Biomedical subjects

Miklós Udvardy

Publications and source records attributed to Miklós Udvardy.

16 recordsLinked to original sources

PubMed2006

[Haptoglobin polymorphism in patients with inflammatory bowel diseases].

BACKGROUND: Since functional differences were found among three major haptoglobin phenotypes, haptoglobin polymorphism was reported to be associated with the risk and clinical course of different inflammatory diseases. The aim of the study was to investigate the Hp polymorphism distribution in Hungarian Crohn's disease patients. METHODS: 511 Hungarian IBD patients were investigated (Crohn's disease patients: 468, m/f ratio: 233/235, duration 8.2 +/- 6.7 ys, and ulcerative colitis patients: 43, m/f: 22/21, duration: 9.5 +/- 10.6 ys) and 384 healthy subjects served as controls. Hp phenotypes were determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis of sera followed by immunoblotting. Clinical data were come by the questionnaires prepared by the physicians. RESULTS: The frequency of haptoglobin-1 allele was significantly higher in Crohn's disease (0.395) compared to the controls (0.345; OR: 1.24, 95%CI: 1.02-1.52, p = 0.03), but the phenotype distribution showed no such differences. Haptoglobin phenotype was associated to disease behavior in Crohn's disease (B1 and B2, in haptoglobin 1-1 and 2-2: 36.6%-34.3% and 32.4%-32.5% vs. in 2-1: 44.9% and 20.3%; ORB1Hp2-1 vs. others: 2.06, 95%CI: 1.29-3.28). Furthermore, an increased frequency of primary sclerosing cholangitis was observed in haptoglobin 2-2, compared to the 1-1 (6.5% vs. 0.0%, p = 0.039). No associations were found in ulcerative colitis. CONCLUSIONS: haptoglobin-1 allele was associated with Crohn's disease, whereas the phenotypes with the disease behavior and frequency of primary sclerosing cholangitis, exhibiting a disease-modifying effect.

Adult↗

PubMed2006

[Chronic neutrophilic leukemia: a long-term analysis of seven cases and review of the literature].

Chronic neutrophilic leukemia is an uncommon hematological entity. According to the WHO classification it is recognized as part of the family of myeloproliferative disorders. In the last 20 years seven patients have been diagnosed with chronic neutrophilic leukemia at our department. All but one had splenomegaly, two patients developed severe anaemia and in one case thrombocytosis was present at the time of diagnosis. White blood cell count ranged between 39 x 10(9)/1-71 x 10(9)/l with 80% of neutrophils and striking myeloid hyperplasia were present in the bone marrow without evidence of any dysplasia resembling chronic myelocytic leukemia. Granulocyte alkaline phosphatase scores were increased except one case and both cytogenetics (Philadelphia chromosome) and molecular biologic analysis (bcr/abl) revealed no alteration of any. Four patients have been followed up. Three of them died due to progression of chronic neutrophilic leukemia. One patient, initially receiving hydroxyurea + interferon therapy and showing progression, developed complete hematological remission with an eight week imatinib mesylate (Glivec) treatment. Beside of their own experiences the authors review the current literature and discuss differential diagnostic and therapeutic challenges, as well.

Aged↗

PubMed2006

Effect of IBD sera on expression of inducible and endothelial nitric oxide synthase in human umbilical vein endothelial cells.

AIM: To study the expression of endothelial and inducible nitric oxide synthases (eNOS and iNOS) and their role in inflammatory bowel disease (IBD). METHODS: We examined the effect of sera obtained from patients with active Crohn's disease (CD) and ulcerative colitis (UC) on the function and viability of human umbilical vein endothelial cells (HUVEC). HUVECs were cultured for 0-48 h in the presence of a medium containing pooled serum of healthy controls, or serum from patients with active CD or UC. Expression of eNOS and iNOS was visualized by immunofluorescence, and quantified by the densitometry of Western blots. Proliferation activity was assessed by computerized image analyses of Ki-67 immunoreactive cells, and also tested in the presence of the NOS inhibitor, 10(-4) mol/L L-NAME. Apoptosis and necrosis was examined by the annexin-V-biotin method and by propidium iodide staining, respectively. RESULTS: In HUVEC immediately after exposure to UC, serum eNOS was markedly induced, reaching a peak at 12 h. In contrast, a decrease in eNOS was observed after incubation with CD sera and the eNOS level was minimal at 20 h compared to control (18%+/-16% vs 23%+/-15% P<0.01). UC or CD serum caused a significant increase in iNOS compared to control (UC: 300%+/-21%; CD: 275%+/-27% vs 108%+/-14%, P<0.01). Apoptosis/necrosis characteristics did not differ significantly in either experiment. Increased proliferation activity was detected in the presence of CD serum or after treatment with L-NAME. Cultures showed tube-like formations after 24 h treatment with CD serum. CONCLUSION: IBD sera evoked changes in the ratio of eNOS/iNOS, whereas did not influence the viability of HUVEC. These involved down-regulation of eNOS and up-regulation of iNOS simultaneously, leading to increased proliferation activity and possibly a reduced anti-inflammatory protection of endothelial cells.

