Epidermal growth factor receptor (EGFR) high gene copy number and activating mutations in lung adenocarcinomas are not consistently accompanied by positivity for EGFR protein by standard immunohistochemistry

The purpose of this study was to investigate whether detectable protein biomarker overexpression is a prerequisite for the presence of increased gene copy number or activating mutations and responsiveness to the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib in patients with lung adenocarcinomas. EGFR status was prospectively analyzed in tumor biopsy samples by three methods: protein expression (n = 117) by standardized immunohistochemistry (IHC), gene copy number (n = 97) by fluorescent in situ hybridization (FISH), and mutation analysis by sequencing (n = 126). Fifty-nine percent of the samples were positive by IHC, 40% were positive by FISH, and 13.5% contained activating kinase domain mutations. Thirty-four percent of the FISH-positive and 27% of the mutant samples were also IHC-negative. All EGFR mutant patients had major clinical responses (five complete response and five partial response) to gefitinib or erlotinib treatment, although three of these tumors were IHC-negative and four were FISH-negative. In a retrospective analysis of samples from nine patients with excellent therapeutic responses (three complete response, five partial response, one stable disease) to erlotinib or gefitinib, mutations were identified in eight cases, but IHC was negative in four of these tumors. These results indicate that molecular diagnostic methods appear to be most important for the identification of lung adenocarcinoma patients who may benefit from EGFR inhibitor treatments.     

Protein kinase C-β and -δ isoenzymes promote arachidonic acid production and proliferation of MonoMac-6 cells

In this study, we investigated the putative roles of certain protein kinase C (PKC) isoenzymes in the regulation of proliferation and arachidonic acid (AA) release in the human monocytoid MonoMac-6 cell line. Experiments employing specific PKC inhibitors and molecular biological methods (RNA-interference, recombinant overexpression) revealed that the two dominantly expressed isozymes, i.e., the "conventional" cPKCbeta and the "novel" nPKCdelta, promote AA production and cellular proliferation. In addition, using different phospholipase A(2) (PLA(2)) inhibitors, we were able to show that the calcium-independent iPLA(2) as well as diacylglycerol lipase (but not the cytosolic PLA(2)) function as "downstream" targets of cPKCbeta and nPKCdelta. In addition, we have also found that, among the other existing PKC isoforms, cPKCalpha plays a minor inhibitory role, whereas nPKCvarepsilon and aPKCzeta apparently do not regulate these cellular processes. In conclusion, in this paper we provide the first evidence that certain PKC isoforms play pivotal, specific, and (at least partly) antagonistic roles in the regulation of AA production and cellular proliferation of human monocytoid MonoMac-6 cells.     

The role of vinpocetine in the treatment of cerebrovascular diseases based in human studies

INTRODUCTION: It shows the importance of cerebrovascular diseases that they are the third main cause of death exceeded only by coronary artery diseases and cancer. Cerebral ischemia leads to irreversible brain damage, thereby it is important to rescue the hypoperfused areas. Patients without stroke but with chronic cerebral hypoperfusion can also benefit from the increasing of the cerebral blood flow. METHODS: The aim of this review was to summarize the indications and the potential effects of vinpocetine in acute and chronic cerebrovascular diseases based on clinical studies. RESULTS: There is no evidence that vinpocetine treatment is applicable in acute ischemic stroke, only few study with low patient number showed a slight but significant improvement in the patients conditions. In chronic cerebrovascular patients after single dose and long-term vinpocetine therapy, PET, TCD, SPECT and NIRS examinations showed increasing perfusion and elevated glucose and O 2 consumption of the examined areas, furthermore significant improvement of the rheologic factors was detected. A meta-analysis of international clinical studies showed a significant improvement in cognitive achievement in chronic stroke patients after oral therapy. CONCLUSION: The cited studies showed the potential multi-pharmacological effects of vinpocetine and its beneficial hemorheological potential. The drug also improves the blood flow and the metabolism of the affected brain areas. There is increasing evidence that vinpocetine improves the quality of life in chronic cerebrovascular patients.     

The effect of carotid stenting on rheological parameters, free radical production and platelet aggregation

INTRODUCTION: Carotid artery stenting has become a possible treatment of significant carotid stenosis. The risk of stent occlusion and restenosis might be increased by abnormal rheological conditions amplified platelet aggregation and free radical production during the operation. AIMS: The aim of this study was to assess the changes of the rheologic parameters, platelet aggregation, and oxidative stress after endovascular treatment of carotid stenosis. METHODS: 18 patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering from significant carotid stenosis and treated with carotid endovascular intervention were examined. Alteration in hemorrheological parameters as well as epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated. Oxidative stress was characterized by the determination of catalase activity. The measurements were carried out directly before and after the procedure and 1, 2, 5 days and 1 month following the intervention. Preceding the operation the patients were administered a maximum dose (300 mg) of clopidogrel. RESULTS: The hematocrit, the plasma fibrinogen concentration (Pfc) and whole blood-, and plasma viscosity (Wbv and Pv) decreased significantly immediately after stenting ( p < 0.001). By the fifth day following the intervention the Pfc, Wdv, Pv, red blood cell (Rbc) aggregation and ADP-induced platelet aggregation increased significantly ( p < 0.0001) compared to values measured after the procedure. At 1 month follow-up these parameters, excepting Wbv, decreased significantly compared to measurements made on the 5th day. On the other hand, catalase activity showed significant elevation by the end of the first month. CONCLUSION: Hemorrheological parameters and platelet aggregation showed specific changes following carotid stenting. Abnormal changes of the rheological conditions and increasing platelet activation are the most pronounced in the first week following stenting, which may lead to the stent's early occlusion. Oxidative stress production returned to baseline levels only by the end of the first month.     

