopenia respectively. The present case report on the association of these autoantibodies with both, recurrent venous thromboembolism and severe thrombocytopenia, supports the hypothesis that anti-phospholipid antibodies may play a crucial part in the pathogenesis of these clinical conditions. A reduced vascular fibrinolytic capacity may be involved in the thrombophilic state induced by anti-phospholipid antibodies.

Autoantibodies↗
PubMed1988

Recombinant single-chain urokinase-type plasminogen activator during acute myocardial infarction.

Recombinant single-chain urokinase-type plasminogen activator was intravenously administered in 2 different doses in 24 patients with acute myocardial infarction and angiographically proved occlusion of the infarct-related artery. Patients with first infarction without contraindications of thrombolysis were treated within the first 4 hours after the onset of symptoms. Group A (12 patients) received 20 mg of rscu-PA as a bolus followed by 60 mg infused over 1 hour and group B received 10 mg as a bolus and 30 mg as infusion. The 2 groups showed no significant difference in age, sex, height, weight, time between onset of symptoms and start of therapy, peak values and course of infarct-related enzymes. Time to reperfusion was 43 minutes in group A versus 67 minutes in group B (p less than 0.005). The rate of reperfusion 90 minutes after start of treatment was 91% in group A and 50% in group B (p less than 0.001). Plasma levels of fibrinogen, plasminogen and alpha-2-antiplasmin did not differ significantly in both groups. Systemic lytic state (fibrinogen less than 100 mg/dl) occurred in 33% of group A and in 9% of group B. Intravenous infusion of 80 mg (but not 40 mg) of rscu-PA led to reperfusion of the occluded coronary artery in nearly all patients. Approximately one-third of the patients treated with this dose demonstrated systemic lysis.

Adult↗
PubMed1986

Comparison of the numbers of plasmalemmal vesicles in arterial and venous endothelia of rats.

The numbers of plasmalemmal vesicles in endothelial cells of rat blood vessels were determined on electron microscopic sections. In all vessels examined which included aorta and carotid and femoral arteries, vena cava and femoral vein, and lung and brain capillaries, the numbers were of the same order of magnitude. For arteries the numbers were about double those for the corresponding veins. About one-third of all vesicles could be stained with ruthenium red after its infusion into the vessels. The results make it improbable that differences in numbers of 'transport' vesicles in different types of blood vessel contribute significantly to the selective accumulation of atherogenic plasma proteins in arteries.

Animals↗
PubMed1986

Factors of the hemostatic system in diabetic patients. A survey of controlled studies.

Diabetes mellitus is associated with a variety of vascular complications like diabetic retinopathy, myocardial infarction, stroke and peripheral vessel disease. These complications are of utmost importance because they lead to disability and premature death of the patients. The pathogenesis of these lesions has been thought to depend at least partly on defects in the hemostatic system. Many alterations of the coagulation and the fibrinolytic system as well as of the reaction of platelets have been found in diabetics. In general these tend to suggest a state of slightly activated coagulation, of increased platelet reactivity and of decreased fibrinolysis. However, no conclusive picture of the role of hemostasis in the development of vascular lesions in diabetics has emerged yet, as contradictive results have been found by many investigators. The aim of this review article is to sum up the knowledge that has accumulated in the last years in controlled clinical trials concerning the state of the diabetic hemostatic system.

Blood Coagulation Factors↗
PubMed1982

Prothrombin determination in plasma and in liver biopsies in chronic liver diseases.

Following ribosomal synthesis of the protein moiety of prothrombin, postribosomal carboxylation in the liver is necessary to obtain prothrombin ready for physiologic activation. Both decarboxyprothrombin and carboxyprothrombin can be determined by means of specific activators. Using synthetic substrates for thrombin, a micro-prothrombin assay suitable for functional determinations of decarboxy- and carboxy-prothrombin in liver biopsies was evolved. Decarboxyprothrombin was not found in plasma, independent of the kind of liver disease. Prothrombin determination in 31 liver samples showed no relation between the absolute concentration of carboxyprothrombin and decarboxyprothrombin and the kind of disease. The carboxyprothrombin fraction of total prothrombin was correlated with the activity of histologically estimated fibrosis in the liver.

Biopsy, Needle↗