Thomayer University Hospital

Prague, Czech Republic

Thomayer University Hospital

Prague, Czech Republic
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Stiborova M.,Charles University | Dracinska H.,Charles University | Martinek V.,Charles University | Svaskova D.,Charles University | And 6 more authors.
Chemical Research in Toxicology | Year: 2013

Sudan I (1-phenylazo-2-hydroxynaphthol) is a suspected human carcinogen causing tumors in the livers and urinary bladders of rats, mice, and rabbits. Here, we investigated for the first time the influence of Sudan I exposure on the expression of several biotransformation enzymes in the livers, kidneys, and lungs of rats concomitantly at the mRNA and protein levels and assayed their enzymatic activities. We also studied its effect on the formation of Sudan I-derived DNA adducts in vitro. Sudan I increased the total amounts of cytochrome P450 (P450) in all organs tested. Western blots using antibodies raised against various P450s, NADPH:P450 reductase, and NAD(P)H:quinone oxidoreductase 1 (NQO1) showed that the expression of P450 1A1 and NQO1 was induced in the liver, kidney, and lung of rats treated with Sudan I. The higher protein levels correlated with increased enzyme activities of P450 1A1/2 and NQO1. Furthermore, 9.9-, 5.9-, and 2.8-fold increases in the formation of Sudan I oxidative metabolites catalyzed by microsomes isolated from the liver, kidney, and lung, respectively, of rats treated with Sudan I were found. The relative amounts of P450 1A and NQO1 mRNA, measured by real-time polymerase chain reaction (RT-PCR) analysis, demonstrated that Sudan I induced the expression of P450 1A1 and NQO1 mRNA in the liver, kidney, and lung, and of P450 1A2 mRNA in kidney and lung. Finally, microsomes isolated from livers, kidneys, and lungs of Sudan I exposed rats more effectively catalyzed the formation of Sudan I-DNA adducts than microsomes from organs of control rats. This was attributable to the higher P450 1A1 expression. Because P450 1A1 is playing a major role in the bioactivation of Sudan I in rat and human systems, its induction by Sudan I may have a profound effect on cancer risk by this azo dye. In addition, the induction of P450 1A1/2 and NQO1 enzymes can influence individual human susceptibility to other environmental carcinogens and have an effect on cancer risk. © 2013 American Chemical Society.

Bortlik M.,Charles University | Duricova D.,Charles University | Machkova N.,Charles University | Kozeluhova J.,University Hospital Plzen | And 10 more authors.
Inflammatory Bowel Diseases | Year: 2014

Background: Prenatal exposure to anti-tumor necrosis factor α (TNF-α) antibodies seems to be safe for fetal development. Data on long-term outcome of exposed children are missing. Our aim was to assess long-term postnatal development of children exposed to anti-TNF-α during pregnancy. Methods: Consecutive children aged ≥12 months exposed to anti-TNFs prenatally for maternal inflammatory bowel disease in 3 centers in the Czech Republic were enrolled. Data on psychomotor development, infections, antibiotics, vaccination, and allergy were retrospectively obtained from mothers, treating pediatricians, and children's vaccination cards. Furthermore, standardized laboratory tests on humoral and cellular immunity were performed. Results: Twenty-five children exposed to biologicals were included (median age, 34 mo; range, 14-70 mo). All children had normal growth, and all but 1 had normal psychomotor development. Majority (80%) experienced at least 1 infection (mainly respiratory), and 60% of infants received antibiotics, 32% of those within the first year of life. Vaccination was undertaken according to vaccination protocol to 23 infants (92%). Fifteen children also had tuberculosis vaccination without serious complication. Immunological investigation was performed with 17 children (68%). Cellular immunity was normal in all infants, and 7 children had mild decrease in IgA and/or IgG immunoglobulins without clinical significance. All children had a detectable serologic response to vaccination. Conclusions: Exposure to anti-TNF-α antibodies seems to be safe for growth and psychomotor development of children, although clinical significance of relatively high frequency of infections and antibiotic use among infants remains questionable because of the lack of a control group. Continuous follow-up of exposed children is absolutely warranted. Copyright © 2014 Crohn's & Colitis Foundation of America, Inc.

