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Biomedical subjects

L Jebavý

Publications and source records attributed to L Jebavý.

At least 19 recordsLinked to original sources

The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia.

Cardiotoxicity is a serious and relatively frequent complication of anti-tumorous treatment. Anthracyclines represent the greatest risk. Biochemical markers of structural and functional myocardial damage have been gaining ground in cardiotoxicity monitoring. The aim of the study was to monitor cardiotoxicity of induction chemotherapy in acute myeloid leukemia (AML) patients and to assess the potential for use of biochemical markers in early diagnostics of cardiotoxicity. Fifteen consecutive adult patients with a newly diagnosed AML were studied. All patients received induction chemotherapy containing Idarubicin (IDA) 3 x 12 mg/m2 and intermediate doses of Cytarabine (8 x 1.5 g/m2). Serial measurements of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) values were performed at the baseline, the day following each IDA infusion, after 14 days and after circa 1 month, i.e. before the next chemotherapy. Cardio-specific markers (cTnT, CK-MB mass) were measured at the baseline and after the last IDA infusion. The mean baseline value of NT-proBNP in newly diagnosed AML patients was 129.7+/-59.6 pg/ml. The mean NT-proBNP value increased after the first IDA infusion to 307.3+/-171.4 pg/ml (p=0.02). In most of the patients, the second and the third IDA infusions were not associated with a further increase in the NT-proBNP value and levels after 2 and 4 weeks were not significantly different from the baseline. However, in one of the patients the NT-proBNP values were increasing after each IDA infusion (after the last one 786.2 pg/ml) and within 14 days he developed congestive heart failure due to left ventricular diastolic dysfunction as assessed by echocardiography. At that time, the NT-proBNP value was 1,184.0 pg/ml; after diuretics it decreased significantly. In all patients, plasma cTnT and CK-MB mass concentrations were within the reference interval at the baseline and after the induction chemotherapy. Our results suggest that induction chemotherapy in AML (IDA 36 mg/m2 and intermediate doses of Cytarabine): 1. does not cause detectable damage of the myocyte structure, 2. is in all patients associated with acute neurohumoral activation (transient elevation of NT-proBNP) indicating acute subclinical cardiotoxicity, 3. may lead to congestive heart failure and NT-proBNP seems to be a promising early marker and predictor of this complication.

Acute Disease↗

Potential risk of infection transmission during storage and transplantation of hematological progenitor cells. Safety assurance.

In a group of 71 patients and 22 donors the danger of infection transmission by infusion of cryopreserved peripheral blood progenitor cells to the patient and/or cross contamination of stored grafts was evaluated. No laboratory signs of active infection were found in 15 donors (13 related, 2 unrelated; 68%) and in 55 patients (77%). Active infection by herpesviruses was the most common (in 13 patients and 7 donors), hepatitis B being found in only one case. The cytomegalovirus IgG test was the most common marker of previous infection; it was found in 14 donors and 55 patients. The rate of clinically unsuspected infections in donors and patients including cases requiring immediate treatment among the patients group is relatively high and fully justifies the practice of prophylactic serological testing in the whole range of tests according to the European Blood and Marrow Transplantation Group and International Society for Hematotherapy and Graft Engineering in both autologous and allogeneic transplantations of hematopoietic stem cells.

Bone Marrow Transplantation↗

Antiapoptotic cytokine IL-3 + SCF + FLT3L influence on proliferation of gamma-irradiated AC133+/CD34+ progenitor cells.

Recovery from radiation-induced bone marrow aplasia depends on appropriate cytokine support. The aim of our work was to find a cytokine combination allowing in vitro gamma-irradiated (2.5 Gy) CD34+/AC133+ haematopoietic stem cells to evade radiation-induced apoptosis and to enhance damage reparation, which should enable proliferation and ex vivo expansion of cells. Cells were isolated using separation in a Cobe separator followed by immunomagnetic selection by antibody against the AC133 antigen. Thus isolated cells were 80% AC133+/CD34+ and 10% of them expressed the CD33+ antigen. Ten thousand of AC133+ cells formed 1146 CFU-GM and 304 BFU-E. We proved a high expansion efficiency of cytokine combination SCF + IL-3 + FLT3L in comparison with the combination SCF + IL-3 + IL-11 in both, non-irradiated cells and cells irradiated with a dose of 2.5 Gy. The D0 value for AC133+ cells was determined by the clonogeneity test. The D0 value for CFU-GM was estimated to be 1.08 Gy and for BFU-E 0.95 Gy. The results of DNA analysis showed that the majority of isolated AC133+ cells were in G0/G1 phase of the cell cycle. We proved that the dose of 2.5 Gy induced massive apoptosis (80%) of these cells without progression through the cell cycle, which indicates interphase cell death. Under the influence of cytokine combination (SCF + IL-3 + FLT3L), the surviving 20% of cells entered the cell cycle and, similarly to non-irradiated control cells, on 7th day 35% of cells were in S phase.

