Biomedical subjects

Attila Juhász

Publications and source records attributed to Attila Juhász.

9 recordsLinked to original sources

PubMed2006

Detection of four lymphotropic herpesviruses in Hungarian patients with multiple myeloma and lymphoma.

It has been suggested that human herpesvirus 8 (HHV-8), also known as KSHV (Kaposi's sarcoma-associated human herpesvirus), might possess a promoting effect in the development and progression of monoclonal gammopathies. In this study, the presence of Epstein-Barr virus (EBV), human cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and human herpesvirus 8 (HHV-8) were tested in patients with multiple myeloma (MM) using both serologic and nucleic acid amplification techniques. The transient reactivation or continuous presence of EBV, CMV, HHV-6 and HHV-8 could be detected in, respectively, 36, eight, 13 and 29 of 69 MM patients; nine, one, four and six of 16 monoclonal gammopathy of unknown significance patients; and seven, four, zero and five of 10 Waldenström's macroglobulinemia patients. The total number of MM patients was 95. HHV-8 PCR-positivity was significantly more frequent in the MM group than in the control group of patients with non-Hodgkin's lymphoma (NHL). However, serologic testing did not reveal significant differences between the two patient groups. The number of MM patients with concomitant herpesvirus infections as detected by PCR was as follows: 15 double, seven triple and two quadruple virus nucleic acid positive. In 13/95 MM patients, the simultaneous presence of acute EBV infection and HHV-8 PCR-positivity was detected compared with none of the control group (P=0.009). These results indicate that in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.

Animals↗

PubMed2006

[A practicing physician's view on obesity].

Overweight and obesity are worldwide problems, its health and psychosocial burden on the individual and on society are tremendous. Diagnosing obesity is rather easy, and is based on simple anthropometric measurements, such as body weight, height and waist circumference. The different classes of obesity are determined by body mass index, which, together with waist circumference and comorbid conditions and other risk factors determine the individual risk for mortality and morbidity. Obesity is due to genetic and environmental factors, mainly is the consequence of excess calorie intake and sedentary lifestyle. The fat mass of the body is under neuroendocrine control, the central controller is the hypothalamus. Leptin, produced by adipocytes in proportion to fat mass, is the afferent signal to the hypothalamus. Decreasing or increasing levels of leptin result in orexigen and anorexigen neurotransmission, which mediate efferent activation towards food consumption and energy storage, or towards food restriction and energy expenditure, respectively. The balance of these events and/or the ,set point" of the controller--if leptin resistance is present--is shifted towards higher body/fat mass in obesity. Management of obesity is complex, however, in all stages of obesity lifestyle changes are mandatory--including diet, exercise and behavior modification. Pharmacotherapy might be needed if lifestyle changes alone do not result an acceptable weight loss. For the long-term treatment of obesity sibutramin and orlistat are the available approved drugs. In case of morbid obesity (body mass index > 40 kg/m2, or > 35 kg/m2 plus comorbid conditions and other risk factors) surgery might be the treatment of choice. There are different surgical methods, among those a widely used method nowadays is the laparoscopic adjustable gastric banding procedure.

Algorithms↗

PubMed2005

[Kaposi's sarcoma].

In recent years large amounts of findings have accumulated about Kaposi's sarcoma, a virus induced angioproliferative disorder appearing in four clinical forms: classical, epidemic, endemic and iatrogenic, as it has been in focus of not only from the dermatologic but also from the viral tumorgenesis perspective. The common characteristics are the histopathological appearance, the causative role of the human herpesvirus 8 and the similar clinical picture (bluish-red macules, papules, and nodes). Frequency of the distinguished clinical forms differs with geographical location. Viruses, genetic -, and environmental factors have been shown to play a role in the pathomechanism of the disease, of which the most important is the human herpesvirus-8. The mechanisms by which viral proteins and virus infection enhance tumorgenesis and alter immune functions directed at cells have been studied in detail. During the initiation of tumorgenesis, virus induced viral and host cell products (cytokines, receptors and oncogens) initiate inflammatory and angiogenic polyclonal cell proliferation, which later, by the synergistic action of other viruses and/or environmental factors, give rise to malignant proliferation and allow the selected cell to clonally expand and behave like a true malignant tumor. In light of newly published results the authors not only present the clinical appearances and summarize diagnostic possibilities and the pathomechanism of the disease, but also give a thorough overview of the therapeutic tools of Kaposi's sarcoma, and share their experiences obtained during the follow-up of classical Kaposi's sarcoma patients.

