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Z Nagy

Publications and source records attributed to Z Nagy.

At least 19 recordsLinked to original sources
PubMed2006

Increase in hepatitis C virus incidence in HIV-1-infected patients followed up since primary infection.

BACKGROUND: An increase in the incidence of sexually transmitted infections and hepatitis C virus (HCV) infections in HIV-infected men who have sex with men (MSM) has recently been reported. OBJECTIVE: To estimate HCV incidence and risk factors among HIV-1-infected patients followed up since primary HIV infection in the French PRIMO Cohort between 1996 and 2005. PATIENTS AND METHODS: All patients with at least 18 months of follow-up were studied. HCV antibody tests were performed on baseline plasma samples and repeated on the latest available sample when negative at baseline. RESULTS: In total, 402 patients with a median follow-up of 36 (range 18-104) months were eligible. HCV seroconversion was observed in 6 patients (4 men and 2 women), corresponding to an HCV incidence rate of 4.3 per 1000 person-years. Incidence rates in men and women were 3.5 and 7.8 per 1000 person-years, respectively. The incidence rate was 1.2 per 1000 person-years before January 2003 and 8.3 per 1000 person-years after January 2003 (p = 0.06). The classic risk factors for HCV infection were found in women (intravenous drug use, and body piercing), whereas the only identified risk factor for HCV acquisition was unsafe sex in the four men. CONCLUSIONS: Increase in the incidence of acute HCV infection in recently HIV-infected patients confirms the shift in sexual behaviour in the recent years, especially in HIV-infected MSM. Repeated testing for HCV antibodies should be carried out in HCV-negative HIV-infected patients and specific recommendations about protected sex should be clearly provided.

AIDS-Related Opportunistic Infections↗
PubMed2006

Role of the yeast ABC transporter Yor1p in cadmium detoxification.

Growth of yeast strains, either deleted for the vacuolar ABC transporter Ycf1 or deleted for the plasma membrane ABC transporter Yor1p or overexpressing Yor1p, were compared for their sensitivity to cadmium. On solid medium cell death (or growth inhibition) was observed at cadmium concentrations higher than 100 microM when yeasts were grown at 30 degrees C for 24 h. However, for all tested strains cell death (or growth inhibition) was already observed at 40 microM cadmium when incubated at 23 degrees C for 60 h. Thus cadmium is more toxic to yeast at 23 degrees C than at 30 degrees C. At 23 degrees C, the Deltayor1 strain grew more slowly than the wild-type strain and the double Deltayor1, Deltaycf1 deleted strain was much more sensitive to cadmium than each single Deltayor1 or Deltaycf1 deletant. Overexpression of Yor1p in a Deltaycf1 strain restores full growth. Cadmium uptake measurements show that Deltaycf1 yeast strains expressing or overexpressing Yor1p store less cadmium than the corresponding Deltaycf1, Deltayor1 strain. The strains expressing Yor1p display an energy-dependent efflux of cadmium estimated for the yeast overexpressing Yor1p to be about 0.02 nmol 109Cd/mg protein/min. Yeast cells loaded with radiolabeled glutathione and then with radioactive cadmium displayed a twice-higher efflux of glutathione than that of cadmium suggesting that Yor1p transports both compounds as a bis-glutathionato-cadmium complex. All together, these results suggest that in addition to being accumulated in the yeast vacuole by Ycf1p, cadmium is also effluxed out of the cell by Yor1p.

ATP-Binding Cassette Transporters↗
PubMed2006

Talampanel a non-competitive AMPA-antagonist attenuates caspase-3 dependent apoptosis in mouse brain after transient focal cerebral ischemia.

