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Biomedical subjects

K Rák

Publications and source records attributed to K Rák.

At least 19 recordsLinked to original sources
PubMed2003

Frequent methylation of p16INK4A and p14ARF genes implicated in the evolution of chronic myeloid leukaemia from its chronic to accelerated phase.

The frequency and mechanism of p16(INK4A) and p14(ARF) gene alterations were studied in cell samples from 30 patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukaemia (CML), both at diagnosis and at the onset of the accelerated phase (AP) of the disease. No alterations in the p16(INK4A) or p14(ARF) genes were found in any of the chronic phase (CP) samples. DNA sequencing analyses detected p16(INK4A) or p14(ARF) mutations in 17 AP samples. All mutations were heterozygous without loss of the other allele. Aberrant methylation of the p16(INK4A) or p14(ARF) promoters was found in 14 of 30 AP samples. The most common situation was the simultaneous methylation of both promoters. Our data indicate that p16(INK4A) and p14(ARF) are primary targets for inactivation by promoter methylation in the acceleration of CML. Transcriptional silencing of the p16(INK4A) and p14(ARF) genes may be important in the conversion of CML from the CP to the AP.

Chromosome Disorders↗
PubMed2001

[Comments about dosing of low molecular weight heparins (LMWH)].

Low molecular weight heparins (LMWHs) have different schedules for dosage according to the official descriptions and recommendations prepared by the particular manufacturer. Therapeutic regimens are mainly depending on bodyweight, even if data concerning the possible effects body composure (i.e. in obesity, lean body mass) are apparently more or less missing. Prophylactic doses are either based on bodyweight (or just an approximation, weight-frames) or mainly perioperative cases on the assessment of the surgical risk. Manufacturers are busy to supply easy and convenient way to approach dosage and prepare, providing fixed, frequently used amounts of LMWHs in disposable syringes. On the other hand haematologist may or should assess bodyweight, history of thrombosis, thrombophilia or bleeding risk, and disease or intervention simultaneously, and may look for a synthetic estimation of an individual dose for each patient. It is rather difficult to establish, which way should be preferred. This review tries to analyse pros and cons in respect of dose estimation with LMWHs in therapy or prophylaxis.

Anticoagulants↗
PubMed2001

[Molecular biology examination in chronic lymphocytic leukemia].

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia characterised by the accumulation of monoclonal CD5 + B-lymphocytes. The pathogenesis and the biology of CLL is complex and many details are still unknown. Several molecular biological methods have been used in the investigation of CLL, among them the study of apoptosis appears to be one of the most important. Initial experiences obtained by the spontaneous and fludarabine induced apoptosis, multidrug resistance (MDR)-test and fluorescent in situ hybridization (FISH) are reported by the authors. Apoptosis of CLL cells could be induced by fludarabine, while more studies should be performed to determine the exact role of MDR-test and FISH.

Adult↗
PubMed2000

[Fluorescence in situ hybridization in the diagnosis and follow-up of chronic myelogenous leukemia].

Chronic myelogenous leukaemia is a clonal myeloproliferative stem cell disease. Its cytogenetical hallmark is the Philadelphia chromosome (Ph) or the BCR/ABL fusion gene. Their identification is important both in the diagnosis and the follow-up of the disease. In our department we have investigated the BCR/ABL gene arrangement in 21 patients with fluorescence in situ hybridization. The aim of the analysis in freshly suspected patients without any previous therapy was to confirm diagnosis and mapping the ratio of Philadelphia positive cells. In contrast to the 95-100% Ph-positivity of mononuclear cells by classical cytogenetical examinations we found BCR/ABL gene arrangement only in various but always lower proportions. Therefore the latter examination gives a better representation of residual normal hemopoesis. Out of 9 patients who had received interferon treatment for at least 6 months, 4 gave a major, 4 a minor cytogenetical answer and in 1 case there was no cytogenetical response. Seven patients reached a complete and 2 a partial hematological remission. Among 5 other patients receiving interferon treatment, in 2 cases with double Ph-positivity we found a rapid progression. The data of 3 patients had to be excluded from the evaluation due to the so far short following time.

Diagnosis, Differential↗
PubMed1999

[Clinical aspects of heparin induced thrombocytopenia].

Heparin induced thrombocytopenia has remained the major complication of therapy or prophylaxis with heparin. Although low molecular weight heparins seem to confer much lesser chance to induce thrombocytopenia, the danger is still considerable, and the fatal outcome is not rare. A lot of new data have been published about the origin, binding, physicochemical properties of the antibodies, the responsive platelet membrane receptors, and laboratory diagnosis in particular, however, many issues are still unresolved. The anticoagulant treatment of cases, in which heparin induced thrombocytopenia in associated with progressive, frequently arterial thrombosis still needs great skills, experience and the use of new generation antithrombotic agents. This review summarizes briefly the internationally accepted standard diagnostic and therapeutic protocols with heparin induced thrombocytopenia.

