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Biomedical subjects

M Penka

Publications and source records attributed to M Penka.

At least 19 recordsLinked to original sources
PubMed2006

Isolation and expansion of allogeneic myeloma-specific interferon-gamma producing T cells for adoptive immunotherapy.

Adoptive immunotherapy is a promising approach in the treatment of multiple myeloma. We have tested the identification, separation, and expansion of allogeneic myeloma-specific T cells in vitro. Irradiated myeloma cell line ARH 77 has been used to stimulate allogeneic CD4(+) and CD8(+) T lymphocytes. Activated myeloma-specific T cells that produced interferon-gamma were isolated using immunomagnetic beads and further expanded in vitro to numbers of up to 400 x 106 T cells. Specificity of the T lymphocytes was tested using a 5-(6-)carboxyfluoresceine diacetate succinimidyl ester (CFSE)-based cytotoxicity test. This study demonstrates the feasibility of identification and isolation of tumor-specific T cells from allogeneic donors that can be expanded in vitro to numbers useful for clinical applications.

CD4-Positive T-Lymphocytes↗
PubMed2006

[Prevention of venous thromboembolism: generally accepted guidelines].

This article summarizes the published data on the prevention of venous thromboembolism. Routine thromboprophylaxis is the best way to lower the risk. It is recommended to sort patients according the thrombosis risk and to make use of the standard prophylactic modes. In low risk patients, no specific thromboprophylaxis is needed. Patients with moderate risk levels are candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression. At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people after major orthopaedic surgeries and with a history of heparin induced thrombocytopenia over the past three months. An alternative to the administration of LMWH even after the end of the hospitalization can be warfarin in certain situations. The sole use of acetylsalicylic acid or Rheodextran is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis.

Anticoagulants↗
PubMed2006

[The preparation of a patient with long-term anticoagulant cumarin treatment for invasive surgery].

Coumarins belong to drugs widely used and the spectrum of their use is going to grow. From this point of view and/or because the coumarins are adminstrated in patients who are treated for the other diseases--medical or surgical--at the same time, it is necessary to modify, interrupt or replace peroral anticoagulant treatment in the dependence on various aspects. It requires to compound different algorithms for given situations solution. It is always to decide, if the situation is imperative from the view of solution planed, what risk brings proposed treatment and what is the risk of anticoagulant treatment modification.

Anticoagulants↗
PubMed2006

[Prevention of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology].

The article summarizes published data regarding the prophylaxis of venous thromboembolism in surgery, in laparoscopic surgery, in venous surgery and in urology. In surgical patients with low risk, no specific thromboprophylaxis is needed. Patients with moderate risk levels are the candidates for administration of subcutaneous low molecular weight heparin (LMWH) at doses under 3 400 anti-Xa units a day and patients with increased risk at doses higher than 3 400 anti-Xa units a day during the period of higher risk. In order to decrease the risk of bleeding, a half dose 2 hours prior or 4-6 hours after the operation can be administered. Under the highest risk conditions, there is a recommendation to combine LMWH over 3 400 anti-Xa units with elastic panty-hose or, alternatively, with intermittent pneumatic compression (IPC). At moderate risk levels, subcutaneous administration of unfractionated heparin at the doses of 5 000 units twice a day is also possible and at increased risk levels, a TID administration (LDUH) over the increased risk period. In patients with a significant bleeding risk, the physical method of thromboprophylaxis can be used and pharmacological prophylaxis can set in after the risk of bleeding has passed. Fondaparinux is the alternative to LMWH in people with a history of heparin induced thrombocytopenia over the past three months. The sole use of acetylsalycilic acid is not recommended. While undertaking epidural anaesthesia or analgesia, it is necessary to follow strictly the guidelines of the use of pharmacological thromboprophylaxis. Thromboprophylaxis with LMWH, LDUH, elastic panty-hose or IPC is indicated only in those patients who undergo laparoscopic surgeries and who moreover display the additional thrombosis factors. Patients with additional risk thrombosis factors undergoing major venous reconstructions require prophylaxis with LMWH (or LDUH). Uncomplicated patients undergoing transurethral or other low risk urologic surgery require no specific thromboprophylaxis. If they undergo a major intervention and/or they display additional risk thrombosis factors, they require the administration of LMWH or LDUH. Elastic panty-hose and/or intermittent pneumatic compression have the same indication as in abdominal surgeries.

