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Biomedical subjects

M Mistrík

Publications and source records attributed to M Mistrík.

At least 19 recordsLinked to original sources

[Transfusion-induced immunomodulation and infectious complications].

Transfusions are not without risk. One of the side effects of transfusions is the development of transfusion-induced immunomodulation (TRIM)--primarily immunosuppression, but also a strong proinflammatory effect. This may be the cause of acute lung injury (TRALI), multiorgan failure (MOF), transfusion related acute-graft-versus-host-disease (TR AGvHD), as well as of the development of secondary nosocomial infections, mostly pulmonary infections, sepsis and wound infections, and also of elevated number of tumour relapses in oncological patients. The causes of TRIM development are the induction of microchimerism, different cells and also soluble factors--complement components, such as C3a, soluble HLA-I and HLA-II molecules (HLA--human leukocyte antigen), soluble Fas ligand (sFasL), and others. The immunosuppressive potential of blood products grows with the time of their storage and becomes highest in non-leukoreduced blood products stored for a long time. In view of possible adverse effects of a transfusion, the expected benefit should be balanced against possible risks.

Cross Infection↗

A significance of additional chromosomal aberrations and other variables on post transplantation outcome of patients with CML.

Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by the bcr/abl gene rearrangement. Allogeneic transplantation of stem cells (SCT) is a routinely used treatment method of patients with this diagnosis and remains the only curative mode of treatment. From January 1990 to December 2002, 78 patients with CML underwent allogeneic transplantation and were examined at the Department of Genetics in the National Cancer Institute in Bratislava. Using conventional cytogenetic and FISH 6 patients (7.7%) showed additional chromosomal changes before SCT. These patients had statistically worse post transplantation prognosis compared to the patients without additional changes before SCT (mean survival in month+/-standard error (58.08 (+/-6.70) vs. 5.17 (+/-0.98), p-value=0.001), patient mortality (67% vs. 31%)). In addition five other variables were evaluated for transplant outcome, namely, patient's age at the time of transplantation, sibling or non-sibling donor, higher than 1st chronic phase CML, time from diagnosis to transplantation and sex of donor and recipient. Only the comparison of HLA-identical sibling transplantation to unrelated donor transplantation was statistically significant (mean survival in month- 56.6 (+/-7.2) vs. 13 (+/-0.0), patient mortality 31% vs. 67%).

Adult↗

[Richter's syndrome (bimorphologic malignant lymphoma)].

Two distinct morphological types of malignant lymphoma in the same patient occur mostly due to transformation of a low grade lymphoma (CLL) into a large--cell non-Hodgkin lymphoma (high-grade lymphoma). Later reports have brough evidence of a clonal relationship between CLL and supervening NHL. The Richter's syndrome was found to be more frequent in patients with CLL displaying either multiple chromosomal aberrations or monoclonal gammapaties. In the last two decades reports have evidenced the existence of two types of the Richter's syndrome: one, the "classical" as a terminal event in a long evolving CLL, the other "variant" as the first clinical manifestation of a previously unrecognized subclinical CLL. Aggressive chemotherapy of CLL play a role in transformation of CLL to Richter's syndrome.

Cell Transformation, Neoplastic↗

[Bone changes in multiple myeloma--current etiopathogenic, diagnostic and therapeutic aspects].

Myelomatous bone disease affects about 90% patients with multiple myeloma and solitary myeloma as well. In initial stage it is manifested as osteopenia with osteoporosis or osteolytic foci, pathologic fractures followed by neurologic complications. Ethiopathogenitically a role is played by cytokine interactions with local chemokines produced by myeloma cells and activated stromal and hemopoietic cells (osteoblasts, monocytes, macrophages) resp. From the TNF-alpha family glycoprotein complexes are liberated (RANK-L), which support activation and proliferation or are inhibitory (osteoprotegerins). Similarly in the family TGF-beta several izotypes of antiinflammatory cytokines are known (the most important is TGF-beta 1 and the morphogenetic protein-2), which have a fibrotizing effect in bones, because the produced osteoid is insufficiently mineralized. The effect is a pathologic remodelation of the skeleton. In the diagnosis of multiple myeloma the immunological knowledge is used in the initial diagnosis (immunophenotypization, follow up of TNF-alpha, TGF-beta 1, IL-1, IL-6 etc). Important are also biochemistry values of increased osteoresorption (changes of calcium, parathormone, excretion of collagen fission products, osteocalcin, the bone alkaline phosphatase). In the following part the authors inform about favourable results of long-term treatment with bisphosphonates (Bonefos, Ibandronate) in combination with anti-tumor chemotherapy in 364 patients. During a 15 years observation period median survival of 94 months with a 35% probability of 10 year survival was achieved with a significant decrease of bone complications in 58% compared to 14% in the placebo group.