O'Donnell S.M.,Coombe Women and Infants University Hospital | Curry S.J.,Coombe Women and Infants University Hospital | Buggy N.A.,Coombe Women and Infants University Hospital | Moynihan M.M.,Coombe Women and Infants University Hospital | And 4 more authors.
Journal of Pediatrics | Year: 2013

Objective: To determine if low-flow nasal prongs therapy with room air, compared with no treatment, facilitates weaning from nasal continuous positive airway pressure (NCPAP) in very low birth weight (VLBW, birth weight <1500 g) infants. Study design: VLBW infants who received respiratory support for ≥48 hours and who were stable on NCPAP for 24 hours were eligible for inclusion in this multicenter, randomized controlled trial. On stopping NCPAP, infants were randomized to receive 1 L/min air via nasal prongs or to spontaneous breathing in room air. The primary outcome measure was failure to wean. Secondary outcome measures included length of time to failure and change in heart rate, respiratory rate, oxygen saturation, and respiratory distress score. Results: Seventy-eight infants were randomized: 39 to nasal prongs and 39 to spontaneous breathing. The groups were similar at birth and at randomization. Sixteen infants (41%) in the nasal prongs group failed the weaning process compared with 12 infants (31%) in the spontaneous breathing group (OR 1.57, 95% CI 0.56 to 4.43, P =.48). There were no significant differences between the groups in secondary outcomes. Conclusions: In this study, we did not demonstrate a benefit of low-flow room air via nasal prongs to wean VLBW infants from NCPAP. © 2013 Mosby Inc. All rights reserved.

Pardini B.,Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units | Pardini B.,University of Turin | Rosa F.,Genomic Variation in Human Population and Complex Diseases and Molecular and Genetic Epidemiology Units | Rosa F.,University of Turin | And 15 more authors.
Carcinogenesis | Year: 2015

Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies worldwide. It is routinely cured by a 5-fluorouracil (5-FU)-based chemotherapy which improves outcomes in patients. We investigated the effect of single nucleotide polymorphisms (SNPs) in two microRNA (miRNA)-encoding genes that have been previously reported as important in prognosis in patients with stage III CRC and treated with 5-FU-based chemotherapy. Two SNPs (rs4919510 in miR-608 and rs213210 in miR-219-1) were genotyped in 1083 CRC patients recruited in the Czech Republic to evaluate their effect on clinical outcomes. Carriers of the variant T allele in rs213210 and receiving 5-FU chemotherapy were associated with a significantly worse survival [hazard ratio (HR) = 2.18; 95% confidence interval (CI): 1.20-3.98; adjusted P = 0.01] and an increased risk of relapse (HR = 1.94; 95% CI: 1.16-3.25; adjusted P = 0.01). After further stratification for tumor grading, stage III patients carrying the G allele of rs4919510 and undergoing adjuvant chemotherapy were at decreased risk of relapse (HR = 0.44; 95% CI: 0.20-0.94; adjusted P = 0.03). The present study confirms that variations in miRNA-encoding genes may be an important factor for modulating CRC prognosis and predicting therapy response. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email:

Calda P.,Charles University | Sipek A.,Thomayer University Hospital | Gregor V.,Thomayer University Hospital
Acta Obstetricia et Gynecologica Scandinavica | Year: 2010

Objective. To evaluate the implementation of first trimester screening in the Czech Republic during 1996-2007 on the number of infants born with numerical chromosomal anomalies, the gestational age at diagnosis and the number of invasive procedures. Design. A population based cohort study. Setting. National Registry of Congenital Anomalies, 53 Czech Republic Genetic Departments. Population. About 100,000 pregnancies per year. Main outcome measures. Primary outcomes were the rates of fetuses and newborns with diagnosed numerical chromosomal anomalies and the gestational age at diagnosis. Secondary outcomes were the rates of chorion villus sampling (CVS) and amniocenteses and the contribution of age groups on the detection rate of trisomy 21. Results. The number of newborns with Down's syndrome decreased from 5.42/10,000 in 1996 to 3.66/10,000 newborns in the 2007. The total incidence of Down's syndrome increased from 13.42 to 20.66/10,000. The detection rate in women <35 years increased from 35.59 in 1996 to 45.08 in 2007; in women >35 years from 23.73 to 38.52. The number of amniocenteses/detected case of Down's syndrome was 124 in 1996 and 123 in 2007. The corresponding number of CVS decreased dramatically from 83 in 1996 to 10 in 2007. Conclusions. Despite the increase of maternal age and the corresponding increase of Down's syndrome, the number of newborns with Down's syndrome decreased. Implementation of the first trimester combined screening leads to a shift towards earlier diagnosis of all major chromosomal abnormalities. © 2010 Informa UK Ltd.

Brabcova D.,University of South Bohemia | Lovasova V.,University of West Bohemia | Kohout J.,University of West Bohemia | Zarubova J.,Thomayer University Hospital | Komarek V.,Faculty Hospital Motol
Seizure | Year: 2013

