- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Úvod: Rádioterapia je v súčasnosti štandardnou metódou liečby u pacientov s malígnym melanómom uvey. Na Slovensku je jedinou možnosťou stereotaktická rádiochirurgia na lineárnom urýchľovači LINAC. Ožiarenie okolitých tkanív oka a orbity vedie ku vzniku postradiačných komplikácií. Jednou z najzávažnejších a zrak ohrozujúcich je postradiačná retinopatia, ktorá sa rozdeľuje na makulopatiu a periférnu retinopatiu. Medzi jej klinické prejavy patria mikroaneuryzmy, teleangiektázie, tvrdé exsudáty, vatovité ložiská a edém makuly, neovaskularizácie, krvácanie do sklovca. Postradiačný edém makuly sa na základe nálezu na optickej koherentnej tomografii rozdeľuje na cystoidný a necystoidný. Podľa nálezu na fluoresceínovej angiografii ho delíme na neischemický a ischemický, pričom strata zraku pri ischemickom edéme makuly je zvyčajne už trvalá. Naša práca sa zameriava na rizikové faktory vzniku postradiačnej retinopatie vzhľadom na jej závažný vplyv na funkčný výsledok rádioterapie z hľadiska zachovania centrálnej ostrosti zraku. Cieľ práce: S využitím metód bivariačnej a multivariačnej analýzy zistiť, či a do akej miery sú dávka ožiarenia makuly a vybrané charakteristiky pacientov asociované s rizikom vzniku makulopatie. Materál a metodika: Retrospektívna analýza 168 pacientov s malígnym melanómom corpus ciliare a chorioidey, ktorí podstúpili stereotaktickú rádiochirurgiu v rokoch 2007-2016. Výsledky: Prevalencia postradiačnej makulopatie v našom súbore bola 29 %, s mediánom výskytu po 16 mesiacoch od ožiarenia. Medián dávky ožiarenia makuly bol 37 Gy. Premenné štatisticky signifikantne asociované so vznikom makulopatie v multivariačnej analýze boli dávka ožiarenia makuly (p = 0,0016), postekvatoriálna lokalizácia tumoru (p = 0,0271) a lepšia centrálna ostrosť zraku s korekciou pred ožiarením (p = 0,0006). Premenná dotyk makuly okrajom tumoru v bivariačnej analýze silno korelovala s centrálnou ostrosťou zraku (p = 0,0006), preto ju nebolo potrebné do finálneho modelu zahrnúť. Diskusia: Dávka ožiarenia makuly je hlavným rizikovým faktorom pre rozvoj postradiačnej makulopatie, a to na základe výsledkov iných autorov, ako aj našej štúdie. Ostatné premenné súviseli s blízkosťou tumoru pri makule, čím takisto nepriamo spôsobili zvýšenie dávky ožiarenia makuly. Lepšia centrálna ostrosť zraku pred ožiarením mohla byť dôvodom pre vyššie riziko vzniku makulopatie pre: a) včasnejšiu diagnostiku tumorov, ktoré sú v blízkosti zadného pólu, b) nižšie riziko enukleácie; enukleácia bola 1,6-krát častejšia u pacientov bez makulopatie. Pacienti, ktorí podstúpili enukleáciu, sa k rozvoju makulopatie prirodzene nedopracovali. Piati pacienti podstúpili intravitreálnu aplikáciu bevacizumabu ako liečbu postradiačnej makulopatie, avšak centrálna ostrosť zraku sa u nich nezlepšila. Záver: Postradiačné komplikácie môžu viesť k ohrozeniu zraku aj oka. Postradiačná makulopatia je dôsledkom vyššej dávky ožiarenia na oblasť makuly, pričom jej súčasné liečebné možnosti sú málo efektívne.