The laboratory diagnosis of food allergies

This paper summarizes the most common allergens in Hungary, the various forms of food allergies, the tools of their diagnosis, with special respect to the possibilities of in vitro laboratory tests. These thoughts are in accordance with the position papers of European Academy of Allergology and Clinical Immunology and Hungarian College of Clinical Immunology and Allergology.     

Applicability of the abbreviated version of the World Health Organization's quality of life questionnaire in Hungary

INTRODUCTION: Quality of life, as a subjective parameter of the general condition, is suitable for characterization of the health status of populations or patient groups, and for studying the effects of therapeutic or preventive interventions. AIMS: To test the applicability and reliability in Hungary of the abbreviated form of the quality of life questionnaire developed by WHO, one of several ways to measure the quality of life. METHODS: Questionnaire-based cross-sectional investigation was performed among altogether 814 persons, in small settlements of population under 1000 and 2000, and in a small town for control, in Csongrád county, Hungary. The reliability and validity of the quality of life questionnaire was tested, within each group of questions, by means of Cronbach's alpha, ANOVA and Kruskal-Wallis tests, and by Spearman's rho correlation coefficient. RESULTS: The mean values of the four domains of quality of life - physical, psychological, social and environmental - showed no noteworthy differences. The Cronbach's alpha figures of the internal consistency test on separate groups of questions and on all questions were in all cases above the expected minimum of 0.7. The means calculated for each domain of quality of life were decreasing with increasing age. Healthy people estimated each aspect of quality of life as significantly better, compared to the sick. Correlation tests showed that all dimensions of the quality of life were in close positive correlation with the general quality of life, with the level of satisfaction with the own health, with the self-assessed health, and with the responses given on other questions related to the social or health situation of the questioned. CONCLUSION: The variation of the questionnaire, adapted to Hungarian conditions, proved to be suitable for testing the quality of life of persons with various demographical, social and health conditions, and for distinction between the healthy and the sick. The sheet, which can be filled in quickly and easily, enables the measurement of quality of life in the Hungarian population, and the comparison of that with international data.     

Myotubular myopathy. Case report and review of the literature

The first Hungarian report of a case of myotubular myopathy is presented here, which is a recessive congenital disorder linked to X chromosome. The patient presented at birth with severe hypotonia, weak spontaneous movements, arthrogryposis and respiratory insufficiency. The biopsy showed the appearance of myotubular myopathy. The diagnosis was further confirmed by genetic analysis revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene.     

Botulism in infancy - survey of literature based on a case report

The authors have drawn attention to a rare disease called infant botulism, which raises some difficulties with regard to differential diagnosis. In the case of the six-month-old infant portrayed, infant botulism and food-born botulism appeared together. As a result of the severity of the disease and due to its rapid course observed in the presented case as well, the diagnosis has to be raised relying on the accurate patient's history and on the clinical examination, then it should be confirmed by appropriate examinations. In relation to presenting a case, the authors examine the microbiological background of the disease, its symptomatology, its epidemiological characteristics, the appropriate methods of electrophysiological examination and laboratory analysis as recommended in current literature, together with the difficulties that arise in differential diagnosis and also the possibilities of treatment. They pay special attention to the particular characteristics of the infant form of the disease, to the difficulties of making a diagnosis due to the characteristics of the age group and also to the questions in relation to the guiding principles of therapy. The rapid and fatal process observed in the presented case warns us that serious complications can occur even when up-to-date therapy is used. Therefore, despite the improvement in prognosis we have to strive to prevent the disease by spreading the proper regulations of nutritional hygiene.     

Features of publications of Hungarian medical universities as reflected in numbers

INTRODUCTION: The majority of scientific results from Hungarian Medical Universities are published in international periodicals in foreign languages. Aim: This study shows that in what numbers, with what kind of impact factors and where the results of the scientific work in the Hungarian Medical Universities are published. METHODS: The examined period is between 2000 and 2003. These scientific publications were explored by two methods based on the own assembled bibliographies of the Hungarian medical universities - University of Debrecen Medical and Health Science Center, University of Pecs Medical School, University of Semmelweis and University of Szeged Albert Szent-Gy?rgyi Medical and Pharmaceutical Center - and the Web of Science's recording. RESULTS: The scientific publications from our medical universities are published in great number and generally with increasing impact factors to guarantee the international publicity for the Hungarian researches. The 90-95 percent of publications which are intended for international publicity is published in those international journals which have impact factor. Among these journals there are many prestigious ones. CONCLUSIONS: Neither of the two methods which were used for exploring of publishing activity has decisive validity. The institutional reason for this is the insufficiency and the lack of precision of the bibliographies of the universities. In the authors' opinion it would be necessary to develop a uniform, electronic processing and take it over in each universities. So a national scientific database of medical universities would be created by joining these universities' databases.