Heparin↗
PubMed1999

[Hairy cell leukemia: authors' own experience (1977-1998)].

Hairy cell leukaemia (HCL) is a rare, clinically and haematologically well characterised entity. The prognosis of patients with hairy cell leukaemia has significantly improved due to the new therapeutic approaches. Development of diagnostic and therapeutic methods, together with the analysis of their own hairy cell leukaemia patients, is reviewed by the authors. Between 1977 and 1998 twenty five patients (16 male, 9 female) were treated. The malignant cells were usually analysed by morphological and cytochemical methods and recently flow cytometric analysis could be performed in eight patients. Splenectomy with lethal outcome in six patients was performed in 21 cases. Approximately one third of patients received interferon, while 2-chlorodeoxyadenosine was given only to three patients. Favourable experiences obtained by splenectomy and efficacy of interferon treatment are emphasised, but according to the literature and their own results administration of purine analogues can be highly recommended in the future.

Adult↗
PubMed1999

[Heparin therapy: 1998 (current use of the 80-year-old heparin)].

The 80th anniversary of the best known glycosaminoglycan, a mixture of mucopolysaccharides, named heparin by Howell and Holt in 1918 is celebrated this year. It was widely used during the last six decades in prevention and treatment of venous thromboembolism causing a significant decrease of death from pulmonary embolism and the morbidity of deep venous thrombosis. Conventional, unfractionated heparin is also administered on many other topics. Some more than ten years ago the fractionated, low-molecular-weight heparins were introduced into clinical practice and it seems increasingly likely that the fractionated preparations of this classic drug will take over the dominating role. The present study intends to summarize the today's possibilities of prevention and treatment of thromboembolism mostly on the venous side of circulation.

Heparin↗
PubMed1998

Different effects of an oligonucleotide uptake stimulating protein on leukemic cells in their primitive and differentiated state.

The single stranded [3H]oligonucleotide uptake by HL-60 human promyelocyte and K562 human erythroleukemia cells was stimulated 20-45-fold by DUSF (DNA uptake stimulating protein), and this effect was drastically reduced (to 1.6-13x) if the cells were induced to differentiate. The oligonucleotide uptake stimulating effect of DUSF was not altered in HL-60 and K562 cells, if the proliferation of the cells was inhibited by hydroxyurea (HU) treatment. The oligonucleotide uptake by separated granulocytes and mononuclear cells from healthy donors was not stimulated by DUSF, while the uptake of oligonucleotides by myeloid and lymphoid leukemic cells was greatly stimulated (10-15x). The uptake of oligonucleotides by differentiated mononuclear cells of healthy donors could not be stimulated by DUSF, but the oligonucleotide uptake was greatly increased (11x) by DUSF if the cells were subjected to blast transformation.

Biological Transport↗
PubMed1998

Reduced in vitro clot lysis and release of more active platelet PAI-1 in polycythemia vera and essential thrombocythemia.

Because platelets interact with fibrinolysis in a complex manner, it can be expected that with abnormal platelet numbers and quality this interference can be even more profound. The aim of this work was to study the lysis-resistance of platelet-rich clots in diseases with high platelet counts: polycythemia vera (PV), essential thrombocythemia (ET) and to make comparison with polyglobulia (PG). Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were analyzed by an in vitro clot lysis test. Plasminogen activator inhibitor-1 (PAI-1) activity was measured in plasma and in the supernatants of the washed and gel-filtered platelets after activation by thrombin. The lysis showed decreased speed of PPP-clots in PV and ET. This phenomenon was even more marked in PRP-clots from PV and ET, but further increased lysis resistance after retraction was not observed in PV and ET, most likely due to abnormal platelet functions. Our results suggest that the fibrinolytic activity is reduced in PV and ET, and may play a role both in the increased aptitude for venous thrombosis and in the arterial complications. These are partly caused by higher plasmatic PAI-1 activity as well as by more active platelet PAI-1. The PAI-1 activity was significantly higher in the supernatants of the washed and gel-filtered platelets of PV after activation by thrombin compared with controls. Other factors might have influenced the reduced fibrinolysis.

Adolescent↗
PubMed1997

[Pure red cell aplasia, associated with chronic lymphoid leukemia, successfully treated with closorine].

