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Trends in incidence of Tuberculosis and Nontuberculous Mycobacterial Infections in years 2001-2020
Doležalová, Karolína ; Göpfertová, Dana (advisor) ; Skřičková, Jana (referee) ; Svatoň, Martin (referee)
Trends in incidence of tuberculosis and non-tuberculous mycobacteriosis in children and adolescents in Czech republic in years 2001-2020 BCG vaccination programs were introduced into Czechoslovakia more than 60 years ago under an entirely different epidemiological situation than that of today. Compulsory mass BCG vaccination was abolished in November 2010 and changed to a selective vaccination program for infants at high risk of contracting tuberculosis. This work wants to ascertain the risk of tuberculosis and non-tuberculous mycobacterial infection in 10 years following the change of the vaccination program and a comparison with the same period of mass BCG vaccination. The design of this work is a descriptive study, comparison, and statistical analysis of data for the period 2001-2020 about cases of tuberculosis and mycobacteriosis as reported in the Tuberculosis Register. The conclusions are that the trend of TB incidence in children in both compared periods is identical and statistically significantly decreasing (p <0,001). The trend of incidence of NTM cervical lymphadenitis in children is in the first period degressive and non-significant (p=0,561). However, in the second period, the trend is significantly increasing (p <0,001), in every, compared two subsequent years is an increase of 8 %....
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Clinical use of gene expression of RNA in non-small cell lung carcinoma (NSCLC)
Svatoň, Martin ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
The clinical use of determination of gene expression of RNA in non-small cell lung cancer (NSCLC) Abstract Introduction Non-small cell lung cancer (NSCLC) belongs to the most frequent causes of cancer deaths worldwide. Chemotherapy (CHT) has still (except pemetrexed) administered according to stages and patients comorbidities, without the use of other predictive markers. It results into only low objective therapeutical response that differs in indivial patients without more clearly known causes. Aims The aim of our research was to find possible predictive markers in the form of mRNA or miRNA, which would help to reduce the effect of NSCLC / CHT for selected groups of patients. Methods In three groups of patients (42 patients with radically resected adenocarcinomas stage 1; 90 patients with NSCLC who have undergone surgical resection and 59 of them consequently adjuvant CHT; 81 patients palliatively treated in combination platinum derivative + paclitaxel/gemcitabine +/- sequential radiotherapy with advanced squamous NSCLC stages 3B, 4), we examined the effect of expression of mRNA and miRNA until relapse (DFI) / progression (PFS) and overall survival (OS). Expressions were determined with the real-time PCR methodology using UPL probes. Statistical analysis used cox regression model and Kaplan - Meier...
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Options for prediction of treatment efficacy of EGFR tyrozine kinase inhibitors in patient with advanced non-small cell lung cancer
Fiala, Ondřej ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
Introduction: Targeted therapy with low molecular-weight tyrosine kinase inhibitors (TKI) directed at inhibition of epidermal growth factor receptor (EGFR) is a novel effective option for systemic treatment of locally-advanced or metastatic non-small cell lung cancer (NSCLC). Finding biomarkers that predict the efficacy of targeted treatment may increase the treatment efficacy and also prolong survival of patients. Aims: To assess the frequency of activating EGFR mutations and KRAS mutations in our patients and their role for prediction of EGFR-TKI treatment efficacy. To compare the efficacy and safety of EGFR-TKI and chemotherapy in the first-line treatment of patients harboring activating EGFR mutations. Methods: 613 patients with cytologically or histologically confirmed NSCLC were tested for activating EGFR mutation, of which 448 patients were also tested for KRAS mutation. First-line therapy was evaluated in 54 patients harboring activating EGFR mutations. Mutations were detected using denaturing capillary electrophoresis, and verified by direct DNA sequencing. Survival of patients was assessed using the methodology of Kaplan-Meier, the comparison was calculated using log-rank test. Results: Activating EGFR mutations were detected in 73 (11.9%) patients, more frequently in patients with...