Talampanel (IVAX) is a non-competitive AMPA-antagonist has a remarkable neuroprotection in different rodent stroke models. The focal cerebral ischemia in mice was induced by transient (60 min.) MCA occlusion and 48 h reperfusion and treated with talampanel (6 x 2 mg/kg, i.p.). The apoptotic and necrotic cells were analyzed by double immune histochemical staining on confocal laser microscope. The infarct size is decreased significantly by talampanel treatment (from 57.1+/-7.2mm(2) to 18.9+/-2.6 mm(2), p< 0.001). The number of TUNEL-positive cells localized mostly in the border zone of ischemic lesions is significantly decreased after talampanel treatment (from 962+/-13.0 to 604+/-6.9, p < 0.01). A strong, significant reduction of caspase-3 active cells was visualized. Talampanel as a neuroprotective drug candidate has a significant effect in mice transient MCA occlusion model.

Animals↗
PubMed2005

Peripheral nerve and skeletal muscle involvement in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by degeneration of vascular smooth muscle cells (VSMC) of nearly all tissues studied so far. The clinical phenotype of CADASIL shows great variability. The disease is caused by mutations of the Notch3 gene encoding the transmembrane receptor Notch3, which is expressed predominantly in VSMC. In some patients, neuromuscular symptoms have been described. To investigate the fine structural features of peripheral nerve and muscle biopsy specimens in more cases and greater detail, seven electron microscopically confirmed CADASIL patients showing a variable amount of granular osmiophilic material on the surface of VSMC were included in this study. Pathogenic mutations within the cluster region (exon 3 and 4) of the Notch3 gene were identified in six cases. Degeneration and regeneration of nerve fibers in the sural nerves, studied in four cases, was present, although moderate, in all nerve biopsy specimens, whereas an intramuscular nerve fascicle showed more severe changes. Enlarged mitochondria with needle-like calcium precipitates were repeatedly seen. In muscle biopsy specimens, some degree of neurogenic atrophy was apparent in addition to myopathic changes, including occasional ragged red fibers with abnormally large mitochondria, focal tubular aggregates, abnormal terminal cisternae, and myofibrillary abnormalities. Automated sequence analysis of the whole mitochondrial DNA performed in one patient revealed several nucleotide polymorphisms, which were not considered pathogenic. The findings suggest that in CADASIL degeneration of small blood vessels is initiated by defects of the surface membrane of VSMC. Dysfunction of these blood vessels may cause low-grade chronic ischemia with secondary hypoxidosis and a large variety of structural changes noted in skeletal muscle and peripheral nerves, although a primary influence of the underlying genetic defect can not be excluded.

CADASIL↗
PubMed2005

Low dose (-)deprenyl is cytoprotective: it maintains mitochondrial membrane potential and eliminates oxygen radicals.

Hypoxia leads to a collapse in mitochondrial transmembrane potential (Deltapsi(M)), a fall in the ATP/ADP ratio, and finally cell death. Since (-)deprenyl directly modulates Deltapsi(M) and production of reactive oxygen species (ROS) by altering the respiratory function of mitochondria, we were interested in the dose-response relations of these effects. The changes in JC-1 red/green signal ratios {mitochondrial transmembrane potential}, and the changes in the cerium staining (intracellular ROS) in hypoxic and normoxic PC12 cell cultures were measured following 1 h of Argon hypoxia and 24 h of re-oxygenation in the absence and in the presence of various concentrations of (-)deprenyl. Deltapsi(M) shifted to lower values following hypoxia/re-oxygenation and all cells had decreased and uniform Deltapsi(M) levels. The amount of ROS increased. Following 24 h of treatment with various concentrations of (-)deprenyl during the re-oxygenation period, survival increased, the Deltapsi(M) shift caused by oxygen deprivation was reversed and the peroxy radical levels decreased except for at 10(-3) M.

Animals↗
PubMed2005

Outcome after extended arch repair for aortic coarctation.

