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K Chroust

Publications and source records attributed to K Chroust.

At least 19 recordsLinked to original sources
PubMed2006

[Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation].

BACKGROUND: In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions. GROUP OF PATIENTS AND METHODS: Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome). RESULTS: At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature). CONCLUSION: Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.

DNA Mutational Analysis↗
PubMed2006

[Extension of QT interval as a consequence of risk factor accumulation--case study].

BACKGROUND: Many non-cardiovascular drugs have a potential for QT interval prolongation. This phenomenon can be related to occurence of ventricular tachycardia torsades de pointes, syncopi and even sudden death. DESCRIPTION OF THE CASE: A female patient treated with antracycline cytostatics developed a depression of left ventricle ejection fraction. At the same time she was administered 2 common drugs with proarrhythmic potential--terfenadine and itraconazole. In this patient hypokalemia also occured. Combination of the above mentioned risk factors led to QT interval prolongation and frequent ventricular tachycardias torsades de pointes degenerating in ventricular fibrillations with need of repeated defibrillations. Both drugs were withdrawn and dysiontaemia corrected. Then arrhythmias disappeared and QT interval completely normalized. In this patient the congenital long QT syndrome was not proved. DISCUSSION AND CONCLUSIONS: In proarrhythmic effect of non-cardiovascular drugs the following factors play role: predisposition of a particular individual, "repolarization reserve", interindividual differences in drug metabolism. The risk factors are age, sex, dysiontaemia, heart disease and drug interactions. By different choice of medication and attention to risk factors teh life threat to the described patient could have been avoided.

Adult↗
PubMed2004

Treatment of associated anemia in different hematological disorders with epoetin alpha.

The communication is summarizing results of study aimed to ascertain the efficacy of treatment with epoetin alpha in patients with different hematological disorders and, at the same time to evaluate the impact of this treatment on quality of their lives. Treatment efficacy in separate patients of the monitored population has been evaluated not only according to hemoglobin level increase, but also according to its effect on erythrocyte products consumption needed to control anemic syndrome. Overall 134 patients with different lymphoproliferative disorders were included in the evaluation. Full-extended monitoring, i.e. at least 3-month treatment with epoetin alpha, was passed by 127 (94.8%) patients. Favorable effect of epoetin alpha administration was most often reported in patients with multiple myeloma (85.7%), Waldenstrom s macroglobulinemia (80%) and chronic lymphatic leukemia (76.7%). Conversely the lowest efficacy was reported in the group of patients with myelodysplastic syndrome. Administration of epoetin alpha within treatment of underlying anemia in numerous hematological disorders represents suitable alternative to the substitution therapy via erythrocyte transfusions. Approximately 75% of monitored patients showed improvement of life quality, in some cases irrespective of results of treatment of their underlying disorder.

Anemia↗
PubMed2003

[Occurrence of bleeding in women using combined hormonal contraceptives (ethinylestradiol 35 micrograms/norgestimate 250 micrograms in relation to regularity of administration and cycle start day].

OBJECTIVE: To assess the frequency of irregular intermenstrual bleeding in combined oral contraceptive (ethinylestradiol 35 micrograms/norgestimate 250 micrograms, COC) users and the influence of regularity of pill use on this frequency; to assess the occurrence of withdrawal bleeding during weekends in women using the COC from the first Sunday in the cycle (Sunday start method). DESIGN: Prospective, open, non-comparative, multicenter study in 27 centers. METHODS: The first day of the pill use, occurrence of intermenstrual and withdrawal bleeding and regularity of use were assessed by means of patient's bleeding diary. Body weight, blood pressure and side effects were monitored before the oral contraceptive use and after the third cycle. RESULTS: 358 (94%) of 382 women completed the study. Frequency of intermenstrual bleeding was generally low (6.7%, 5.0% and 5.0% in the first, second and third cycle) and highly influenced by regularity of pill use (2.6%, 0% a 1% in regular users versus 30.2%, 32.1% a 24.2% in irregular users). 28%, 40% and 47% of Sunday start users achieved bleeding-free weekends after the first, second and third cycle. Body weight and blood pressure did not change during the study. CONCLUSION: Frequency of intermenstrual (breakthrough) bleeding during the first three months of COC use is highly influenced by regularity of use. In regular users of monophasic COC containing ethinylestradiol 35 micrograms/norgestimate 250 micrograms the frequency of intermenstrual bleeding is bellow 2.6%. In Sunday start users the proportion of women with bleeding-free weekends (i.e. weekends without the occurrence of withdrawal bleeding) increases to 47% after the third cycle.

