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Biomedical subjects

K Nagy

Publications and source records attributed to K Nagy.

At least 19 recordsLinked to original sources

Hungarian experience with Langerhans cell histiocytosis in childhood.

The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of children's LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male-female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 +/- 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 +/- 3.1% at 5 years and 87.3 +/- 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.

Adolescent↗

Localization of human T-cell lymphotropic virus-1 gag proviral sequences in dermato-immunological disorders with eosinophilia.

The mechanisms leading to the development of eosinophilia were investigated in 65 patients with immunodermatological disorders, including the role of eosinophilotactic cytokines and the possible involvement of human T-cell leukemia virus, HTLV. HTLV-1 gag proviral sequences were revealed in two cases of lymphoproliferative disorders such as angiolymphoid hyperplasia with eosinophilia (ALHE) and CD4+ cutaneous lymphoma, respectively. Increased level of GM-CSF was detected in 33% of disorders studied. Elevated level of IL-5 and eotaxin was detected in 27% and 30%, respectively, of patients with bullous diseases. Elevated level of GM-CSF and eotaxin was found in 33% and 46%, respectively, of patients with inflammatory diseases. Neither of the four cytokines, however proved to be responsible alone or together for the induction of eosinophilia. The possible indirect role of human retroviruses through induction of eosinophilic chemotactic cytokines is hypothesized.

Base Sequence↗

Uridine release during aminopyridine-induced epilepsy.

Uridine, like adenosine, is released under sustained depolarization and it can inhibit hippocampal neuronal activity, suggesting that uridine may be released during seizures and can be involved in epileptic mechanisms. In an in vivo microdialysis study, we measured the extracellular changes of nucleoside and amino acid levels and recorded cortical EEG during 3-aminopyridine-induced epilepsy. Applying silver impregnation and immunohistochemistry, we examined the degree of hippocampal cell loss. We found that extracellular concentration of uridine, adenosine, inosine, and glutamate increased significantly, while glutamine level decreased during seizures. The release of uridine correlated with seizure activity. Systemic and local uridine application was ineffective. The number of parvalbumin- and calretinin-containing interneurons of dorsal hippocampi decreased. We conclude that uridine is released during epileptic activity, and suggest that as a neuromodulator, uridine may contribute to epilepsy-related neuronal activity changes, but uridine analogues having slower turnover would be needed for further investigation of physiological role of uridine.

Amino Acids↗

Attitudes of Hungarian healthcare professional students to tobacco and alcohol.

Tobacco represents the single most preventable cause of disease and death in the world today. There were an estimated 3 million deaths annually at the end of the 20th century and it has been estimated that this will rise to more than 10 million by 2030. A disproportionate share of the burden of mortality is already being borne in the Russian Federation and the countries of Eastern Europe. For example, some of the highest rates worldwide of cigarette consumption and smoking prevalence are in the Czech Republic, Hungary and Poland. Cancer is one of the major tobacco-related causes of disease and death and Hungary has the highest male incidence rates in the world for both oropharyngeal and lung cancer. A consequence of this is that the mortality rate of middle-aged (50-60-year-old) men in Hungary today is higher today than it was in the 1930s, particularly among the lower socioeconomic groups. Of the many different approaches to tobacco cessation and control, advice or intervention by healthcare professionals ranks high in effectiveness; a recent survey indicated that requests from healthcare professionals to quit ranked second in effectiveness after requests by the smoker's own family. If healthcare professionals are to play a role in reducing death and disease from tobacco related cancers it is necessary to assess the attitudes and behaviours among healthcare professional students. Our survey assesses perceptions, behaviour and consequences among university students.

Adult↗

Differentiation of vegetable oils by mass spectrometry combined with statistical analysis.

The main triacylglycerol (TAG) composition of different plant oils (almond, avocado, corn germ, grape seed, linseed, mustard seed, olive, peanut, pumpkin seed, sesame seed, soybean, sunflower, walnut and wheat germ) were analyzed using two different mass spectrometric techniques: HPLC/APCI-MS (high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry) and MALDI-TOFMS (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry).Linear discriminant analysis (LDA) as a multivariate mathematical statistical method was successfully used to distinguish different plant oils based on their relative TAG composition. With LDA analysis of either APCI-MS or MALDI-MS data, the classification among the almond, avocado, grape seed, linseed, mustard seed, olive, sesame seed and soybean oil samples was 100% correct. In both cases only 6 different oil samples from a total of 73 were not classified correctly.

