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Biomedical subjects

D Lockner

Publications and source records attributed to D Lockner.

36 records · Page 2Linked to original sources

Relationship between thromboembolic complications and intensity of treatment during long-term prophylaxis with oral anticoagulants following DVT.

The frequency of thromboembolic recurrencies during secondary prophylaxis after DVT was retrospectively studied and related to the intensity of the oral anticoagulation. All patients receiving oral anticoagulation after DVT at our hospital during April 1972-May 1980 were studied. Treatment was given to 596 patients for 724 thrombotic events for a total of 4450 months. Thirty-six thromboembolic complications, all objectively verified, occurred. Patients with cancer had complications throughout the entire range of anticoagulation. Patients without neoplastic disease (15 events) never had complications below a prothrombin complex level of 27% as assessed with Simplastin A, corresponding to a BCT-ratio of 1.9. This study confirms, that the lower limit of the therapeutic range, determined by the risk of thromboembolic complications, should be set at a Simplastin A-level of approx. 25% corresponding to BCT 2.0.

Administration, Oral

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

The duration of oral anticoagulation after deep vein thrombosis. A randomized study.

Eighty patients with deep vein thrombosis (DVT) were randomized between our routine duration of oral anticoagulation and 50% reduction thereof, in order to evaluate whether shorter therapy could be given without increased risks. The study was stratified, so that 20 patients with the 1st episode of DVT caused by a temporary risk factor were treated for 1.5 or 3 months, 40 patients with the 1st episode of DVT caused by a permanent risk factor for 3 or 6 months, and 20 patients with the 2nd episode of DVT for 6 or 12 months. When warfarin therapy was discontinued, the patients were followed by means of venous occlusion plethysmography every 3 months for 1 year, and clinically for 15-27 months in the different subgroups. Thromboembolic complications were registered and verified by venography and perfusion lung scan. We could not detect any difference between the groups. The rate of rethrombosis and embolism during 12 and 24 months after cessation of anticoagulant therapy was 8 and 10%, respectively, among the patients with reduced duration of treatment and 8 and 14%, respectively, among those with regular duration. One fatal, warfarin-induced hemorrhage occurred. It is important to reduce unnecessary extension of oral anticoagulation after DVT in order to minimize the negative side-effects without increasing the recurrence rate. More extensive trials should be performed to confirm our results and define the optimal duration of treatment.

Adult

Factors and inhibitors of blood coagulation and fibrinolysis in acute nonlymphoblastic leukaemia.

Factors of coagulation and fibrinolysis have been evaluated in 15 patients with untreated acute nonlymphoblastic leukaemia (ANLL). 10 patients had major bleeding (MB) and 6 had laboratory signs of DIC. 5 patients went into complete remission (CR). Antithrombin III (AT III) was decreased in 7 patients, antiplasmin (AP) in 9, fibronectin (FN) in 6 and factor XIII in 4/12. The ratio between factor VIIIR:Ag and factor VIII:C was over 2.0 in 11 patients, and high values were especially seen in patients with MB and patients with DIC. Spontaneous proteolytic activity, measured with S-2288 was increased in 3 patients who all had MB, and none of whom achieved CR. 2 patients with promyelocytic leukaemia (M3) had low fibrinogen and AP, high FDP and normal AT III, speaking for primary fibrinolysis, which in addition to proteolytic enzymes in the blast cells are important contributing factors regarding MB in ANLL.

Adult

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

Treatment of acute nonlymphoblastic leukemia in adults with daunorubicin-DNA complex: a preliminary report.

Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.

Acute Disease

Treatment of refractory anemias with methenolone.

A therapeutic trial with methenolone (Primobolan) in 19 consecutive patients with different types of refractory anemia is reported. The remission frequencies were: pancytopenia 3/6, bicytopenia 2/4, refractory anemia with hyperplastic marrow 1/5, myelofibrosis 1/4. There was no obvious prolongation of survival in the patients responding. Side-effects were negligible.

Aged

Comparison of a new microcrystalline dicoumarol preparation with warfarin under routine treatment conditions.

1 To determine whether two different oral anticoagulants show difference under routine clinical conditions, 71 patients were randomized to treatment with Apekumarol, a microcrystalline dicoumarol preparation, and 72 patients to treatment with warfarin. 2 During the inpatient phase of treatment both drug groups remained for about 94% of their treatment time within prothrombin value limits of 5-25% (Simplastin A). No statistically significant difference was found between the drugs. 3 While under outpatient care, both drug groups remained for about 80% of their treatment time within prothrombin value limits of 5-25%. No statistically significant difference was found between the drugs. 4 The intensity of control and number of prothrombin-determinations did not differ significantly between the groups. 5 Variations in the daily dose did not differ significantly between the groups. 6 The mean daily dose could not be correlated to mean body weight. 7 The mean daily dose decreased with age for the male patients taking warfarin, not for the female patients. There was no such decrease for either male or female patients taking Apekumarol. An additional 137 patients who at the time of the trial were under routine treatment with warfarin were also studied with regard to mean daily dose, age and sex. In this additional group the mean daily dose could be correlated with age in both males and females. 8 No difference between Apekumarol and warfarin could be demonstrated when tested under routine clinical conditions according to the design of the present study. Sensitivity for warfarin, but not for Apekumarol, seems to increase with age, this sensitivity has been demonstrated in both sexes.

Adult

Clinical trial of a new intramuscular iron preparation in iron deficiency anaemia.

A new intramuscular iron preparation (Ferastral) permitting high doses of iron (500 mg) to be given in two simultaneous of 250 mg, was tested in 20 courses given to 11 patients with iron deficiency anaemia. The total iron doses given ranged from 1 000-2 500 mg. The amount injected was calculated from the degree of haemoglobin deficiency. Additional 500-1 000 mg iron were given to fill the depots. Haemoglobin regeneration was satisfactory. Bone marrow aspiration to assess storage iron 2-14 weeks after treatment was carried out in most patients and showed restoration of stainable iron in bone marrow in those cases given Ferastral in doses of 500-1 000 mg greater than calculated to normalize haemoglobin concentrations. In two patients with persistent continued blood loss the bone marrow remained negative for stainable iron. Side-effects were negligible.

Adult

Hypersensitive reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia.

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.

Adult

L-asparaginase and prednisolone pretreatment followed by rubidomycin and cytosine arabinoside for induction of remission in adult patients with acute myeloblastic leukaemia.

77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.

Adolescent