Anticoagulants↗
PubMed2006

[Antithrombotic prophylaxis and treatment in thrombophilic disorders in gynaecology and obstetrics].

Pregnancy and puerperium are physiological thrombophilic condition and risk of venous thromboembolism in pregnancy is 4 - 6 fold higher. This risk is further increased in the presence of the additional risk factors. Inherited thrombophilia is well-defined risk factor for VTE in pregnancy and also can be the risk for obstetrics complications. So that early diagnostic of inherited thrombophilia can result in the decrease of risk of VTE and the obstetrics complications.

Anticoagulants↗
PubMed2006

[Prevention of venous thromboembolism in internal medicine and neurology].

Many hospitalized patients are under an increased risk of venous thromboembolism. They should have adequate pharmacological prophylaxis. Clinical studies including meta-analyses prove that low molecular weight heparin prophylaxis of venous thromboembolisms is equally effective as that employing unfractionated heparin and it features less bleeding complications. The effectiveness of pharmacological prophylaxis with low molecular weight heparin in hospitalized patients at internal medicine departments has been proven by the MEDENOX study when enoxaparin in a dose of 40 mg was administered subcutaneously and the PREVENT study when subcutaneous dalteparin 5 000 units j. was administered daily. In the MEDENOX study, enoxaparin administration was confirmed to decrease the relative risk of venous thromboembolisms by 63% without increasing any adverse effects during the prophylaxis and the PREVENT study showed that dalteparin administration was followed by a highly significant reduction of asymptomatic venous thromboses in hospitalized patients. According the ACCP guideline for thromboprophylaxis in hospitalized internal medicine patients with clinical risk factor of venous thromboembolism (tumors, heart failures, sepsis, VTE history and serious pulmonary condition), low molecular weight heparin or mini-doses of unfractionated heparin are to be administered. The recent recommendations discourage the use of acetyl-salicylic acid in monotherapy treatment for venous thromboembolism prevention.

Anticoagulants↗
PubMed2006

[Hemorrhagic complications during warfarin treatment].

Bleeding is probably the major complication of anticoagulant treatment with vitamin K antagonists represented nowadays mostly by warfarin in the Czech Republic. The main risk factors in hemorrhagic complications of warfarinisation are the intensity and instability of the anticoagulant treatment, individual patient characteristics, warfarin interactions with other drugs and the length of the anticoagulant therapy. Severe bleeding in warfarin patients is most effectively brought about by a fast and complete undoing of the anticoagulation effect of the drug employing the prothrombin complex concentrate and slow i.v. vitamin K1 infusion regardless of the reason for the anticoagulation. This approach can secure the minimalisation of the bleeding's negative consequences. A less severe bleeding or asymptomatic increase in the international normalized ratio can be treated effectively by skipping or decreasing of the warfarin dosage and/or oral administration of vitamin K1 (i.v. administration only in selected higher risk cases) that does result only in a partial consolidation of coagulopathy but of such type that the risk of thrombotic event requires. The article's goal is to contribute to the treatment standardization in patients with warfarin overdose and/or with hemorrhagic complications due to warfarin treatment and it is available at www.thrombosis.cz. The guidelines include a ready-reference chart whose objective is immediate and quick crash course in the clinical practice.

Anticoagulants↗
PubMed2006

[Anticoagulant treatment failure].