Chromatography, High Pressure Liquid↗

Real-time endoarticular ultrasound imaging of the TMJ--a new diagnostic possibility? A cadaver study.

Recent advances in ultrasound imaging suggested endoarticular ultrasound imaging of the temporomandibular joint (TMJ) in combination with TMJ-arthroscopy as a new diagnostic method. Our investigations were performed on human cadavers, in combination with traditional TMJ-arthroscopy. During our investigations, the main articular structures were identified: the glenoid fossa of the temporal bone, articular disc, condyle of the mandible, and retrodiscal tissue. The combination of arthroscopy and ultrasound imaging provides more information on position, movement, and pathological changes in joint structures. Although all of the advantages, disadvantages, indications, and complications of this new diagnostic procedure are not yet clear, the authors consider this new method a useful diagnostic procedure for TMJ imaging.

Arthroscopy↗

A comparison of the lymphoproliferative capacity of pokeweed mitogen (PWM) and phytohaemagglutinin (PHA) in CCR-5 wild-type and heterozygous HIV-infected and uninfected subjects.

Effect of CCR-5 delta 32 heterozygosity in immunological protection was studied by a lymphocyte proliferation assay. Twenty of 86 HIV+ and eight of 32 healthy subjects showed heterozygous mutation (wt/mut) of the CCR-5 gene. Lymphocyte proliferation to pokeweed mitogen was found significantly higher (P < 0.005) in wt/mut versus wild type homozygous (wt/wt) HIV+ subjects in groups with CD4 > 500 and CD4 < 200 cell/ micro L. Phytohaemagglutinin induced stronger proliferation of cells from wt/mut HIV+ subjects with CD4 < 200 cell/ micro L (P = 0.03). Decline of lymphocyte response was more significant among wt/wt groups with different CD4+ cell counts than that between wt/mut groups to both mitogens. Reduced number of CCR-5 receptors on CD4+ cells may decrease the ability of HIV-1 envelope glycoproteins to transduce intracellular signals through CCR-5. Mutation in CCR-5 gene seems to have a benefit in preventing T-cells from HIV envelope-mediated immunopathogenic effects and maintain a relatively normal response to lectins.

Adult↗

The involvement of hydroxyl free radicals in differentiation of the PC-12 rat pheochromocytoma cell line.

These experiments tested the differentiation properties of the PC-12 cell line under conditions of in vitro generation of OH&z.rad; free radicals by Fenton reaction. This involves the simultaneous addition of the following reactants: ADP-Fe(2+)-complex (0.1 mM for iron) and H(2)O(2) (0.025 mM), final concentrations. Superoxide dismutase activity, the increase of which is considered as a marker of differentiation, catalase and glutathione peroxidase enzyme activities were investigated, which all displayed significant increases after single and repeated interventions with hydroxyl free radicals, while the cell number remained nearly at the starting-value. It is known that the differentiation takes place when the cell number has reached a plateau. These data, therefore, suggest that hydroxyl free radicals can induce in vitro cell differentiation, and that they play a more complex role in cell physiology than simply causing oxidative damages. It is interesting that the cells can maintain high levels of these enzyme activities for a relatively long time (2 or 4 days) after a very short flux of hydroxyl free radicals.

Journal Article↗

Penetrating esophageal injuries: multicenter study of the American Association for the Surgery of Trauma.