Pure red cell aplasia (PRCA) is a rare disorder, which is characterized by severe anaemia associated with reticulocytopenia and absence of erythroid precursor cell from the bone marrow. Mostly immunological mechanisms have a role in its pathogenesis. Primarily the acquired, idiopathic type occurs in adults, however, it is rarely associated with other disorders (autoimmune-, and lymphoproliferative diseases, etc.). The authors present a patient with B-cell chronic lymphocytic leukemia associated with PRCA, which was successfully treated with cyclosporine. The pathogenesis and the therapy of the PRCA is also summarized.

Cyclosporine↗
PubMed1997

[New agents and challenges in the antithrombotic management of arterial diseases].

The past decades have exposed and faced antithrombotic therapy (anticoagulants, antiplatelet agents, and fibrinolytics) to new challenges. The reperfusion treatment modalities of myocardial infarction needed improvement of fibrinolytic agents and adjuvant anticoagulant-antiplatelet therapy. The secondary prevention of stroke, along with the renewal of thrombolytic and anticoagulant therapy seems to be an other major area of new approach to antithrombotic therapy. The reocclusion and restenosis of coronary arteries means the most difficult issue and task for antithrombotic treatment modalities. These requirements accelerated the development of novel antithrombotic agents, the disintegrin family, the monoclonals directed against platelet adhesion and aggregation, the application of hirudin and its analogs and new generation of thrombolytic agents. Combined and sequential administration of different antithrombotic agents receives growing attention and seems also to be promising.

Anticoagulants↗
PubMed1996

[Low-molecular-weight heparin in the prevention of thromboembolism in pregnant thrombophilic patients].

Prophylaxis of thromboembolism with low molecular weight heparin (LMWH) may offer some advantages over unfractionated heparin during pregnancy. Controlled studies with LMWH for thromboprophylaxis in pregnancy are failing, although according to some recent studies LMWH did not cross the placental barrier. LMWH as thromboprophylactic agent was used in three young pregnant women with familial thrombophilia (two with PC one with AT-III deficiency). According to the bodyweight of patients the applied doses of LMWH were 5,000-10,000 ICU once daily. Laboratory control (determination of anti-FXa activity in plasma samples) was made monthly. The three pregnancies were uneventful, thromboembolic or haemorrhagic complications did not develop. Newborns were healthy, with no coincide of disturbances of haemostasis. The LMWH-demand is certainly increased at the late period of pregnancy. LMWH as thromboprophylaxis is recommended for pregnants with familial thrombophilia. The necessary dose of Fraxiparine may be 70 ICU/kg/day in the first and 100 ICU/kg/day in the second half of pregnancy.

Adult↗
PubMed1996

[Fibrinolysis studied by an in vitro clot lysis test in polycythemia vera].

Results obtained by a simple in vitro clot lysis test in polycythemia vera, polyglobulia, essential thrombocythemia and chronic immun thrombocytopenic purpura are reported. Increased lysis resistance of the platelet-rich clots was demonstrated in polycythemia and essential thrombocythemia, ostensibly caused by the high plasma level of plasminogen activator inhibitor-1. Following retraction of platelet-rich clots no further increase of lysis-resistance occurred in polycythemia and essential thrombocythemia. This phenomenon is most likely due to abnormal platelet function. The well known thromboembolic complications may at least partly result from the impaired fibrinolysis in diseases with high platelet counts.

Adult↗
PubMed1995

[Recombinant human erythropoietin in the treatment of anemic patients undergoing chemotherapy for cancer].

Twenty-seven anemic patients with malignant tumour who received chemotherapy were treated with recombinant human erythropoietin (r-HuEPO). The objective of this study was to evaluate the effect of r-huEPO on hematologic and quality of life parameters as well as on transfusion requirement in patients with anemia secondary to cancer and cyclic chemotherapy. Patient population was allocated into two groups based on the chemotherapeutic regimens: 1. cisplatin containing and 2, non cisplatin containing regimen. Using 2 g/dl increase in haemoglobin levels as the criteria for response, twenty women responded to r-huEPO treatment. The response was more marked in the cisplatin group. R-huEPO treatment saved transfusion in both groups. Again, less patients required transfusion among those treated with cisplatin. There was a marked improvement in the quality of life which was more pronounced in patients who responded to r-huEPO treatment and in those receiving non cisplatin chemotherapy. No serious adverse experiences occurred. In conclusion, two third of patients with anemia secondary to cancer and cyclic chemotherapy can be effectively treated with r-huEPO. R-huEPO treatment invariably saves transfusion and is highly effective in improving quality of life. Adverse reaction is exceptional.

Anemia↗