PubMed Health⌕ Search

Biomedical subjects

D Lockner

Publications and source records attributed to D Lockner.

At least 19 recordsLinked to original sources
PubMed1992

Fragmin once or twice daily subcutaneously in the treatment of deep venous thrombosis of the leg.

In an open, randomised controlled study, 101 patients with phlebographically diagnosed deep vein thrombosis of the leg, not extending into more than two thirds of the femoral vein, were randomised to receive Fragmin (a low molecular weight heparin) administered subcutaneously either once or twice daily in doses of 200 U(anti-FXa)/kg/24h or 100 U(anti-FXa)/kg/12h respectively. Prior to Fragmin unfractionated heparin had been administered by continuous iv infusion for not longer than 24h. Warfarin was administered from the first treatment day. Fragmin was administered for at least 5 days or until the prothrombin complex had been within the therapeutic range for at least 2 days. Patients were kept in bed for the first day but thereafter were ambulant. Phlebography was repeated at 5-7 days. Comparison of the phlebograms revealed a similar improvement (reduction in Marder score) in both groups. There were 5 cases of bleeding: 1 major and 3 minor in the twice daily group and 1 minor bleed in the once daily group. There were no cases of clinical pulmonary embolism. It is concluded that Fragmin, administered as a single daily subcutaneous injection, is effective in the treatment of deep vein thromboses, and offers the advantages of reduced costs, despite higher price of the drug, including reduced nursing time.

Adult↗
PubMed1992

Double-blind, randomized comparison of systemic continuous infusion of 0.25 versus 0.50 mg/kg/24 h of alteplase over 3 to 7 days for treatment of deep venous thrombosis in heparinized patients: results of the European Thrombolysis with rt-PA in Venous Thrombosis (ETTT) trial.

Thirty-two patients with acute, proximal-vein thrombosis were treated with heparin and alteplase (0.25 versus 0.5 mg/kg/24 h during 3-7 days) in a randomized, double-blind, multicenter, European (ETTT) trial. The treatment resulted in a decrease of the venographic Marder's score from 18 (6-25) to 13 (2-24) units (median, range) in Group I (0.25 mg/kg/24 h, n = 15, median decrease 3.0, p = 0.32) and from 17.5 (3-33) to 15.5 (0-27) in Group II (0.5 mg/kg/24 h, n = 16, median decrease 4.0, p = 0.23). Comparison of the sequential venograms could be performed in 14 cases of Group I and in 15 cases in Group II. A minority of patients showed substantial partial recanalization of the initially obstructed veins on the control venogram (one in each treatment group) and most of the control venograms showed either thrombus size reductions (5 in Group I, 7 in Group II) or no change or even deterioration (8 in Group I, 7 in Group II). Major bleedings were observed in 7 patients (7/32, 22%), 5 of them occurring in Group II (5/17, 29%). Thus, the results of the ETTT trial show that the used low dosages of alteplase administered intravenously over 3-7 days in heparinized patients cannot be recommended as a treatment for patients with deep venous thrombosis of lower limbs and/or pelvis. Further studies are needed to define a more suitable dosage regimen of alteplase in this indication.

Adolescent↗
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

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↗
PubMed1991

Treatment of myelodysplastic syndromes with recombinant human erythropoietin.

12 patients with myelodysplastic syndromes were treated with recombinant human erythropoietin (r-epo). 5 patients had stable anemia, 78-92 g/l, and 7 were transfusion-dependent. In 11 patients, r-epo was given intravenously three times a week, with dose escalation after 4 and 8 wk if hemoglobin did not increase more than 15 g/l. The doses were 600, 1500 and 3000 U/kg bodyweight/wk. The 12th patient was treated subcutaneously with a dose of 560 U/kg/wk. 3 patients showed a significant response with an increase in hemoglobin of greater than or equal to 15 g/l. 2 of these had stable anemia before treatment and increased in hemoglobin from 87 to 116 g/l and from 80 to 99 g/l, respectively. The 3rd patient was transfusion-dependent and rose to a stable hemoglobin level between 76 and 80 g/l without transfusions. 2 patients showed a reduction of their transfusion need. Mean initial serum erythropoietin in the responding group was 366 U/l compared to 1049 among the non-responders (p = 0.367). Response was observed in 5/7 patients without bone marrow sideroblasts and in 0/5 patients with sideroblasts (p = 0.027). Erythropoietin seems to be an effective and well-tolerated treatment for a certain proportion of patients with MDS. A larger patient material might provide a model for predicting responses.