Purpose: This study was intended to compare the effectiveness of educational animated video and educational drama in improving the knowledge of epilepsy and reducing epilepsy-related stigma among children aged 9-11 years. Method: The first group of children involved in the study (n1 = 762) watched a video and then completed a questionnaire on epilepsy. The second group (n2 = 400) completed the questionnaire after participating in a drama. Both groups were retested 6 months later by the same questionnaire, which was also completed by a control group (n3 = 180) not subjected to intervention. Results: Both groups subjected to intervention achieved significantly higher scores (P < 0.001) than the control group on knowledge of epilepsy and on attitudes towards children with the disease. Educational video was more effective than drama in improving knowledge of epilepsy. On the other hand, there was no significant difference (P > 0.05) between the two kinds of intervention regarding attitudes towards children with this disease. Conclusion: The results suggest that both interventions could be used to reduce epilepsy-related stigma in this age group. © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Pina-Garza J.E.,Childrens Hospital at Vanderbilt | Schiemann-Delgado J.,UCB Inc. | Yang H.,UCB Inc. | Duncan B.,UCB Inc. | And 2 more authors.
Clinical Therapeutics | Year: 2010

Background: In a recent double-blind, placebo-controlled study, adjunctive levetiracetam (LEV) was reported to be effective and well tolerated during 5-day treatment in patients aged 1 month to <4 years with partial-onset seizures. A study was planned to fulfill the regulatory requirement to evaluate the long-term safety of LEV as adjunctive therapy for partial-onset seizures in pediatric patients.Objective: This study evaluated the long-term effectiveness and tolerability of adjunctive LEV in infants and young children with partial-onset seizures.Methods: This was a prospective, open-label, outpatient, multicenter study (N01148; identifier NCT00152516) conducted as an extension of a previously published study (N01009; NCT00175890). Patients were enrolled from 3 sources, as follows: (1) patients who had completed study N01009; (2) patients who had failed screening for entry into study N01009 but fulfilled the eligibility criteria for entry into this study; and (3) patients who were directly enrolled. The study consisted of a 2- to 4-week retrospective baseline period (and a 3- to 10-day prospective baseline period for directly enrolled patients), a 2- to 8-week uptitration/conversion period, and a maintenance period. Eligible patients were required to have epilepsy with partial-onset seizures, treated with a stable regimen of 1 or 2 antiepileptic drugs. Patients received adjunctive LEV, 20 to 80 mg/kg/d, for up to 48 weeks (total study duration). The primary variable for effectiveness was the percentage reduction from baseline in the weekly frequency of partial-onset seizures, as recorded in patients' diaries. Data for effectiveness were also analyzed by age strata (1 month to <1 year, 1 to <2 years, and 2 to <4 years). Neuropsychological assessment was conducted with the Bayley Scales of Infant Development, Second Edition (BSID-II). All analyses were performed on observed data, and the last-observation-carried-forward approach was not used. The intent-to-treat (ITT) population was defined as all patients who took at least one dose of LEV during the study. Treatment-emergent adverse events (TEAEs) were assessed by observation, spontaneous reporting, standard questions, review of diary cards, and neuropsychologists' clinical reports. Additional measures included physical and neurologic examinations, vital signs, ECGs, routine blood chemistry, and routine hematology assessments.Results: The study included 152 patients in the ITT population. In total, 51.3% (78/152) of the patients were male, and mean (SD) age was 23.5 (12.4) months. The mean LEV maintenance dose was 56.1 (16.2) mg/kg/d, and the median (Q1-Q3) treatment duration was 287.8 (209.0-295.5) days. Ninety-seven patients (63.8%) completed the study. The BSID-II subpopulation included 51 patients. During maintenance, the overall median (Q1-Q3) percentage reduction from baseline in the weekly frequency of partial-onset seizures was 56.0% (-10.9% to 92.8%), which was sustained over time and appeared comparable across the age strata (1 month to <1 year, n = 25, 50.9%; 1 to <2 years, n = 48, 58.0%; and 2 to <4 years, n = 59, 55.0%). The overall responder rate (ie, ≥50% reduction from baseline in weekly partial-onset seizures) was 53.8% (71/132), was maintained over time, and was consistent across the age strata (1 month to <1 year, 52.0%; 1 to <2 years, 56.3%; and 2 to <4 years, 52.5%). Mean BSID-II raw scores for psychomotor development and behavioral functioning remained static, whereas mental development appeared to improve over time, although this was not tested statistically. At least one TEAE was reported in 143 patients (94.1%). The most frequently reported TEAEs were pyrexia (60/152; 39.5%), upper respiratory tract infection (42/152; 27.6%), and vomiting (28/152; 18.4%). The most common TEAEs affecting the central nervous system were convulsion (25/152; 16.4%), irritability (19/152; 12.5%), and somnolence (16/152; 10.5%). Most TEAEs (77.0%) were mild or moderate in intensity.Conclusion: Adjunctive LEV treatment for up to 48 weeks was associated with effective and sustained seizure control and had an acceptable tolerability profile in this small, selected population of infants and young children aged 1 month to <4 years with partial-onset seizures. © 2010 Excerpta Medica Inc.

