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M Cerná

Publications and source records attributed to M Cerná.

At least 55 records · Page 3Linked to original sources

Urinary cyclophosphamide excretion and chromosomal aberrations in peripheral blood lymphocytes after occupational exposure to antineoplastic agents.

In this study we have compared the results of a method for the detection of cyclophosphamide in urine and the results of analysis of chromosomal aberrations in peripheral blood lymphocytes of four groups of subjects with various exposure statuses. These groups are 17 Dutch and 11 Czech exposed workers (mainly hospital nurses and pharmacy technicians) handling antineoplastic agents and 35 Dutch and 23 Czech controls (nurses, medical doctors, pharmacy and lab technicians) not handling these drugs. The groups were subdivided into smokers and non-smokers because of a confounding effect of smoking. Within the Dutch groups, the percentage of aberrant cells and the number of breaks per cell were increased for smokers compared to non-smokers. The percentage of aberrant cells was increased in Dutch exposed workers in comparison with Dutch control workers. Within the Czech groups the percentage of aberrant cells and the number of breaks per cell were increased in exposed workers in comparison with control workers. However, both Dutch and Czech smokers mainly contributed to the increase. The results suggest an additive effect of exposure and smoking in the Dutch subjects and a more than additive effect in the Czech subjects. In urine samples of three out of 11 Dutch exposed workers cyclophosphamide was found in a range of 0.1-0.5 micrograms/24 h. Higher levels were detected in the urine of eight out of 11 Czech exposed workers, a range of 0.1-2.9 micrograms/24 h. No correlation was observed between the amounts of cyclophosphamide excreted in urine on the one hand and the percentage of aberrant cells and the number of breaks per cell on the other hand. The present study is the first study showing that hospital workers having an increase in chromosome aberrations related to their work are exposed to at least one antineoplastic agent.

Adult↗

HLA and juvenile rheumatoid arthritis.

HLA class II analysis in a group of 153 Czech children with juvenile rheumatoid arthritis by PCR and oligonucleotide hybridization demonstrated associations with several alleles. DRB1*0801 (RR = 5.3, p < 0.005) and DRB1 * 11 (RR = 2.2, p < 0.01) including all subtypes were shown to be increased in the rheumatoid factor-negative group (N = 137). The same results were observed in Italy, England and Norway. In patients with the pauciarticular onset with conversion to polyarticular within 3 years, a statistically significant increase in DR2 (RR = 10.1, p < 0.00005), mostly due to DRB1*1501, was found. In the iridocyclitis and antinuclear factor groups, susceptibility to DRB1*1201 was observed. There was a striking decrease in DRB1*0701 (RR = 0.3, p < 0.00005) in all groups. There was neither an increase in DRB1*1301 or DPB1*0301 nor a decrease in DRB1*04, as reported from other studies in Texas and Norway. The rheumatoid factor-positive group with polyarticular onset (N = 13) was associated with DRB1*04 (RR = 7.1, p < 0.005), as observed in adults. DPB1*0201 was increased in the persistent pauciarticular group (RR = 3.7, p < 0.0005). DPB1*0402 was decreased in all pauciarticular groups with or without conversion (RR = 0.3, p < 0.005). Taken together, there are not only genetic differences and clinical heterogeneity in juvenile rheumatoid arthritis patients but, also, common predisposing factors.

Adult↗

Comparison of HLA class II alleles in Gypsy and Czech populations by DNA typing with oligonucleotide probes.

Czechs (CZ) and Gypsies (GY) have lived in the same country for several centuries but seem to have different migratory origins. We have studied 99 CZ and compared them with 34 GY from an isolated group living in Czechoslovakia. DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 alleles were determined by PCR followed by oligonucleotide hybridization. DRB1*0701 was the most frequent DR allele in CZ (af = 36.3%). In GY, after DRB1*0701, DRB1*1404 was the second most frequent allele (af = 29.4%), while in CZ this allele was not found. Both groups differed also in the distribution of DR4 subtypes. In CZ, DRB1*0401 was the most frequent subtype (50.0%) of DR4. In GY, DRB1*0408 was the predominant type (44.4%). A new DQB1 pattern was found in GY, which we have called DQB1*3.4. This allele was similar to DQB1*0301 in codon 26, but in codon 57 it resembled DQB1*0302. All cells having this new allele were also positive for DRB1*0408. Four-locus associations in CZ showed haplotypes similar to those previously found in other Caucasoid populations. In GY we observed more unusual haplotypes, some previously seen in the Orient, possibly reflecting GY ancestry.

