Michal Vrablik

Charles University in Prague, Praha, Praha, Czech Republic

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Publications (39)70.05 Total impact

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    ABSTRACT: Background Ezetimibe's mechanism of action, complementary to that of statins, makes it a useful therapeutic option in patients intolerant of lipid-lowering drugs or in those not achieving target lipid levels. Objectives To evaluate the efficacy and safety of ezetimibe in a longterm follow-up of lipid clinic patients with emphasis on motivation for use and the impact on achievement of target lipid levels. Methods Two hundred and ninety-five clinic patients who were prescribed and took ezetimibe in the 13-month period following the drug's availability in Canada were identified from our database. Patients’ history and laboratory data were collected before and at first visit after the ezetimibe therapy was started. Paired t-test and chi-square test were used for statistical comparisons of ezetimibe's effect on lipid parameters and the achievement of target lipid-levels respectively. Results Ezetimibe treatment increased significantly the proportion of patients achieving lipid targets (by 25% for LDL-C and by 21.7% for TC/HDL-C) significantly by 18% (p < 0.001) and TC/HDL-C by 15% (p < 0.011). The effect of ezetimibe in combination with other lipid-lowering therapies was similar; LDL-C decreased by 22% (p < 0.001) and TC/HDL-C by 15.4% (p < 0.011). The same lipid-lowering effect was seen in patients with diabetes. In this subgroup, addition of ezetimibe to ongoing therapy led to three- and two-fold increase in LDL-C and TC/HDL-C target levels achievement, respectively. Only 7% of patients discontinued ezetimibe treatment due to side effects. Conclusion In patients referred to the lipid clinic (typically because of side effects or failure to reach targets on other lipid-lowering therapy) treatment with ezetimibe significantly increased proportion of those achieving their target lipid levels. This was not accompanied by significant side effects.
    Cor et vasa 04/2014;
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    ABSTRACT: BACKGROUND: Diabetes mellitus and low levels of high-density lipoprotein cholesterol (HDL-C) are among several known risk factors for coronary artery disease. Recent research has shown potential mechanistic links between these two diseases. OBJECTIVES: The aim of our study was to characterize, by examining particular coronary artery disease risk factors, patients with extremely high and low levels of HDL-C who were referred to a prevention clinic. METHODS: We compared the phenotypes of 113 patients with HDL-C levels greater than the 90th percentile with 212 patients with levels less than the 10th percentile by using a retrospective chart review. RESULTS: The cohort with high HDL-C had a remarkable difference in the incidence of type 2 diabetes (1.8% vs 21.7%). The high HDL-C cohort also had a greater age (52.1 years vs 46.7 years), more light or moderate alcohol consumption (70.8% vs 49.4%), more healthy diet (30.1% vs 22.4%), more light or moderate exercise (90.8% vs 52.2%), and a lower body mass index (25.2 kg/m(2) vs 28.1 kg/m(2)). CONCLUSIONS: Compared with the low HDL-C group-and also the general population-the high HDL-C cohort had a remarkably low prevalence of diabetes mellitus.
    Journal of Clinical Lipidology 05/2013; 7(3):194-198. · 3.59 Impact Factor
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    ABSTRACT: This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.Key words: dyslipidemia - risk stratification - LDL-cholesterol - statins - fibrates - niacin - ezetimibe - resins.
    Vnitr̆ní lékar̆ství 02/2013; 59(2):120-6.
