PubMed Health⌕ Search

Biomedical subjects

N Egberg

Publications and source records attributed to N Egberg.

At least 19 recordsLinked to original sources
PubMed1995

Treatment with recombinant human erythropoietin induces a moderate rise in hematocrit and thrombin antithrombin in healthy subjects.

Recombinant human erythropoietin (EPO) therapy in uremic patients raises the hematocrit (Hct) and increases physical exercise capacity (1,2) and quality of life (1). In general, partial correction of anemia to subnormal levels in uremic patients has proven to be safe with few serious adverse effects apart from hypertension (3). Ever since the advent of EPO the prospect of abuse of the hormone by sportsmen has been subject to scrutiny. Both maximal oxygen uptake and endurance capacity are increased after EPO treatment in healthy subjects (4). Moreover, EPO treatment in healthy subjects has been found to induce an accentuated blood pressure reaction after submaximal exercise (5). Previous studies have shown that extreme physical exertion can predispose to an increased intravascular coagulation (6). Moreover there is a significantly increased risk of thrombosis in patients with myeloproliferative disorders, particularly in polycythemia vera (7). An enhanced risk of cardiovascular events may therefore arise should sportsmen abuse EPO as a blood doping agent. The aim of this study was to examine the effects of an EPO-induced increase in Hct on the coagulation system in healthy subjects.

Adult↗
PubMed1992

Significance of platelet beta-adrenoceptors for platelet responses in vivo and in vitro.

The significance of platelet beta-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the beta-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed alpha- and beta-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma beta-thromboglobulin levels. Adrenaline levels were 3-4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels. beta-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that beta-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an alpha-adrenoceptor mediated proaggregatory action.

Adenosine Diphosphate↗
PubMed1992

Studies of the platelet fibrinogen receptor in Glanzmann patients and uremic patients.

The purpose of the present study was to investigate the binding of fibrinogen to the platelet fibrinogen receptor. Glycoprotein (GP) IIIa was measured utilizing a fluorescein isothiocyanate (FITC)-labelled monoclonal antibody and an Ortho Spectrum III flow cytometer. The number of binding sites per platelet was calculated to be 30,200. Using this technique it appears possible not only to diagnose Glanzmann's thrombasthenia but also to identify carriers. In uremic patients a slightly lower number of GPIIIa molecules per cell than in control subjects was found. Treatment with erythropoietin had no significant effect on the expression of GPIIIa. Thrombin, and to a less extent ADP, increased the binding of FITC-conjugated fibrinogen to normal platelets but had no significant effect on the expression of GPIIIa.

Adolescent↗
PubMed1992

Twenty-four-hour heparin-free veno-right ventricular ECMO: an experimental study.

Platelets and coagulation factors were studied during 24-hour heparin-free veno-right ventricular extracorporeal membrane oxygenation (ECMO) in 6 healthy pigs. An endpoint attached and covalently bonded heparin-coated ECMO system was used in these experiments. The veno-right ventricular ECMO supplied the total lung function of the animals, and after 24 hours, all the animals were successfully weaned from ECMO. Lung function and central hemodynamics were not affected by the procedure. Because all the animals showed a significant reduction in plasma volume, the concentration of measured coagulation variables was corrected both for plasma volume changes and for hemodilution. The platelet count and the plasma-free hemoglobin level were not significantly altered by ECMO. Similarly, the prothrombin complex, antithrombin, thrombin-antithrombin complex, factor XII, and the urinary excretion of 2,3-dinor-thromboxane B2 were not significantly altered. Fibrinogen and fibrin monomer increased significantly, whereas von Willebrand factor was significantly decreased after ECMO. In summary, 24-hour heparin-free veno-right ventricular total extracorporeal lung assistance does not affect the platelets and the coagulation system significantly in healthy juvenile pigs.

Animals↗
PubMed1992

Platelet activation and prostacyclin release in essential hypertension.