OBJECTIVES: To assess survival and long term arch patency rates in a consecutive group of children after extended arch repair for coarctation of the aorta. METHODS: Review of 191 consecutive children (154 (81%) under 1 year of age) operated on between 1990 and 2002 by a single surgeon using extended arch reconstructive techniques. For assessment of survival patients were divided into three groups: 1, coarctation alone, n = 104; 2, coarctation and ventricular septal defect, n = 38; and 3, coarctation in association with complex intracardiac anomalies, n = 49. A prospective and systematic clinical and echocardiographic evaluation of the aortic arch was undertaken. RESULTS: Median time to follow up was 4.2 years (range 1-10.6 years). Overall actuarial survival was 92%, 88%, and 88% at two, five, and 10 years. Mortality was significantly higher in those patients with complex intracardiac anatomy. Arch obstruction recurred in seven of 165 (4.2%) patients: four of 139 (2.9%) term and three of 10 (30%) premature infants (p < 0.001). CONCLUSIONS: Survival after extended arch reconstruction for coarctation is excellent. At long follow up recurrent arch obstruction is rare, with prematurity the only risk factor.

Adolescent↗
PubMed2004

Objective assessment of neurotoxicity while shifting from carbamazepine to oxcarbazepine.

OBJECTIVES: Objective assessment of non-overt neurotoxicity of carbamazepine (CBZ) vs oxcarbazepine (OXC) in patients with difficult-to-treat partial epilepsy, who were resistant to CBZ treatment and were converted from CBZ monotherapy to OXC monotherapy. MATERIAL AND METHODS: Therapeutically equivalent doses (150 mg OXC for every 100 mg CBZ) were compared in 20 adult patients. Neurological investigation, conventional and spectral EEG analysis, brainstem auditory evoked responses (BAER) were carried out in both treatment conditions. EEG and BAER data of 20 age-matched healthy controls helped interpretation. Primary target variables (electrophysiological parameters) were evaluated blindly. RESULTS: There were no significant differences between treatment conditions concerning the neurological condition, lack of clinically evident neurotoxicity, seizure frequency and EEG spike frequency. OXC treatment was characterized by less delta, theta, and alpha power, more beta power, and significantly greater mean alpha frequency (P = 0.03 and 0.05 for the left and right occipital leads, respectively), than CBZ treatment. Interpeak latencies were prolonged in the CBZ condition as compared with normals (P = 0.01) and OXC (P = 0.02). CONCLUSION: In this cohort of patients substitution of OXC for CBZ was associated with significant normalization of electrophysiological parameters, indicating decreasing neurotoxicity while shifting from CBZ to OXC monotherapy.

Adult↗
PubMed2004

Nailfold digital capillaroscopy in 447 patients with connective tissue disease and Raynaud's disease.

The presence of megacapillaries and a decreased capillary density are the hallmarks of the scleroderma capillary pattern, which can be detected by nailfold capillarmicroscopy. One hundred and eighty-six patients with Raynaud's phenomenon, 65 cases with undifferentiated connective tissue disease (UCTD), 47 patients with systemic lupus erythematosus (SLE), 26 patients with dermato/polymyositis, 14 with rheumatoid arthritis, seven cases with primary Sjögren's syndrome and 102 patients with systemic sclerosis (SSc) were investigated. Of the 16 patients with diffuse cutaneous SSc and the 86 limited cutaneous SSc cases, 14 (87.5%) and 53 (61.6%) showed the scleroderma capillary pattern, respectively. Nine of the 65 (13.8%) cases with UCTD and 24 of the 186 (12.9%) cases with Raynaud's phenomenon also exhibited the same pattern. Four of the 47 (8.5%) with SLE and seven of the 26 (26.9%) with dermato/polymyositis, and no patients with rheumatoid arthritis or Sjögren's syndrome, exhibited the scleroderma capillary pattern. The conclusion is that the scleroderma capillary pattern is often present in SSc and dermato/polymyositis. Furthermore, patients with Raynaud's phenomenon and UCTD may also occasionally exhibit this pattern. Therefore, capillarmicroscopy seems to be a useful tool for the early selection of those patients who are potential candidates for developing scleroderma spectrum disorders.

Adult↗
PubMed2004

Vasoreactivity in patients with periventricular white matter lucency.