Introduction: Nowadays radiotherapy is the standard treatment care for patients with uveal melanoma. In Slovakia the only one option is a one-day session stereotactic radiosurgery at linear accelerator LINAC. Irradiation of surrounding tissues of the eye and orbit causes radiation complications. One of the most serious and vision-threatening is the radiation retinopathy, which divides into maculopathy and peripheric retinopathy. The clinical signs include microanerysms, teleangiectases, hard exsudates, cotton wool spots and macular edema, neovascularisation, and vitreous hemorrhage. Radiation macular edema can be classified by optical coherence tomography into cystoid or noncystoid edema. On fluorescein angiography macular edema is divided into non-ischemic and ischemic, while the latter means usually irreversible loss of the visual acuity. This paper is focused on risk factors of radiation retinopathy although it strongly influences functional result of radiotherapy and preservation of the visual acuity. Purpose: By means of bivariate and multivariate analysis to determine the association of radiation dose and other variables with the development of radiation maculopathy. Material and methods: The retrospective analysis of 168 patients with ciliary body or choroidal melanoma who performed one-day session stereotactic radiosurgery on a linear accelerator LINAC in a period 2007–2016. Results: The prevalence of the radiation maculopathy was 29% with the median time from the irradiation to maculopathy 16 months. Median radiation dose on the macula was 37 Gy. Variables statistically significantly associated with the maculopathy were: radiation dose (p = 0.0016), postequatorial location of the tumor (p = 0.0271) and better visual acuity before treatment (p = 0.0007). The tumor touch of the macula was strongly associated with the visual acuity in the bivariate analysis (p = 0.0006), thus it could be omitted from the final model. Discussion: The radiation dose on a macula is the key determinant for radiation-induced maculopathy, according to other authors and our study approvingly. Other variables were related to proximity of the tumor to the macula, so the radiation dose on the macula was higher indirectly. Better visual acuity before treatment as a risk factor for maculopathy can be a consequence of: a) earlier diagnostics of tumor with proximity to the posterior pole, b) lower enucleation rate; frequency of the enucleation was 1.6 higher in patients without maculopathy. Naturally, on enucleated eyes maculopathy was not diagnosed. Five patients underwent intravitreal application of the bevacizumab as a treatment of the radiation maculopathy, without improvement of the visual acuity. Conclusion: Radiation complications can be vision and eye threatening. Radiation maculopathy is a consequence of higher radiation dose on the macula. The treatment modalities of radiation maculopathy are rather ineffective.
- Klíčová slova
- postradiační makulopatie,
- MeSH
- lidé MeSH
- melanom chirurgie radioterapie MeSH
- nádory uvey * chirurgie radioterapie MeSH
- radiochirurgie metody škodlivé účinky MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
OBJECTIVE: In Slovakia, thanks to a highly effective vaccination programme, no domestic cases of measles have been reported since 1999. However, there are several outbreaks of measles currently hitting some countries in Europe. Difficulties in reaching the goal of measles elimination make it necessary to monitor the status of the population susceptibility to prevent similar outbreaks in the future. We hypothesize that immunity wanes overtime, which can substantially impact the population susceptibility. This work introduces a model that estimates a proportion of individuals susceptible to measles in the Slovak population in 2015. METHODS: Our analysis is based on an age-cohort model that incorporates waning immunity, vaccination schedule and changes in demographic structure. The inputs of the model are data on the vaccination coverage, last seroprevalence survey in 2002 and age structure of the population. RESULTS: In a short-term horizon, waning immunity does not affect the estimated proportion of the susceptible population. However, in a long-term horizon, the antibody titers can fall below the level of protection, which would result in a substantial transfer of initially immune individuals to the compartment of the susceptible ones. Incorporating of waning immunity in the cohort model has indicated that the most susceptible cohorts are not-vaccinated youngest children and cohorts born between 1969 and 1986. CONCLUSIONS: Applying the model to the current situation shows that people aged 30-45 years and unvaccinated infants represent the most susceptible groups. Model partially replaces missing seroprevalence survey, but, because the parameters of model and phenomenon of waning immunity are not exactly known, we suggest reintroducing the regular national serosurveys in order to empirically determine the level of susceptibility for measles in Slovakia.
