Nyíregyháza, Hungary
Nyíregyháza, Hungary

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Licitra L.,Instituto Nazionale Tumori | Mesia R.,Catalan Institute of Nanoscience and Nanotechnology | Rivera F.,Santander University | Remenar E.,National Institute of Oncology | And 10 more authors.
Annals of Oncology | Year: 2011

Background: The phase III EXTREME study demonstrated that combining cetuximab with platinum/5-fluorouracil (5-FU) significantly improved overall survival in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) compared with platinum/5-FU alone. The aim of this investigation was to evaluate elevated tumor EGFR gene copy number as a predictive biomarker in EXTREME study patients. Patients and methods: Dual-color FISH was used to determine absolute and relative EGFR copy number. Models of differing stringencies were used to score and investigate whether increased copy number was predictive for the activity of cetuximab plus platinum/5-FU. Results: Tumors from 312 of 442 patients (71%) were evaluable by FISH and met the criteria for statistical analysis. A moderate increase in EGFR copy number was common, with high-level amplification of the gene occurring in a small fraction of tumors (~11%). Considering each of the models tested, no association of EGFR copy number with overall survival, progression-free survival or best overall response was found for patients treated with cetuximab plus platinum/5-FU. Conclusion: Tumor EGFR copy number is not a predictive biomarker for the efficacy of cetuximab plus platinum/5-FU as first-line therapy for patients with R/M SCCHN. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.


Ivady G.,Debrecen University | Madar L.,Debrecen University | Nagy B.,Debrecen University | Gonczi F.,Kenezy Gyula County Hospital | And 7 more authors.
Journal of Cystic Fibrosis | Year: 2011

Background: The aim of this study was characterization of an updated distribution of CFTR mutations in a representative cohort of 40 CF patients with the classical form of the disease drawn from Eastern Hungary. Due to the homogeneity of the Hungarian population our data are generally applicable to other regions of the country, including the sizeable diaspora. Methods: We utilized the recommended "cascade" CFTR mutation screening approach, initially using a commercial assay, followed by examination of the common "Slavic" deletion CFTRdele2,3(21. kb). Subsequently, the entire CFTR coding region of the CFTR gene was sequenced in patients with yet unidentified mutations. Results: The Elucigene CF29Tm v2 assay detected 81.25% of all CF causing mutations. An addition of the CFTRdele2,3(21kb) increased the mutation detection rate to 86.25%. DNA sequencing enabled us to identify mutations on 79/80 CF alleles. Mutations [CFTRdele2,3(21kb), p.Gln685ThrfsX4 (2184insA) were found at an unusually high frequency, each comprising 5.00% of all CF alleles. Conclusion: We have identified common CF causing mutations in the Hungarian population with the most common mutations (p.Phe508del, p.Asn1303Lys, CFTRdele2,3(21. kb), 2184insA, p.Gly542X, and p.Leu101X), comprising over 93.75% of all CF alleles. Obtained data are applicable to the improvement of DNA diagnostics in Hungary and beyond, and are the necessary prerequisite for the introduction of a nationwide "two tier" CF newborn screening program. © 2011 European Cystic Fibrosis Society.


Flaberg E.,Karolinska Institutet | Markasz L.,Karolinska Institutet | Petranyi G.,Karolinska Institutet | Stuber G.,Karolinska Institutet | And 10 more authors.
International Journal of Cancer | Year: 2011

Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stoker's observation (Stroker et al, J Cell Sci 1966;1:297-310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high-throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384-well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV-transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co-cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40-transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high-throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells. © 2010 UICC.


Losonczy G.,Debrecen University | Fekete A.,Debrecen University | Voko Z.,Debrecen University | Takacs L.,Debrecen University | And 6 more authors.
Acta Ophthalmologica | Year: 2011

Purpose: Recent studies strongly support the role of genetic factors in the aetiology of age-related macular degeneration (AMD). We investigated the frequency of Tyr402His polymorphism of the complement factor H (CFH) gene, Ser69Ala polymorphism at LOC387715, rs11200638 polymorphism of the HTRA1 gene and different apolipoprotein E (ApoE) alleles in Hungarian patients with AMD in order to determine the disease risk conferred by these factors. Methods: In a case-control study, we performed clinical and molecular genetic examination of 105 AMD patients (48 patients in the early and 57 in the late subgroup) and 95 unrelated healthy controls. Detailed patient histories were recorded with the use of a questionnaire focusing on known risk factors for AMD. Results: In the early AMD subgroup, homozygous CFH, LOC387715 or HTRA1 polymorphisms conferred a 4.9-fold (95% confidence interval [CI] 1.7-14.2), 7.4-fold (95% CI 2.1-26.2) or 10.1-fold (95% CI 2.5-40.8) risk of disease, respectively. In the late AMD subgroup, carriers of two CFH, LOC387715 or HTRA1 risk alleles were at 10.7-fold (95% CI 3.7-31.0), 11.3-fold (95% CI 3.2-40.4) or 13.5-fold (95% CI 3.3-55.4) greater disease risk, respectively. Two CFH and one LOC387715 risk alleles in combination conferred a 15.0-fold (95% CI 3.2-71.0) increase in risk, whereas two LOC387715 risk alleles combined with one CFH risk allele was associated with a 14.0-fold (95% CI 2.1-95.1) increased risk for late AMD. ApoE alleles neither increased disease risk nor proved to be protective. Conclusions: The CFH, LOC387715 and HTRA1 polymorphisms are strongly associated with the development of AMD in the Hungarian population. The association is particularly pronounced when homozygous risk alleles are present and in the late stages of the disease. © 2009 The Authors. Journal compilation.