OBJECTIVES: Cerebral hypoperfusion has been evidenced in patients with periventricular white matter lucency (PWML), however, our knowledge is limited regarding vasoreactivity (VR) changes in these patients. Therefore, we compared the cerebral blood flow velocity (CBFV) responses during different vasoregulatory challenges in healthy volunteers, to those in patients with PWML. MATERIAL AND METHODS: In 20 patients with PWML and in 20 healthy volunteers the VR of the middle cerebral artery (MCA) system was measured by analyzing the changes of CBFV during different stimulation paradigms (ventilation, tilting and acetazolamide tests). During transcranial Doppler (TCD) registration the systemic blood pressure, the expiratory partial CO(2) pressure (pCO(2)) and the electroencephalograph (EEG) were monitored. RESULTS: The relative velocity change was significantly smaller in the PWML group than in the normal control group during hypercapnia (16 +/- 12% vs 32 +/- 17%; P < 0.001) and this finding was confirmed by assessment of pCO(2)-corrected velocity change (4.7 +/- 3.7 cm/s/kPa vs 18.4 +/- 6.8 cm/s/KPa; P < 0.001). Although CBFV measurements during acetazolamide test tended to support these findings, the changes of other parameters measured did not reach the level of significance. One patient showed considerable orthostatic reaction (mean arterial blood pressure decrease by 70 mmHg) but it was not associated with significant changes in CBFV. CONCLUSION: Patients with PWML showed an impaired VR in the MCA flow territory supporting the concept of the microangiopathic origin of leukoaraiotic changes.

Acetazolamide↗
PubMed2004

Anti-inflammatory effect and soft properties of etiprednol dicloacetate (BNP-166), a new, anti-asthmatic steroid.

In vitro and in vivo anti-inflammatory properties and soft characteristics of etiprednol dicloacetate (BNP-166) a new steroid, which has been developed for the treatment of asthma, were investigated in this study. The compound effectively decreased cytokine production in lipopolysaccharide stimulated lymphocytes and attenuated lectin-induced proliferation of blood mononuclear cells in tissue culture. In an animal model of allergen sensitized and challenged Brown Norway rats, using topical treatment, etiprednol dicloacetate substantially attenuated the extent of allergen induced bronchoalveolar fluid eosinophilia. At every examined parameter its pharmacological effects were comparable to those of budesonide. By means of in vitro biological and analytical methods the soft character of BNP-166 was also investigated. The anti-inflammatory effect of etiprednol dicloacetate in vitro was shown to be the function of the quantity of serum components, present in the assay. This loss of activity was most likely the result of the fast metabolism of etiprednol dicloacetate, which in the presence of sera could have been demonstrated by LC/MS/MS. Our data indicate that the significant local effect of the compound will very likely be accompanied with a drastically reduced systemic activity indicating an encouraging selectivity of the pharmacological action of etiprednol dicloacetate.

Adrenal Cortex Hormones↗
PubMed2003

Philadelphia chromosome and/or bcr-abl mRNA-positive primary thrombocytosis: morphometric evidence for the transition from essential thrombocythaemia to chronic myeloid leukaemia type of myeloproliferation.