Apoptosis↗

[Comparison of the effectiveness of idarubicin (Zavedos) and mitoxantrone (Refador) in induction therapy of acute myeloid leukemia in elderly patients (55-75) (a prospective multicenter randomized study conducted 1998-2000].

The presented study compares the efficacy and the toxicity of idarubicine and mitoxantrone in combination with cytosar (3 + 7) in induction treatment of the patients with AML aged 55-75. 31 patients at the age of 55-75 (median 62) were evaluated in the arm with idarubicine and 29 patients at the age of 57-74 (median 64) in the arm with mithoxantrone. Complete haematological remission was achieved in 13 patients (41.9%) in the arm with idarubicine and 15 patients (51.7%) in the arm with mitoxantrone. The medians of overall survival time (OS) and disease free survival time (DFS) were 22 and 44 weeks in the idarubicine arm and 35 and 40 weeks in the mitoxantrone arm, respectively. Statistical analysis did not prove any significant difference in the complete remission rates, in the number of deaths during cytopenia, in the OS or DFS, in the duration of hospitalisation, severe neutropenia and thrombopenia, in the number of days with febrile neutropenia, or in the consumption of platelets and erythrocytes transfusion units between both arms. Despite the fact that these results are not statistically significant in favour of any treatment arm, which is probably influenced also by the small number of evaluated patients, more favourable results were achieved in the arm with mithoxantrone with the respect to the evaluated parameters. From the point of view of cost-effectiveness, the difference could be observed when considering the price of both intercalating cytostatics. The use of mitoxantrone (Refador, Lachema) is 15x times cheaper per course of treatment than the use of idarubicine (Zavedos, Pharmacia). Autologous peripheral blood stem cells transplantation (APBSC) was carried out only in 4 patients younger than 60. No one of them was cured by APBSC but the median of OS of these patients was longer than the median in the other patients of the group. The results achieved are comparable with those of other trials conducted by various foreign groups. The possible causes of our unfavourable treatment results in this high-risk category of aged patients and the ways how to individualize the treatment with the use of prognostic factors analysis and how to improve the quality of life of the patients has been discussed.

Acute Disease↗

[The treatment of multiple myeloma with an allogeneic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen].

Between November 1998 and October 1999 authors treated five multiple myeloma patients with an allogeneic peripheral blood stem cell transplantation from HLA-identical sibling using a non-myeloablative conditioning regimen. The median age at the time of transplantation was 58 (range: 47-65) years. In all patients one (n = 3) or two (n = 2) autologous peripheral blood stem cell transplantations were already performed. Conditioning was performed with fludarabine, oral busulfan and anti-T-lymphocyte globulin. All patients engrafted from 13 to 18 (median: 17) days from transplantation. The duration of neutropenia (absolute neutrophiles count < 500/microl) and thrombocytopenia (platelets < 20,000/microl) ranged between 4 and 19 (median: 18) and between 13 and 18 (median: 17) days, respectively. In the period of posttransplant pancytopenia two patients developed mild gastrointestinal mucositis and two pulmonary complications (bronchopneumonia and dyspnoe of unknown etiology). Two patients had grade III-IV acute graft-versus-host disease (GvHD), none had extensive chronic GvHD. Two patients received prophylactic donor-lymphocytes infusions 200 and 225 days from transplantation. One of them developed grade III acute GvHD. All patients responded. One achieved complete and four partial remission of the disease. One patient died 111 days from transplantation due to bronchopneumonia, four are alive and well, in the stable disease, 35, 36, 51 and 52 weeks after transplantation. It can be concluded that allogenic peripheral blood stem cell transplantation using a non-myeloablative conditioning regimen is an effective way of the multiple myeloma treatment with an acceptable toxicity.

Aged↗

Ex vivo expansion CD34+/AC133+-selected autologous peripheral blood progenitor cells (PBPC) in high-risk breast cancer patients receiving intensive chemotherapy.