Adolescent↗
PubMed2003

[Comparison of various methods of correction of QT intervals during exercise in familial long QT interval syndrome].

BACKGROUND: Pathologic prolongation of QT interval is related to increased risk of arrhythmias. Changes of this parameter are influenced by many conditions, the most important is heart rate. Several formulas have been proposed for mathematical description of QT interval/heart rate relationship. The aim of this study was comparison of different QT interval correction formulas in families with congenital long QT syndrome (LQTS). METHODS: In 28 members of 6 families with LQTS occurrence bicycle ergometry testings were performed. QT and RR intervals were measured before exercise, at peak exercise and in the 1st and the 6th minute of restitution. For QT interval correction single-parameter formulas by Bazett, Fridericia, Malik and Framingham study were used. In 3 families the results could be correlated with genetically proved diagnosis (KCNQ1 gene mutations in 2 families, HERG-KCNH2 gene mutation in the other). RESULTS: In the described group the genetically established diagnosis of LQTS correlated at best with values obtained with correction by Bazett. All the mutation carriers were correctly identified only by this method. The Fridericia, Malik and Framingham formulas failed to identify 2 patients--mutation carriers (both KCNQ1 and HERG-KCNH2 mutations). DISCUSSION: Because of simplicity the Bazett formula remains the most common method of QT interval correction. Moreover, in our study this formula appeared to be the most sensitive for clinical diagnosis of LQTS.

Algorithms↗
PubMed2001

Activation or detoxification of mutagenic and carcinogenic compounds in transgenic Drosophila expressing human glutathione S-transferase.

Sensitivity of transgenic Drosophila melanogaster with expression of a human gene encoding the glutathione S-transferase alpha subunit (GSTA1-1) to 1,2:5,6-dibenzanthracene (DBA) and 1,2-dichloroethane (DCE) was investigated in the somatic mutation and recombination test (SMART). We performed the same assay in control transgenic flies expressing the bacterial lacZ gene. Three types of transgenic Drosophila strains carrying GSTA1-1 were used: two transgenic strains homozygous for the second chromosome with a single-copy transgene insertion and one strain with two transgene insertions. Larvae carrying the lacZ gene were significantly more sensitive to genotoxic effects of DBA than those carrying three copies of the GSTA1-1 gene. The larvae with lacZ expression showed significantly lower sensitivity to DCE compared with those expressing GSTA1-1. Finally, a pretreatment with buthionine-sulphoximine (BSO) in experiment with DCE significantly decreased the frequency of mutation events in larvae with three GSTA1-1 copies in comparison with others.

Animals↗
PubMed2000

[Prediction of the effect of a triphasic contraceptive agent with norgestimate on acne].

OBJECTIVE: Prediction of complexion changes in users of triphasic oral contraceptive containing norgestimate. DESIGN: Analysis of data from a prospective multicentre open study. SETTING: Department of Obstetrics and Gynaecology, Charles University, Prague. METHODS: Acne severity was evaluated in users of a triphasic norgestimate-containing contraceptive within a six month period. Based on subjective evaluation of acne, three subgroups of patients were selected: A) users where acne improved or disappeared; B) users in whom acne deteriorated, C) users who newly developed acne. Differences between group A and the other groups were established in the proportion or distribution of parameters related to the etiology of acne: age, weight, weight changes during the study, presence of hirsutism, presence of a regular menstrual cycle prior to the start of hormonal contraception use, and smoking. RESULTS: The effect of the pill use on acne was assessed in a total of 3,990 women. Out of 1,201 women with acne before the start of the study, improvement or disappearance of acne during the study was reported by 940 users (subgroup A) (78.27%). In 221 women (18.40%), the extent of acne remained unaltered whereas it increased (subgroup B) in only 30 women (2.50%). Acne newly developed during the study in 49 women (subgroup C), i.e., in 1.2% of the whole group. Users showing deterioration of acne (subgroup B) were found to have hirsutism less frequently. The subgroup even showed a decrease in mean weight during the study. Users with newly developed acne were--compared with subgroup A--significantly older, had a lower weight at the start of the study, and showed a higher frequency of regular menstrual cycles prior to starting hormonal contraception. The differences in the incidence of clinical parameters in the subgroups reached only borderline statistical significance and, hence, are not relevant. CONCLUSION: An extensive multicentric study confirmed the beneficial effect of a triphasic norgestimate-containing contraceptive on complexion. The presence of clinical parameters related to the etiology of acne does not allow to predict the individual response of the skin to hormonal therapy.