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A Validatation of non-invasive method for diagnostic of cystic fibrosis based on ion ratios determined by CE-C4D
Ďurč, P. ; Lačná, J. ; Dosedělová, V. ; Foret, František ; Homoľa, L. ; Pokojová, E. ; Malá, M. ; Skřičková, J. ; Dastych, M. ; Vinohradská, H. ; Dřevínek, P. ; Skalická, V. ; Kubáň, Petr
A validation of novel approach for diagnosis of cystic fibrosis (CF) is presented. The method is very simple and fast, since for collection of samples, only wiping of the skin of forearm is needed. The collected sample is analyzed by capillary electrophoresis with contactless conductometric detection (CE-C4D). Ion ratios are determined as ratios of peak area of chloride anion and peak areas of selected cations. It is possible to distinguish between cystic fibrosis patients and healthy individuals when ion ratio is applied as diagnostic factor. In here, we present analytical parameters of developed method (limits of detection, limits of quantification, repeatability of migration times, repeatability of peak areas) and ROC curve, which reveals high sensitivity and specificity of the developed method.
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Clinical use of gene expression of RNA in non-small cell lung carcinoma (NSCLC)
Svatoň, Martin ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
The clinical use of determination of gene expression of RNA in non-small cell lung cancer (NSCLC) Abstract Introduction Non-small cell lung cancer (NSCLC) belongs to the most frequent causes of cancer deaths worldwide. Chemotherapy (CHT) has still (except pemetrexed) administered according to stages and patients comorbidities, without the use of other predictive markers. It results into only low objective therapeutical response that differs in indivial patients without more clearly known causes. Aims The aim of our research was to find possible predictive markers in the form of mRNA or miRNA, which would help to reduce the effect of NSCLC / CHT for selected groups of patients. Methods In three groups of patients (42 patients with radically resected adenocarcinomas stage 1; 90 patients with NSCLC who have undergone surgical resection and 59 of them consequently adjuvant CHT; 81 patients palliatively treated in combination platinum derivative + paclitaxel/gemcitabine +/- sequential radiotherapy with advanced squamous NSCLC stages 3B, 4), we examined the effect of expression of mRNA and miRNA until relapse (DFI) / progression (PFS) and overall survival (OS). Expressions were determined with the real-time PCR methodology using UPL probes. Statistical analysis used cox regression model and Kaplan - Meier...
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Options for prediction of treatment efficacy of EGFR tyrozine kinase inhibitors in patient with advanced non-small cell lung cancer
Fiala, Ondřej ; Pešek, Miloš (advisor) ; Salajka, František (referee) ; Skřičková, Jana (referee)
Introduction: Targeted therapy with low molecular-weight tyrosine kinase inhibitors (TKI) directed at inhibition of epidermal growth factor receptor (EGFR) is a novel effective option for systemic treatment of locally-advanced or metastatic non-small cell lung cancer (NSCLC). Finding biomarkers that predict the efficacy of targeted treatment may increase the treatment efficacy and also prolong survival of patients. Aims: To assess the frequency of activating EGFR mutations and KRAS mutations in our patients and their role for prediction of EGFR-TKI treatment efficacy. To compare the efficacy and safety of EGFR-TKI and chemotherapy in the first-line treatment of patients harboring activating EGFR mutations. Methods: 613 patients with cytologically or histologically confirmed NSCLC were tested for activating EGFR mutation, of which 448 patients were also tested for KRAS mutation. First-line therapy was evaluated in 54 patients harboring activating EGFR mutations. Mutations were detected using denaturing capillary electrophoresis, and verified by direct DNA sequencing. Survival of patients was assessed using the methodology of Kaplan-Meier, the comparison was calculated using log-rank test. Results: Activating EGFR mutations were detected in 73 (11.9%) patients, more frequently in patients with...
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Histopathologic and molecular diagnostics of lung and pleural neoplasms
Čapková, Linda ; Kodet, Roman (advisor) ; Matěj, Radoslav (referee) ; Skřičková, Jana (referee)
The aim of the presented thesis is to introduce modern molecular methods that may contribute to deepening our knowledge of pulmonary carcinogenesis. Furthermore, we would like to point out the significance of immunohistochemistry in differential diagnostics of the most common primary pulmonary and pleural neoplasms. Lung carcinoma of all histological subtypes is a result of stepwise accumulation of genetic and epigenetic changes, including allelic losses (LOH), chromosomal instability and imbalance, oncogene and tumor suppressor gene mutations, epigenetic silencing by promotor hypermethylation or aberrant gene expression guidinig cell proliferation. In our study, certain genetic changes were detected in squamous cell carcinomas (SCC) of the lung, their precancerous lesions as well as in normal bronchial mucosa in a selected group of heavy smokers with limited ventilation. We investigated the relation between molecular changes of LOH type in chromosomal regions harbouring mismatch repair genes and cell cycle regulators and human telomerase reverse transcriptase (hTERT) mRNA expression. We also evaluated the relation between these molecular changes and histologic pattern in bronchial mucosa in this patient group. hTERT mRNA expression analysis in correlation with LOH in bronchial mucosa of heavy...
