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Biomedical subjects

J Nagy

Publications and source records attributed to J Nagy.

At least 37 records · Page 2Linked to original sources

[Analgesics-induced chronic renal failure in patients on dialysis therapy in Hungary].

In recent years elaboration of the diagnosis of analgesic-nephropathy (ANP) with the help of imaging techniques significantly increased the possibility of diagnosing the disease. Therefore, evaluating the prevalence of ANP has become more accurate in our country as well. The prevalence of ANP has been investigated in patients who have newly been taken into the dialysis program due to renal disease of unknown aetiology in 22 dialysis centers between December 1994-December 1997. The diagnosis of ANP has been based on revealing chronic drug abuse in the history and positive results of renal imaging (decrease in length of both kidneys combined with either bumpy contours and/or papillary calcification). Among 284 patients dialysed with unknown diagnosis 42 (14.8% of all cases) proved to have ANP. All patients except 2 took analgesic mixtures containing phenacetin/paracetamol, phenason derivatives, acetilsalysilic acid, caffeine and/or codeine. According to their investigations, ANP is a common disease resulting in end-stage renal failure in Hungary as well.

Acetaminophen↗

Cytotoxic effect of alcohol-withdrawal on primary cultures of cortical neurones.

Physical dependence on alcohol was observed previously at the cellular level in cultured IM-9 human lymphoblast cells. To answer the question whether physical dependence can also develop in neurones and to investigate the neuronal processes involved in the development of alcohol dependence and withdrawal symptoms, cultures of cortical neurones were adapted to alcohol. Morphological characteristics of neurones were not altered during the chronic (3-day) repeated (once per day) ethanol (50-100 mM) treatment, whereas obvious signs of neuronal damage were seen after the following 24 h of alcohol-withdrawal. The extent of the damage, quantitated by measuring the release of lactate dehydrogenase (LDH) into the culture media, was dependent on the concentration of ethanol in the medium during adaptation. LDH-release induced by alcohol-withdrawal was significantly reduced by re-addition of ethanol, as well as by administration of non-competitive (MK-801) or NR2B selective (threo-ifenprodil) N-methyl-D-aspartate (NMDA) receptor antagonists. The sigma ligand haloperidol and the L-type voltage sensitive calcium channel blocker nimodipine were also effective, whereas the effect of the gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol was not significant. Furthermore, chronic ethanol treatment potentiated the NMDA induced neurotoxicity and the ability of acute alcohol to inhibit LDH-release in response to NMDA. According to these results, (i) the phenomenon of alcohol-dependence can be observed at the level of neurones and (ii) NMDA receptors seem to play a central role in the development of ethanol dependence and in neurotoxicity induced by alcohol-withdrawal.

Alcohol-Induced Disorders↗

Prognostic histological and immune markers of renal cell carcinoma.

Recent development on the fields of molecular genetics and immunology of human renal cell carcinoma (RCC) have resulted in more successful treatment of advanced and metastatic RCCs. Re-evaluation of the prognostic/predictive data aim the initial tumor staging of RCC patients to achieve better patient selection for immune and gene therapy. 125 RCC patients diagnosed according to the Heidelberg histological classification, graded, Robson staged, immune treated (Interferon-a a+ Vinblastine or Broncho-Waxom/Decaris) were followed-up clinically for 36 months. Tumor immunity markers by immunohistochemistry of tumor infiltrating lymphocytes (TIL) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (TIC) were visualized by fluorescent polyclonal antibodies. Histologically oncocytomas defined a better (p<0.02) and sarcomatous RCCs a worse (p<0.01) follow-up prognosis. Basically, the metastatic status (related with the stage and grade) determined the clinical outcome (p<0.00002) of the RCC patients. Tumoral immune complexes (TIC) were weak positive, while tumor infiltrating lymphocytes (TIL) weak negative predictors of the succes of Broncho-Waxom/Decaris immune therapy. Molecular genetic based histological classification, grade, stage and metastatic status parameters together with some tumor immunity parameters (TIL, TIC) can predict the success of immunotherapy of RCC patients.

Antineoplastic Agents, Phytogenic↗

Specific von Hippel-Lindau protein expression of clear cell renal cell carcinoma with "immunogenic" features.