- MeSH
- dítě MeSH
- dospělí MeSH
- epidemický výskyt choroby MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- náchylnost k nemoci * MeSH
- novorozenec MeSH
- očkovací schéma MeSH
- předškolní dítě MeSH
- rizikové faktory MeSH
- séroepidemiologické studie MeSH
- spalničková vakcína imunologie MeSH
- spalničky epidemiologie imunologie prevence a kontrola MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika epidemiologie MeSH
Inhibítory faktora VIII (FVIII), ktoré predstavujú závažnú komplikáciu hemofílie A spôsobujúcu neúčinnosť substitučnej liečby, sa vyšetrujú klasickou Bethesda metódou a modifikovanou Nijmegen metódou. V práci sme vyhodnotili koreláciu výsledkov inhibítorov zistených obidvomi metódami a sledovali sme vplyv hraničných titrov inhibítorov na farmakodynamiku (in vivo recovery a vzostup aktivity FVIII) a farmakokinetiku FVIII (biologický polčas – T1/2 a klírens) po jeho intravenóznej aplikácii. Porovnali sme 265 paralelných vyšetrení inhibítora Bethesda a Nijmegen metódou vykonaných u 77 pacientov s ťažkou hemofíliou A; z nich 60 pacientov bez inhibítora (súbor 1) a 17 pacientov s anamnézou inhibítorov (súbor 2) po absolvovaní imunotolerančnej liečby (ITT) s parciálnym (n = 4) alebo kompletným (n = 13) úspechom. Nijmegen metóda spoľahlivo vylúčila falošnú pozitivitu nízkych titrov inhibítora medzi 0,51–0,9 Bethesda jednotiek/ml (BU/ml) zistených Bethesda metódou. Potvrdili sme dobrú koreláciu medzi cut-off 0,7 BU/ml a 0,5 Nijmegen BU/ml (NBU/ml). Hodnotenie 120 vyšetrení farmakodynamiky FVIII v súbore 1 ukázalo pri aktuálnom titri inhibítora 0,2 ? 0,1 NBU/ml hodnoty in vivo recovery (IVR) 109 ? 19,4 % (rozptyl 60–160 %) a vzostup FVIII 2,2 ? 0,7 (1,4–3,5) %/1 IU/kg. V súbore 2 (72 vyšetrení) sme pri aktuálnom titri inhibítora 0,5 ? 0,15 NBU/ml zistili signifikantne nižšie hodnoty IVR 86 ? 32 % (rozptyl 44–136 %) a vzostupu FVIII 1,6 ? 0,6 (0,72–2,8) %/1 IU/kg (p < 0,05). Aj vyšetrenie farmakokinetiky ukázalo signifikantné rozdiely medzi súborom 1 (20 pacientov/20 vyšetrení) a súborom 2 (13 pacientov po ITT/26 vyšetrení): T1/2 11,5 ? 1,8 (8,2–16,2) h versus 8,14 ? 3,61 (2,9–16,4) h a klírens 3,7 ? 1,2 (2,6–6,5) ml/kg/h versus 6,48 ? 2,24 (2,9–11,9) ml/kg/h; (p < 0,05). Záver: Ako referenčnú metódu vyšetrenia inhibítorov odporúčame Nijmegen modifikáciu s hranicou negativity 0,5 NBU/ml. Keďže u časti pacientov po ITT negatívny výsledok inhibítora nekoreluje s výsledkami farmakodynamiky a farmakokinetiky FVIII, pre spoľahlivé hodnotenie úspechu ITT je potrebné ďalšie sledovanie a metódy s vyššou senzitivitou a špecificitou na detekciu inhibítorov.
Inhibitors of FVIII represent serious complication of hemophilia A resulting in the ineffectiveness of replacement therapy. Classical Bethesda method and Nijmegen modification are used for an inhibitor detection. We performed correlation analysis of inhibitors titres investigated by both methods and we evaluated an impact of marginal/low inhibitor titres on pharmacodynamics (in vivo recovery and incremental response of FVIII) and pharmacokinetics (half life-T1/2 and clearance) after intravenous administration of FVIII. We compared the results of 265 parallel inhibitor measurements by Bethesda and Nijmegen assay performed in 77 severe hemophilia A patients; out of them 60 patients with the negative history of inhibitors (Group 1) and 17 patients with history of inhibitors after immune tolerance induction (ITI) (Group 2) with partial (n = 4) and complete success (n = 13). Nijmegen method excluded the false positivity of low titer inhibitors between 0,51 and 0,9 BU/ml detected by Bethesda method and a good correlation between cut-off 0.7 Bethesda units/ml (BU/ml) and 0,5 Nijmegen BU/ml (NBU/ml) was confirmed. Comparison of 120 and 72 investigations of FVIII pharmacodynamics in Group 1 (inhibitor titre of 0,2 ? 0,1 NBU/ml) and in Group 2 (inhibitor titre 0,5 ? 0,15NBU/ml), respectively, showed in vivo recovery 109 ? 19,4 (range 60–160) % and 86 ? 32 (44–136) %, and incremental response 2,2 ? 0,7 (1,4–3,5) %/1IU/kg and 1,6 ? 0,6 (0,72–2,8) %/1 IU/kg, respectively. Twenty pharmacokinetics studies in 20 patients from Group 1 and 26 studies in 13 patients from Group 2 showed the half life 11,5 ? 1,8 h (8,2–16,2 h) and 8,14 ? 3,61 h (2.9–16.4 h), respectively, and a clearance 3,7?1,2 (2,6-6,5) ml/kg/h versus 6,48 ? 2,24 (2,9–11,9) ml/kg/h; (p < 0.05) respectively. Conclusion: We recommend Nijmegen assay as a reference method for inhibitor testing with negativity cut-off 0,5 NBU/ml. However, in several patients after ITI negative inhibitor titre does not correlate with pharmacodynamics and pharmacokinetics of FVIII. Definite evaluation of the ITI success requires further study and new methods of inhibitor detection with a higher sensitivity and specificity.