Acne Vulgaris↗
PubMed2000

[The factor V Leiden mutation in users of hormonal contraceptives].

OBJECTIVE: To assess the frequency of factor V Leiden in oral contraceptive users and to define possible anamnestic data that could predict the presence of factor V Leiden. METHODS: Between 1997 and 1998, 583 users of oral estrogen-progestin contraceptives with no history of thrombotic disease were examined. Factor V Leiden was assessed by PCR after isolating DNA from a peripheral venous blood sample. Among other factors, such things as a family history of thromboembolic disease, myocardial infarction and/or stroke in a first-degree relative were monitored. In 448 users cardiovascular complications were evaluated during six months of oral contraceptive use. The data were analyzed using a MS Excel program. P-values were assessed by pair-tests and chi-square tests. SETTING: 1st Department of Obstetrics and Gynecology of Medical Faculty, Masaryk University, Brno. RESULTS: Factor V Leiden frequency was 6.5% in the study group. There were no differences between carriers and others in age, body weight, body mass index and blood pressure. Carriers had significantly more frequently positive family histories of thromboembolic disease or myocardial infarction or stroke. There were no cardiovascular complications observed in a group of 448 users. The positive family histories of any of the above-mentioned conditions have high specificity (97-99%) and a negative predictive value (0.94) with a low sensitivity (2.6-15.8%) in predicting factor V Leiden presence. CONCLUSION: We found a relatively high incidence of Factor V Leiden among oral contraceptive users without a history of thrombotic disease. Through a positive family history of thromboembolic disease or myocardial infarction or stroke, we can predict a Factor V Leiden presence with high specificity but low sensitivity.

Adolescent↗
PubMed2000

[Liver function tests during administration of triphasic contraceptives containing Norgestimate].

OBJECTIVE: To evaluate serum levels of liver enzymes and bilirubin before and after six cycles of use of a triphasic oral contraceptive containing 35 micrograms of ethinylestradiol and 180/215/250 micrograms of norgestimate (Pramino, Janssen-Cilag). DESIGN: A prospective, open-label, non-comparative, multicentric phase IV study. SETTING: Department of Obstetrics and Gynaecology, 1st Medical Faculty, Charles University, Prague. METHOD: Before the start and after six cycles of Pramino use, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GMT), and bilirubin were determined in women. As the analyses were performed in different laboratories, the evaluation involved: 1. Subgroups of women examined in laboratories with the same reference range; 2. A group of women examined in laboratories with the upper reference range within the mean +/- SD interval; 3. Percentage variations of the measured values from a concrete upper reference limit. RESULTS: When evaluating subgroups of women from laboratories with the same standards, significant decreases in AST and bilirubin were seen in some subgroups, a rise in GMT in one subgroup; the other changes were non-significant. When assessing the entire group and percentage variations from standard, a mild rise in GMT was again seen; however, the values remain deep within the normal range. Values above the upper reference limit at the start of the study either do not change significantly throughout the study, or they normalize spontaneously. CONCLUSION: No clinically significant changes in liver function tests occurred in users of a triphasic oral contraceptive containing norgestimate along with 35 micrograms EE over a period of six cycles of use. The results, as judged by their dynamics, suggest liver function tests are not a useful tool for routine monitoring a healthy combined oral contraceptive user.