Bone Diseases, Metabolic↗

Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.

PURPOSE: To evaluate the impact of an additive therapy with an oral enzyme (OE) preparation given for more than 6 months additionally to standard combination chemotherapy (vincristine/melphalan/cyclophosphamide/prednisone (VMCP)- or methylprednisolone/ vincristine/CCNU/cyclophosphamide/melphalan (MOCCA)-regimen) in the primary treatment of patients with multiple myeloma stages I-III. METHODS: A cohort of 265 patients with multiple myeloma stages I-III was consecutively treated at our institution in two parallel groups (control group (n = 99): chemotherapy +/-OE for less than 6 months; OE-group (n = 166): chemotherapy + OE for more than 6 months). The median follow-up time in the stages I, II, and III for the OE-group was 61, 37, and 46.5 months, respectively; for the control group the respective values were 33, 51.5, and 31.5 months. The primary endpoint of the study was disease-specific survival. Secondary endpoints were response to therapy, duration of first response and side effects. The chosen method for evaluation was the technique of a retrolective cohort analysis with a concurrent control group. Survival analysis was performed by the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model. RESULTS: Significantly higher overall response rates and longer duration of remissions were observed in the OE-group. Primary responders showed a longer mean survival time than non-responders. Additive therapy with OE given for more than 6 months decreased the hazard of death for patients at all stages of disease by approximately 60%. Observation time was not long enough to estimate the median survival for patients at stages I and II; for stage III patients it was 47 months in the control group versus 83 months for the patients treated with OE (P = 0.0014) which means a 3-year gain of survival time. Significant prognostic factors for survival, in the Cox regression analysis, were stage of disease and therapy with OE. The OE-therapy was generally well tolerated (3.6% of patients with mild to moderate gastrointestinal symptoms). CONCLUSION: OEs represent a promising new additive therapy in multiple myeloma which will be further evaluated in a randomized phase III trial in the USA.

Administration, Oral↗

Prognostic significance of genetic markers in chronic myelogenous leukemia patients after bone marrow transplantation.

Chronic myelogenous leukemia (CML) is a malignant disease of hematopoietic stem cell with a biphasic or triphasic clinical course and most often, with a fatal outcome. Significant progress in improving outcome for patients with CML has been achieved over past years. This can be attributed to marked improvement in therapeutic protocols and increased use of bone marrow transplantation (BMT) which remains the most effective option for long-term disease control of patient with CML. The residual leukemic activity in patients after BMT remains a central clinical question. To effectively monitor minimal residual disease leukemic activity after BMT, molecular genetic techniques are currently utilized in conjunction with cytogenetic assays. Because the clinical significance of detection minimal residual disease in CML remains to be determined, we performed cytogenetic analysis and PCR amplification technique in 37 Ph+ CML patients. All patients received transplants for CML in Bratislava between years 1992 and 1999. Our results suggest that PCR positivity after transplant is of limited prognostic significance for particular individuals and can be used to identified groups of individuals at elevated risk of relapse.

Bone Marrow↗

[Autologous stem cell transplantation in a patient with juvenile chronic arthritis].

In the submitted case-history the authors describe autologous haematopoietic stem cell transplantation (ASCT) in a patient suffering from juvenile chronic arthritis (JCA). ASCT was indicated by rheumatologists and haematologists for refractory polyarticular JCA. Mobilization with cyclophosphamide and granulocyte-colony stimulating factor was effective in terms of CD34+ cell shift to peripheral blood and the good quality autograft reliably led to haematopoetic recovery after megachemotherapy. The peritransplant period was not complicated with life threatening events. Immunosuppressive effect of autotransplant has reduced signs of rheumatoid disease activity and enabled conventional drug dose reduction. Autotransplant of haematopoietic stem cells has a potential to reduce activity of juvenile chronic arthritis.

Adult↗

[Osteoporosis in multiple myeloma].

The problem of osteoporosis is world-wide in people above 50 years of age. As this period is also a risk period for the development of multiple myeloma or other malignant processes, comprehensive differential diagnosis of malignant and benign osteoporosis is essential. By retrospective analysis of a 12-year group of 270 patients treated by chemotherapy on account of multiple myeloma the authors selected a group of 151 patients treated in addition to chemotherapy and immunomodulating drugs (mixture of proteolytic enzymes-Wobe Mugos) for 2-3 years, also with biphosphonates. At the time ofdiagnosis osteoporosis was in 24.5% patients the only finding on bones. When biphosphonates (Bonefos, Ibandronate) and chemotherapy were administered during a three-year observation period the bone process was stable in 61.59%, osseous changes disappeared in 11.26% and progression of osteolysis was recorded in 27.15%. The objective of the work was to emphasize the importance of a correct diagnosis of osseous changes which can progress even in clinically asymptomatic myelomas.