Adult↗
PubMed1990

Two daily subcutaneous injections of fragmin as compared with intravenous standard heparin in the treatment of deep venous thrombosis (DVT).

In a prospective, randomized, open study 119 consecutive patients with phlebographically verified deep venous thrombosis (DVT) of the leg (36% distal and 64% proximal) were treated either with a low molecular weight heparin (Fragmin, Kabi-Vitrum) subcutaneously (120 anti-FXa U/kg) twice daily or standard heparin (SH) as continuous intravenous infusion (480 IU kg-1 day-1). The Fragmin doses were adjusted to achieve an anti-FXa activity of 0.2-0.4 U/ml before injection and not greater than 1.5 U/ml 4 h after the morning injection. The SH dose was modified to prolong the APTT 2-3 times. Repeat phlebography after 5-7 days showed improvement in 34/45 patients (76%) in the Fragmin group and in 30/49 patients (61%) in the SH group and progress in 2/45 (4%) and 3/49 (6%), respectively. The mean Marder scores decreased from 18.7 +/- 12.1 to 15.7 +/- 12.7 in the Fragmin group and from 16.9 +/- 12.0 to 14.4 +/- 11.8 in the SH group (ns). Two patients in the SH group and none in the Fragmin group had major bleedings. After 22 +/- 7 months follow up 6 rethromboses had occurred in the SH group and 4 in the Fragmin group. Postthrombotic signs and symptoms were similar in both groups. We conclude that two daily sc Fragmin doses seem as effective and safe as continuous SH in the treatment of DVT of the leg.

Adult↗
PubMed1990

Fatal pulmonary embolism caused by streptokinase treatment of deep venous thrombosis of the leg?

During the last 10 years, four of 150 (2.7%) patients with deep venous thrombosis (DVT) treated with streptokinase (SK) at our department have died of pulmonary embolism (PE). A retrospective study of 1393 DVT patients treated with heparin during the period 1973-1986 showed that five (0.36%) of these patients died of PE while still on heparin. In this paper we describe the four patients treated with SK who developed fatal PE. In our opinion this increase in mortality does not warrant the use of SK in routine treatment of DVT of the leg before a proper trial has been conducted to compare the frequencies of pulmonary embolism after both treatments.

Adult↗
PubMed1988

Clinical experiences in the administration of a low molecular weight heparin (Fragmin, Kabi-Vitrum) to healthy volunteers and in the treatment of established deep venous thrombosis.

A low molecular weight heparin (Fragmin, Kabi-Vitrum) with a mean molecular weight of 4,000-5,000 D has been investigated in healthy volunteers and in patients with DVT. We found a T 1/2 of 4 hours and a high bioavailability after subcutaneous injection in volunteers. In a randomised study, patients with phlebographically verified DVT, 120 U(anti-FXa)/kg Fragmin injected twice daily was found to be as effective as 240 U/kg, 12 h standard heparin as continuous infusion in preventing DVT progress. No major bleedings were seen in the Fragmin group. We conclude that Fragmin administered subcutaneously twice daily results in adequate anticoagulation and is safe and practical in the treatment of DVT.

Biological Availability↗
PubMed1987

A pilot study; desmopressin (DDAVP) in the treatment of deep venous thrombosis.