OBJECTIVE: The purpose of this study was to define the period of time after which delays in management incurred by investigations cause increased morbidity and mortality. The outcome study is intended to correlate time with death from esophageal causes, overall complications, esophageal related complications, and surgical intensive care unit length of stay. METHODS: This was a retrospective multicenter study involving 34 trauma centers in the United States, under the auspices of the American Association for the Surgery of Trauma Multi-institutional Trials Committee over a span of 10.5 years. Patients surviving to reach the operating room (OR) were divided into two groups: those that underwent diagnostic studies to identify their injuries (preoperative evaluation group) and those that went immediately to the OR (no preoperative evaluation group). Statistical methods included Fisher's exact test, Student's T test, and logistic regression analysis. RESULTS: The study involved 405 patients: 355 male patients (86.5%) and 50 female patients (13.5%). The mean Revised Trauma Score was 6.3, the mean Injury Severity Score was 28, and the mean time interval to the OR was 6.5 hours. There were associated injuries in 356 patients (88%), and an overall complication rate of 53.5%. Overall mortality was 78 of 405 (19%). Three hundred forty-six patients survived to reach the OR: 171 in the preoperative evaluation group and 175 in the no preoperative evaluation group. No statistically significant differences were noted in the two groups in the following parameters: number of patients, age, Injury Severity Score, admission blood pressure, anatomic location of injury (cervical or thoracic), surgical management (primary repair, resection and anastomosis, resection and diversion, flaps), number of associated injuries, and mortality. Average length of time to the OR was 13 hours in the preoperative evaluation group versus 1 hour in the no preoperative evaluation group (p < 0.001). Overall complications occurred in 134 in the preoperative evaluation group versus 87 in the no preoperative evaluation group (p < 0.001), and 74 (41%) esophageal related complications occurred in the preoperative evaluation group versus 32 (19%) in the no preoperative evaluation group (p = 0.003). Mean surgical intensive care unit length of stay was 11 days in the preoperative evaluation group versus 7 days in the no preoperative evaluation group (p = 0.012). Logistic regression analysis identified as independent risk factors for the development of esophageal related complications included time delays in preoperative evaluation (odds ratio, 3.13), American Association for the Surgery of Trauma Organ Injury Scale grade >2 (odds ratio, 2.62), and resection and diversion (odds ratio, 4.47). CONCLUSION: Esophageal injuries carry a high morbidity and mortality. Increased esophageal related morbidity occurs with the diagnostic workup and its inherent delay in operative repair of these injuries. For centers practicing selective management of penetrating neck injuries and transmediastinal gunshot wounds, rapid diagnosis and definitive repair should be made a high priority.

Adolescent↗

Changes in cellular autophagic capacity during azaserine-initiated pancreatic carcinogenesis.

Growth regulation is a crucial event in tumour progression. Surprisingly, relatively few papers have dealt with the catabolic side of regulation, and there are practically no data regarding the autophagic process during tumour development. We approach this problem by morphometrical investigation into the possible changes of autophagic activity during the progression of rat pancreatic adenocarcinoma induced by azaserine. In the present study, autophagic capacity of the azaserine-induced premalignant and malignant cells were characterised and compared to the respective host tissue cells of the rat pancreas and to the acinar cells in other stages of tumour development. Using vinblastine (VBL) as an enhancer, and cycloheximide (CHI) as an inhibitor of autophagic segregation we observed that autophagic capacity of premalignant cells (month 6 and 10 after initiation) is much higher than in the host tissue cells. We found a sharp decrease in self-digesting capacity in adenocarcinoma cells (month 20) where VBL induced a minimal accumulation of autophagic vacuoles which was, surprisingly, not inhibited by CHI, i.e. the CHI-sensitive regulatory step was lost. The changes in autophagic capacity are probably associated to specific steps of tumour progression in our system.

Adenocarcinoma↗

Quantitative microvascular changes during azaserine-initiated pancreatic carcinogenesis.

Although angiogenesis is considered to be indispensable for continuous tumour growth, only very few studies have been published performing microvessel quantification during tumour progression. We measured the tumour vascularity in different stages of rat pancreatic carcinogenesis induced by azaserine and promoted by raw soya flour-containing pancreatotrophic diet. Besides the tumour samples taken at 6 (atypical acinar cell nodules), 15 (adenomas) and 20 (localised adenocarcinomas) months after carcinogen initiation, we also investigated 3 control groups: tumour-bearing host tissue of azaserine-treated rats and normal tissue of untreated rats kept on standard or pancreatotrophic diet. In contrast with the usual microvessel counting on hot spots, we determined microvascular surface density (Sv) and volume density (Vv) by electron microscopic morphometry. There was no significant difference in these respect between the control groups. At month 6 after the azaserine induction Sv and Vv showed slight, nonsignificant decrease as compared to the host control. Both values remained unchanged until the 15th month and increased significantly by the 20th month. These results may indicate comparable growth rate of tumour and new microvessels in the premalignant stages of carcinogenesis while a more intense angiogenesis than tumour growth afterwards.

Adenocarcinoma↗

Comparison of the quantitative competitive and semiquantitative RT-PCR methods for the determination of interferon-gamma mRNA levels in AIDS-free HIV-infected individuals.