Alleles↗

Some epidemiological characteristics of pneumonia in Czechoslovakia and several neighbouring countries from the aspect of mortality rates.

The authors evaluated the dynamics of mortality rates due to pneumonia in Czechoslovakia and several neighbouring countries over the period of 1974 to 1985. The relative risk of death and proportional mortality rates were calculated and epidemiological curves plotted using data provided by the World Health Organization. It is concluded that during the period in question there was no positive change in the dynamics of mortality rates in Czechoslovakia. Particular attention should be paid to persons in the age group of 75 and more years, where the relative risk of death is at least 4 times greater than in the general population.

Aged↗

[Mutagenic activity analysis of body fluids in the first phase of clinical drug trials].

On the example of the model drugs metronidazole and ornidazole, a possible use of an analysis of mutagenic activity of blood and urine in the first stage of clinical testing of drugs is demonstrated. Mutagenicity of blood and urine after metronidazole administration in the dose of 1 and 2 g was examined in 3 experiments with 6 volunteers, the presence of mutagenic drugs in urine in the dose of 1 g was observed till 48 h, in the dose of 2 g till 72 h after administration. Besides base-substitution mutations also frameschif mutations were detected, but with considerable individual variability. Mutagenic activity in blood and urine after the administration of 1 g of ornidazole was investigated in the 1st experiment in 3, in further two experiments in 8 volunteers. It was characterized by a two-peak increase in mutagenicity in blood and urine in the intervals of 1-6 h and 48-72 h. Saturation of 1 g of ascorbic acid daily in the course of 1 week prior to the administration of ornidazole was manifested by a decrease in mutagenic activity in blood and increased excretion of mutagenic drugs in urine.

Adult↗

[The development of myocardial infarct in a patient treated with 5-fluorouracil].

The authors describe the first case of myocardial infarction in their department which occurred during 5-fluorouracil treatment. In a 37 year-old patient two years before the infarction an epidermoid carcinoma of the lower lip was found. The patient was subjected to operation and radiotherapy. Because of a relapse of the process after one year the patient was re-operated with subsequent chemotherapy (vincristine, methotrexate, cis-platinum). Because the effect was not satisfactory, after another year 5-fluorouracil treatment was started (i.v. infusion of 3000 mg in two days). In the course of the infusion the patient developed the clinical picture of a non-transmural infarction of the anterior wall. The course was uncomplicated. The ECG returned to normal on the 9th day after discontinuation of 5-fluorouracil treatment. The effect of 5-fluorouracil on the heart is explained by a coronary vascular spasm. The authors recommend therefore administration of calcium blockers.

Adult↗

Effect of ascorbic acid prophylaxis on the frequency of chromosome aberrations, urine mutagenicity and nucleolus test in workers occupationally exposed to cytostatic drugs.

The genetic risk of workers occupationally exposed to a series of newly developed cytostatic drugs and the presumed antimutagenic potential of ascorbic acid (AA) were studied in a group of 38 chemical laboratory personnel examined for chromosome aberrations in lymphocytes, urine mutagenicity and nucleolar RNA activity before and after a 6-month prophylactic administration of AA at daily doses of 1 g for 5 days a week. Chromosome aberration tests revealed elevated aberrant cell (AB.C) rates both prior to and after AA supplementation (3.9% and 3.65% of AB.C., respectively). These values were significantly higher than those found in 18 non-exposed matching controls (1.05% of AB.C.). Tests for mutagenic activity in the urine of drug-exposed workers revealed 64% positive urine samples prior to vitaminization and 60% positive urine specimens after it; positive urine samples in the group of controls accounted for 21% of samples. In the nucleolus test, numbers of inactivated micronuclei in the exposed were initially higher than those of controls (33.4% versus 24.3%), but dropped to 20.5% after AA supplementation. These findings show that AA prophylaxis alone cannot substantially reduce the hazards associated with exposure to anti-cancer drugs.