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Monitoring of airway inflammation in patients with various types of bronchial obstructionMonitoring of oxidative stress biomarkers in exhaled breath condensate of patients with severe refractory asthma
Sedlák, Vratislav ; Salajka, František (advisor) ; Skřičková, Jana (referee) ; Panzner, Petr (referee)
Monitoring of airway inflammation in patients with various types of bronchial obstruction. Monitoring of oxidative stress biomarkers in exhaled breath condensate of patients with severe refractory asthma. Background: Asthma is chronic inflammatory disease associated with bronchial hyperreactivity. Various cells plays and cellular products are involved in asthma pathogenesis. Oxidative stress plays also a significant role in mechanisms of asthma via action of reactive oxygen (ROS) and nitrogen (NOS) species. These free radicals develop from inflammatory airway reaction and from exogenous exposure of air-pollution (ozone, cigarette smoke). ROS and NOS and its products cause damage of bio- membranes, proteins and nucleic acid. Several studies showed correlation of asthma severity to intensity of oxidative stress. Aim of the study: The main goal of the study was to describe differences in concentrations of various markers of oxidative stress in exhaled breath condensate of severe refractory asthma (SRA) patients and healthy controls (HC). Secondary aim was to show correlation of oxidative stress intensity to severity of eosinophilic inflammation described by peripheral blood eosinophilia or exhaled nitric oxide concentration. Methodology: We harvested exhaled breath condensate in 40 SRA patients and 19...
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Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to the presence of a chronic bronchitis phenotype
Koblížek, Vladimír ; Salajka, František (advisor) ; Skřičková, Jana (referee) ; Marel, Miloslav (referee)
AJ Impairment of nasal mucociliary clearance in former smokers with stable chronic obstructive pulmonary disease relates to presence of a chronic bronchitis phenotype Background: Associations between nasal and bronchial impairment have been repeatedly described in chronic obstructive pulmonary disease (COPD) whereas nasal mucociliary clearance (MCC) in COPD patients is not yet fully understood. We studied nasal MCC parameters in COPD patients and compared them with healthy adults (HA) and with cystic fibrosis (CF) patients with compromised MCC. Methodology: Pilot study of seventeen COPD patients without exacerbation; all of them were examined to investigate and compare nasal and bronchial ciliary beat frequency (CBF) and ciliary beat pattern. Main observational study of 98 COPD ex-smokers and subjects from control groups (15 CF and 39 HA) evaluated for nasal MCC time (NMCCt) and by digital video microscopy of nasal mucosa recording ciliary beat frequency (CBF) and ciliary beat pattern (index of ciliary dyskinesia). Results: It was found no difference in mean ciliary beat frequencies between nasal (6.0 Hz ± 1.3) and bronchial (5.9 ± 1.3) mucosa (p = 0.427). We found medium association in degree of ciliary dyskinesia (κ = 0.733). In the main observational study: the NMCCt was decreased in HA (575...
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A Reflection of Differentness? Travelling Noblewomen in the First Half of the 19th Century
SKŘIČKOVÁ, Jitka
In this thesis is researched the phenomenon of women{\crq}s travelling on the basis of the theories of structuring of space, perception of {\clqq}the others`` and self-positioning. The attention is paid to study of noblewomen{\crq}s journeys from the Habsburg Monarchy to west of their homes in the first part of the 19th century. It is examined, by which means they could get exercise in the public space, how could they engage in it and how did they deal with perception of {\clqq}the others`` on the pages of their travel journals. The initial point is the proposition that women could not travel free on the basis of the contemporary prescriptive literature for the travellers but after all did they go on journeys above all before their marriages. Consequently it is compared the contemporary literature intended for travellers with the travel journals of several noblewomen to contribute to understanding of the phenomenon of women{\crq}s travelling that appears new in the first part of the 19th century. Within the researches of gender history and cultural anthropology is examined by the means of the study of resources dedicated to travellers the contemporary gender discourse and his implications for the everyday life on roads and the way of writing of the noblewomen{\crq}s travel journals.
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