AIDS-Related Opportunistic Infections↗

PubMed2005

Prevalence of human herpesvirus-8 infection in HIV-positive patients with and without Kaposi's sarcoma in Hungary.

Human herpesvirus-8 (HHV-8) infection of 130 Hungarian HIV-positive individuals with or without Kaposi's sarcoma was investigated from 158 serum and 122 peripheral blood samples using anti-latency-associated nuclear antigen (LANA) indirect immunofluorescence assay (IFA), recombinant orf65 and orfK8.1 antigen enzyme-linked immunosorbent assays (ELISAs), Western blot assays and orf26 specific nested polymerase chain reaction (PCR). The overall prevalence of HHV-8 infection was found to be 31.5% (41/130) among the Hungarian HIV-positive patients. This seroprevalence rate is 7-11-fold higher than that of healthy HIV-negative blood donors in Hungary. The highest prevalence of HHV-8 infection (36.1%, 35/97) was observed in homo- or bisexual patients. Similar to the serologic results, HHV-8 DNA was not always detectable in all serial samples previously shown to be positive for HHV-8 DNA.

Adolescent↗

PubMed2005

Chromosomal imbalances in laryngeal and hypopharyngeal cancers detected by comparative genomic hybridization.

BACKGROUND: The prognostic divergence of laryngeal and hypopharyngeal carcinomas is well known. Hypopharyngeal tumors are characterized by frequent metastasis formation and local recurrence, which is the source of the unfavorable prognosis of this subtype. The aim of this study was to define chromosomal alterations associated with the aggressive behavior of hypopharyngeal tumors. METHODS: Twenty-nine head and neck squamous cell carcinomas (larynx n = 14 and hypopharynx n = 15) were analyzed by comparative genomic hybridization (CGH). Fluorescence in situ hybridization (FISH) was used to validate the CGH data and to compare the amplification pattern of the most frequently altered gene (cyclin-D1, CCND1) located on 11q13. RESULTS: The average number of genetic alterations was significantly higher in the hypopharyngeal tumors (P = 0.02). A good correlation of FISH and CGH data were seen. Gains on 11q13 were present in both subtypes, whereas amplification of CCND1 was associated with the aggressive phenotype by FISH. Chromosomal alteration, which was rarely detected in hypopharyngeal tumors but was observed in more than 50% of laryngeal carcinomas, was 8q gain. CONCLUSION: Our CGH and FISH data show that head and neck squamous cell carcinomas contain complex cytogenetic alterations and further support the hypothesis that different molecular pathways are responsible for the progression of differently localized tumors of the upper aerodigestive tract.

Aged↗

PubMed2005

Unified pharmacogenetics-based parent-metabolite pharmacokinetic model incorporating acetylation polymorphism for talampanel in humans.

The N-acetylation of the noncompetitive AMPA antagonist talampanel (TLP) represents a route of varying significance in various species. For a detailed analysis in humans, plasma concentrations of TLP and its N-acetyl metabolite (NAc-TLP) were measured for up to 48 h after administration of a single oral dose of 75 mg in 28 healthy volunteers following genotyping for the N-acetyltansferase NAT2 isozymes (alleles NAT2*4, *5, *6, and *7). Unified parent-metabolite pharmacokinetic (PK) models that allowed three different rates of acetylation were used to simultaneously fit plasma levels for both the parent drug and its metabolite following genotype-based classification as slow, intermediate, or fast acetylator. A perfect correspondence was found between the phenotype inferred from genotyping and the phenotype determined by using plasma metabolite-to-parent molar ratios indicating that this route of metabolism is indeed mediated by NAT2. Linear parent-metabolite PK models (first-order input, first-order elimination through two parallel routes one of which is through a metabolite with polymorphic rate of formation) gave adequate and sufficiently consistent fit. Parameters obtained suggest that for TLP in humans, N-acetylation represents only about 1/4th of the total elimination even in true (*4/*4 homozygous) fast acetylators, acetylation is about 8-12 times faster in fast and 3-6 times faster in intermediate acetylators than in slow acetylators, and the N-acetyl metabolite is eliminated faster than the parent drug. Such PK models can provide quantitative estimates of relative in vivo metabolism rates for routes catalyzed by functionally polymorphic enzymes.