A 2×2 factorial design was used to evaluate possible preservation of mitochondrial functions in two cardioprotective experimental models, remote ischemic preconditioning and streptozotocin-induced diabetes mellitus, and their interaction during ischemia/reperfusion injury (I/R) of the heart. Male Wistar rats were randomly allocated into four groups: control (C), streptozotocin-induced diabetic (DM), preconditioned (RPC) and preconditioned streptozotocin-induced diabetic (DM+RPC). RPC was conducted by 3 cycles of 5-min hind-limb ischemia and 5-min reperfusion. DM was induced by a single dose of 65 mg/kg streptozotocin. Isolated hearts were exposed to ischemia/reperfusion test according to Langendorff. Thereafter mitochondria were isolated and the mitochondrial respiration was measured. Additionally, the ATP synthase activity measurements on the same preparations were done. Animals of all groups subjected to I/R exhibited a decreased state 3 respiration with the least change noted in DM+RPC group associated with no significant changes in state 2 respiration. In RPC, DM and DM+RPC group, no significant changes in the activity of ATP synthase were observed after I/R injury. These results suggest that the endogenous protective mechanisms of RPC and DM do preserve the mitochondrial function in heart when they act in combination.
- MeSH
- experimentální diabetes mellitus metabolismus MeSH
- ischemické přivykání metody MeSH
- krysa rodu rattus MeSH
- myokard metabolismus MeSH
- náhodné rozdělení MeSH
- potkani Wistar MeSH
- reperfuzní poškození myokardu metabolismus prevence a kontrola MeSH
- spotřeba kyslíku fyziologie MeSH
- srdeční mitochondrie fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of cardioprotection assessed as limiting myocardial infarct size. The aim was to explore the possibility of existence of another in vitro mechanism, which could be contributory to cardioprotection mediated by diazoxide treatment. Mitochondrial membrane fluidity and ATP synthase activity in isolated heart mitochondria were determined under the influence of two factors, STZ-DM condition and treatment with diazoxide. Both factors independently increased the ATP synthase activity (p<0.05), as no interaction effect was observed upon the combination of STZ-DM with diazoxide. On the other hand, the mitochondrial membrane fluidity was significantly increased by STZ-DM only; no significant main effect for diazoxide was found. Based on the results from measurements of enzyme kinetics, we assume a direct interaction of diazoxide with the molecule of ATP synthase stimulated its activity by noncompetitive activation. Our present work revealed, for the first time, that cardioprotection induced by diazoxide may not be caused exclusively by mitochondrial K(ATP) opening, but presumably also by a direct interaction of diazoxide with ATP synthase, although the mechanisms for achieving this activation cannot be fully delineated.
- MeSH
- diazoxid farmakologie terapeutické užití MeSH
- experimentální diabetes mellitus enzymologie MeSH
- fluidita membrány účinky léků MeSH
- mitochondriální membrány účinky léků MeSH
- mitochondriální protonové ATPasy metabolismus MeSH
- nemoci srdce prevence a kontrola MeSH
- potkani Wistar MeSH
- sukcinátdehydrogenasa antagonisté a inhibitory MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
Acute streptozotocin diabetes mellitus (DM) as well as remote ischemic preconditioning (RPC) has shown a favorable effect on the postischemic-reperfusion function of the myocardium. Cardioprotective mechanisms offered by these experimental models involve the mitochondria with the changes in functional properties of membrane as the end-effector. The aim was to find out whether separate effects of RPC and DM would stimulate the mechanisms of cardioprotection to a maximal level or whether RPC and DM conditions would cooperate in stimulation of cardioprotection. Experiments were performed on male Wistar rats divided into groups: control, DM, RPC and DM treated by RPC (RPC+DM). RPC protocol of 3 cycles of 5-min hind limb ischemia followed by 5-min reperfusion was used. Ischemic-reperfusion injury was induced by 30-min ischemia followed by 40-min reperfusion of the hearts in Langendorff mode. Mitochondria were isolated by differential centrifugation, infarct size assessed by staining with 1 % 2,3,5-triphenyltetrazolium chloride, mitochondrial membrane fluidity with a fluorescent probe DPH, CoQ(9) and CoQ(10) with HPLC. Results revealed that RPC as well as DM decreased the infarct size and preserved mitochondrial function by increasing the mitochondrial membrane fluidity. Both used models separately offered a sufficient protection against ischemic-reperfusion injury without an additive effect of their combination.
- MeSH
- časové faktory MeSH
- experimentální diabetes mellitus chemicky indukované metabolismus patologie MeSH
- fluidita membrány MeSH
- fyziologická adaptace MeSH
- infarkt myokardu metabolismus patologie prevence a kontrola MeSH
- mitochondriální membrány patologie MeSH
- modely nemocí na zvířatech MeSH
- myokard metabolismus patologie MeSH
- potkani Wistar MeSH
- preparace izolovaného srdce MeSH
- přivykání k ischémii metody MeSH
- regionální krevní průtok MeSH
- reperfuzní poškození myokardu metabolismus patologie prevence a kontrola MeSH
- srdeční mitochondrie metabolismus patologie MeSH
- streptozocin MeSH
- zadní končetina krevní zásobení MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