To evaluate platelet activation thromboxane A2 (TxA2) and beta-thromboglobulin (beta TG) were used as markers and in addition we studied the biosynthesis of prostacyclin. Synthesis of TxA2 and prostacyclin was assessed by measurement of urinary metabolites. Fifteen untreated hypertensive patients (HT) and 15 age-matched normotensive controls (NT) were investigated at rest, during and after exercise. HT patients were re-examined after 3 months on enalapril. During basal conditions there was no difference in the excretion of Tx-M, PGI-M or beta TG between the groups. During strenuous exercise HT exhibit a significantly higher increase in prostacyclin synthesis (162%) compared to NT (76%). The levels of beta TG increased with 82% in the HT and 24% in the NT group, Tx-M increased with 27% and 23% respectively. Treatment with the ACE-inhibitor enalapril did not significantly alter these findings. These results indicate that there is no evidence of basal platelet activation in early essential hypertension. Strenuous exercise leads to some increase in Tx-M in both groups, with no pronounced differences between the groups. Hypertensive patients exhibit a significantly increased prostacyclin response to exercise which could be due to differences in vessel-wall reactivity. Enalapril seems to exert no effect on platelet activation or on prostacyclin biosynthesis.

Adult↗
PubMed1992

Bleeding complications and coagulopathy in acute leukaemia.

Factors and inhibitors of coagulation and fibrinolysis were investigated on admission in 57 patients with acute leukaemia and they were correlated to the occurrence of haemorrhage. Coagulation disturbances were found in 98%. Seventeen of the patients with haemorrhagic symptoms had major bleeding. Severe thrombocytopenia (< 20 x 10(9)/l) was found in 16%. Patients with major bleedings had significantly lower concentrations of prothrombin complex, fibrinogen, protein C and platelets. Low levels of antiplasmin and fibrinogen were characteristic of 'bleeders' with promyelocytic and lymphoblastic leukaemia. We found a positive correlation between vWF:Ag and leukaemic cell count especially in lymphoblastic leukaemia (ks = 0.72). Reduced levels of antithrombin indicated a poorer prognosis.

Acute Disease↗
PubMed1992

Peroperative anticoagulation with antithrombin or heparin in infrainguinal bypass surgery.

Patients suffering from atherosclerosis may have a hypercoagulable state which is further aggravated by surgery. Thrombin, a central enzyme in the coagulation process, cleaves fibrinogen to fibrin. Therefore, inhibition of thrombin is an important anticoagulant mechanism. This is accomplished by heparin in concert with antithrombin III (AT), but vessel wall glycosaminoglycans may act as substitutes for heparin and catalyse thrombin inhibition. The present study examines whether administration of AT or heparin is effective as an anticoagulant during infrainguinal bypass surgery. Preoperatively and during surgery the patients had elevated levels of fibrinogen, fibrinopeptide A (FPA) and thrombin-antithrombin (T-AT) complexes. There were higher levels of FPA in the venous outflow from the ischemic leg than in the arterial inflow. Taken together these measurements indicate ongoing coagulation in the operated leg. Administration of heparin decreased FPA levels and prevented intraoperative graft thrombosis, whereas in patients receiving AT, T-AT levels increased but FPA levels were unchanged. In the latter group, intraoperative graft thrombosis occurred in a high proportion. Based on additional case histories in these patients with hypercoagulability, it is suggested that fibrinogen is a risk factor for thromboembolic complications and that a combination of low dose of heparin and AT might be an effective regimen to prevent intraoperative thrombosis with a low risk of haemorrhage.

Adult↗
PubMed1992

Alpha-adrenoceptor blockade by phentolamine inhibits adrenaline-induced platelet activation in vivo without affecting resting measurements.