Acetylation↗

PubMed2003

Design, pharmacokinetic, and pharmacodynamic evaluation of a new class of soft anticholinergics.

PURPOSE: To design and evaluate a new class of soft anticholinergics with subtype selectivity. METHODS: A new class of soft anticholinergics was designed based on the "inactive metabolite" approach. Four compounds were synthesized. The potency and soft nature of the compounds were evaluated by receptor binding, cardiac, and mydriatic studies. Stability and pharmacokinetic studies were also performed on these newly synthesized soft anticholinergics. RESULTS: Receptor binding studies of the soft anticholinergics on cloned muscarinic receptors indicated pKi values in the range of 7.5 to 8.9. Two compounds, 9a and 13a, of the series showed muscarinic subtype receptor selectivity (M3/M2). In mydriatic studies, 13a and 13b showed shorter duration of action in the treated eyes than tropicamide. In the control eyes, significant dilation of pupils was found only in rabbits treated with atropine and tropicamide, indicating that the soft anticholinergics lack systemic effects because of their facile hydrolytic deactivation. Consistent with their soft nature, this new class of soft anticholinergics displayed much shorter cardiovascular effects in the carbachol-induced bradycardia (10 to 15 min) in rats than atropine (> 60 min). Stability and pharmacokinetic studies suggested that the new soft anticholinergics were rapidly eliminated from plasma (systemic circulation) after i.v. administration. CONCLUSIONS: A new class of anticholinergics was designed and synthesized, and the PK/PD evaluation confirmed they were potent "soft" anticholinergics; two of them showed muscarinic receptor subtype selectivity (M3/M2).

Administration, Topical↗

PubMed2002

Effects of haemodialysis on maximum P wave duration and P wave dispersion.

BACKGROUND: Analysing a 12-lead surface electrocardiogram (ECG), the inter-lead variability of the P wave interval, i.e. P wave dispersion, is defined as the difference between the maximum and the minimum P wave duration. Our aim was to assess the effect of haemodialysis on P wave duration and dispersion in non-diabetic patients with end-stage renal failure on chronic haemodialysis. METHODS: Twenty-eight patients (14 men and 14 women, mean age 58+/-16 years, average duration of dialysis 4.5+/-2.8 years) were examined. Prior to haemodialysis, echocardiography (M-mode and two-dimensional) was performed. Haemodialysis sessions were carried out with polysulfone dialysers and bicarbonate dialysate fluids. Twelve-lead ECGs were recorded at the beginning, 15 and 30 min after starting dialysis, at the end, and 2 h after completion of each session. Ionic parameters were checked during the study. P wave durations were measured with calipers in three consecutive complexes of each lead by one observer. RESULTS: P maximum was 58+/-16 ms at the beginning, and showed an increase by the end of dialysis to 98+/-8.9 ms (P<0.0001). Pre-dialysis P dispersion was 23+/-10 ms and increased to 41+/-16 ms by the end of the sessions (P<0.0001). In patients with a left atrial diameter larger than 45 mm, P dispersion increased from 23+/-11 to 53+/-10 ms (P<0.0003) by the end of the sessions. CONCLUSIONS: According to our results, ionic imbalance and dialysis itself may cause changes in P duration and dispersion simultaneously.

Atrial Fibrillation↗

PubMed2000

[Characterization of laryngopharyngeal tumors. Tumor size and vascularization]

A recent survey of head and neck cancer indicated a sharp difference in survival between cancer of the hypopharyx and cancers formed in other head and neck sites. We have analyzed tumor size relative to clinical stage and vascularization as possible causes for such a difference in a series of 21 patients with cancers of the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the volume of the smallest cancers of the larynx at stage 2 are significantly larger than the volume of the cancers of the hypopharynx at stage 4 (p<0.05). Next, we have determined by immunohistochemistry and morphometry the microvessel density (MVD), microvessel perimeter (MVP) and VEGF expression of laryngo-hypopharyngeal cancers. Analysis of these data indicates that there is no difference in vascularization and VEGF expression between these two tumor types. These data strongly suggest that the invasive-but not the angiogenic phenotype of hypopharyngeal cancer cells could be responsible for the more aggressive biological behavior of this head and neck cancer subtype.

Journal Article↗