AC133 antibody provides an alternative to CD34 for the selection and characterization of cells necessary for engraftment in transplant situations. We studied the effect of stem cell factor (SCF), interleukin 3 (IL-3) and interleukin 11 (IL-11) on the ex vivo expansion of human CD34+/AC133+ progenitors isolated from leukapheresis products from chemotherapy plus granulocyte-colony-stimulating factor (G-CSF) -mobilized adult donors. MiniMACS AC133+ isolated cells contained a mean of 85% (80-90) AC133+ cells. Enriched AC133+ cells co-expressed CD34+ 80%, CD71low 36.6% and CD33+ 6.6%. After a seven-day ex vivo expansion in the presence of SCF + IL-3 + IL-11, the number of cells increased 19 times. These cells expressed a mean 12% CD34+ and 74% CD71+ (23% CD 71high) and 59% CD33+. This means that the absolute number of CD34+ cells increased slightly, the number of CD33+ increased 100 times and cells with high density CD71high (23%) appeared. These cells represent the cells committed to erythroid differentiation. The increase in the number of CFU-GM with various combinations of cytokines SCF + Il-3 + IL-11 will be discussed. The number of CFU-GM in culture after a seven-day ex vivo expansion in the presence of SCF + IL-3 + IL-11 increased 45 times.

AC133 Antigen↗

[Antithrombin III in various conditions in internal medicine].

In a group of 993 patients with serious medical diseases an important deficiency of antithrombin III was found in patients with hepatic insufficiency, pulmonary embolism and with disseminated intravascular coagulation. Acquired antithrombin III deficiency in these conditions develops when the antithrombin production in the liver is low and also in patients with shock syndrome and disseminated intravascular coagulation. Assessment of antithrombin III is of diagnostic and prognostic value in thrombotic and prethrombotic conditions and its results is decisive for adequate substitution. Adequate AT III substitution without concurrent heparin administration in patients with septicaemia and manifestations of DIC improves the prognosis of patients with an increased endothelial resistance.

Antithrombin III Deficiency↗

Biological skin covers in treatment of two cases of the Lyell's syndrome.

The treatment of two cases of toxic epidermal necrolysis (Lyell's syndrome) is described. Although some features were common for both ones (young men practically of the same age, reaction after using the same drug) the clinical course of illness was very different. Spontaneous epithelisation of partial-thickness lesions and definitive healing under the xenografts in one patient and full-thickness skin-loss on 12% of body surface with severe septic complications requiring application of cultured keratinocytes and/or skin autografting in the other patient were the main differences. The interdisciplinary approach using a burns treatment protocol in non-burned patient including the close co-operation with the tissue bank in preparing different types of biological covers has been applied.

Adolescent↗

[Changes in platelet activity in invasive cardiologic procedures].

The authors revealed some changes in the platelet activity in patients with invasive cardiological procedures. Changes of the platelet function were manifested by an enhanced aggregation of platelets in vivo, an increased secretion from alpha granules and increased release of prostaglandin metabolites from platelets and from the vascular wall. Acetylsalicylic acid (ASA) suppressed the formation of circulating platelet aggregates in vivo, but the platelet activity was manifested by another mechanism, independent on ASA. The authors recorded therefore an increase of prostaglandin metabolites and PF4 even in patients who were treated with ASA before the invasive examination.

Angioplasty, Balloon, Coronary↗

[Changes in platelet function in patients with arterial hypertension].

The authors examined some indicators of platelet activity in patients with hypertension stage II (according to WHO). They revealed an increased platelet activity which was manifested by an increased concentration of platelet factor 4 (50.2 +/- 28.2 ng/ml) and thromboxane B2 (49.9 +/- 20.1 pg/ml) in plasma. The increase of indicators of platelet activation associated with hypertension is a molecular marker of activation of haemostasis and according to data in the literature it is an indicator of vascular complications in hypertension. It is not clear whether the increased platelet functions in hypertension is primary or an induced change.

Adult↗

[Bleeding time in incisions in patients with thrombocyte transfusion].

The authors used the Simplate test (Organon Teknika) to examine the bleeding time from an incision in 15 healthy blood donors and found normal values of 3.45 +/- 0.90 min. The authors proved a close correlation between the improvement of the number of platelets in 10 patients with thrombocytopenia, treated with thrombocyte infusions and the improvement of the bleeding time when using the Simplate R test after one hour and after 24 hours following thrombocyte administration. Examination of the bleeding time by means of the Simplate R test (Organon Teknika) was well tolerated by the authors' patients and the test does not produce any side-effects.

Adult↗

Migraine--a haematological disorder?

We analysed 22 patients suffering from migraine to evaluate the possible activation of platelet function utilizing the following methods: platelet factor 4, thromboxane B2 and 6 - keto prostaglandin F 1 alpha levels in platelet poor plasma. Laboratory tests were performed on all patients during headache-free period and the results obtained were compared with those of a normal healthy individuals. The mean results obtained in the patients group during pain-free period indicated a significant activation of platelet function when compared with the normal group.