Diagnosis, Differential↗

Allogeneic BMT for haematological disorders: single centre experience of University Hospital Bratislava.

Data on 65 sibling bone marrow transplantations (BMT) for various hematological disorders are reported. 51 patients had leukemia, 8 severe aplastic anemia, 4 myelodysplastic syndrome, one suffered from non-Hodgkin lymphoma and one from myeloid metaplasia. All but two patients have engrafted. Overall, 43 (66%) of 65 patients were alive 0,03-7,2 years (median not reached) as of June 23, 1997. Median time of observation was 13 months. Outcome of standard risk patients was significantly better than that of high risk patients (p=0,006). Our data confirm, that sibling BMT is an effective treatment modality with acceptable toxicity for younger patients with an early stage of serious hematological disorders.

Adolescent↗

[Fibronectin and the human spleen].

Fibronectins are glycoproteins with a function of molecular glue. The aim of the study is to encourage interest in processes in extracellular matrix of the spleen. Undigested cryostat or formol-paraffin sections and commercially available antibodies were used. We were mostly successful in extracellular localization of fibronectin in trabeculae, vessel walls and lamellae of circumferent reticulum of periarterial lymphatic sheaths and in the ring fibres of the sinuses. Changes in the amount of fibronectin occurred, for example, in circulation disturbances. In hereditary spherocytosis the ring fibres were reduced. Increase of fibronectin can suggest the development of fibrosis.

Extracellular Matrix↗

[Comparison of the effectiveness and tolerance of Aktiferrin, a ferrous sulfate capsule preparation and Tardyferon pills in patients with uncomplicated sideropenic anemia].

BACKGROUND: The most frequent complications of oral administration of medicinal iron are gastrointestinal complaints the incidence of which correlates with the iron content of the preparation. The objective of the present work was to compare the effectiveness and tolerance of two ferrous sulphate preparations, Aktiferrin capsules and Tardyferon dragées which differ as to the elemental iron content. METHODS AND RESULTS: To two groups of patients with sideropenic anaemia selected at random (39 women and 1 men, age 14-61 years, median 28 years) Aktiferrin or Tardyferon was administered. Administration of the preparations which have a more than double different elemental iron content had a comparable effect on the investigated haematological parameters. In the group treated with Akiferrin no GIT intolerance was observed, in the group with Tardyferon it was observed in four patients. CONCLUSIONS: Aktiferrin has a comparable therapeutic effect although it contains 2.5 times less elemental iron, as compared with Tardyferon.

Adolescent↗

[Density of adhesive proteins after oral administration of proteolytic enzymes in multiple myeloma].

The authors present information on the presence of adhesive proteins on membranes of myeloma and precursor cells isolated from bone marrow and blood from a group of 33 patients examined by fluorescent flow cytometry. They also compare the density of integrins (CD29, CD49e, CD41, CD51 and CD61) and adhesive proteins from the group of "homing" receptors (CD44) and IgG "superfamily" (LFA-1, LFA-3, ICAM-1, N-CAM) and their changes after a single oral dose of a mixture of proteolytic enzymes (Wobe Mugos, Wobenzym, MUCOS Pharma, FRG). The authors observed a significant drop of CD29, CD54 (ICAM-1), CD58 (LFA-3) after Wobe Mugos, CD49, CD51, CD58 after Wobenzyme. The insignificant decline of density of CD44 on cells, as well as of the soluble receptor of CD44 after oral administration of proteolytic enzymes in serum, incl. the mentioned changes of integrins and other adhesive proteins, indicate the importance of enzyme preparations in the supporting treatment of malignant processes.

Adjuvants, Immunologic↗

[Long-term survival in multiple myeloma].

The authors present the results of 23-year protocol studies of survival with multiple myeloma, focused on problems of perspective long-term survival. Of 535 diagnosed patients between 1970 and 1990 the authors checked regularly and treated 475. In addition to 60 latent forms where treatment was administered only when clinical symptoms developed or after progression of laboratory signs, to all patients treatment was administered according to protocols (monotherapy-cyclophosphamide prednisone in 1970-1975 only to 30 patients, the remainder had combined treatment--COPP, VMCP, MOCCA); in the third stage of the disease MOCCA treatment is better. The median of survival of patients after VMCP treatment (in stage II) MOCCA (in stage III) is more than 90 months, 15% survive for more than 10 years. The authors emphasize the importance of combined intensive treatment of patients for the prognosis of survival. Long-term experience revealed that patients achieve an objective response in 85%, while the risk of leukaemic and cancerogenic complications is low (1.1%). The therapeutic effect and survival period are favourably affected by immunomodulation treatment (Interferon, proteolytic enzymes, thymus factor).

Adult↗

Prognostic value of plasma-cell immunophenotype in patients with multiple myeloma.