In a pilot study on 9 patients with acute deep venous thrombosis of the leg the fibrinolytic response and the possible thrombolytic effect of desmopressin (DDAVP), when given supplementary to standard heparin treatment, was examined. Six injections of 0.3-0.4 microgram DDAVP/kg b.w. at 12 hours intervals were given. No serious side effects were observed. The fibrinolytic variables that followed showed that plasma levels of t-PA increased significantly and most pronounced after the first injection. Rephlebography 4-7 days after hospitalization showed partial thrombolysis in 7 out of 9 patients. The phlebographic score according to Marder was reduced from 22.7 +/- 12.1 to 18.4 +/- 10.1 (p = 0.018), corresponding to a thrombus size reduction of 19%. No correlation between the level of the fibrinolytic variables measured and the degree of thrombolysis in the individual patients, could be demonstrated in this small number of patients.

Antigens↗
PubMed1987

Acute unidentified hepatitis in a hypogammaglobulinaemic patient on intravenous gammaglobulin successfully treated with interferon.

A 59-year-old male with acquired hypogammaglobulinaemia since 1978 developed a fulminant hepatitis. The hepatitis appeared after two years intravenous treatment with Sandoglobulin (Sandoz, Switzerland). No virus markers could be detected in the body fluids or liver tissue. Blood transfusions had not been given within one year before development of the liver disease. There was strong suspicion that the patient had acquired non-A non-B hepatitis from the gammaglobulin infusions. Treatment with alpha-interferon ran parallel to a normalization of the pathological liver enzymes and the histology of the liver. This observation suggests a direct antiviral effect of alpha-interferon, despite the anecdotical and noncontrolled character of these data.

Agammaglobulinemia↗
PubMed1986

Low molecular weight heparin (KABI 2165, Fragmin): pharmacokinetics after intravenous and subcutaneous administration in human volunteers.

The pharmacokinetics of a low molecular weight heparin (LMWH) with a mean mw of 4000-6000 D (KABI 2165, Fragmin) was studied in 6 healthy volunteers after intravenous (iv) and subcutaneous (sc) administration of 120 U (anti FXa)/kg. The half-life in plasma of the anti FXa activity after iv injection was 119 +/- 17 min, the volume of distribution (Vd) 3.4 +/- 0.5 1 and the total clearence 20.5 +/- 2.5 ml/min. The maximal anti FXa activity determined 3 min after iv bolus injection amounted to 2.2 +/- 0.3 U (anti FXa)/ml with a corresponding increase of the APTT from 31 +/- 7 sec to 113 +/- 35 sec. The elimination of the anti FXa activity was a monoexponential first order process. After sc administration the plasma half-life of the anti FXa activity was longer than after iv injection, 228 +/- 40 min, corresponding to the absorption rate thus found to be the rate limiting step. After sc administration the peak was reached after 4 hours (0.6 +/- 0.1 U (anti FXa)/ml; APTT increase 5 sec). The bioavailability after sc injection was calculated to be 87 +/- 6%. As a consequence of the high bioavailability and long T1/2 of the anti FXa activity, Fragmin administered sc seems to induce adequate levels of heparin-like activity making this regimen worth further investigation as an alternative for the treatment of deep venous thrombosis.

Adult↗
PubMed1986

Long-term sequelae of calf vein thrombosis treated with heparin or low-dose streptokinase.

A prospective randomized study was performed to investigate the long-term sequelae of calf vein thrombosis (CVT) and correlate them to the success of the initial treatment. Thirty-six patients with symptomatic CVT, verified by venography, were treated with heparin or low-dose streptokinase (SK) combined with low-dose heparin. Venography was repeated after 1 week, and long-term follow-up was performed clinically and with foot volumetry after an average of 5 years. Since the low-dose SK regimen led to serious hemorrhagic side-effects in a parallel study, the present investigation was discontinued prematurely. The thrombolysis achieved was greater with SK but, since the initial thrombi were somewhat larger in this group, no significant difference in the average size of the thrombi after therapy could be displayed between the groups. The long-term sequelae and results of foot volumetry were also equal. Signs or symptoms of venous insufficiency were found in 37%, and foot volumetry showed deep venous insufficiency in 26% of the cases. There was a correlation between the hemodynamic change, as assessed by foot volumetry, and the venographic severity. This relation was stronger for the size of the thrombus after treatment than for the initial size. Thus, it seems important to limit the extent of a CVT in order to minimize the long-term sequelae, but administration of SK is not justified due to side-effects.

