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Prague, Czech Republic

Paulu P.,Charles University | Osmancik P.,Charles University | Tousek P.,Charles University | Minarik M.,Genomac Research Institute | And 5 more authors.
Journal of Thrombosis and Thrombolysis | Year: 2013

Dual antiplatelet therapy is important treatment modality across the spectrum of coronary artery disease manifestations. However, a significant number of patients do not have a completely effective response to clopidogrel. This study assessed the impact of response after clopidogrel with Verify Now device on prognosis on patients undergoing coronary interventions. Consecutive patients following percutaneous coronary intervention were prospectively enrolled. A loading dose of 600 mg of clopidogrel was administered before or during PCI. Blood samples were drawn within 24 h after clopidogrel administration. The effect of clopidogrel was measured using VerifyNow. All patients were evaluated at 6 months. The primary end-point was the combination of death, MI and stroke. 378 patients (69.3 % men and 30.7 % women) were enrolled. The mean age was 67.2 ± 12.8 years, BMI 28.9 ± 17.7, and 116 patients had diabetes (30.7 %). During the 6-months follow-up 30 patients (7.94 %) experienced a monitored end-point: 12 patients (3.17 %) had MI; five patients (1.32 %) strokes and 15 patients (3.97 %) died. The remaining 248 patients (71.26 %) were end-point free. Factors associated with a poor prognosis were: leukocytes (OR 1.7 [1.2-2.4], p < 0.01), creatinine (OR 1.4 [1.1-2.5], p < 0.05) and at a borderline level the presence of AA allele of gene CYP2C19*2 (OR 2.5 [0.99-4.1], p = 0.052). The results using VerifyNow were similar between both groups (Group End-point: 208.5 ± 85.5, group No end-point 203.1 ± 91.3) and failed to show any prognostic value (OR 1.00 [0.992-1.007], p = 0.9). The measurement of clopidogrel efficacy using VerifyNow had no prognostic value for our unselected cohort of patients after PCI. © 2012 Springer Science+Business Media New York.

Tomasov P.,Charles University | Minarik M.,Genomac Research Institute | Zemanek D.,Charles University | Cadova P.,Charles University | And 7 more authors.
Folia Biologica (Czech Republic) | Year: 2014

Hypertrophic cardiomyopathy is the most common genetic cardiac disease with vast genetic heterogeneity. First-degree relatives of patients with HCM are at 50% risk of inheriting the disease-causing mutation. Genetic testing is helpful in identifying the relatives harbouring the mutations. When genetic testing is not available, relatives need to be examined regularly. We tested a cohort of 99 unrelated patients with HCM for mutations in MYH7, MYBPC3, TNNI3 and TNNT2 genes. In families with identified pathogenic mutation, we performed genetic and clinical examination in relatives to study the influence of genetic testing on the management of the relatives and to study the usefulness of echocardiographic criteria for distinguishing relatives with positive and negative genotype. We identified 38 genetic variants in 47 patients (47%). Fifteen of these variants in 21 patients (21%) were pathogenic mutations. We performed genetic testing in 52 relatives (18 of them (35%) yielding positive results). Genetic testing of one HCM patient allowed us to omit 2.45-5.15 future cardiologic examinations of the relatives. None of the studied echocardiographic criteria were significantly different between the relatives with positive and negative genotypes, with the exception of a combined echocardiographic score (genotype positive vs. genotype negative, 3.316 vs. -0.489, P = 0.01). As a conclusion, our study of HCM patients and their relatives confirmed the role of genetic testing in the management of the relatives and found only limited benefit of the proposed echocardiographic parameters in identifying disease-causing mutation carriers.

Tomasov P.,Charles University | Minarik M.,Genomac Research Institute | Zemanek D.,Charles University | Cadova P.,Charles University | And 3 more authors.
Experimental and Clinical Cardiology | Year: 2014

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease with vast genetic heterogeneity. Genetic testing of sarcomeric genes yields a positive result in a limited number of HCM patients. Methods: We tested a cohort of 48 unrelated consecutive patients with HCM for mutations in MYH7, MYBPC3, TNNI3 and TNNT2 genes and compared clinical and echocardiographic parameters between groups with positive and negative results of genetic testing. Results: We identified genetic variants inside the coding exons and flanking intronic regions of the MYH7, MYBPC3, TNNI3 and TNNT2 genes in 19 of 48 HCM patients (40 %). Younger age at diagnosis (48, IQR 39.5-55.5 vs. 56, IQR 49-70, p 0.028) and reverse curvature septum (56% vs. 9%, OR 12.5, 95% CI 1.760-88.78, p 0.012) were associated with a positive result of genetic testing. Sigmoid septum was associated with older age at diagnosis (60, IQR 55.75-68.75 vs. 49, IQR 38-59.5, p 0.017). Conclusion: Our study shows that septal morphology and age at diagnosis could be stronger predictors of positive results of genetic testing than presence of family history of HCM and could be used for a selection strategy in HCM genetic analysis. © 2013 et al.

Benesova L.,Genomac Research Institute | Benesova L.,Applied Genomics | Belsanova B.,Genomac Research Institute | Belsanova B.,Applied Genomics | And 13 more authors.
Analytical Biochemistry | Year: 2013

Prognosis of solid cancers is generally more favorable if the disease is treated early and efficiently. A key to long cancer survival is in radical surgical therapy directed at the primary tumor followed by early detection of possible progression, with swift application of subsequent therapeutic intervention reducing the risk of disease generalization. The conventional follow-up care is based on regular observation of tumor markers in combination with computed tomography/endoscopic ultrasound/magnetic resonance/positron emission tomography imaging to monitor potential tumor progression. A recent development in methodologies allowing screening for a presence of cell-free DNA (cfDNA) brings a new viable tool in early detection and management of major cancers. It is believed that cfDNA is released from tumors primarily due to necrotization, whereas the origin of nontumorous cfDNA is mostly apoptotic. The process of cfDNA detection starts with proper collection and treatment of blood and isolation and storage of blood plasma. The next important steps include cfDNA extraction from plasma and its detection and/or quantification. To distinguish tumor cfDNA from nontumorous cfDNA, specific somatic DNA mutations, previously localized in the primary tumor tissue, are identified in the extracted cfDNA. Apart from conventional mutation detection approaches, several dedicated techniques have been presented to detect low levels of cfDNA in an excess of nontumorous (nonmutated) DNA, including real-time polymerase chain reaction (PCR), "BEAMing" (beads, emulsion, amplification, and magnetics), and denaturing capillary electrophoresis. Techniques to facilitate the mutant detection, such as mutant-enriched PCR and COLD-PCR (coamplification at lower denaturation temperature PCR), are also applicable. Finally, a number of newly developed miniaturized approaches, such as single-molecule sequencing, are promising for the future. © 2012 Elsevier Inc. All rights reserved.

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