Human clear cell renal cell carcinoma (CCRCC) is characterized by specific von Hippel-Lindau (VHL) gene alterations and immunogenic features. In the present study, the immunohistochemical expression of the von Hippel-Lindau gene protein (pVHL) was compared with the presence of major histocompatibility complex (MHC I-II), tumor infiltrating lymphocytes (TIL) and tumoral immune complexes (TIC) in CCRCC. Native tumor tissues of 132 RCC patients (95 with the common clear cell subtype), diagnosed according to the Heidelberg classification, were obtained for immunohistochemistry. Tumor stainings with pVHL, MHC I-II and tumor infiltrating lymphocytes (T and B lymphocytes, monocytes) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (IgG, IgA, IgM and C1q, C3 complement proteins) were visualized by fluorescent polyclonal antibodies. Immune stainings were semiquantitatively evaluated. Specificity and sensitivity of these markers in relation to the common histological subtype of RCC (CCRCC) were calculated. CCRCC was characterized by specific pVHL expression. At the same time, CCRCC was associated with constitutional MHC I-II expression and highly specific degree of TIL and TIC. It is concluded that specific pVHL expression of CCRCC is frequently associated with immunogenic features. Immunohistochemical analysis aims the initial tumor staging of RCC patients to achieve better patient selection for immunotherapy. However, the association of pVHL expression with the immunogenic CCRCC is statistically relevant, the mechanism and its clinical relevance in immunotherapy still remains to be tested.

Adenocarcinoma, Clear Cell↗

Introducing DRG-based financing in Hungary: a study into the relationship between supply of hospital beds and use of these beds under changing institutional circumstances.

Most hospital reforms carried out in Europe over the past few decades concern the supply of hospital beds and hospital financing systems. In Hungary, financing was not tied to hospital input or output until a Diagnosis-Related-Group system was introduced. This change provided an opportunity to study the effect of the new system, taking the supply of hospital beds into account. We studied the effect of the financing system and bed supply on four output parameters, average length of stay; admission rate; occupancy; and case-mix. The incentives of the financing system influenced the length of stay (shorter) and the admission rate (more admissions). Although the case-mix did increase, occupancy was not affected. The supply of more beds resulted in higher admission rates and a slightly lower efficiency (a lower occupancy rate). No interaction effects of (variations in) the bed supply and the financing system were found.

Delivery of Health Care↗

N(epsilon)-(carboxymethyl)lysine levels in patients with type 2 diabetes: role of renal function.

Advanced glycation end products (AGEs) such as N(epsilon)-(carboxymethyl)lysine (CML) have been implicated in the development and progression of diabetic nephropathy. The aim of the present study is to investigate AGE levels in patients with type 2 diabetes with special regard to the role of renal impairment. Serum and urine CML levels (using a newly developed enzyme-linked immunosorbent assay), as well as serum AGE-fluorescence, were measured in 109 patients with type 2 diabetes. Patients were divided into groups with normal and impaired renal function. We found elevated serum fluorescent AGE and CML levels, as well as decreased urinary CML excretion rates, in patients with diabetes with renal impairment, but not those with normal renal function. In the presence of impaired renal function, serum CML and fluorescent AGE levels showed a significant inverse relation with creatinine clearance and a significant direct correlation with each other. No relationship could be found between serum AGE levels and parameters of blood glucose control or the presence of the following clinical complications: ischemic heart disease, diabetic retinopathy, and neuropathy. We conclude that the decline in renal function leads to increased serum AGE levels in patients with type 2 diabetes.

Adult↗

Economic evaluation of kidney transplantation versus hemodialysis in patients with end-stage renal disease in Hungary.

BACKGROUND: Kidney transplantation is generally acknowledged as the more clinically effective and more cost-effective option in managing patients with end-stage renal disease, compared with dialysis. This study looked for confirmatory evidence in a Hungarian population. METHODS: Patients (n = 242) with end-stage renal disease who received cadaveric kidney transplantation during 1994 were followed up for 3 years. They were compared with patients (n = 840) receiving hemodialysis who were on a waiting list for transplantation. Data were collected retrospectively. Treatments were compared for clinical efficacy and for cost-effectiveness. RESULTS: At month 36, the standard mortality hazard function was 3.5 times higher in the group receiving hemodialysis (P < .0001) than in the transplant recipients. Average treatment costs per patient over the 3 years were also significantly higher (P < .0001) in the hemodialysis group than in the group than received transplants. The cost of 1 year gained by transplantation was significantly less (P < .0001) than the cost associated with hemodialysis. CONCLUSIONS: Compared with hemodialysis, kidney transplantation provides greater survival benefits to patients with end-stage renal disease, at less cost.

Adult↗

Insulin-induced peroxynitrite production in human platelet-rich plasma.