IFN-gamma mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of HIV-infected and seronegative individuals using quantitative competitive and semiquantitative RT-PCR and the sensitivity of these methods was compared. A significant correlation was found between quantitative competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P = 0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected individuals presented a remarkable increase of IFN-gamma mRNA expression, as determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without an internal standard is also acceptable for measuring cytokine mRNA expression, but less reliable if small amounts are quantified. Moreover, we found that increased IFN-gamma mRNA expression is independent of CD4+ cell count in AIDS-free HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

Delivery of bioactive peptides and proteins across oral (buccal) mucosa.

The identification of an increasing array of highly potent, endogenous peptide and protein factors termed cytokines, that can be efficiently synthesized using recombinant DNA technology, offers exciting new approaches for drug therapy. However, the physico-chemical and biological properties of these agents impose limitations in formulation and development of optimum drug delivery systems as well as on the routes of delivery. Oral mucosa, including the lining of the cheek (buccal mucosa), floor of mouth and underside of tongue (sublingual mucosa) and gingival mucosa, has received much attention in the last decade because it offers excellent accessibility, is not easily traumatized and avoids degradation of proteins and peptides that occurs as a result of oral administration, gastrointestinal absorption and first-pass hepatic metabolism. Peptide absorption occurs across oral mucosa by passive diffusion and it is unlikely that there is a carrier-mediated transport mechanism. The principal pathway is probably via the intercellular route where the major permeability barrier is represented by organized array of neutral lipids in the superficial layers of the epithelium. The relative role of aqueous as opposed to the lipid pathway in drug transport is still under investigation; penetration is not necessarily enhanced by simply increasing lipophilicity, for other effects, such as charge and molecular size, also play an important role in absorption of peptide and protein drugs. Depending on the pharmacodynamics of the peptides, various oral mucosal delivery systems can be designed. Delivery of peptide/protein drugs by conventional means such as solutions has some limitations. The possibility of excluding a major part of drug from absorption by involuntary swallowing and the continuous dilution due to salivary flow limits a controlled release. However these limitations can be overcome by adhesive dosage forms such as gels, films, tablets, and patches. They can localize the formulation and improve the contact with the mucosal surface to improve absorption of peptides and proteins. Addition of absorption promoters/permeabilizers in bioadhesive dosage forms will be essential for a successful peptide/protein delivery system.

Animals↗

[Perioperative treatment after esophagogastric surgery].

Extended gastric and esophageal resection is still associated with high postoperative morbidity and mortality. We performed a retrospective analysis of the perioperative management of 72 patients who had undergone such operations during a one-year period. Patient and management variables were analyzed by multivariate statistical methods to identify pre-, intra-, and postoperative factors which influence the results. The investigation of preoperative data revealed an increase of esophageal cancer among younger (< 55 years) patients (12 patients underwent gastrectomy and 22 esophageal resection). The intensity of smoking was significantly higher compared to the elderly (11.27 vs. 7.4 cigarettes/day; p < 0.05); and the same applies to alcohol consumption. In older patients (> 55 years of age), the duration of postoperative artificial ventilation was significantly longer (10.1 vs. 4 hours, p < 0.05) and the prevalence of septic complication was higher, than in younger patients. All three postoperative deaths recorded in this series occurred in the group of elderly patients. A preoperative weight loss exceeding 10 per cent of body weight was associated with significantly longer postoperative stay (21.6 vs. 17.4 days; p < 0.001), as well as with need for longer parenteral feeding (13.05 vs. 10.06 days; p < 0.005). Operations longer than 6 hours were associated with significantly longer postoperative ventilation period (14.44 vs. 5.31 hours; p < 0.02), need for longer stay intensive care unit (10.56 vs. 6.55 days; p < 0.001) and longer postoperative stay (21.56 vs. 17.64 days; p < 0.05). The prevalence of pulmonary complications was connected to the duration of the operation (10/16 vs. 3/55). We also describe and analyse two contemporary methods designed for monitoring circulatory parameters (PICCO) and tissue oxygenation (gastrotonometry). The analysis of postoperative data demonstrates that postoperative pain control with continuous epidural analgesia is superior to methods as it shortens the length of stay on the intensive care unit (7.15 vs. 10.67 days; p < 0.05) and postoperative hospitalisation (18.06 vs. 23.50 days; p < 0.05). Nutritional support is essential after esophageal anastomosis till oral feeding can start. Enteral nutrition was given through a jejunal tube that had been inserted intraoperatively. Calorie intake was built up step by step to a maintenance level of 31.2 kcal/day, which was administered until oral feeding could be started (mean duration 10.94 days; maximum duration: 42 days). We conclude that careful selection of patients, appropriate intra- and postoperative management, with adequate postoperative pain control can reduce postoperative morbidity and length of inpatient stay.