AIMS: The incidence, bone marrow morphology and genetic features of bcr+ essential thrombocythaemia were investigated. METHODS AND RESULTS: Sixty-four consecutive patients meeting the criteria of essential thrombocythaemia have been investigated for bcr-abl rearrangement and chimera mRNA expression. Reverse transcriptase-polymerase chain reaction indicated bcr-abl expression in six patients, in two of whom large fraction of the blood and bone marrow cells proved to be positive for Philadelphia chromosome (Ph) by fluorescent in-situ hybridization (FISH) and conventional cytogenetic analysis. In the remaining four patients FISH analysis could not detect Ph+ cells among the blood cells, but in one of these four patients conventional cytogenetic analysis indicated a very small fraction (2%) of Ph+ mitoses in the bone marrow (bcr+ essential thrombocythaemia patients). In three of these four patients, X-chromosome-linked clonality assay showed that the disease is of uncommitted stem cell origin. During an average of 57 month long follow-up no transformation to chronic myeloid leukaemia type of disease or acceleration/blastic crisis could be observed in the four bcr+ essential thrombocythaemia patients. They did not differ significantly from typical essential thrombocythaemia patients in quantitative indices of bone marrow cellularity or the size of megakaryocytes. In these two parameters as well as in the total nucleolus organizer region area per nucleus, however, significant differences could be detected between these four as well as typical chronic myeloid leukaemia patients. Statistical analysis of the morphometric data obtained from all six Ph+ and bcr+ essential thrombocythaemia patients combined indicated a shift of the bone marrow morphology towards the chronic myeloid leukaemia type of myeloproliferation. CONCLUSIONS: These investigations indicate that bcr+ essential thrombocythaemia is infrequent among essential thrombocythaemia patients, and this condition resembles essential thrombocythaemia more than chronic myeloid leukaemia. Various expansions of the Ph+ clone appear to lead to either essential thrombocythaemia or, rather, chronic myeloid leukaemia type of myeloproliferation; however, data in the present study do not indicate that bcr+ essential thrombocythaemia would be a form fruste variant of chronic myeloid leukaemia.

Adult↗
PubMed2003

Calcium metabolism and endocrine functions in a family with familial hypocalciuric hypercalcemia.

OBJECTIVE: We report two Hungarian patients with familial hypocalciuric hypercalcemia (FHH) caused by a mutation of the calcium-sensing receptor (CaSR) at codon 55. The proband and her father were heterozygous for this mutation. DESIGN: We performed detailed clinical and laboratory assessments of this family to characterize the effects of CaSR mutation on several endocrine organs expressing CaSR. RESULTS: Interestingly, we could not detect any failure in the function of any tissues we examined, except in serum calcium levels. CONCLUSIONS: To our knowledge, this has been the first report from Eastern and Central Europe showing P55 L mutation of the CaSR, as well as the first publication discussing the effect of this mutation on several endocrine systems containing CASR.

Adult↗
PubMed2002

Successful repair of intraoperative type-A dissection in an infant.

A case of intraoperative type-A aortic dissection caused by partial displacement of the aortic cannula in a 6-month-old infant is presented, which was successfully managed by reapproximation of the dissected layers of the ascending aorta. At 1 year of follow-up the imaging studies show a normal appearance of the operation site.

Aorta↗
PubMed2002

Lack of association between calcium-sensing receptor gene "A986S" polymorphism and bone mineral density in Hungarian postmenopausal women.

Calcium-sensing receptor (CaSR) is an attractive candidate gene for osteoporosis susceptibility. The CaSR "A986S" genotype has been shown to have an effect on serum calcium. Recently, an association has been reported between the CaSR gene A986S polymorphism and bone mineral density in healthy white girls. In this study, we examined whether CaSR gene A986S polymorphism is associated with decreased bone mass in 230 Hungarian postmenopausal women. From this cohort, 108 osteoporotic patients were compared with 122 healthy control women. Bone mineral density (BMD) was measured at the lumbar spine (L2-4) and femoral neck using dual-energy X-ray absorptiometry. Allele-specific polymerase chain reaction was used to amplify A986S polymorphisms of the CaSR gene. We found no difference in the distribution of different alleles or genotypes between groups (p = 0.762). No significant effect of CaSR genotype on BMD was observed either in the whole population or in the subgroups. Our data do not support the idea that CaSR gene A986S polymorphism has an impact on bone mass.

Aged↗
PubMed2002

The quantification of pulmonary valve haemodynamics using MRI.

