[The spectrum of mutations in the CFTR gene in patients with cystic fibrosis in Slovakia]. / Spektrum mutácií v géne CFTR u pacientov postihnutých cystickou fibrózou z populácie Slovenska.

Up to present, more than 500 mutations have been described in the CFTR gene of patients affected by cystic fibrosis (CF). The vast majority of them, however, are extremely rare, and in fact, were detected only in the original reported cases. This study is aimed at analysis of 9 known mutations in the CFTR gene in CF patients within the population of Slovakia. The region in question of the human genome was analysed by means of polymerase chain reaction (PCR), digestion with the appropriate restriction enzyme, followed by electrophoretic separation of generated DNA fragments. 7 different mutations were identified on 234 CF-chromosomes, which made up 74.36% of all CF-mutations: delta F508--59.4%, G542X--5.56%, R553X--3.42%, N1303K--2.99%, R347P--1.71%, W1282X--0.85%, and 3849 + 10kb--0.43%. In 57.26% of patients mutations were identified on both homological chromosomes, in 33.33% on one of them, and only in 9.4% of patients there were none of the analysed mutations found. These results provide a good basis for the planning and setting up of an effective strategy for direct DNA-based diagnosis of CF in Slovakia. (Tab. 4, Ref. 19.)

PKU in Slovakia: mutation screening and haplotype analysis.

The restriction fragment length polymorphism haplotypes and seven common mutations in the phenylalanine hydroxylase gene were analysed in 49 unrelated Slovak phenylketonuria (PKU) families of Caucasian origin. The predominant mutation in this population sample is R408W, with a frequency of 45.9%. In addition, four other mutations have been identified at relatively high frequencies: IVS12nt1, 10.2%; R158Q, 7.1%; R261Q, 7.1%; R252W, 2.0%. The mutation-haplotype associations correspond to those described in other European populations. The high proportion of mutations (72.4%) amenable to simple rapid detection based on the polymerase chain reaction provides a good basis for direct DNA-diagnosis of PKU in the Slovak population.

Magnetic resonance imaging in children receiving quinolones: no evidence of quinolone-induced arthropathy. A multicenter survey.

Twenty-nine children with cystic fibrosis (CF) were investigated for quinolone-induced arthropathy. Magnetic resonance imaging (MRI) was performed in 14/14 children treated with ofloxacin or ciprofloxacin and in 10/15 of those never treated with quinolones. The frequency of pathologic MRI findings, concerning cartilage thickness, careful analysis of the cartilage structure, presence of edema, cartilage-bone borderline and the presence of fluid in joints did not show any difference between both groups. Thus the presence of quinolone-induced arthrotoxicity cannot be confirmed in this study.

[DNA analysis in classic phenylketonuria--screening for mutations and haplotype analysis in Slovak families]. / DNA-analýza pri klasickej fenylketonúrii--skríning mutácií a haplotypová analýza v slovenských rodinách.

Authors in this contribution present the results of screening for mutations in PAH gene responsible for classical phenylketonuria (PKU), and that of haplotype analysis, based on DNA analysis in 49 Caucasian families with at least one affected child from Slovak Republic. The clearly predominant PKU mutation in this population was the R408W with proportion of 45.9% among all PKU mutations. In addition four other mutations have been identified: IVS12nt1-10.2%, R158Q-7.1%, R261Q-7.1%, and R252W-2.0%. the overall proportion of identified PKU mutations equals 72.4%. Considering the fact, that these mutations are amenable to rapid and rather simple detection using PCR, the DNA analysis is recommended as a method of direct diagnosis in clinical practice as well as in prevention.

[New recommendations for nutritional requirements for the Czechoslovak population]. / Nové odporúcané výzivové dávky pre obyvatel'stvo CSFR.

The authors present new recommended energy and nutrient allowances for the population of CSFR. The allowances are defined for 29 physiological groups, incl. 11 groups of children and adolescents and 18 groups of adults (productive age and more advanced age groups). The recommended allowances are the result of research of two teams--a Czech and a Slovak one--, results are published in the world literature, FAO and WHO reports. The recommended system can be considered an important step in the area of nutritional prevention of cardiovascular diseases, diabetes and obesity.

[The delta F508 mutation which causes cystic fibrosis and its association with closely linked DNA polymorphisms in the Slovak population]. / Mutácia deltaF508 zaprícinujúca cystickú fibrózu a jej asociácia s tesne viazanými polymorfizmami DNA v slovenskej populácii.