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    ABSTRACT: OBJECTIVES: This study aimed to determine whether there is a relationship between common FTO (rs17817449) and MC4R (rs17782313) gene variants and body mass reduction or weight loss after a one-month lifestyle intervention in overweight/obese children. DESIGN AND METHODS: We genotyped 357 unrelated non-diabetic Czech children (age 13.7 ± 4.9 years, average BMI at baseline 30.8 ± 4.6 kg/m(2)). Biochemical and anthropometrical measurements were performed before and after 4 weeks of lifestyle interventions (comprising a reduction in energy intake to the age-matched optimum and a supervised exercise program consisting of 5 exercise units per day, 50 min each). RESULTS: The mean weight loss achieved was 6.2 ± 2.1 kg (P<0.001). Significant associations were found between a BMI decrease and the FTO and MC4R variants. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight compared to noncarriers (P<0.0009 for BMI and P<0.002 for body weight). These differences remained significant following adjustment for sex, age and baseline values (P=0.004 for BMI and P=0.01 for body weight). CONCLUSIONS: FTO and MC4R gene variants modify the impact of an intensive lifestyle intervention on BMI decrease in overweight/obese children. Carriers of the FTO GG genotype and MC4R CC genotype benefit significantly more from the lifestyle intervention.
    Clinical biochemistry 11/2012; · 2.02 Impact Factor
  • Nutrition, metabolism, and cardiovascular diseases: NMCD 07/2012; 22(9):e22-3. · 3.52 Impact Factor
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    Dita Kasparova, Michal Vrablik, Tomas Fait
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    ABSTRACT: OBJECTIVE: The aim of the study was to evaluate the importance of screening for thrombophilic mutations after the first early pregnancy loss. Setting: Thrombophilic mutations were examined in a sample of 100 women with at least one miscarriage. DNA was isolated from venous blood sample. We used methods of microarray, fragmentation analysis, High Resolution Melting and PCR-ARMS with following gel electrophoresis and visualisation. Chi-square test and in cases of low expected frequencies Yates correction were used to compare relative frequencies of individual mutations. The comparison of averages was performed by t-test. Results: We detected prevalence of factor V and II mutation of 9% and 3%, respectively. Single MTHFR mutation was found in 59% and double heterozygous MTHFR mutation in 23% of cases. No mutation was present in only 6% of the study group. Heterozygous mutations of factor V occurred 1.8 times more frequently in our study group compared to the general Czech women population. Also, the frequency of factor II mutation was 1.5-3 times higher. No carrier of these mutations had overt coagulation disorder, history of thromboembolic disease or that of habitual abortions. Conclusions: The frequency of thrombophilic mutations in the group of women with early pregnancy loss is 1.5-3 times higher than in the general population.
    Neuro endocrinology letters 01/2012; 33(1):76-80. · 0.93 Impact Factor
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    ABSTRACT: Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:51-4. · 0.93 Impact Factor
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    ABSTRACT: Obesity is associated with increased inflammation which represents a link to atherosclerosis and cardiovascular disease. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an independent marker of inflammation and atherosclerosis risk. To assess the impact of weight loss on metabolic markers of atherosclerosis including Lp-PLA2 we examined a group of Czech non-diabetic obese/overweight children exposed to a lifestyle intervention. Fourty unrelated overweight/obese non-diabetic Czech children (13.7 ± 2.1 years, average BMI at baseline 29.8 ± 2.6 kg/m2) underwent 4 weeks of lifestyle modification (reduction of energy intake to age matched optimum and supervised physical activity). Anthropometrical and biochemical variables were determined at baseline and after the intervention. Lp-PLA2 mass concentration was assessed using the ELISA kit. Wilcocson's rank test and Spearman's correlation were used for statistical analysis. A significant decrease of BMI and waist circumference was associated with significant changes of plasma lipoprotein and glycaemia levels. Mass concentration of Lp-PLA2 at the baseline was 402 ± 94 μg/ml, after the intervention 368 ± 105 μg/ml (p=0.008). Change in Lp-PLA2 was associated with triglyceride level decrease (p=0.009). Intensive lifestyle modification leading to body weight decrease results in significant changes of plasma lipoprotein levels and, also, a drop of Lp-PLA2 levels in paediatric obese patients. However, even after the intervention Lp-PLA2 concentrations in this patient group remain elevated suggesting possible increased atherosclerosis risk in later life.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:55-9. · 0.93 Impact Factor
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    ABSTRACT: Vascular erectile dysfunction (ED) predicts future development of cardiovascular diseases (CVD). We performed a study in men seeking consultant medical advice regarding vascular ED for the first time without a history of cardiovascular disease, diabetes mellitus or renal insufficiency. Our goal was to evaluate the prevalence of CVD risk factors in this cohort of patients. Furthermore, we assessed the prevalence of asymptomatic subclinical atherosclerosis. All study subjects underwent a thorough physical examination including anthropometric measurements. Laboratory analyses comprising assessment of lipid spectrum, liver and kidney function tests, glycaemia and glycated haemoglobin were measured using automated analysers. Intima-media thickness of carotid arteries was measured using SONOS machine and ankle-brachial index using a mini-duplex device. CVD risk was calculated by standard SCORE charts. Chi-square test, t-test and ANOVA were used for statistical analysis. We examined 35 men, average age 46.5 ± 9.9 years. Six (17.1%) had a positive family history of CVD, 19 (54.3%) had dyslipidemia, 10 (28.6%) were obese, 9 (25.7%) were active smokers, and 14 (40.0%) had arterial hypertension. Eighteen (51.4%) subjects had subclinical atherosclerosis as determined by ABI and CIMT assessment. Patients with vascular erectile dysfunction have similar prevalence of CVD risk factors to general population.