Dusek L.,Masaryk University | Muzik J.,Masaryk University | Gelnarova E.,Masaryk University | Finek J.,University Hospital | And 2 more authors.
Klinicka Onkologie | Year: 2010

Backgrounds: The Czech Republic is ranked among those countries with the highest cancer burden in Europe and worldwide. The purpose of this study is to summarize long-term trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates from 2007. Material and Methods: The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information over a 30-year period of standardized registration covering 100% of cancer diagnoses and the entire Czech population. The analysis of CNCR is supported by demographic data of the Czech Republic and by the Death Records Database as civil registration systems. The epidemiology of malignant tumours in the Czech population is available online at Results: All neoplasms, including non-melanoma skin cancer, reached a crude incidence rate of almost 736 cases per 100,000 men and 648 cases per 100,000 women in 2007. The annual mortality rate exceeded 263 deaths per 100,000 population; each year, more than 27,000 persons die of cancer. The overall incidence of malignancies has increased during the last decade with growth index + 26.4% (1997-2007) while the mortality rate has stabilized over this time span (growth index in 1977-2007: -2.5%). Consequently, the prevalence has significantly increased in the registration period and in 2007 it exceeded 400,000 cases. In addition to the demographic ageing of the Czech population, the cancer burden is increased by the growing incidence of multiple primary tumours (recently more than 11 % of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e.g. proportion of stage I + II in female breast cancer: 71.9%, skin melanoma: 81.3%), in general early diagnostics is insufficient in the Czech Republic. This is the case even for highly prevalent colorectal carcinoma (only 43.2% of incident cases recently diagnosed at stage I or II). Conclusion: The Czech Republic is well equipped with high-quality and functional facilities for collecting and analysing population-based data on malignant tumours. The data survey has enabled the priorities of cancer management in the Czech Republic to be defined. This will undoubtedly lead to a sustained reduction in late diagnosed cases and a reduction in the remarkable regional differences in diagnostic efficiency.

Termerova J.,Thomayer University Hospital
Prague medical report | Year: 2011

The traumatic intracranial haemorrhage still remains a serious complication of instrumental deliveries with an uncertain prognosis. Regarding tentorial haemorrhage, surprisingly few clinical neurological data are available. Most of the references in literature are older case reports, associated frequently with an unfavourable outcome. We report a newborn after a serious tentorial haemorrhage with an excellent neurodevelopmental outcome. Computed tomography (CT) scan of our patient demonstrated an extensive bilateral tentorial haemorrhage extending to the foramen magnum. The newborn showed a good respiratory effort, but a neurological impairment including anisocoria, apathy, hypotonia, incomplete grasp and Moro reflex. Despite these signs, the development at 9 and 18 months of age was appropriate. The aim of this report is to accentuate that the prognosis of infants with tentorial haemorrhage should be always evaluated carefully with main respect to clinical signs. The outcome of the newborn even after a large tentorial haemorrhage can be surprisingly without a serious neurological deficit. Spontaneous breathing without support, normal blood pressure and absence of seizures are clinical indicators that may be associated with a good outcome despite an extensive tentorial haemorrhage.

Lassuthova P.,University Hospital Motol | Mazanec R.,University Hospital Motol | Vondracek P.,The University Hospital Brno | Siskova D.,Thomayer University Hospital | And 3 more authors.
Clinical Genetics | Year: 2011

Charcot-Marie-Tooth (CMT) neuropathy type 4C (CMT4C) is an autosomal recessive (AR), demyelinating neuropathy with early spine deformities caused by mutations in the SH3TC2 gene. To determine the spectrum of SH3TC2 mutations in the Czech population, the entire coding region of SH3TC2 was sequenced in 60 unrelated Czech patients. The prevalent mutation was shown to be the p.Arg954Stop. Therefore, 412 additional patients referred for CMT testing were tested for the presence of p.Arg954Stop only. Of 60 patients in whom the SH3TC2 gene was sequenced, at least one mutation was detected in 13 (21.7%) patients and biallelic pathogenic mutations were detected in 7 (11.6%) patients. Of the 412 patients tested for p.Arg954Stop, the mutation was found in 8 patients (1.94%), 6 were homozygous and 2 were heterozygous. The second causative mutation was detected by sequencing in one of the patients but not in the other. Nine novel sequence variants were detected. Their pathogenicity was further tested in silico and in control samples. Mutations in the SH3TC2 gene are a frequent cause of demyelinating hereditary neuropathy among Czech patients. In total, at least one mutation was found in 21 unrelated patients. CMT4C seems to be the most frequent type of AR CMT and one of the most frequent of all CMT types. Mutation p.Arg954Stop is highly prevalent in the Czech population. Patients with demyelinating neuropathy along with non-dominant mode of inheritance and negative for CMT1A/hereditary neuropathy with liability to pressure palsy should be tested for the presence of the p.Arg954Stop mutation or other mutations in the SH3TC2 gene. © 2011 John Wiley & Sons A/S.

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