6-Ketoprostaglandin F1 alpha↗

[Diagnosis and therapy of disseminated intravascular coagulation].

The syndrome of disseminated intravascular coagulation (DIC) is an acquired coagulation disorder which is characterized by a significant activation of haemostasis and the formation of intravascular microthrombi, the consumption of coagulation factors and activation of fibrinolysis. DIC has similar clinical stages and a similar laboratory picture, regardless of the causal factor. The diagnosis of DIC should be based on anamnestic, clinical and laboratory data. The laboratory diagnosis of DIC is possible by using relatively simple tests, which have the character of statim examinations. DIC treatment is based on the principle of treatment of the cause, discontinued consumption of haemostatic material, substitution of lacking factors and restoration of the microcirculation. The possible development of DIC must be taken into account in a number of acute conditions, in particular the development of shock syndrome. The presented article summarizes some views on causes, diagnosis and possible treatment of DIC.

Disseminated Intravascular Coagulation↗

[Treatment of the leukostasis syndrome in chronic lymphadenosis using leukapheresis].

The authors draw attention to the leukostasis syndrome which develops in haematological patients in case of enormous leucocyte proliferation. It occurs most frequently in chronic myelosis but may occur also in other types of leukaemia. The diagnosis is not easy. Most frequently disorders of the microcirculation develop in the lungs and brain. These are frequently very urgent clinical situations which can be resolved by leukapheresis. The authors described a patient where during chronic lymphadenosis proliferation of lymphocytes occurred to values of 1432 x 10(9)/l. After leukapheresis and cytostatic treatment rapid improvement of the condition occurred and the leucocyte values were approximately 30 x 10(9)/l. The patient's condition improved for a long period of time and became stabilized.

Humans↗

[Preparation of thrombocyte concentrates in the Travenol CS-3000 separator (factors affecting the thrombocyte yield and presence of leukocytes)].

The authors made 184 thrombocytaphereses for the preparation of thrombocyte concentrates on a Travenol CS-3000 separator. They evaluate indicators on which the thrombocyte yield depends: it was found that the yield is higher in donors with a higher number of platelets and that it increases with the period of separation. The mean thrombocyte yield was 2.91 +/- 0.84 x 10(11). It corresponded to the average lower platelet number of donors--182 x 10(9)/L. In those donors where the number of platelets was higher than 180 x 10(9)/L, the yield was 3.21 x 10(9)/L. The undesirable presence of leucocytes (in 98% lymphocytes) increases in relation to the number of leucocytes in the donor and their decline after separation. It was lower in longer separations. The authors discuss the possibility to increase the thrombocyte yield without contamination with leucocytes.

Adolescent↗

Changes in the activity of thrombocytes by smoking.

Platelet function was investigated in 11 healthy non-smokers, 11 medium smokers (less than 10 cigarette/day) and 11 heavy smokers (greater than 20 cigarette daily). Cigarette consumption was in medium smokers 6.2 cigarette/day, and in heavy smokers 30.7 cigarette/day. Erythrocyte count, platelet count, plasma levels of cholesterol and triglycerides, and circulating platelet aggregates showed no significant difference between smokers and non-smokers. Thromboxane B2 level in plasma was higher in heavy smokers (20.1 +/- 17.3 pg/0.1 ml) than in non-smokers (58.8 +/- 37.1 pg/0.1 ml) and medium smokers (65.4 +/- 32.1 pg/0.1 ml) (P less than 0.01). Platelet factor 4 level was high in non smokers prior to smoking 1 cigarette and normal in medium and heavy smokers. Plasma concentration of beta thromboglobulin and 6-ketoprostaglandin F1 alpha showed no significant changes between non-smokers and heavy smokers. No dependence on smoking 1 cigarette was found in any group. The data suggest that long term cigarette smoking increases platelet activity manifested by an increased activity of thromboxane A2. Cigarette smoking contributes to the development of coronary artery disease also by means of activation of platelet functions.

Adult↗

[Use of the isoradial chamber in the preparation of thrombocyte concentrates using the Travenol CS-3000 separator].

During intensive treatment of haemoblastoses it is important to administer repeatedly high-quality platelet concentrates. The authors describe the first results obtained with the use of an isoradial chamber of Travenol Co. for separation on a CS-3000 separator. Using the chamber, they achieved in the first 20 patients a reduction of the separation time by 30 mins. (23%) and the thrombocyte yield was not reduced. The resulting product contained, however, more leucocytes. The chamber can be used to reduce the separation period also under Czechoslovak conditions where donors have smaller numbers of thrombocytes than reported by western authors (the microcomputer of the separator is set for a regime suited for larger thrombocyte numbers).

Blood Component Removal↗