Analgesia, Epidural↗

No change in impaired cellular immune response of HIV-negative homosexuals after 15 years of HIV epidemic in Eastern/Central European region.

Impaired cell-mediated immune reactivity to polyclonal mitogens was determined in HIV-negative homosexual men (HIV-MSM). Results were compared to those we reported in a complex clinical and immunological investigation in the same risk groups 15 years ago, before the onset of the AIDS epidemic in Hungary. Cellular immune reactivity to polyclonal mitogens was studied in 74 HIV-infected or HIV-uninfected homosexual men and heterosexual controls. Lymphocytes in whole-blood cultures were stimulated with various doses of phytohaemagglutinin (PHA), concanavalin-A (Con-A), and pokeweed mitogen (PWM) in a blast transformation assay. A significant difference (p = .0002) in lymphocyte proliferation between HIV-MSM vs. heterosexuals using PWM in both concentrations was found. Proliferative capacity was similar in HIV- MSM and HIV infected males with CD4+ > 500/microl. Con-A and PHA showed a less expressed proliferative response. Decreased lymphocyte reactivity to PWM, similar to the one in early HIV infection, could be observed in HIV-MSM. This HIV-independent mild immunodeficiency in MSM is a sign of an increased susceptibility and predisposes to subsequent HIV infection. It seems, however, that MSM's impaired immune response observed over a period of 15 years is an immunodeficiency not changed by the emerging HIV/AIDS epidemic. Our study provides an explanation why the incidence of new HIV cases in homo-/bisexual individuals is still high (> 70%), and it indicates that it remains high in Hungary.

Case-Control Studies↗

[Haemodialysed, hemiparetic patient operated on for aortic aneurysm followed by successful renal transplantation].

The authors present the case of a 58 years old male patient. According to his preceding record in 1991 he suffered speech disturbance and left-side hemiparesis due to multiplex vascular lesions. A fresh cerebral ictus caused a right side hemiparesis mainly in the upper limb in 1993 and sensomotororic aphasia has also been developed. In 1995 the patient was begun acute haemodialysis treatment due to his gravis uremic state, then his dialysis was continued 3 times 4 hours weekly. In 1997 the then 56 years old inveterate right-sided hemiparetic patient, treated with chronic haemodialysis requested to be put on the transplantation waiting list. The first thing that had to be done in case of this high-risk patient was the resection of the abdominal aortic aneurysm (38 mm x 67 mm x 115 mm in size) noticed at the ultrasound examination which was carried out in January 1997. The continuity of the vessel was secured by graft-interposition where the arteria mesenterica was also implanted. Following the successful operation, the patient was qualified for the transplantation list and in the February of 1998 a successful kidney-transplantation was carried out. Following the temporary, post-transplantation difficulties (post-operative 5th day acute rejection well-reacting to 3 steroid-shots; the two re-operations due to partial necrosis in the uretero-ureteralis anastomosis and successfully overcoming the Pseudomonas aeruginosa uroinfection) the patient is currently doing well and has no complaint.

Aortic Aneurysm, Abdominal↗

Mutations in RAD3, MSH2, and RAD52 affect the rate of gene amplification in the yeast Saccharomyces cerevisiae.

We report here the use of the ADH4:CUP1 amplification detection system to identify five high amplification rate (HAR) strains of Saccharomyces cerevisiae that display 40- to 600-fold higher amplification rates than those of parental strains. We have identified a mutation in RAD3 DNA repair helicase gene in HAR strain B9-40 that results in a 40-fold increase in amplification rate. RAD3 is the functional homolog of the human XPD gene, suggesting that this model system will provide important candidates for genes that affect gene amplification in human cells. Isolation of the HAR strains has allowed us to test whether RAD52, which is essential for recombinational repair of DNA double-strand breaks, is also essential for amplification. Deletion of RAD52 in HAR strains B3-10 and B11-60 decreases amplification approximately 100-fold. In contrast, deletion of MSH2, which increases recombination between sequences with limited similarity, increases the amplification rate about 10-fold. These results suggest that recombination is an important step in amplification.

Adenosine Triphosphatases↗