Adolescent↗

PubMed2005

Shielding of the A1 domain by the D'D3 domains of von Willebrand factor modulates its interaction with platelet glycoprotein Ib-IX-V.

Soluble von Willebrand factor (VWF) has a low affinity for platelet glycoprotein (GP) Ibalpha and needs immobilization and/or high shear stress to enable binding of its A1 domain to the receptor. The previously described anti-VWF monoclonal antibody 1C1E7 enhances VWF/GPIbalpha binding and recognizes an epitope in the amino acids 764-1035 region in the N-terminal D'D3 domains. In this study we demonstrated that the D'D3 region negatively modulates the VWF/GPIb-IX-V interaction; (i) deletion of the D'D3 region in VWF augmented binding to GPIbalpha, suggesting an inhibitory role for this region, (ii) the isolated D'D3 region inhibited the GPIbalpha interaction of a VWF deletion mutant lacking this region, indicating that intramolecular interactions limit the accessibility of the A1 domain, (iii) using a panel of anti-VWF monoclonal antibodies, we next showed that the D'D3 region is in close proximity with the A1 domain in soluble VWF but not when VWF was immobilized; (iv) destroying the epitope of 1C1E7 resulted in a mutant VWF with an increased affinity for GPIbalpha. Our results support a model of domain translocation in VWF that allows interaction with GPIbalpha. The suggested shielding interaction of the A1 domain by the D'D3 region then becomes disrupted by VWF immobilization.

Animals↗

PubMed2005

[Chronic myeloid leukemia].

Chronic myeloid leukemia is still the most characteristic entity of the chronic myeloproliferative diseases. The tumor promoter role of able-dependent tyrosine kinase activation, which is enhanced by bcr/abl rearrangement (due the classical translocation of Philadelphia chromosomal abnormality) has been quite well clarified. The better understanding of the role of altered cell signalling pathways in the pathogenesis of chronic myeloid leukaemia opened new areas for extensive and fruitful pharmacological research. The first, non-myelosuppressive agent, which was able to reduce the number of Philadelphia positive clonal cells was the interferon group, which drug could substantially prolong the chronic phase and mortality of chronic myeloid leukaemia. Imatinib mesylate, a tyrosine-kinase inhibitor seems to be able to produce clinical and major cytogenetic response in more than 80% of patients. Imatinib is also a powerful agent in the accelerated or blastic phased of chronic myeloid leukaemia. With the advent of these new drugs the therapeutic algorithm of chronic myeloid leukaemia and allogenous bone marrow transplantation seems to be reconsidered, too.

Antineoplastic Agents↗

PubMed2005

[Primary treatment of advanced Hodgkin's disease].

Primary treatment of advanced Hodgkin's disease. Hodgkin's disease is one of the few malignant diseases that can be cured even in an advanced stage in the majority of cases. By employing a polychemotherapy containing anthracyclines, a long remission and recovery can be achieved in 60-70% of the patients. At present the standard treatment is ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) scheme for the following reasons: besides good treatment results early side effects are more favourable; sterility and secondary acute leukemia present themselves less often than by employing regimens containing alkylating agents. Unfortunately, some of the patients do not react properly to the treatment and about one third of the patients who are in remission following primary treatment will relapse at a later stage. The main goal is now to further improve treatment (recovery) results without an increase, or even a decrease of early or late side effects. Awareness of prognostic factors should lead to the employment of a less intensive but not toxic therapy in patients with good prognosis to prevent overtreatment, while in cases with bad prognosis a more effective regimen is needed (even for the price of expected complications). The latest meta-analysis on the subject has shown that--similarly to sequential high dose therapy--the addition of radiotherapy to an effective chemotherapy does not seem to prolong the survival of patients. Despite the excellent therapeutic results achieved by the many new "intensive" chemotherapies, there is unfortunately no optimal therapy or protocol available today. The multicentre analysis to confirm these results and to compare them with standard scheme is still under way. It is to be hoped that risk adapted management for advanced stage Hodgkin's disease will also be available soon.