1. The effects of phentolamine (500 micrograms/min) on platelet aggregability in vivo at rest and during adrenaline infusion were assessed by ex vivo filtragometry and measurements of plasma beta-thromboglobulin levels in 10 healthy male subjects. Plasma levels of von Willebrand factor antigen and free fatty acids were also measured. 2. Adrenaline induced marked and expected increases in heart rate and systolic blood pressure and decreased diastolic blood pressure when venous plasma adrenaline levels were elevated from 0.12 +/- 0.02 to 2.9 +/- 0.3 nmol/l (P less than 0.01). 3. Adrenaline caused platelet activation in vivo. Ex vivo filtragometry readings were shortened by 58 +/- 9% (P less than 0.01), plasma beta-thromboglobulin levels increased by 99 +/- 44% (P less than 0.01) and platelet counts increased by 26 +/- 6% (P less than 0.01). Plasma levels of von Willebrand factor antigen and free fatty acids increased by 53 +/- 5% and 475 +/- 113% (both P less than 0.01), respectively. 4. Phentolamine enhanced the beta-adrenergic vasodilator responses to adrenaline, as both the decrease in diastolic blood pressure and the reflexogenic increase in heart rate were enhanced (both P less than 0.01). Marked elevations in plasma noradrenaline levels were found during infusions of phentolamine and adrenaline (P less than 0.001). 5. Phentolamine did not alter platelet indices at rest, but abolished adrenaline-induced platelet activation, as filtragometry readings, plasma beta-thromboglobulin levels and platelet counts remained at, or below, resting levels. Responses of plasma levels of von Willebrand factor antigen and free fatty acids to adrenaline were not influenced by phentolamine and did not seem to influence platelet responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhanced platelet function in acute myocardial infarction is attenuated by streptokinase treatment.

The aim of this study was to determine whether platelets are activated and aggregation is increased in myocardial infarction treated with streptokinase. Twelve consecutive patients were studied. Before streptokinase infusion (1.5 x 10(6) IU i.v. over a period of 1 h), 7 +/- 4 h after the onset of symptoms, fibrinogen, leucocyte and platelet functions were enhanced compared to reference values. Plasma fibrinogen was 3.1 +/- 0.6 g 1-1 (P less than 0.03), leucocyte count was 14.3 +/- 3.3 x 10(3) l-1 (P less than 0.0005), elastase was 39 +/- 8 micrograms l-1 (P less than 0.0002), beta-thromboglobulin was 68 +/- 71 micrograms 1-1 (P less than 0.0001) and filtragometer platelet aggregation time was 137 +/- 40 s (P less than 0.0001). After streptokinase the leucocyte count, elastase and beta-thromboglobulin levels increased further, by about 40% (P less than 0.02), 130% (P less than 0.02) and 140% (P less than 0.005), respectively. Fibrinogen was almost eliminated. Despite signs of increased activation, platelet aggregation was decreased as indicated by both filtragometer aggregation time, which increased by about 480% (P less than 0.003), and whole-blood aggregometry, in which electrical impedance decreased by about 65% (P less than 0.01).

Female↗
PubMed1992

Elastase activity in leukaemic cells and plasma in patients with acute leukaemia.

Proteolysis of coagulation factors and inhibitors resulting in haemorrhage can be mediated by elastase. Indirect signs of this are elevated levels of elastase complexed to its inhibitor in plasma, alpha 1-antitrypsin (E alpha 1-AT). We have measured intracellular elastase activity in leukaemic cells from 60 patients with acute leukaemia. Elastase activity was detected in 92% of the patients with acute nonlymphoblastic leukaemia (ANL), no activity was found in the patients with acute lymphoblastic leukaemia (ALL). High levels were found in cells from patients with promyelocytic leukaemia. Moderate to high total circulating blast elastase activity was measured in 70% of the ANL patients with haemorrhage compared with 36% of the patients without bleeding complications (p < 0.05). The available intracellular elastase activity was correlated to the level of E alpha 1-AT (rs = 0.42, p < 0.01) but not to the elastase specific split product of fibrinogen, B beta 30-43. In complete remission the levels of E alpha 1-AT were normalized. Intracellular elastase activity might be a useful supplement to differentiate ANL and ALL.

Adolescent↗
PubMed1992

Elastase activity in leukemic cells.

Elastase, a proteolytic enzyme which digests different clotting factors, has previously been isolated from monocytes, macrophages and granulocytes. In the present work, we have isolated leukemic cells from 1 patient with acute lymphoblastic leukemia (ALL) and from 6 patients with acute nonlymphoblastic leukemia. Detectable elastase activity was found in the cells from all patients with acute nonlymphoblastic leukemia and ranged from 0.016 to 0.619 mukat/l/micrograms DNA. The highest elastase activity was found in 1 patient with promyelocytic leukemia (M3), and no activity was found in the cells from the patient with ALL. It is possible that elastase-mediated proteolysis of coagulation factors is the mechanism responsible for bleeding complications which are frequent in M3.