Contraceptives, Oral, Combined↗
PubMed1999

[Clinical study of a triphasic contraceptive preparation (Norgestimate 180/215/250 micrograms + ethinylestradiol 35 micrograms) in a population of Czech women].

OBJECTIVE: To assess the efficacy, acceptability and safety of triphasic oral contraceptive pill containing norgestimate 180/215/250 micrograms and ethinylestradiol 35 micrograms. DESIGN AND SETTING: Prospective, open-label, non-comparative, multicenter study in 409 centers in the Czech Republic. METHODS: Body weight, blood pressure, bleeding pattern, headaches, nausea, breast tenderness, acne, pregnancies and side effects were monitored before the start of the treatment, after three and six cycles of oral contraceptive use. Liver function tests were carried out before and after the treatment. RESULTS: Evaluating 26,432 cycles in 4,720 women the theoretical Pearl index was 0.15. There were no significant changes in body weight (61.45 kg before vs 61.58 kg after the treatment). There were clinically significant changes neither in the blood pressure nor in the liver function tests. Evaluating the bleeding pattern there were similar incidences of irregular bleeding/spotting before the treatment and up to the third treatment cycle (16.15%, resp. 17.86%); then the incidence dropped down (8.41% after the third cycle). Amenorhea was very rare (0.41% resp. 0.35% up to, resp. after the third cycle). Decreasing incidences compared to pretreatment state were observed for headache, breast tenderness and acne. The effect on acne was remarkable (28.3% of women complaining of acne before the treatment vs 6.51% after the six treatment cycles). There were no serious adverse events observed during this study. CONCLUSION: Triphasic oral contraceptive pill containing norgestimate and ethinylestradiol proved in a large multicenter study high both efficacy and acceptability.

Adolescent↗
PubMed1997

Use of thiopropyl sepharose for the synthesis of an adsorbent for the affinity chromatography of glutathione S-transferase.

Thiopropyl Sepharose 6B in the 2-thiopyridyl-activated form was used for the reversible immobilisation of reduced glutathione (GSH). The resulting affinity matrix was successfully tested as a sorbent for the partial purification of glutathione S-transferase (GST) from pig kidney. The specific elution of the enzyme was performed with 10 mM GSH in Tris-HCl buffer (pH 7.8), non-specific elution with 20 mM dithiotreitol (DTT) in the same buffer.

Animals↗
PubMed1997

Genotoxicity of N-nitroso-N-methylurea and acetone oxime in the transgenic Drosophila carrying the human gene encoding a subunit of glutathione S-transferase.

The genotoxic effects of N-nitroso-N-methylurea (MNU) and acetone oxime (ACOX) were tested in the Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. We have performed the same assay on transgenic flies expressing the human gene encoding a glutathione S-transferase alpha subunit (HGST). The SMART assay is used here to demonstrate genotoxicity and to determine the effect of human glutathione S-transferase on the genotoxic response. Three types of Drosophila strains were used: non-transgenic strains first described by Szabad (1986), transgenic strains derived from the Szabad strains but expressing the bacterial lacZ gene, and similarly derived transgenic strains expressing the HGST gene. MNU was highly genotoxic in both transgenic and non-transgenic flies. The non-transgenic lies were significantly more sensitive to the genotoxic effects of MNU compared to both types of transgenic flies. There were statistically significant differences between the transgenic HGST crosses and transgenic lacZ and non-transgenic control crosses but there was no significant difference between the genotoxic response to MNU in flies from the transgenic cross with lacZ and from the cross carrying three copies of HGST. ACOX also proved to be genotoxic to both non-transgenic and transgenic flies. However, flies carrying three copies of the gene were significantly more resistant to the genotoxic effect of ACOX than those transgenic flies with two or no copies of the human gene.

Animals↗
PubMed1997

Drosophila melanogaster, Vicia faba and Arabidopsis thaliana short-term bioassays in genotoxicity evaluation of air and soil samples from sites surrounding two industrial factories in the Czech Republic.

