[Risk factors for recurrent disease in borderline ovarian tumors]. / Rizikové faktory pro vznik recidivy u borderline nádoru ovaria.

OBJECTIVE: To evaluate risk factors for development of recurrent disease in borderline ovarian tumors. DESIGN: Retrospective study of 10-years single institution population. SETTING: Dept. of Gynecology and Obstetrics, 3rd Medical Faculty of Charles University in Prague. METHOD: 59 consecutive cases of borderline ovarian tumors (BOT) were analyzed for age, histopathological type, DNA ploidy, stage, presence of invasive and non-invasive peritoneal implants, type of surgical procedure, residual disease, adjuvant therapy, recurrence and long-time prognosis of the patients. RESULTS: Median follow-up was 47 months (range 1-144). There were 5 (8.5%) patients with DNA aneuploid tumors in the study group; 4 of them were younger than 50 years, 4 of them were early stage serous BOT; no one recur so far. No death of disease was described in the whole study group; only 2 patients (3.4%) developed recurrent disease - both were young patients after conservative surgery for serous diploid stage I/II BOT. Conservative surgery was the only significant factor for recurrence in univariate analysis (p = 0.0159) in our setting. CONCLUSION: DNA ploidy was not proved to be prognostic factor in borderline ovarian tumors in our study group. The only significant risk factor for development of recurrent disease was conservative surgery, with no influence on overall survival.

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

INTRODUCTION: Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic beta-cell dysfunction. OBJECTIVE: We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents. SUBJECTS AND METHODS: We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1alpha (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4alpha (HNF4A) (those with a positive family history of diabetes). RESULTS AND DISCUSSION: We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.

Association of MHC class I chain related gene-A microsatellite polymorphism with the susceptibility to T1DM and LADA in Czech adult patients.

The results in this study suggest that microsatellite polymorphism within the transmembrane region of MIC-A gene is associated with genetic susceptibility to adult-onset of type 1 diabetes mellitus (T1DM), MIC-A5.1 allele, corrected P = 0.001, whereas it is not associated with latent autoimmune diabetes in adults (LADA) in Czech population. According to our findings, we can hypothesize that adult-onset T1DM and LADA may have partly different immunogenetic aetiopathogenesis.

S65C and other mutations in the haemochromatosis gene in the Czech population.

HFE-linked hereditary haemochromatosis is a common autosomal recessive disease among Caucasians. The primary pathogenetic mechanism is excessive absorption of iron, which is deposited in various organs with their subsequent damage. In 1996 the gene responsible for haemochromatosis was detected--the HFE gene and its major mutation C282Y. The discovery of further mutations followed. Two sites of point mutations in the HFE gene, C282Y and H63D, are associated with more than 80% of haemochromatosis cases. Another mutation-- S65C--was detected on 8% of chromosomes of haemochromatosis patients, which were negative for mutations C282Y or H63D. The objective of this study was to identify the allele frequency of S65C and other HFE mutations in the Czech population. DNA extracted from 481 randomly selected newborn screening cards (Guthrie cards) from all over the country was analysed by PCR-RFLP. No (0%) sample was identified as homozygous for S65C or C282Y mutation and 8 (1.67%) were homozygous for H63D mutation. Twelve (2.49%) samples were S65C heterozygous, 33 (6.86%) samples were C282Y heterozygous, and 128 (26.61%) were H63D heterozygous. Of these, 11 (2.29%) carried one copy of each mutation, i.e. were compound heterozygous. Two samples were S65C/H63D compound heterozygous and nine were C282Y/H63D compound heterozygous. Allele frequencies for S65C, C282Y, and H63D were 1.25% (95% CI, +/- 0.70), 3.43% (95% CI, +/- 1.15), and 14.97% (95% CI, +/- 2.25), respectively. The observed genotype frequency for S65C, C282Y, and H63D mutations in the Czech Republic agrees with those reported for other Central European populations.

The frequency of alleles of the Pro12Ala polymorphism in PPARgamma2 is different between healthy controls and patients with type 2 diabetes.

The aim of this initial case-control study was to determine the association between common Pro12Ala polymorphism in the PPARgamma2 gene and type 2 diabetes in the Czech Republic. Furthermore, the effect of this polymorphism on phenotypic characteristics and on levels of lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides) was studied. One hundred thirty-three patients with type 2 diabetes and 97 control subjects were investigated. PCR and RFLP analysis were used for identification of individual genotypes. In the group of patients, three samples (2.26%) were identified as homozygous for the Ala/Ala genotype and 99 samples (74.44%) were homozygotes for the Pro/Pro genotype. Thirty-one samples (23.31%) were identified as Pro12Ala heterozygous. In the control group, six samples (6.19%) were homozygous for the Ala/Ala genotype and 61 samples (62.89%) were homozygotes for the Pro/Pro genotype. Thirty samples (30.93%) were identified as Pro12Ala heterozygous. The allele frequency for the Ala allele was lower in the type 2 diabetic group than in the control group (13.91% vs. 21.43%, P = 0.022). There was no difference (at P < 0.05) between the phenotypic characteristics (BMI, sex) studied in the group of patients according to the Pro12Ala genotype. There was no significant effect of the Pro12Ala polymorphism on lipid levels.