The optimum slice location within the pulmonary root to quantify pulmonary valve haemodynamics was examined using magnetic resonance (MR) phase velocity mapping. MRI was carried out on 15 patients with congenital aortic valve disease. Although the patients had aortic valve disease, all measurements were made on the pulmonary valve. Systolic (Q(SYS)) and diastolic (Q(DIAS)) blood flow volume and cardiac index (CI) were determined at four pulmonary artery locations. The change in diastolic flow volume relative to slice 1, closest to the pulmonary valve, was also calculated. For a change in axial position of 1.5 cm, i.e. from 0.5 to 2 cm from the annulus, there was a change in diastolic flow volume of 4.4 ml. There was a significant increase in the mean diastolic flow from 3.4 to 7.7 ml (p = 0.01 between slice positions 0.5 and 2 cm. However, there was no significant change in CI, 3.4-3.7 l/min/m2 (p = 0.14) over the same distance. We believe that two factors are responsible for these results. The first is that of compliance, whose effects can be minimized by placing the MR slice close to the valve, however, this will not account for the second factor, being that of valve motion, and hence diastolic pulmonary valve flow or regurgitant volume will be underestimated. The degree of underestimation may only be important at mild and moderate levels of regurgitation or if changes in regurgitation are to be temporally measured.

Adolescent↗
PubMed2002

Hypertension and clusters of risk factors in different stroke subtypes (an analysis of Hungarian patients via Budapest Stroke Data Bank).

Our aim was to determine the frequency of hypertension in the Hungarian stroke population, and to compare it with the data of other stroke registries. We attempted to find characteristic cluster-like associations between hypertension and another nine risk factors in different stroke subtypes and to ascertain the role of hypertension in leukoaraiosis, in early mortality, in stroke recurrence and in the case fatality rate up to 10 years. Risk factor profile of 500 unselected acute stroke cases of the Budapest Stroke Data Bank were analysed. We compared data of hypertensive stroke patients to those of unaffected ones. LIFEREG procedure of the SAS software package, cluster analysis, logistic regression, Pearson's correlation coefficient and Student's t-test were used as statistical methods. Hypertension was documented in 75% of the patients. The largest clusters were formed by the following groups: atherosclerotic stroke, hypertension with ischaemic heart disease; lacunar stroke and haemorrhage, hypertension with elevated serum cholesterol, cardiogenic embolism, ischaemic heart disease with atrial fibrillation. The case fatality rate was significantly higher in the group of hypertensive patients with ischaemic heart disease relative to those without it during the 10 years follow-up period. In the leukoaraiosis-group, systolic blood pressure was significantly higher than in the non-leukoaraiosis group. The rate of hypertension was higher than in other stroke registries. Hypertension appears to be the most frequent risk factor in stroke patients but case fatality rate is determined by presence or absence of ischaemic heart disease.

Aged↗
PubMed2002

Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease.

Reductions in regional cerebral perfusion, particularly in the posterior temporo-parietal lobes, are well recognized in Alzheimer's disease. We set out to correlate perfusion changes, using (99m)Tc-HMPAO single photon emission tomography (SPET), with the pathological stage of Alzheimer's disease. The 'Braak stage' of the distribution of neurofibrillary pathology in post-mortem brains was used to classify SPET scans taken in life from a mixed (dementia and control) elderly population into the entorhinal stage (n = 23 subjects), limbic stage (n = 30 subjects) and neocortical stage (n = 36 subjects) Alzheimer's disease pathology. The SPET scans were then registered to a common, standard Talaraich space, and single template scans produced for each pathological stage. Comparison of these templates revealed an evolution in the pattern of reduction in regional perfusion. Additional comparisons were performed using earlier SPET scans obtained 5 years before death. For comparisons between templates, a threshold of 10% perfusion change was chosen so as to be clinically relevant as well as statistically significant. Reduced perfusion appears between the entorhinal and limbic stages in the anterior medial temporal lobe, subcallosal area, posterior cingulate cortex, precuneus and possibly the supero-anterior aspects of the cerebellar hemispheres. Large posterior temporo-parietal perfusion defects then appear between the limbic and neocortical stages, before finally large frontal lobe perfusion defects. The time course of these perfusion defects appears relatively long, suggesting that perfusion changes may have scope to be a diagnostic aid in staging Alzheimer's disease in life. The reduction in anterior medial temporal lobe perfusion may have future relevance on modern high resolution SPET and PET systems and also perfusion-type MRI sequences.

Aged↗