Szemfenéki betegségek molekuláris genetikai és epidemiológiai vizsgálata = Molecular genetical and epidemiological investigation of diseases of the ocular fundus

Genetikai eset-kontroll tanulmányunkba 213 nedves és 67 száraz AMD-ben szenvedő beteget, valamint 106 kontrolt vontunk be. Nem találtunk összefüggést az AMS és 4 vizsgált gén között (Apolipoprotein E, complement factor I, FXIII and MerTK). A GAS6 gén c.834+7G>A polimorfizmusa a nedves típusú AMD-vel szemben protektívnek bizonyult (OR=0.50, 95%CI: 0.26-0.97, p=0.04). Többszörös logisztikus regresszióval bizonyítottuk, hogy a C3 gén egyik polimorfizmusa a CFH és HTRA1 polimorfizmusok hiányában a száraz AMD kialakulására rizikót jelent (OR=4.93, 95%CI: 1.98-12.25, p=0.0006). Öt, von Hippel-Lindau szindrómában szenvedő család 7 tagját vizsgáltuk. Genetikai vizsgálatunk 4 új (c.163G>T, c.232A>T, c.340+1G>A, c.555C>A) és egy korábban közölt (c.583C>T) mutációt igazolt a VHL génben. Alátámasztottuk, hogy a protein trunkációhoz vezető mutációk I-es típusú VHL betegséghez és világossejtes veserákhoz vezetnek. Molekulamodellezéssel igazoltuk, hogy az újonnan leírt p.Asn78Tyr mutáció a VHL-HIF-1alpha interakció felbomlásához vezet, ezért a mutáció I-es típusú VHL betegséget és magas veserák kockázatot okoz. Egy új nonszensz mutáció c.163G>T (p.55X) kapcsán a VHL betegségben eddig előfordult legkoraibb veserák megjelenést regisztráltuk egy 15 éves betegben. Eredményeink hozzájárulnak a VHL betegség genotípus-fenotípus összefüggéseinek pontosabb megértéséhez és a VHL betegek sikeres követéshez. | In a case-controll study we enrolled 213 patients with exudative, 67 patients with dry AMD and 106 controls. No association was found between AMD and the polymorphisms in the Apolipoprotein E, complement factor I, FXIII and MerTK genes. GAS6 c.834+7G>A polymorphism was found to be significantly protective, reducing the odds of wet type AMD by a half (OR=0.50, 95%CI: 0.26-0.97, p=0.04). Multiple regression models revealed that the risk allele of C3 was carried a significant risk in the simultaneous absence of homozygous CFH and HTRA1 polymorphisms only (OR=4.93, 95%CI: 1.98-12.25, p=0.0006) in dry AMD. Seven members of 5 unrelated families with type I VHL disease were enrolled in the study. Molecular genetic investigations detected 4 novel (c.163G>T, c.232A>T, c.340+1G>A, c.555C>A) and one previously described (c.583C>T) VHL point mutations. Our observations highlight that truncating mutations predispose to type I phenotype and high risk of renal cell carcinoma. Molecular modeling showed that the p.Asn78Tyr amino acid exchange disrupts the VHL-HIF-1alpha interaction prediciting type I phenotype with high risk of renal cell carcinoma. The novel c.163G>T (p.55X) nonsense mutation associated to bilateral RCC and retinal angioma in a 15-years-old boy, representing the earliest occurrence of RCC in VHL disease reported so far. Our observations add to the understanding of genotype-phenotype correlation in VHL disease and help genetic counseling and follow-up of VHL patients

Chemical etching of nitinol stents

At present the main cause of death originates from cardiovascular diseases. Primarily the most frequent cause is vessel closing thus resulting in tissue damage. The stent can help to avoid this. It expands the narrowed vessel section and allows free blood flow. The good surface quality of stents is important. It also must have adequate mechanical characteristics or else it can be damaged which can easily lead to the fracture of the implant. Thus, we have to consider the importance of the surface treatment of these implants. In our experiments the appropriate design was cut from a 1.041 mm inner diameter and 0.100 mm wall thickness nitinol tube by using Nd:YAG laser device. Then, the stent was subjected to chemical etching. By doing so, the burr created during the laser cutting process can be removed and the surface quality refined. In our research, we changed the time of chemical etching and monitored the effects of this parameter. The differently etched stents were subjected to microscopic analysis, mass measurement and in vivo environment tests. The etching times that gave suitable surface and mechanical features were identified

Catheter directed thrombolytic therapy and aspiration thrombectomy in intermediate pulmonary embolism with long term results