Age Factors↗

PubMed2005

Changes in the expression and distribution of the inducible and endothelial nitric oxide synthase in mucosal biopsy specimens of inflammatory bowel disease.

OBJECTIVE: The role of nitric oxide (NO) in the pathophysiology of inflammatory bowel disease (IBD) is controversial. The aim of this study was to investigate the expression and localization of nitric oxide synthase isoforms (iNOS, eNOS) in IBD colonic mucosa. MATERIAL AND METHODS: Forty-four patients with IBD (24 ulcerative colitis (UC), 20 Crohn's disease (CD) and 16 controls) were investigated by colonoscopy. iNOS and eNOS in tissue sections was demonstrated by histochemistry (NADPH-diaphorase reaction) and immunohistochemistry. Cell type analysis and quantitative assessment of the iNOS immunoreactive (IR) cells and densitometry of iNOS in immunoblots were also performed. RESULTS: iNOS-IR cells were significantly numerous in inflamed mucosa of UC (64+/-4 cells/mm2) than in CD (4+/-2 cells/mm2). iNOS-IR/CD15-IR cells showed significant elevation in inflamed (i) versus uninflamed (u) UC mucosa (UCu 8+/-3%, UCi 85+/-10%) In CD, the percentage of iNOS-IR/CD68-IR cells was lower in inflamed sites (CDu 23+/-8%, CDi 4+/-3%). Immunoblot of biopsies revealed significant elevation of iNOS in active UC compared with uninflamed sites, whereas in CD no significant changes were detected. Differences were observed in eNOS and endothelial marker CD31 immunoreactivity. In patients with UC and in controls the ratios of eNOS/CD31-IR vessels were 82.3% and 92.0% respectively, whereas in CD the ratio was 8.3% with a concomitantly significant increase of CD31-IR vessels. The distribution and morphological characteristics of the NOS-IR inflammatory cells and endothelia were similar to those showing NADPH-diaphorase reactivity. CONCLUSIONS: Differences observed in the expression and distribution of NOS isoforms in immune and endothelial cells may contribute to better understanding of the structural and physiological changes in UC and CD.

Adult↗

PubMed2005

Chromosomal aberrations and CD38 expression in two siblings with B-cell chronic lymphocytic leukemia: a report of two siblings.

In this study our purpose was to define chromosomal aberrations and CD38 expression in male siblings 69 and 66-years-old with B-cell chronic lymphocytic leukemia (B-CLL). Cells from peripheral blood were analysed by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The alteration detectable by CGH was the over-representation of the Y chromosome in both samples. Interphase FISH were performed using locus (13q14 and 17p53) and centromere (chromosome 12, 17 and Y) specific DNA probes. One brother (patient 1, 69 years of age) showed deletion of the 13q14 region, this alteration was associated with low CD38 expression, both predicting a favourable prognosis. However, the younger patient's (patient 2, 66 years of age) cells expressed CD38 in high percent, which is considered as an indicator of poor prognosis, and deletion of the 13q14 was not seen. Other, relatively frequent chromosomal alterations including trisomy 12 and deletion of 17p53 were not present in any of the samples. The cytogenetic findings and the CD38 expression are in concordance with the clinico-pathological data of the siblings. Thus, we found the variability of these parameters described in B-CLL even in the familial form of the disease.

ADP-ribosyl Cyclase↗

PubMed2004

[New perspectives in the evolution of prognosis and treatment of chronic lymphocytic leukaemia].

Chronic lymphocytic leukaemia is a disease with a variable clinical course and prognosis. New prognostic factors like immunoglobulin gene mutational status, cytogenetic abnormalities, CD38 and ZAP70 expression of malignant cells have been described recently. Conventional and biological prognostic factors allow to identify patients with unfavorable prognosis at early stage. Purin analogues, fludarabine and fludarabine based combinations can achieve complete hematological remission in approximately one third of patients with chronic lymphocytic leukaemia. Chemoimmunotherapy (most experience is obtained by combination of fludarabine + cyclophosphamide + rituximab) can increase not only complete remission rate, but also induce molecular remission in some cases. Stem cell transplantation as well as early and effective chemotherapy are curative choices of treatment in patients with chronic lymphocytic leukaemia.