Szanto A.,Debrecen University | Szabo K.,Josa Andras County Hospital | Nagy G.,Debrecen University | Molnar C.,Debrecen University | Zeher M.,Debrecen University
Pathology and Oncology Research | Year: 2016

Differential diagnosis of patients with Sjögren’s syndrome (SS), IgG4-related disease (IgG4-RD) and SS patients having high risk for lymphoma (LHR) can be challenging. Some patients with IgG4-RD might be misdiagnosed as having SS. There are special symptoms of SS that raise the possibility of IgG4-RD whereas other symptoms identify patients as having LHR. The purpose of this study was to characterize and compare patients with SS, possible IgG4-RD and SS patients with LHR. Sixty-five SS patients were divided into 4 subgroups according to having possible IgG4-RD (n = 15), LHR (n = 16), eligible for both aforementioned groups (n = 20) and not eligible for either group (n = 14), respectively. Four patients fulfilled the diagnostic criteria for IgG4-RD. The serum levels of IgG4 were significantly higher in patients suspicious for IgG4-RD compared to that of LHR patients (0.46 g/l vs. 0.12 g/l, p = 0.032). Shared features of the patient groups (salivary gland swelling (SGS) and lymphadenopathy), were separately analysed: SGS patients had higher IgG4/IgG ratio (p = 0.036), lymphadenopathic patients had higher IgG4 levels (p = 0.042). Some patients may be “hidden” under the diagnosis of SS. Although patients with LHR and patients with possible IgG4-RD share some symptoms, they differ significantly regarding IgG4 levels and IgG4/IgG ratio. © 2016 Arányi Lajos Foundation


Francz M.,Josa Andras County Hospital | Egervari K.,Debrecen University | Szollosi Z.,Josa Andras County Hospital
Cytopathology | Year: 2011

Objective: We analysed the utility of imprint cytology with rapid immunocytochemistry and frozen section analysis for the evaluation of sentinel lymph nodes in breast cancer patients.Methods: The sensitivity, specificity, and positive and negative predictive values have been calculated for each method individually, each pair and all three together. We compared these results with those of routinely processed paraffin sections.Results: The sensitivity and specificity of each of the three methods for detection of metastatic carcinoma were as follows: 69.4% and 97.8% for touch imprint cytology; 58.3% and 100% for frozen sections; 68.5% and 98.9% for rapid immunocytochemistry. When the methods were combined, the highest accuracy was achieved by touch imprint cytology, frozen sections, touch imprint cytology plus rapid immunocytochemistry, or touch imprint cytology frozen section analysis and rapid immunocytochemistry, each of these having identical sensitivity and specificity of 72.2% and 97.8%, respectively.Conclusions: In our study the combined accuracy of the three methods was the same as combining touch imprint cytology and frozen sections or touch imprint cytology plus rapid immunocytochemistry. Rapid immunocytochemistry provides an additional parameter and preserves tissue for permanent sections. © 2010 Blackwell Publishing Ltd.


PubMed | Josa Andras County Hospital and Debrecen University
Type: Journal Article | Journal: Pathology oncology research : POR | Year: 2016

Differential diagnosis of patients with Sjgrens syndrome (SS), IgG4-related disease (IgG4-RD) and SS patients having high risk for lymphoma (LHR) can be challenging. Some patients with IgG4-RD might be misdiagnosed as having SS. There are special symptoms of SS that raise the possibility of IgG4-RD whereas other symptoms identify patients as having LHR. The purpose of this study was to characterize and compare patients with SS, possible IgG4-RD and SS patients with LHR. Sixty-five SS patients were divided into 4 subgroups according to having possible IgG4-RD (n=15), LHR (n=16), eligible for both aforementioned groups (n=20) and not eligible for either group (n=14), respectively. Four patients fulfilled the diagnostic criteria for IgG4-RD. The serum levels of IgG4 were significantly higher in patients suspicious for IgG4-RD compared to that of LHR patients (0.46g/l vs. 0.12g/l, p=0.032). Shared features of the patient groups (salivary gland swelling (SGS) and lymphadenopathy), were separately analysed: SGS patients had higher IgG4/IgG ratio (p=0.036), lymphadenopathic patients had higher IgG4 levels (p=0.042). Some patients may be hidden under the diagnosis of SS. Although patients with LHR and patients with possible IgG4-RD share some symptoms, they differ significantly regarding IgG4 levels and IgG4/IgG ratio.