Background: Catheter directed thrombolysis (CDT) and thrombectomy represent well established techniques for the treatment of intermediate pulmonary embolism (IPE). The long-term effect of catheterdirected thrombolysis of IPE is unknown.Methods: Clinical, interventional and echocardiographic data from 80 consecutive patients with IPE who were treated with CDT were evaluated. Primary end-points were technical success and major adverse events. Secondary end-points were cardiovascular mortality, all-cause mortality, clinical success, rate of bleeding complications, improvement in pulmonary pressure and echocardiography parameters. CDT completed with alteplase (10 mg bolus and 1 mg/h maintenance dose) through a pig-tail catheter for 24 h. After 24 h, control pulmonary angiography was performed. Results: In total, 80 patients with a mean age of 59.0 ± 16.8 years were treated. CDT was successful after the first post-operative day in 72 (90%) patients, but thrombus aspiration and fragmentation was performed due to failed thrombolysis in 8 (10%) patients. Final technical and clinical success was reached in 79 (98.8%) and 77 (96.3%) patients, respectively. The mean CDT time in IPE was 27.8 ± 9.6 h. Invasive pulmonary pressure dropped from 57.5 ± 16.7 to 38.9 ± 13.5 (p < 0.001). A caval filter was implanted in 4 (5%) patients. The 1-year major adverse events and cardiovascular mortality rate was 4.0% and 1.4%, respectively. Access site complications (6 major and 6 minor) were encountered in 12 (16.2%) patients.Conclusions: Catheter directed thrombolysis in submassive pulmonary embolism had excellent results. However, additional mechanical thrombectomy was necessary in some patients to achieve good clinical outcomes

Switching between parathormone (PTH) assays: the impact on the diagnosis of renal osteodystrophy

Background: Clinical guidelines for decision-making in chronic kidney disease (CKD) consider parathormone (PTH) levels. The measured PTH values differ if novel full length PTH(1-84) assays are used instead of earlier intact iPTH assays. In this study we analyzed how the classification of CKD patients alters when iPTH assays are switched to PTH(1-84) assays. Methods: Plasma samples were collected prior to dialysis sessions from 110 consecutive CKD patients on maintenance hemodialysis. PTH levels were determined with iPTH assays (Elecsys, Architect and DiaSorin Liaison N-tact) and PTH(1-84) assays (Elecsys and Liaison). Using KDIGO guidelines patients were classified as being below, above and in the recommended target range (RTR) of PTH. The results of classification with different assays were evaluated and, a novel calculation method of RTR was implemented. Results: The prevalence of patients with PTH in RTR is comparable with each assay, but the individual patients differed. PTH(1-84) Elecsys and Liaison assays classified more patients as being below RTR than iPTH Elecsys and Architect but not Liaison N-tact assay (27.3%, 22.7% vs. 41%, 31.8%, and 36.4%, respectively). In turn, PTH(1-84) Elecsys and Liaison assays identified less CKD patients with PTH above the RTR than iPTH except N-tact assays (6.4%, 10% vs. 16.3%, 19%, and 6.3%, respectively). Using our calculation method, our discrimination values for PTH(1-84) assays to achieve classification identical to that with iPTH Elecsys were lower than those recommended by the manufacturer. Conclusions: Current guidelines for the treatment of secondary hyperparathyroidism in CKD should consider the type of assays used for PTH measurement. Each laboratory should assess its own RTR for PTH tests to achieve comparable classification. The presented calculation is simple, it mimics an everyday situation, switching from one assay to another one, and provides useful RTR values for PTH tests

T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy

Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: ( 1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; ( 2) in anti-TNF responders as well as in nonresponders, the frequencies of naive CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; ( 3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; ( 4) pending confirmation, a CD4CD69 ratio <2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA

Szemelvények a Semmelweis Egyetem, az Országos Onkológiai Intézet és az Országos Korányi Tbc és Pulmonológiai Intézet együttműködésén alapuló tüdőrák-kutatási programból

Lung cancer places a significant socio-economic burden on the Hungarian population. This overview summarizes the findings of collaborative translational lung cancer research efforts of three Hungarian flagship academic institutions, the Semmelweis University, the National Institute of Oncology and the National Koranyi Institute of TB and Pulmonology. With regards to the molecular factors regulating tumor angiogenesis, we identified the prognostic significance of apelin and erythropoietin receptor (EPOR) expression in non-small cell lung cancer (NSCLC). Furthermore, the impact of KRAS mutation subtypes and ERCC1 (excision repair cross-complementation group 1) expression on the response to platinum-based chemotherapy have been studied. We also described the epidemiology and predictive power of rare EGFR (epidermal growth factor receptor) mutations in a large Hungarian patient cohort. Lastly, the expression of molecular factors associated with NSCLC progression was studied specifically in brain metastatic matched cases series. These preclinical and clinical studies provide clinically relevant information that hopefully will contribute to the improvement of lung cancer patient care