ADP-ribosyl Cyclase↗

PubMed2003

[Expanding possibilities, strategic considerations, and novel methods in the diagnosis and chemotherapy of adult acute myeloid leukemia].

The WHO classification of adultory acute myeloid leukemia puts the main emphasis on prognosis, based mainly upon cytogenetic findings and gene-expression profiles. The complex prognostic assessment provides a more solid basis for early therapeutic stratification. This review focuses mainly on medical therapy. Induction phase is quite uniform, it consists of antracyclin and cytosin arabinosid. High-dose cytosin arabinosid is the predominant tool of postinduction therapy, especially in the favorable cytogenetic pattern cases. All-trans retinoic acid resulted in extremely good results in the promyelocytic cases, and this therapy seems to be advantageous in respect of acute DIC, too. Arsenic trioxide could be the drug of choice in relapsed promyelocytic leukemia. Some new agents are promising in refractory or relapsed cases, i.e. antibodies (Mylotarg) or farnesyltransferase inhibitors. The near future may bring about new therapeutic approaches, involving immunotherapy (dendritic cell vaccines) or gene-therapy as well.

Adult↗

PubMed2003

[Prognositc value of CD38 cell surface marker in chronic lymphocytic leukemia].

CD38 is expressed on the surface of leukemic cells in a significant percentage of patients with B-cell chronic lymphocytic leukaemia (CLL). From the literature it is known that CD38 expression has prognostic value in CLL, suggesting an association between CD38 expression and the mutational status of IgV genes. Peripheral blood samples from 82 patients with CLL were analyzed by flow cytometry for CD38 expression on CD19+ leukemic cells. CD38 was expressed in 30% or more of leukemic cells in 26 patients (patients with 30% or more B cells coexpressing CD19/CD38 were considered positive). Seven of the 26 patients with high CD38 expression and eight of the 56 patients with low CD38 expression had advanced-stage disease (RAI III-IV). Higher than 4 mg/l levels of beta 2-microglobulin was measured in the serum of nine of 26 CD38+ and seven of 56 CD38- patients. Our analyses showed that the high CD38 expression is associated with other risk factors, identifying an aggressive disease, which require treatment. It will be important to conduct further studies to establish the prognostic value of the high CD38 expression in early-stage disease.

ADP-ribosyl Cyclase↗

PubMed2003

[Changes in hematologic and hemostatic parameters after transjugular intrahepatic portosystemic shunt (TIPS) implantation].

BACKGROUND: The pathogenesis of thrombocyte- and leukopenia associated with liver cirrhosis is far from being understood. Hypersplenism is considered to play a major role in this hematologic complication. The effect of transjugular intrahepatic portosystemic shunt (TIPS) implantation--a more recent technique in portal decompression--on platelet count is controversial in the literature. One of the main problems related to TIPS is the frequent occurrence of shunt malfunctions. There have been no reports on consistent clinical or biochemical parameters being able to predict the occlusive and rebleeding episodes after TIPS implantation. AIM AND METHOD: Platelet counts, white blood cell counts and different haemostatic data (prothrombin time, activated partial thromboplastin time and fibrinogen level) of the 24 patients undergoing TIPS placement were analyzed retrospectively prior to the procedure, after one month, after 3 months and 3 monthly thereafter for 18 months. RESULTS: The portal pressure gradient decreasing below the desired 12 mmHg after TIPS placement seems to be the only factor, which can result in moderate but significant increase in platelet counts. There was no significant alteration in white blood cell counts during the follow-up period. The different haemostatic parameters scattered in a wide range, no real tendency was demonstrable. Patients in whom recurrent variceal bleeding occurred, the platelet count at the 3rd month was significantly lower compared to the basal platelet count. The decrease in the platelet count preceded shunt malfunction detected with color-Doppler or the appearance of the clinical symptoms. CONCLUSION: Monitoring platelet count may be of prognostic interest in the assessment of the shunt function and the risk of imminent variceal rebleedings during the follow-up period.

Adult↗

PubMed2003

Thrombotic and fibrinolytic alterations in the aseptic necrosis of femoral head.