Antineoplastic Agents↗

Mutagenicity of some substituted 1-phenyl-3,3-dimethyltriazenes. I. The salmonella/mammalian microsome assay and repair test.

The mutagenic activity and related biological properties of Br-, Cl-, NO2- and CH3-derivatives of 1-(phenyl)-3,3-dimethyltriazene were investigated in Salmonella/microsome assays with standard and preincubation metabolic activation and in the repair test using Salmonella and E. coli B/r. In the repair test, the CH3-derivative was slightly positive in the E. coli recA and uvrA repair system, the NO2-derivative had a killing effect on Salmonella typhimurium uvrB-deficient strains. In Salmonella mutagenicity assays, all tested triazene derivatives reverted frameshift tester strains, especially TA1537. The highest number of frameshift mutations was induced by the CH3-derivative in the presence of a standard metabolic activation system; direct mutagenicity of this derivative was weak, reaching about the same level of activity as seen after preincubation. The only test compound that induced mutations of the base-substitution type was the NO2-derivative; this derivative showed the highest mutagenicity when activated by preincubation.

Animals↗

Mutagenicity of some substituted 1-phenyl-3,3-dimethyltriazenes. II. Chromosomal aberrations in human peripheral lymphocytes in vitro.

The chromosome-breaking activity of four 1-(phenyl)-3,3-dimethyltriazenes was tested in vitro on human peripheral blood lymphocytes using S9 mix as a metabolic activation system. 1-(4-Nitrophenyl)-3,3-dimethyltriazene was the most active compound. The difference in the frequency of chromosomal aberrations in a test with and without metabolic activation was significant at the 1% level of significance. The lowest frequency of chromosomal aberrations was induced by 1-(4-methylphenyl)-3,3-dimethyltriazene which, under the conditions of this experiment, is the least stable and probably rapidly degraded to non-active compounds. The chromosomal aberrations were also induced by 1-(4-chlorophenyl)-3,3-dimethyltriazene and 1-(4-bromophenyl)-3,3-dimethyltriazene, this activity was unrelated to metabolic activation.

Cells, Cultured↗

Chromosomal aberrations, SCE and urine mutagenicity in workers occupationally exposed to cytostatic drugs.

The genetic risk run by workers occupationally exposed to chemicals, including the newly developed cytostatics, was assessed in large chemical laboratories. The exposed group comprising 38 people consisted of chemists, laboratory assistants and pilot plant workers. The average rate of aberrant cells in peripheral blood lymphocytes (AB.C). was 3.9% and the value of break/cell ratio was 0.046. The group of matched controls (N = 18) was found to have 1.5% of AB.C. and 0.020 breaks/cell. In the exposed group, there were, on average, 8.94 SCEs/cell, and in controls, 5.81. Urine mutagenicity tests on Salmonella typhimurium tester strain TA98 revealed a significant increase of activity in 23 (64%) out of 36 urine samples tested as compared to the control group (N = 19) with 4 (21%) positive urine samples. Strain TA100 showed only a weak response to urine mutagens.

Antineoplastic Agents↗

Mutagenicity in the Salmonella/microsome assay of tobacco condensates formed during pipe smoking.

The condensates collected after pipe smoking of a natural tobacco and a cavendish type tobacco, either unwrapped or wrapped in a paper "saver" bag, were tested for mutagenicity in the Salmonella/mammalian microsome assay with strains TA100 and TA98. The number of revertants induced with cavendish type tobacco in the presence of metabolic activation (mouse-liver S9) was higher in both strains compared to the natural tobacco. Further increase in the number of revertants (approx. 3 times) was consistently seen when the tobacco was smoked after paper wrapping "savers".

Animals↗

Mutagenicity of beta-glucuronidase in the Ames test.

The enzyme preparation beta-glucuronidase/arylsulphatase from Helix pomatia (Boehringer) caused base-pair substitutions in Salmonella typhimurium TA100 and TA1535 strains within the dose range of 0.50-50 microliter per plate. No effect was observed in the TA98 strain. The presence of S9 mix did not substantially affect the mutagenic potential of beta-G. The number of induced revertants decreased continually from experiment to experiment carried out in the course of 12 weeks.

Animals↗