    Neuro endocrinology letters 11/2011; 32 Suppl 2:60-3. · 0.93 Impact Factor
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    ABSTRACT: The aim of this study was to compare HDL-cholesterol and triglyceride levels in patients with familial hypercholesterolemia (FH) with a representative sample of the Czech population. For the FH group: data of 1728 adult patients with FH (600 males and 1128 females) were taken from the MedPed CR database. The control group were 1995 individuals of the population sample of the Czech post-MONICA study (956 males and 1039 females). Compared with controls, FH males showed higher levels of HDL-cholesterol (1.35±0.35 mmol/l vs. 1.31±0.35 mmol/l; P<0.05) and triglycerides (1.98±1.00 vs. 1.81±1.45 mmol/l; P<0.01). After adjustment for age and BMI, the increase in triglycerides remained significant in the subgroup of non-FDB males only (2.22±0.06 vs. 1.74±0.04 mmol/l; P<0.001). Compared with controls, HDL-cholesterol was lower (1.55±0.40 mmol/l vs. 1.65±0.37 mmol/l; P<0.001), while triglycerides were higher (1.72±0.82 mmol/l vs. 1.28±0.75, P<0.001) in FH females. After adjustment for age and BMI, HDL-cholesterol remained lower in the subgroup of FH females without FDB (1.52±0.01 vs. 1.67±0.01 mmol/l, P<0.001) whereas triglycerides were higher in both female subgroups. A lower HDL-C in the group of FH patients compared with control subjects was demonstrated in FH females without FDB only. Elevated triglyceride levels were found in FH males and females, except for males with FDB.
    Clinica chimica acta; international journal of clinical chemistry 05/2011; 412(11-12):920-4. · 2.54 Impact Factor
  • Jaroslav A Hubacek, Michal Vrablik
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    ABSTRACT: Hypercholesterolemia or dyslipidemia is an independent risk factor for cardiovascular disease and statins (inhibitors of a key enzyme of cholesterol synthesis, 3-hydroxymethyl glutaryl coenzyme A reductase) are the drugs of choice for decreasing plasma cholesterol. It has been estimated that genetic factors can explain 40%-60% of final cholesterol concentrations and approximately 70% of the efficacy of statin treatment. The gene most often analyzed in the context of statin efficacy is the gene for apolipoprotein E (APOE). This review summarizes evidence of the association between variations in the APOE gene locus and the response of plasma lipids to statin therapy. Although the results are not consistent, carriers of the APOE4 allele seems to be less responsive to statins than carriers of APOE2 and APOE3 alleles. This effect is partially context-dependent (gene-gender interactions; gene-nutrition and gene-smoking interactions have not yet been studied) and the absolute differences vary between different population groups.
    Drug metabolism and drug interactions 01/2011; 26(1):13-20.