Anticoagulant therapy includes unfractionated heparin and vitamin K antagonists' administration. In both of these two types of drugs a treatment failure could occur. Currently available anticoagulants have a numerous disadvantages which could be involved in causes of their malfunctioning. During every new event of the re-thrombosis it is necessary to analyse all circumstances which influence this unfavourable outcome. Firstly, cases during adequate and non-adequate therapy should be distinguished. Secondly, it is important to identify the reasons of the treatment failure. Cancer and/or antiphospholipid antibodies are the main causes of re-thrombosis during adequate therapy. The conditions, which could steer for to non-adequate anticoagulation are various, and their identification could be difficult. The most important thing in this process is the objective documentation of the re-thrombosis. More efficacious, safer, and easier to use anticoagulants are under development. Some of them could bring a problem solution for these patients who underwent anticoagulant treatment failure.

Anticoagulants↗
PubMed2006

[Anagrelide in the treatment of essential thrombocythemia (ET) and other myeloproliferative disorders with thrombocythemia based on data from patient register in the CR].

Anagrelide hydrochloride is an effective drug used in patients with ET and other myeloproliferative disorders with thrombocythemia to selectively decrease the number of thrombocytes. Indications for use of anagrelide were described in detail in Czech medical literature. Since 2005 data concerning treatment with anagrelide in some medical clinics have been collected in patient register showing course of treatment from 2004, when the medicament obtained marketing authorization from State Institute for Drug Control to be used in the treatment of thrombocythemia in myeloproliferative disorders. Aim of patient register is to monitor medical effect of anagrelide therapy and incidence of adverse effects in patients with ET and other myeloproliferative disorders and subsequent analysis of collected data. At the moment patient register contains data from 154 patients.

Humans↗
PubMed2005

[Comparison of standard prognostic factors with the deletion of 13q14 detected by interphase fluorescence in situ hybridization on separated and unseparated bone marrow cells in multiple myeloma].

BACKGROUND: Cytogenetic abnormalities of chromosome 13 are emerging as important prognostic factors in multiple myeloma and have been associated with poor prognosis. METHODS AND RESULTS: The occurrence of 13q14 deletion and other standard laboratory parameters were determined in 40 patients with multiple myeloma. We found that interphase fluorescence in situ hybridization using a locus specific probe for RB1 gene on immunomagnetically selected myeloma cells was more sensitive than non selected cells. The 13q14 deletion was found in 10 of 40 (25.0%) of bone marrow samples without cell selection and in 25 of 40 (62.5%) of samples with CD138+ enriched myeloma cells. Negative correlation was found between albumin and the 13q14 deletion in separated (p = 0.003) as well as in cells without selection (p = 0.010). No significant correlation was found in overall survival of separated and unseparated cells (p = 0.830; p = 0.260) and a similar result was obtained for treatment response after transplantation of separated cells (p = 0.520) or non-separated cells (0.190). CONCLUSIONS: Our results confirm that immunomagnetic selection of CD138+ cells increases the probability of detection of the 13q14 deletion in bone marrow samples. The correlation was found between albumin and the 13q14 deletion in both of type of cells.

Bone Marrow Cells↗
PubMed2004

[Successful treatment of chronic hepatitis C in hemophiliacs based on historical development of therapeutic protocols].

Chronic infection with hepatitis C virus is very frequent among hemophilic patients in all developed counties, including the Czech Republic. Because of a possibility of developing serious terminal stages of infection, liver cirrhosis and hepatocellular carcinoma, the tendency in treatment of patients with chronic hepatitis C is to start it as soon as possible and thus reduce the probability of developing these advanced stages of disease which are difficult to treat. Treatment of hemophilic patients with chronic hepatitis C started in the Department of Infectious Diseases, University Hospital Brno Bohunice, in 1996. Used treatment schemes have reflected historical evolution of treatments used to treat chronic hepatitis C. Initially, alpha-interferon (IFN) was administered in monotheraphy (6 patients), later, since 1999, a combination of alpha-IFN and ribavirin was administered (13 patients), and since 2001 a combination of pegylated interferon (PEG-IFN) and ribavirin (3 patients) was administered. In all the patients the individual treatments took 12 month. Sustained negativization of HCV RNA in serum has not been achieved in any patient treated only with alpha-IFN. In patients who were administered the combination of alpha-IFN and ribavirin this effect appeared in 4 from 7 cases without history of treatment with alpha-IFN (57%), one from 2 relapses and one from 3 non-responders. The combination PEG-IFN and ribavirin was effective in the only one patient who relapsed after alpha-IFN and ribavirin and in one from the two non-responders to this combination. The tolerance and safety of treatment was good in haemophilia patients and could be fully compared to those in other patients with chronic hepatitis C.