Recent reports seem to support the role of the thrombophilia and decreased fibrinolysis in the aetiopathogenesis of aseptic necrosis of bone. In the present study, haemostatic disturbances were analysed in adults (n = 49) and patients in childhood (Perthes disease) (n = 47) with aseptic necrosis of the femoral head. Fibrinolytic parameters (in vitro clot lysis, plasminogen, plasmatic plasminogen activator inhibitor-1 activity, D-dimer) along with lipoprotein (a) [Lp(a)] and fibrinogen were measured. von Willebrand factor, platelet activation and some thrombophilic factors (activated protein C resistance and factor V Leiden mutation, protein C, protein S activity) were also determined. Impaired fibrinolysis, an increased Lp(a) level along with slow clot lysis and increased platelet activation were found in adult cases. We detected five cases of factor V Leiden mutations (one heterozygotic and four homozygotic) among patients with Perthes disease. The clinical course of the heterozygous case was similar to the usual form of Perthes disease. The most severe form of Perthes disease has been observed in homozygous factor V Leiden mutation cases. The mutation of factor V Leiden per se probably does not induce the development of aseptic necrosis of bone tissue in childhood, but it does play a role in its acceleration. Homozygous factor V Leiden mutation definitely runs a more severe course. On the other hand, in adult cases, the disturbances of haemostasis, impaired fibrinolysis, elevated Lp(a) level, increased platelet activation and slight elevation of fibrinogen might have clinical relevance. Further studies should focus on proving the role of the haemostatic alterations in the pathogenesis of severe forms of aseptic bone necrosis. The use of antithrombotic drugs in order to slow the process of aseptic necrosis also has to be addressed in future surveys.

Adolescent↗

PubMed2002

[Experience with fludarabine treatment and review of the literature].

INTRODUCTION: Fludarabine is the most commonly used purine analog, its mechanism of action is complex. Fludarabine inhibits DNA synthesis, acts on non-dividing (G0 phase) cells influencing apoptosis. PATIENTS, RESULTS, CONCLUSIONS: In our institute 47 patients were treated with fludarabine or fludarabine based combination chemotherapy. Fludarabine was given in 19 patients with chronic lymphocytic leukaemia (CLL), complete remission (CR) was achieved in one case, partial remission (PR) was obtained in 10 patients. Fludarabine was more effective in patients who received less intensive chemotherapy prior to fludarabine therapy and in those patients who had less advanced diseases. Elderly patients (over sixty years of age) also responded to fludarabine therapy. Fludarabine and cyclophosphamide combination (FCy) were used in three lymphocytic lymphoma patients, two of them obtained PR, in the third case the disease progressed. Fludarabine + mitoxantrone (Novantrone) + dexamethasone (FND) regimen was administered in nine patients who were previously heavily treated (one patient with B-CLL, one with T-CLL, one with peripheral T-cell lymphoma and six with indolent B-cell lymphoma). More patients and longer follow up is needed to determine the efficacy of FCy and FND protocol. FLAG-IDA (fludarabine, high dose Ara-C, granulocyte colony-stimulating factor, idarubicin) was applied in 16 acute leukaemia patients with poor prognosis including therapy refractory and relapsing cases. Three CR and two PR, one CR and three PR was achieved in nine patients with acute myeloid leukaemia and in seven patients with acute lymphoid leukaemia, respectively. For this reason, despite the short period of remission, this regimen can be recommended to patients who are candidate for stem cell transplantation.

Adult↗

PubMed2002

[Paroxysmal nocturnal hemoglobinuria].

The current knowledge of the history, clinical course, diagnosis and treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) are summarized in this article.

Bone Marrow Diseases↗

PubMed2002

[Acute gastrointestinal bleeding in patients with antithrombotic therapy].

Approximately one-fifth of the patients, referred to the acute gastrointestinal bleeding unit took antithrombotic drugs (anticoagulants and antiplatelet agents) in a dose or with an effect, which made the causal relationship with acute bleeding episodes unequivocal. This paper analyzes the data of the first 100 such patients of the ward. The majority used acethyl-salicylic acid derivatives, however, a substantial number were on coumarol, and some bleeding patients with prosthetic heart valves were also observed. Haemostasis was forced by urgent, accurate, intervention based endoscopy along with simultaneous rapid efforts to correct the underlying clotting abnormalities. Prosthetic valve patients needed special care and attendance, and the reinstitution of anticoagulant treatment as soon as possible to maintain valve patency. The experiences and schedules of the authors, as well as the proposals of the literature are reviewed and summarized.

Acute Disease↗