Linkage relationships between DNA polymorphism metH/TaqI as well as KM19/PstI and the mutation causing cystic fibrosis (CF) were analyzed in 48 families from Slovakia with th occurrence of CF. The polymorphism metH/TaqI did not show linkage disequilibrium with CF mutation. A pronounced allelic association was however found between CF mutation and KM19/PstI polymorphism. Of the 83 CF chromosomes analyzed, the given mutation was associated with the 6.6 kb allele in 82% of cases, while the rate of this allele in chromosomes without the mutation amounts only to 24%. The value of the standardized disequilibrium coefficient SCD = 0.58. Delta F508 deletion was addressly studied in 25 patients (i.e. 50 CF chromosomes). Of the 50 CF mutations, the given deletion was in 64% (32), while the remaining 36% (18) of mutations were of other, closely not identified types. Delta F508 deletion is in marked allelic association with the 6.6 kb allele of KM19/PstI polymorphism (SCD = 0.68). Between the given allele of KM19/PstI polymorphism and CF mutation no other allelic association was found but with delta F508. (Tab. 6, Fig. 1, Ref. 18).

[Rapid prenatal diagnosis of cystic fibrosis using the polymerase chain reaction: results of the first 5 cases]. / Rýchla prenatálna diagnostika cystickej fibrózy metódou polymerázovej ret'azovej reakcie (PCR): výsledky prvých piatich vysetrení.

Cystic fibrosis (CF) is an autosomal recessive lethal disease with an incidence in Slovakia of 1 affected in 1800 newborns. Within a year the incidence amounts to about 50 cases. Though the responsible gene has already been cloned, the only effective approach to prevention is prenatal diagnosis in the first and second trimester of pregnancy. The paper presents the results of the first five cases of prenatal diagnosis of CF established by the new rapid method of DNA analysis, polymerase chain reaction (PCR). Delta F508 deletion mutation and closely linked DNA polymorphism KM19/PstI were assessed. In two of the five cases studied the fetuses were found to be affected and pregnancy termination was indicated. To exclude the possibility of fetal DNA contamination with maternal DNA, the hypervariable DNA polymorphism VNTR apoB was determined simultaneously. The advantages of this approach are demonstrated on cases of prenatal diagnosis performed in two families where contamination of fetal DNA could be excluded. The value of the PCR method is being compared with that of Southern's hybridization method. (Tab. 2, Fig. 4, Ref. 27.).

[Treatment of nephrotic syndrome with cyclosporin A]. / Liecba nefrotického syndrómu cyklosporínom A.

The authors treated eight children with corticoid dependent syndrome caused by minor abnormalities of the glomeruli with Cyclosporin A. They administered Cyclosporin, 5 mg/kg/24 h., for a period of 8-16 weeks. In three patients they used Cyclosporin A alone, 5 children were given in addition 10 mg Prednisone per day. They achieved complete remission in all patients. During treatment they monitored haematological and biochemical parameters as well as Cyclosporin A levels; before treatment and after its termination they examined also immunological indicators. They did not observe any serious side effects of treatment.

[Growth in children living in areas with air pollution]. / Rast detí zijúcich v oblasti so znecisteným ovzdusím.

In a group of 8-12-year-old children from two areas of Bratislava with a different degree of air pollution the authors investigated repeatedly the growth of the children. It was revealed that in boys and girls from the exposed area growth was retarded, as compared with children from a relatively clean area as well as when compared with the Bratislava population. After improvement of the living environment in the exposed area children who grew up in an environment, where the two areas did not differ as to contamination of the atmosphere, achieved the same growth level at the age of 10 years. The results draw attention to the importance of care of the living environment and of attempts to eliminate noxious substances from the atmosphere which is reflected in a better health status and development of the child organism.

Care for cystic fibrosis patients in Czechoslovakia.

A long-term study was carried out in a group of 325 patients with cystic fibrosis (CF) aged 6 months to 34.5 years who lived in Czechoslovakia to December 31, 1988. Care for CF patients is concentrated in so called CF centres which are established mainly by children's clinics. The patients have been systematically examined both clinically and in the laboratory. There is a close cooperation with the department of rehabilitation. Special attention is paid to psychological and social problems of patients and their families. Care for patients older than 18 years is provided in the departments of internal medicine and respiratory diseases for adults. Due to a complex care coordinated by CF centres the mean age of surviving CF patients has kept on increasing and the quality of their life has been improving.