Antiviral Agents↗
PubMed2004

Treatment of chronic hepatitis C in hemophilic patients.

Chronic hepatitis C infection is common among hemophiliacs in all the developed countries. Since 1996, only alpha-interferon (alpha-IFN) in monotherapy has been used for the treatment of chronic hepatitis C in hemophiliacs (6 patients). In Czech Republic a combination therapy with alpha-IFN and ribavirin has been used since 1999 (13 patients). Finally, a combination therapy with pegylated alpha-IFN (PEG-alpha-IFN) and ribavirin is being used since 2001 (still 3 patients). In all cases, the treatment lasted 48 weeks. A sustained virological response (SVR, defined as an undetectable serum HCV RNA level 24 weeks after the treatment was completed) was not achieved in any of 6 patients treated with alpha-IFN alone. A combination therapy with alpha-IFN and ribavirin yielded better results: four of eight patients still untreated with alpha-IFN (naive patients), one of two relapsers, and one of three non-responders to previous alpha-IFN monotherapy achieved SVR. So far the combination therapy with PEG-alpha-IFN and ribavirin has been used only in 3 patients. SVR was achieved in one patient who had relapsed after the combination therapy with IFN-alpha and ribavirin, and in 1 of 2 non-responders to this therapy. We conclude that the efficacy and tolerability of the treatment of chronic hepatitis C in hemophiliacs did not differ from that of chronic hepatitis C in other patients.

Antiviral Agents↗
PubMed2003

[Specific features of hematopoiesis and hemostasis in advanced age].

The ageing process affects also haematopoiesis and haemostasis and these changes can have a far reaching effect on other organ systems and their function. The authors decided therefore to present a review on involutional changes on the formation and function of blood elements and the system of blood clotting. The review is divided into description of changes in the bone marrow and explanation of hitherto known facts on the pathophysiological background of these changes. Furthermore the authors deal with changes in the peripheral blood stream and their mutual relations with administered drugs, diseases under way, reactions to external stimuli such as immunization etc. In the second part of the review the authors describe changes of haemocoagulation, emphasize the tendency of hypercoagulation and the mutual relationship of the development of atherosclerotic changes and hypercoagulation trends and their pathophysiological background. Attention is paid to thromboembolic disease and its increasing risk in elderly patients incl. the possible late manifestation of congenital defects of coagulation inhibitors. The authors mention also the influence of lifestyle and dietary factors on the coagulation activity in old age. They analyze in detail possibilities and pitfalls of prophylaxis of thromboembolic disease in elderly patients and the risks of haemorrhagic complications of different operations.

Aged↗
PubMed2003

Low antigen-dependent activity of T cells after repeated stimulation using dendritic cells and expansion with interleukin-2.