A review is given of the prognostic significance of immunophenotyping of blood lymphoplasmocytic cells. From a group of 250 patients followed from 1981 through 1991 a subgroup of 70 patients (followed 1986 through 1991) were phenotyped at 6-month intervals by immunofluorescence tests with monoclonal antibodies for cytoplasmic immunoglobulin, kappa-lambda index, CD71, CD10, CD20, CD38, and HLA-DR receptors. In course of a longitudinal study it was found that prognostic significance for shortened survival can be derived from the presence of circulating CD10, CD71, and CD20 positive undifferentiated cells in peripheral blood. There was a correlation between increase of CALLA positive and CD71 positive cells. Further, an increase of undifferentiated clone occurred during transition of the disease to an aggressive phase. The median survival of the total group of 250 patients treated by the VMCP/MOCCA protocol, according to statistical analysis, was 90 months, the median survival of the aggressive stage with plasmoblastic and lymphoplasmocytic cell type, respectively, was only 12 months. The significance of phenotypization in the prognostic evaluation of variant heterogenous myeloma types is stressed.

Adult↗

[Immunotyping of medullary and circulatory cells for prognostic evaluation of plasmacytoma].

The authors discuss the prognostic impact of immunophenotyping of circulating lymphoplasmatic cells in the peripheral blood stream in patients with generalized plasmocytoma. From a group of 250 patients followed up from 1981 to 1991 they selected a sub-group of 70 patients where they evaluated in 1986-1991 after six-month intervals the phenotype of medullary and circulating cells. They used the method of immunofluorescent detection of the presence of cytoplasmic Ig, the kappa-lambda index and phenotyping of antigens CD 9, CD 10, CD 20, CD 38, HLA-DR by monoclonal antibodies. In a longitudinal investigation of the survival period they revealed that the finding of circulating cells with signs of non-differentiation (presence of antigen CD 10 detected by antibody CALLA, presence of antigens B 1 (CD 20), CD 9 on circulating lymphocytes) has a prognostic meaning suggesting shorter survival. There was a direct correlation between the increase of CALLA positive cells and CD 9 positive cells. The authors found also that release of the clonus with signs of immaturity was present when the disease developed into the aggressive stage. While the group of 250 patients had according to statistical analyses, when treated according to protocol VMCP/MOCCA, a median survival of 90 months, the median survival of the aggressive stage (with the plasmoblast and lymphoplasmocytic type resp.) was only 12 months. The authors emphasize the prognostic importance of immunological typing of heterogeneous plasmocytoma populations.

Adult↗

[The favorable effect of hydrolytic enzymes in the treatment of immunocytomas and plasmacytomas].

At present attention is focused on research of biomodulating influences on tumorous processes, in particular inhibition of metastatic spread of tumors. In the aetiopathogenesis an important part is played by immune complexes, interaction of cytokines. The authors tested the supporting effect of hydrolytic enzymes in plasmocytoma and immunocytoma. The enzymes were administered along with cytostatic preparations according to the MOCCA pattern. They recorded a more rapid onset and longer persistence of remissions, a marked decline of total proteins, paraproteins, beta-2-microglobulin. Complications associated with paraprotein (hyperviscosity syndrome, nephrotic syndrome, peripheral angiopathy) improved. A combination of chemotherapy and enzymatic treatment proved effective and suitable, in particular for patients with interferon intolerance.

Chymotrypsin↗

[Erythrocyte kinetics in myelodysplastic syndromes].

The authors made radioisotope examinations of the erythrokinetics in 21 patients with primary myelodysplastic syndrome: refractory anaemia and sideroblastic anaemia. He investigated the importance of changes of several conventional erythrokinetic parameters as well as the turnover of transferrin molecules which is an indicator of erythropoietic activity independent on sideraemia. The author presents ferrokinetic and erythrokinetic findings associated with myelodysplastic syndrome, as described in the literature. Sideroblastic anaemia produces a typical picture during examination of the erythrokinetics, quite different from other sub-types of the disease in refractory anaemia the changes of parameters are very variable.

Erythrocyte Aging↗

[Possibilities of finding identical HLA donor-recipient pairs for bone marrow transplantation].

With the aim to detect genotypically identical donors for patients suffering from some type of leukemia or aplastic anemia, HLA antigens and MLC reactivity were determined in 72 families, having together 209 children. HLA identical, MLC negative sibling donors were found for 31 patients, i.e. 43%. Compared to the healthy population, no significant differences were found in the frequency of HLA antigens and haplotypes in 58 leukemic patients. Two recombinations were recorded, one between the loci HLA-A and HLA-B, and the other one between HLA-B and HLA-D/DR. Only 9 persons (2.5%) homozygous for HLA-D antigens were found in the whole series of 353 subjects investigated.

Bone Marrow Transplantation↗