  • European Journal of Internal Medicine - EUR J INTERN MED. 01/2011; 22.
  • Michal Vrablik, Jaroslav A Hubacek
    Clinical Lipidology - CLIN LIPIDOL. 01/2010; 5(4):543-554.
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    ABSTRACT: Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.
    Pharmacogenomics 07/2009; 10(6):945-50. · 3.86 Impact Factor
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    ABSTRACT: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23% [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G carrier was homozygous for LPL W86G, yet only experienced severe hypertriglyceridemia when pregnant. The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression.
    Arteriosclerosis Thrombosis and Vascular Biology 10/2008; 28(10):1866-71. · 6.34 Impact Factor
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    ABSTRACT: We tested the hypothesis that the MLXIPL rs3812316 variant predicts plasma triglyceride (TG) levels. We compared three groups of adult individuals: 162 persons with TG > 10 mmol/L, 266 persons with TG < 0.65 mmol/L, and 2,043 population-based controls (range of TG concentrations 0.7-8.7 mmol/L). We found a small difference in the frequency of the Gln allele carriers between population controls (20.4%) and persons with low TG (26.3%, P = 0.033). We found no difference between individuals with high TG and population controls, and there was no association between the MLXIPL variant and plasma TG levels among the population controls.
    Human Genetics 10/2008; 124(5):553-5. · 4.63 Impact Factor
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    ABSTRACT: The role of hormone replacement therapy and estrogen replacement therapy (ERT) in cardiovascular disease prevention has not been unambiguously defined yet. The metabolic effects of estrogens may vary depending upon the route of administration. Therefore, we compared the impact of unopposed oral or transdermal ERT on plasma lipids and lipoproteins in 41 hysterectomized women. This was an open-label, randomized, crossover study (with 2 treatments and 2 periods). The 41 hysterectomized women were randomized to receive oral or transdermal 17beta-estradiol in the first or second of two 12-week study periods. Plasma lipid and lipoprotein levels were assayed before and after each treatment using standard automated methods. Lipid content of lipoprotein subclasses was assessed by sequential ultracentrifugation. The atherogenic index of plasma (AIP) was calculated as log(triglyceride [TG]/high-density lipoprotein [HDL] cholesterol). The difference between the 2 forms of administration was tested using a linear mixed model. The change from baseline for each of the forms was tested using paired t test. Oral ERT resulted in a significant increase in HDL cholesterol and apolipoprotein A-I levels, whereas it significantly decreased total and low-density lipoprotein (LDL) cholesterol and increased TG concentrations. Transdermal ERT had no such effect. Oral ERT led to a significant TG enrichment of HDL (0.19 +/- 0.06 vs 0.27 +/- 0.07 mmol/L, P < .001) and LDL particles (0.23 +/- 0.08 vs 0.26 +/- 0.10 mmol/L, P < .001) compared with baseline, whereas transdermal therapy did not have any effect on lipoprotein subclasses composition. The difference between the 2 treatments was statistically significant for HDL-TG and LDL-TG (0.27 +/- 0.07 vs 0.19 +/- 0.05 mmol/L, P < .001 and 0.26 +/- 0.10 vs 0.22 +/- 0.07 mmol/L, P< .001, respectively). The transdermal but not oral ERT significantly reduced the AIP compared with baseline (-0.17 +/- 0.26 vs -0.23 +/- 0.25, P = .023), making the difference between the therapies statistically significant (-0.23 +/- 0.25 vs -0.18 +/- 0.22, P = .017). Oral administration of ERT resulted in TG enrichment of LDL and HDL particles. Transdermal ERT did not change the composition of the lipoproteins and produced a significant improvement of AIP. Compared with transdermal ERT, orally administered ERT changes negatively the composition of plasma lipoproteins.