Recent data support the possible role of nitric oxide (NO*) in the development of insulin signalling. The aim of this study was to examine the effect of insulin on NO* production by platelets. The chemiluminescence of platelet-rich plasma prepared from the blood of healthy volunteers was measured in the presence of luminol. Indirect detection of NO* by luminol is possible in the form of peroxynitrite produced in the reaction of NO* with a superoxide free radical. Luminol oxidation induced by hydroxyl free radical and lipid peroxidation was prevented by 150 micromol/l of desferrioxamine mesylate. Insulin, in the range of 0.084-840 nmol/l, induced a concentration-dependent increase in chemiluminescence, which was inhibited both by the competitive antagonist of the NO* synthase enzyme. N(omega)-nitro-L-arginine methyl ester (at concentrations of 2.0-4.0 mmol/l, P<0.001), and by the elimination of superoxide free radicals using superoxide dismutase (72-144 IU/ml, P<0.001). In conclusion, we assume that the insulin-induced increase in chemiluminescence of platelet-rich plasma was due to increased production of NO* and superoxide free radicals forming peroxynitrite. The data are consistent with production of peroxynitrite from human platelets under insulin stimulation.

Area Under Curve↗

Cks1 mediates vascular smooth muscle cell polyploidization.

Vascular smooth muscle cells (VSMC) at capacitance arteries of hypertensive individuals and animals undergo dramatic polyploidization that contributes toward their hypertrophic phenotype. We report here the identification of a defective mitotic spindle cell cycle checkpoint in VSMC isolated from capacitance arteries of pre-hypertensive rats. These cells demonstrated a high predisposition to polyploidization in culture and failed to maintain cyclin B protein levels in response to colcemid, a mitotic inhibitor. Furthermore, this altered mitotic spindle checkpoint status was associated with the overexpression of Cks1, a Cdc2 adapter protein that promotes cyclin B degradation. Cks1 up-regulation, cyclin B down-regulation, and VSMC polyploidization were evidenced at the smooth muscle of capacitance arteries of genetically hypertensive and Goldblatt-operated rats. In addition, angiotensin II infusion dramatically increased Cks1 protein levels at capacitance arteries of normotensive rats, and angiotensin II treatment of isolated VSMC abrogated their ability to down-regulate Cks1 and maintain cyclin B protein expression in response to colcemid. Finally, transduction of VSMC from normotensive animals with a retrovirus that drives the expression of Cks1 was sufficient to alter their mitotic spindle cell cycle checkpoint status and promote unscheduled cyclin B metabolism, cell cycle re-entry, and polyploidization. These data demonstrate that Cks1 regulates cyclin B metabolism and ploidy in VSMC and may contribute to the understanding of the phenomena of VSMC polyploidization during hypertension.

Animals↗

[Kinetics of aluminum absorption and serum concentration in chronic renal insufficiency].

After administration of a single dose of an aluminium containing antacid (Tisacid) to eight non dialysis patients in various stages of chronic renal insufficiency, the kinetics of serum aluminium absorption was studied. Serum aluminium peaked at two points of time, aluminium absorption being biphasic in renal patients comparing with monophasic kinetic in controls. At the same time, already at 24 hrs after Tisacid ingestion, the aluminium concentration was almost twice as high as initially even in mild renal insufficiency. These results are at variance with the rapidly reversible, monophasic aluminium absorption observed earlier in healthy subjects and in non-renal patients with duodenal ulcer. To ward off complications, a strong warning is given against administration of any aluminium-containing medicament or food to subjects with reduced renal function.

Administration, Oral↗

[Health prospects in the alternative strategies of renal replacement therapies].

The authors are publishing the health outcome results of a cost-effectiveness analysis on renal replacement therapies. They analysed the mortality data of the main renal replacement therapies between the 3-year time period of 1994-1997 in a retrospective way. They found that although there is a high initial postoperative mortality risk of the surgical procedure, the kidney transplantation reduces the relative risk of 3-year mortality by 27.7% (p = 0.0601) in comparison with the waiting listed hemodialysis. This means 5.6% absolute risk reduction. As it is proved that transplantation improves quality of life of patients on renal replacement therapy, the loss of a potential donor decreases the expected quality adjusted life years (QALY) benefit of those dialysed patients who are on the waiting list.

Adult↗

[Forecasting the number of patients with end-stage renal disease (Model of the system)].

The authors are dealing with the renal replacement therapies in Hungary. They are on the opinion that in view fo patient flow renal replacement therapies (such as various methods of dialysis and kidney transplantation) can be considered as one system. With analysing the number of patients in the past years they can establish that end-stage renal disease puts significant burden on the health insurance fund. According to their calculations the number of patients with end-stage renal disease will increase by 14-16% in the next few years if current trends continue. If we want to operate the system efficiently, we can reduce--up to a certain extent--the economic burden of dialysis by increasing the number of kidney transplantations.

Adolescent↗

[Nephropathy in non-insulin-dependent (type-2) diabetes mellitus].