Acute Disease↗
PubMed1986

Pharmacokinetics of intravenously and subcutaneously administered Fragmin in healthy volunteers.

Studies in 8 healthy volunteers showed that the low molecular weight heparin Fragmin KabiVitrum is eliminated according to first order kinetics without dose dependency after intravenous injection of doses between 40 and 120 anti-Xa U/kg. Fragmin remains in the circulation more than twice as long as unfractionated heparin (UFH). Fragmin administered subcutaneously has a bioavailability which is much greater than that of UFH. Fragmin administered subcutaneously twice a day results in a significant anti-Xa activity and provides an alternative to intravenous infusions.

Adult↗
PubMed1986

Intravenous and subcutaneous administration of Fragmin in deep venous thrombosis.

54 patients with venographically verified deep venous thrombosis (DVT) were randomized to treatment with either intravenous infusions of 240 anti-Xa U/kg/12 h unfractionated heparin (UFH) or 240 or 120 anti-Xa U/kg/12 h of the low molecular weight heparin Fragmin. Repeated venographies showed improvement in 48% of the UFH-treated patients and 50 and 77%, respectively, in the Fragmin-treated patients. Progression was seen only in the UFH-treated patients and was observed in 11%. Two bleeding complications were seen in the Fragmin group in 2 patients receiving the very high dose of 240 anti-Xa U/kg/12 h. Anti-Xa activity in plasma and activated partial thromboplastin time (APTT) does not correlate in the Fragmin-treated patients. Fragmin was as effective as UFH in preventing the progress of thrombosis in DVT. In another study 120 anti-Xa U/kg Fragmin given subcutaneously 2 times daily to 13 patients with DVT resulted in adequate anti-Xa activity but with a tendency for accumulation of the Fragmin-induced activity. Subcutaneous injections of Fragmin 2 times daily also appears to prevent the progression of thrombosis effectively.

Adult↗
PubMed1985

Kinetics of the spontaneously occurring common variable hypogammaglobulinemia: an analysis of two individuals with previously normal immunoglobulin levels.

Two males with previously normal serum immunoglobulin levels who spontaneously developed common variable hypogammaglobulinemia were investigated. In one patient serum samples obtained before and after the development of hypogammaglobulinemia were analyzed. A parallel decrease in serum IgM, IgG (all 4 subclasses), IgA (both subclasses) as well as kappa and lambda light chains was found. Serum IgD and IgE also decreased but reached a minimum level before the other immunoglobulin classes. A bone marrow aspirate obtained before the development of hypogammaglobulinemia in this patient showed 1.2% plasma cells, whereas the frequency was only 0.1% when low serum immunoglobulins were recorded. These observations demonstrate the existence of adult onset hypogammaglobulinemia.

Adult↗
PubMed1979

Uptake of free and DNA-bound daunorubicin and doxorubicin into human leukemic cells.

Leukemic cells from seven patients with acute nonlymphoblastic leukemia and granulocytes, and mononuclear cells from three healthy controls were isolated by centrifugation on metrozoate-dextran. The intracellular accumulation of both the free and DNA-bound forms of daunorubicin and doxorubicin was studied in vitro. The uptake of unbound daunorubicin was higher than that of doxorubicin. At drug concentrations of 1.75 microM and higher the uptake of the free drugs was greater than that of the bound forms, but at lower drug concentrations the uptake was about the same. This could at least partly be explained by a greater dissociation of the DNA-drug complexes at lower drug concentrations. The uptake into normal leukocytes was of the same order of magnitude as that into leukemic cells. There was a great interindividual variation in the accumulation of both free and DNA-bound drugs in the cells from leukemic patients. This variation might be of importance for the prediction of individual sensitivity to the different drugs.

Bone Marrow Cells↗