    Metabolism: clinical and experimental 08/2008; 57(8):1088-92. · 3.10 Impact Factor
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    ABSTRACT: Particle size distribution in both HDL and LDL is reflected in the fractional esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT) in plasma depleted of apoB containing lipoproteins (FER(HDL)). We studied FER(HDL) in a group of patients with type 2 diabetes and determined the impact of two different PPAR agonists (fenofibrate and rosiglitazone) on this marker of lipoprotein particle quality. 66 patients with type 2 diabetes (26 women) and 32 control subjects (19 women) were included in the study. 33 patients received fenofibrate and 33 rosiglitazone as add on therapy. Average duration of treatment was 4 months. Plasma lipoprotein glucose levels were determined using an automated analyzer (COBAS Mira, Roche). LDL cholesterol concentrations were calculated by Friedewald formula. FER(HDL) was determined by a radioassay after precipitating apo-B containing particles of plasma. The assays were performed at baseline and at the end of each treatment. SPSS base program was used for statistical evaluation. Both fenofibrate and rosiglitazone resulted in a significant decrease of FER(HDL) (24.62 +/- 11.27%/h vs. 19.93 +/- 10.34%/h; 20.0 +/- 6.1%/h vs. 15.8 +/- 5.8%/h, p < 0.001). Rosiglitazone was significantly more effective in FER(HDL) lowering than fenofibrate (p < 0,02) Both fenofibrate and rosiglitazone improve FER(HDL) in patients with type 2 diabetes. The effect is more pronounced for rosiglitazone. Qualitative change of plasma lipoproteins reflected by FER(HDL) can contribute to antiatherogenic action of PPAR agonists. On contrary, changes of lipoprotein composition induced by PPAR agonists cannot explain adverse cardiovascular effects observed in some large clinical trials with PPAR agonists.
    Neuro endocrinology letters 03/2008; 29(1):146-50. · 0.93 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the changes of biochemical risk factors for thromboembolisms using different administration routes of early estrogen replacement therapy. In a 12-week prospective, randomized crossover trial, estradiol was administered orally (2 mg daily) or transdermally (0.05 mg daily). Forty-five healthy early postmenopausal women were included into the study within 12 weeks after hysterectomy and oophorectomy. Forty-one women (age 49 +/- 6 years) completed the study, and their data were analyzed. The hemocoagulation parameters were determined prior to beginning of the study and at the end of each treatment period, separated by a 1-week washout period. After oral therapy, the average tissue factor pathway inhibitor levels decreased statistically significantly (p < 0.0001) from 87.5 +/- 39.1 to 68 +/- 37.49 ng/ml. The plaminogen activator inhibitor-1 levels also decreased statistically significantly (p = 0.001) after the oral estrogen therapy from 11.39 +/- 12.02 to 5.0 +/- 5.27 IU/l. These changes were also significant when compared with the nonsignificant changes after the transdermal therapy. No significant changes occurred in the levels of D-dimers. After both treatment methods, the antithrombin III and fibrinogen levels decreased, but within their physiological ranges. Oral administration of estrogen statistically significantly reduced the tissue factor pathway inhibitor and plasminogen activator inhibitor-1 levels when compared with the transdermal route. These changes cannot be unambiguously considered risky, and the zero change of D-dimers suggests that there was no activation of the coagulation cascade. We consider the neutral effect of the transdermal therapy more beneficial.
    Gynecologic and Obstetric Investigation 02/2008; 65(1):47-51. · 1.10 Impact Factor
  • Tomáš Fait, Michal Vrablík, Richard Češka
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    ABSTRACT: Terminologický slovník
    01/2008;

Publication Stats

182 Citations
70.05 Total Impact Points

Institutions

  • 2003–2014
    • Charles University in Prague
      • • 1st Faculty of Medicine
      • • Centrum preventivní kardiologie
      Praha, Praha, Czech Republic
  • 2011
    • Masaryk University
      • Interní hematologická a onkologická klinika
      Brno, South Moravian Region, Czech Republic
    • The Police Academy of the Czech Republic in Prague
      Praha, Praha, Czech Republic
    • University General Hospital
      Houston, Texas, United States
  • 2009
    • Institute for Clinical and Experimental Medicine (IKEM)
      Praha, Praha, Czech Republic