Both CD8+ and CD4+ T cells with specific activity against tumor antigens are needed for an efficient antitumor immune response. Activation and proliferation of T cells require cellular interactions including adhesion, recognition of peptides presented by MHC molecules to the T cells receptor, and costimulation. In a series of experiments we attempted to generate and expand specific T cells by repeated stimulation using antigen-loaded autologous dendritic cells (DCs). DCs were obtained from peripheral blood mononuclear cells (PBMC) in the presence of IL-4 and GM-CSF. TNF-a was added to induce maturation. A conjugate of myeloma idiotypic protein with keyhole limpet hemocyanin was used as antigen. Nonadherent peripheral blood mononuclear cells were cultured in the presence of Il-2 and IL-7. Autologous DCs were added to the lymphocyte cultures on days 3, 10, and 17. The lymphocytes were stimulated by high concentration of IL-2 between days 21 and 27. Lymphocytes harvested on day 27 proliferated in response to antigen-loaded DC but failed to do so if less than 0.3 x 10(6) DCs were added for stimulation during culture. However, no cytotoxic activity against autologous DCs was detected and IFN-g production in the T cell cultures was low at the end of culture. In conclusion, the generation and expansion of T cells using repeated stimulation by autologous DCs is feasible but defective cytotoxic response of these cells occurs, possibly as a consequence of repeated frequent exposure to antigen.

Antigens, CD↗
PubMed2002

Interleukin-2 activation of haematopoietic stem cells.

BACKGROUND: Recent findings concerning the role of immunity in the eradication of residual malignant disease after autologous haematopoietic stem cell transplantation have led to extensive studies of T-cell and natural killer (NK) mediated anti-tumour effects. Interleukin 2 (IL-2) activation of autologous bone marrow (BM) or peripheral blood stem cells (PBSC) before transplantation is one of the methods of adoptive cell therapy. METHODS: Autologous BM of patients with chronic myelogenous leukaemia (n = 11) and PBSC of patients with multiple myeloma (n = 14) were activated by IL-2 in laboratory conditions with the aim of evaluating the feasibility of this method, the activation of T and NK cells, recovery of active progenitor cells, microbial contamination, and reduction of malignant cell content. RESULTS: Samples of BM (mean 2.6 x 10(6) cells) and PBSC (mean 10.3 x 10(6) cells) were cultured in complete culture medium with IL-2 (6000 Ul/ml) for 24 h. The recovery of CD34+ cells and CFU-GM was 82.5% and 51.5%, respectively, for BM, and 85% and 86%, respectively, for PBSC (mean values). No purging effect was detected by flow cytometry and a small decline in malignant cell contamination was observed by quantitative PCR in BM samples. No microbial contamination occurred during the sample processing. CONCLUSIONS: The described in vitro activation of BM and peripheral blood stem cells using IL-2 was evaluated as a safe and reliable method suitable for clinical application.

Bone Marrow↗
PubMed2002

Detection of 13q abnormalities in multiple myeloma using immunomagnetically selected plasma cells.

Accurate prognostic evaluation of patients with multiple myeloma (MM) is required for their stratification for more adequate therapy. Chromosomal G-banding and interphase fluorescence in situ hybridization (FISH) on cell-nonspecific samples and on myeloma cells selected by magnetic-activated cell separation (MACS) were used to study 13 samples from 12 multiple myeloma (MM) patients. Bone marrow (BM) samples were analysed using three approaches. Standard mitotic samples were prepared and analysed after G-banding. Interphase FISH was performed to detect the 13q14 deletion in unselected BM cells. In parallel, myeloma cells were selected from the BM using the CD138-specific antibody. The high-purity myeloma cell suspension was then analysed by interphase FISH for the 13q14 deletion. Magnetic separation yielded enriched myeloma cell suspensions with the mean viability of 98.0% (range: 97.0%-99.0%), and the purity of 97.6% (range: 87.2%-99.2%) as detected morphologically, and 85.2% (range: 44.8%-98.4%) as detected by immunophenotyping for CD138+ cells. Interphase FISH revealed the 13q14.3 deletion in 5 of 13 (38.5%) of cell-nonspecific samples and in 9 of 13 (69.2%) of enriched myeloma cell suspensions. In conclusion, interphase FISH on immunomagnetically selected MM cells increases the detection of the 13q14 deletion in BM samples from the patients with MM.

Cells, Cultured↗
PubMed2001

[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↗