The Somatic Mutation and Recombination Test (SMART) in wing cells of Drosophila melanogaster, the Vicia faba cytogenetic tests-Sister Chromatid Exchange (SCE) and Micronucleus Test (MN), and the Müller test for gametic mutations in Arabidopsis thaliana were used for genotoxicity testing of environmental samples of pollutants from the surroundings of LACHEMA chemical factory (Brno, Czech Republic) and DEZA factory in Valasské Mezirící (Moravia, Czech Republic). Tested soil and air samples were taken from the near vicinity of both factories. The surroundings of both sites are heavy loaded by exhalation of chemicals from the factories. Chemical analyses of the 16 Polycyclic Aromatic Hydrocarbons (PAHs) according to the United States Environmental Protection Agency (US EPA) list of priority pollutants and heavy metals were performed in both soil and air samples. The Drosophila wing spot test was positive in 70.6% of the tested samples, the Vicia sister chromatid exchange test in 62.5%, and the Arabidopsis Müller test in 58.9%. The micronucleus Vicia faba test was quite insensitive in tested environmental samples. The concordance between SMART and SCE was 62.5%, between SMART and Müller test 76.5%, and between Müller test and SCE 100%. Total concordance of these three tests was 79.7%. Müller test for gametic mutation in Arabidopsis thaliana and cytogenetic SCE test in Vicia faba seem to be quite sensitive and convenient plant bioassays for assessing the mutagenic potential of environmental agents, when compared to the SMART test in Drosophila melanogaster.

Air Pollutants, Occupational↗
PubMed1997

[Control of gastrointestinal helminthiasis in pasture-reared lambs].

Two sheep herds kept in different geographic conditions with spring lambing by the end of March and April (herd No. 1: 400 ewes, 600 metres above sea level; herd No. 2: 450 ewes, 300 metres above sea level) were examined. The dynamics of gastrointestinal nematode and Moniezia spp. cestode egg counts in samples taken regularly every 4 to 5 weeks was studied during the year 1995 with the intention to verify the system of effective control of these helminth infections under pasture conditions of lamb rearing. In ewes a significant rise in gastrointestinal nematode egg counts was proved during the lambing season, "spring rise phenomenon", and during the summer pasture until autumn months with maximum EPG values reaching 150 (Figs. 1 and 2). In lambs that started grazing at 1 to 4 weeks of age, the excretion steeply rose to maximum EPG values 350 and 290, respectively, after 4 to 5 weeks of grazing (Figs. 1 and 2). In order to control these rising infections, ewes were treated with antihelmintic albendazol by the end of February (herd No. 1) and in March (herd No. 2) and lambs during the first or third decade of July. This anthelmintic treatment significantly lowered egg excretion to EPG values lower than 30 in ewes and 50 or 60, respectively, in lambs. Later, during the summer and autumn months, a mild rise of egg counts was found in lambs. These maxima were liquidated anthelmintis treatment in both herds in late autumn months and it also lowered helminth infections to minimum during winter months (EPG values lower than 50). The excretion of Moniezia spp. eggs had the same dynamics as that gastrointestinal nematodes. Values of lamb infection prevalence reached 21% in herd No. 1 and 29% in herd No. 2. Anthelmintic treatment during July controlled cestode findings in lambs. Albendazol (Vermitan susp. 2.5%), dosed 5 mg/kg of body weight, proved highly effective in the control of gastrointestinal nematodes and Moniezia spp. cestodes.

Albendazole↗
PubMed1989

[Epizootiology and prevention of helminthiasis of game animals in Czechoslovakia and its relationship to the parasitic diseases of cattle].

Decades of surveying helminthic diseases in domestic and free-living ruminants in the CSR evidenced extensive infestation by lungworms, gastrointestinal nematodes, and liver flukes. In some years, parasitic invasion caused up to 50% of total losses of roe deer. Programmes to control systematically dictyocaulosis and fascioliasis were carried out with cattle and sheep in 1970-1980, with deer in 1981-1985. In the eighties, the incidence of F. hepatica in cattle and sheep dropped to less than 1%, of D. viviparus in cattle to 0.2%; no D. filaria is to be encountered in sheep presently. The share of parasitic diseases in total losses of roe deer decreased to 19% in 1983-1985.

Animals↗