There is a dramatic increase in the incidence of end-stage renal disease in non-insulin dependent diabetes mellitus (NIDDM) requiring renal replacement therapy. The most important risk factors of the onset of nephropathy in NIDDM are genetic predisposition (history of diabetes, hypertension and cardiovascular events in first-degree relatives), hypertension, quality of glycaemic control and smoking. These risk factors play an important role also in the progression of diabetic nephropathy. In about 20-25% of NIDDM patients nondiabetic renal diseases cause the renal damage (other primary nephropathies, ischaemic nephropathy). NIDDM is mainly the part of metabolic x syndrome (hypertension, obesity, dyslipidaemia, impaired glucose tolerance or NIDDM) and, for this reason, all members of metabolic x syndrome has to be involved in treatment strategies e.g. blood pressure "subnormalization", aggressive glycaemic control, cessation of smoking, the treatment of obesity and dyslipidaemia with diet, physical activity and antilipidaemic drugs, as well as restriction of dietary protein and salt intake. The successful prevention and treatment of diabetic nephropathy needs the development of an interdisciplinary interaction that involves general practitioners, diabetologists and nephrologists.

Albuminuria↗

Data processing of digital recordings of microscopic examination of urinary sediment.

The analysis of urine was actually the beginning of laboratory medicine. The important part of the routine urinalysis is the microscopic examination of the urinary sediment [Fogazzi and Cameron, Kidney Int 1996;50(3):1058-1068; Diamondopoulos, Am J Nephrol 1997;17(3-4):222-227; Fogazzi et al., Clin Chem Lab Med 1998;36(12):919-924]. The microscopic examination of the urine is the least standardised and most time-consuming part of the routine urinalysis, even though it is now known that careful analysis of the sediment components can provide early information concerning the anatomic integrity of the kidney and the existence and extent of recent damage. Our objective was to develop a computerised image processing system and an interactive software package for the backing of clinicians, medical research and medical students. The system consists of: (a) a CCD camera attached to a microscope. (b) Digital processing device. (c) Computer equipped with special video card. (d) Printer. (e) Software. Image analysis begins with a digital capturing of the image as data. The image is detected with 256 gray levels and displayed with a resolution of 512x512 pixels. A pixel is an abbreviation for picture elements and represents the dots on a screen. Once the image is acquired in digital format, the data can be manipulated for changes in the display image or for statistical purposes. The digitised microscope images are a very important part of renal diagnosis and of teaching nephrology.

Humans↗

Association of a uteroglobin polymorphism with rate of progression in patients with IgA nephropathy.

Uteroglobin gene-disrupted mice develop a nephritis very similar to immunoglobulin A (IgA) nephropathy. Megsin codes for a protein overexpressed in mesangium in patients with IgA nephropathy. Both are candidate genes that might have variants associated with an accelerated progression in patients with IgA nephropathy. We performed an association study of patients with IgA nephropathy and matching control subjects to test whether the G38A polymorphism in the uteroglobin gene, the C2093T polymorphism in the megsin gene, or the angiotensin-converting enzyme (ACE) insertion/deletion polymorphism is associated with IgA nephropathy or rate of disease progression in patients with IgA nephropathy. Of 110 patients with IgA nephropathy, 87 patients were followed up for at least 3 years for the progression study. We also studied 104 healthy volunteers. The uteroglobin, megsin, and ACE polymorphisms were not distributed differently in the 110 patients with IgA nephropathy compared with healthy controls; Hardy-Weinberg equilibrium criteria were fulfilled. The GG genotype of the G38A uteroglobin polymorphism was more common in patients with progression (odds ratio [OR], 3.5; P< 0.006) than the AG+AA genotypes. The G allele was also more common (OR, 2.6; P< 0.009) in patients with versus without progression. The 1/serum creatinine over time plot (in deciliters per milligram per day) was sevenfold steeper in GG patients than the other two genotypes (P = 0.08). No significant associations with disease progression were found for the other gene polymorphisms, and a multivariate analysis showed no interactions. We suggest the hypothesis that the uteroglobin gene contains variant(s) with a bearing on progression rate in patients with IgA nephropathy.

Adult↗

A randomized trial of two treatments for mild traumatic brain injury: 1 year follow-up.

The purpose of this study was to provide 1 year follow-up data to a previous paper that compared single-session (SS) treatment to treatment-as-needed (TAN) outcomes for mild traumatic brain injury (MTBI) survivors at 3 months post-injury. Participants were 105 adults with MTBI who were recruited from consecutive admissions to two hospital emergency wards, and randomly assigned to either the SS or TAN modality. No group differences in outcome were evident at 12 months post-injury. As well, improvements seen in the groups after 3 months were maintained at 12 months. As improvements between 3 and 12 months were negligible, self-reported improvement after a treated MTBI typically occurred within the first 3 months. Brief educational intervention given soon after MTBI appears to be as helpful as more intensive treatment for most MTBI survivors for at least 12 months post-injury.

Adult↗