Bone Marrow↗
PubMed1992

Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I.

von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA----TGA) were detected in exons 28, 32, and 45 by screening of all the 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicated that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I were found to be heterozygous for the mutation.

Adolescent↗
PubMed1991

A new assay for beta-thromboglobulin in urine.

Measurements of beta-thromboglobulin (beta TG) excretion in urine may be of value for "field" studies and due to problems with sampling artifacts for beta TG in plasma. Previous studies have used a radioimmunoassay designed for plasma without characterizing the "beta TG" immunoreactivity in urine. We describe modifications of the assay which increase its sensitivity and a sample work-up procedure using Sephadex G-25M columns separating high molecular weight (HMW) components (presumably intact beta TG) from low molecular weight (LMW) immunoreactivity (i.e. beta TG fragments and/or non-specific interferences). The sensitivity of the assay (with 2.5 ml sample) is less than 12 pg/ml HMW beta TG. Inter- and intraassay coefficients of variation were 7-10%. Only 33 (range 5-75)% of beta TG immunoreactivity in urine represented HMW beta TG. LMW immunoreactivity may be related to salt and other non-specific influences in the sample. Recoveries of beta TG were quite variable (9-100%) in unextracted urines, but high and reproducible (80 +/- 2%) in the HMW fraction. Thus, nonspecific interferences with beta TG measurements in certain urines are overcome by the separation step. Using Sephadex fractionation beta TG immunoreactivities in night urines (n = 15) were: 20 +/- 3 pg/ml in the HMW fraction, 70 +/- 8 pg/ml in the LMW fraction, and 85 +/- 10 pg/ml by direct assay. HMW beta TG increased in daytime samples (to 30 +/- 5 pg/ml; p less than 0.01), but no diurnal variation was seen in the LMW fraction or with the direct assay. Thus, selective analysis of HMW beta TG in urine circumvents problems with nonspecific immunoreactivity and apparent interferences with measurements of intact beta TG. The present more selective assay for HMW immunoreactivity increases the possibility of detecting physiological changes in beta TG release in vivo by urinary measurements.

Chromatography, Gel↗
PubMed1991

Prophylaxis with factor concentrates in preventing hemophilic arthropathy.

Seven children with severe hemophilia A on prophylactic substitution therapy since a mean age of 5 years (group I) were investigated in 1978 (at ages 6-12 years) and in 1988 (at ages 16-22 years). The results were compared with those of seven children aged 5-12 for whom such treatment was started at a mean age of 3 years (group II). In group I, four had each had more than 20 ankle hemarthroses at the first investigation, while in group II, only one boy had experienced such a high bleeding frequency. Radiological changes in ankles were found in one of seven in group II compared with five of seven in group I. Progression of these changes was shown in eight of 10 ankles of group I at reinvestigation. Regular prophylactic therapy must start early, at ages 1-2 years, to prevent changes in ankle joints, and parents and children must learn to recognize ankle bleeding. Modern Factor VIII concentrates must be administered to children two or three times per week in dosages of 3,000 U/kg/year in order to reduce hemarthroses to a minimum. The dosages can probably be lowered if the intervals are shortened. Children on prophylactic treatment can engage in regular sports activities.

Adolescent↗
PubMed1990

Homozygous protein C deficiency in two siblings.

Homozygous protein C (PC) deficiency is reported in two siblings (girl and boy) who received their proper diagnoses at the ages of 7 4/12 and 1 3/12 years respectively. The girl had perinatal asphyxia without bleeding. At 1 year of age she developed purpura fulminans. Treatment with heparin and plasma was successful. At 7 4/12 years she developed tender, bluish nonnecrotic skin changes after an orthopedic operation. The PC level was 0.08 U/ml. The boy had had a large intraventricular hemorrhage neonatally and developed severe brain damage. At 1 3/12 years he manifested the same skin changes as his sister and was treated similarly. The PC level was 0.05 U/ml. Both children now receive warfarin continuously and are essentially free of symptoms. The cases represent homozygous phenotypes in a family with a recessive trait of PC deficiency without thrombotic disease. The cases also show that severe PC deficiency may be compatible with life beyond infancy without any specific therapy.

Blood Transfusion↗