Endreffy I.,Josa Andras County Hospital | Bjorklund G.,Council for Nutritional and Environmental Medicine | Dicso F.,Josa Andras County Hospital | Urbina M.A.,University of Exeter | And 2 more authors.
Metabolic Brain Disease | Year: 2016

Autism research continues to receive considerable attention as the options for successful management are limited. The understanding of the autism spectrum disorder (ASD) etiology has now progressed to encompass genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. Glycosaminoglycans (GAGs) are a family of linear, sulfated polysaccharides that are associated with central nervous system (CNS) development, maintenance, and disorders. Proteoglycans (PG) regulate diverse functions in the central nervous system. Heparan sulfate (HS) and chondroitin sulfate (CS) are two major GAGs present in the PGs of the CNS. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and has minimal to no side effects, since no molecules foreign to the body are needed. Given GAGs are involved in several neurological functions, and that its level can be somewhat modulated by the diet, the present study aimed to evaluate the role of GAGs levels in ASD symptoms. Both tGAG and its different fractions were evaluated in the urine of ASD and healthy control childrens. As levels differed between groups, a second trial was conduted evaluating if diet could reduce tGAG levels and if this in turn decrease ASD symptoms. The present study found that tGAG concentration was significantly higher in the urine of children with ASD compared to healthy control children and this was also evident in all GAG fractions. Within groups (controls and ASD), no gender differences in GAG excretion were found. The use of a 90 days elimination diet (casein-free, special carbohydrates, multivitamin/mineral supplement), had major effects in reducing urinary tGAG excretion in children with ASD. © 2015, Springer Science+Business Media New York.


PubMed | University of Exeter, Council for Nutritional and Environmental Medicine, University of Szeged and Josa Andras County Hospital
Type: Journal Article | Journal: Metabolic brain disease | Year: 2016

Autism research continues to receive considerable attention as the options for successful management are limited. The understanding of the autism spectrum disorder (ASD) etiology has now progressed to encompass genetic, epigenetic, neurological, hormonal, and environmental factors that affect outcomes for patients with ASD. Glycosaminoglycans (GAGs) are a family of linear, sulfated polysaccharides that are associated with central nervous system (CNS) development, maintenance, and disorders. Proteoglycans (PG) regulate diverse functions in the central nervous system. Heparan sulfate (HS) and chondroitin sulfate (CS) are two major GAGs present in the PGs of the CNS. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and has minimal to no side effects, since no molecules foreign to the body are needed. Given GAGs are involved in several neurological functions, and that its level can be somewhat modulated by the diet, the present study aimed to evaluate the role of GAGs levels in ASD symptoms. Both tGAG and its different fractions were evaluated in the urine of ASD and healthy control childrens. As levels differed between groups, a second trial was conduted evaluating if diet could reduce tGAG levels and if this in turn decrease ASD symptoms. The present study found that tGAG concentration was significantly higher in the urine of children with ASD compared to healthy control children and this was also evident in all GAG fractions. Within groups (controls and ASD), no gender differences in GAG excretion were found. The use of a 90 days elimination diet (casein-free, special carbohydrates, multivitamin/mineral supplement), had major effects in reducing urinary tGAG excretion in children with ASD.


Turcsanyi I.,Josa Andras County Hospital | Friden J.,Josa Andras County Hospital
Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi | Year: 2010

Our aim was to evaluate the functional outcome of reconstruction of elbow extension in tetraplegia using a new technique for improving the attachment sites of posterior deltoid-to-triceps transfer in conjunction with an active rehabilitation programme. Ten tetraplegic patients (15 arms) had modified deltoid-to-triceps transfer using a tibialis anterior tendon graft. The operation included large overlaps between the tendon attachments, and additional security by anchoring the distal stump of the tendon graft to the olecranon. During the first 3 weeks of immobilisation, isometric contractions were made and during the following 4 weeks the flexion angle of the elbow was increased by 15 degrees a week; weights were also used to reinforce muscle strength. The mean follow up was 10 months (range 5-19). The elbow extension strength after posterior deltoid-to-triceps transfer was measured in horizontal and vertical planes. After rehabilitation the active range of motion and strength of elbow extension had improved substantially. The mean active elbow extension range of motion was 132 degrees (range 120 degrees -145 degrees ) and the elbow could be extended actively in all planes. Elbow extension strength was restored to well above the counteraction of the weight of the arm. Mean (SEM) elbow extension was significantly greater in the horizontal shoulder plane compared with the vertical plane (10.4 (1.0) compared with 6.5 (1.2) Nm, p < 0.001) and strength increased roughly linearly as the degree of flexion of the elbow increased. The most dramatic increase was in the range between 120 degrees and 135 degrees of flexion, regardless of the plane of action of the shoulder. We have shown good functional results and a shorter rehabilitation period using a rigorous suturing technique that allows for active strength and mobility training without additional adverse effects.

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