Polycystic ovarian syndrome, insulin resistance and thickness of the endometrium.

INTRODUCTION: Disorders possibly associated with insulin resistance (IR) are hyperandrogenemia, hirsutism, irregular menstrual cycles, central obesity and polycystic ovarian syndrome (PCOS). It is known that PCOS is related to a high risk of endometrial hyperplasia after many years of estrogen stimulation from anovulation. OBJECTIVES: The purpose of the study was to estimate the thickness of the endometrium in women with IR without a diagnosis of PCOS and in women with PCOS without IR. STUDY DESIGN: Three groups of women included in the study: 15 women diagnosed as IR without PCOS, 16 women diagnosed as PCOS without IR and 20 women used as controls matched for age and body mass index (BMI) with the previous patients. Thickness of the endometrium was estimated in all cases with a transvaginal ultrasound in three consecutive measures during a cycle. RESULTS: The mean thickness of the endometrium was statistically higher in the PCOS group (11.1mm), and in the IR group (9.6mm), compared with the control group (6.2mm) (F=13.1, p<0.001). CONCLUSIONS: It is concluded that both in women diagnosed as having insulin resistance without PCOS, and in women with PCOS without insulin resistance, the ultrasonographically estimated thickness of the endometrium is relatively high and a closer follow-up of these women is required in order to detect those in risk to develop hyperplasia and/or atypia.

Monitoring for DNA damage of humans occupationally exposed to methyl bromide.

BACKGROUND: Methyl bromide (MeBr) is a methylating agent, weak mutagen and possible animal carcinogen. A molecular epidemiological study to examine human exposure to, and consequent DNA damage by MeBr was conducted in an area where this agent is used extensively for soil sterilisation in greenhouses. MATERIALS AND METHODS: During the first part of the study, blood samples were collected from 21 persons within 24 hours after use of MeBr for greenhouse sterilisation, as well as from 19 non-exposed subjects. Personal air sampling was also carried out, indicating mean air concentrations for different subjects in the range 11-78 mg/m3. In the second part of the study, an attempt was made to examine professional applicators of MeBr who suffered particularly high exposures (mean exposures, based on personal monitoring 23-165 mg/m3). The levels of N7-methylguanine and O6-methylguanine, two DNA adducts known to be induced by MeBr, were assessed in blood leukocyte DNA. RESULTS: Concerning the first part, two subjects (one exposed and one control) were found to be positive for N7-methylguanine, while none of the blood samples analysed had detectable levels of O6-methylguanine. Among 6 such persons examined during the second part, 2 were found positive for N7-methylguanine while none was positive for O6-methylguanine. CONCLUSION: Within the detection power of this limited study, no significant evidence of induction of DNA damage in blood leukocyte DNA by MeBr was found.

Impact of phase I or phase II enzyme polymorphisms on lymphocyte DNA adducts in subjects exposed to urban air pollution and environmental tobacco smoke.

Little is known about the impact of genetic variation on the genetic damage induced by urban air pollution or environmental tobacco smoke (ETS) in exposed populations. The levels of bulky DNA adducts ( 32P-postlabelling, nuclease P1 enrichment) and chromosomal aberrations were measured in lymphocytes of 194 non-smoking students living in the city of Athens, and the rural region of Halkida, Greece. In these individuals personal exposure to PAH was also measured. Furthermore, genetic polymorphisms were examined in cytochromes P450 1A1, 1B1, in the GSTM1, GSTP1 and GSTT1 as well as in microsomal epoxy hydrolase (EPHX) genes. Subjects with the CYP1*2A mutant genotype also suffering significant ETS exposure tended to exhibit higher adduct levels and % aberrant cells. In contrast, CYP1B1 polymorphisms seemed to have an impact on the DNA adduct levels only among individual with negligible ETS exposure. Subjects carrying both the CYP1*2A mutant genotype and the GSTM1 null genotype tended to have higher DNA adduct levels. A similar effect was also observed with the combined CYP1A1*2A/GSTP1 (Ile/Val) and the CYP1A1*2A/mEH "slow" polymorphisms. In both cases, the effect was more pronounced among subjects with higher levels of ETS exposure. Stepwise restriction of the observations to subjects characterised by (a) GSTP1 mutant, (b) GSTM1 null, (c) mEH "slow" (His139His) genotypes and (d) ETS exposure resulted in a significant trend of increasing DNA adduct levels only among individuals with at least one CYP1A1*2A mutated allele, illustrating the importance and complexity of gene-exposure and gene-gene interactions in determining the level of genotoxic damage on an individual levels.

Personal exposures to PM(2.5) and polycyclic aromatic hydrocarbons and their relationship to environmental tobacco smoke at two locations in Greece.

In the context of a large-scale molecular epidemiology study of biomarkers of genotoxicity of air pollution, 24-h mean personal exposures to airborne PM(2.5) (particulate matter <2.5 microm) and associated polycyclic aromatic hydrocarbon (PAHs) were measured in 194 non-smoking technical institute students living in the city of Athens, Greece (an area with moderately high levels of air pollution) and the nearby small town of Halkida anticipated to have lower pollution levels. Extensive information relevant to the assessment of long-term and recent exposure to PAH was obtained from questionnaires as well as a time-location-activity diary (TLAD) which was kept by all subjects during a 4-day observation period. During the last 24 h of this period, subjects underwent personal exposure monitoring for PM(2.5) and PAH, while a sample of blood was donated at the end of this period. All subjects were monitored in this way twice; once during a winter season (October-February) and once during the following summer season (June-September). Nine subjects with plasma cotinine levels above 20 ng/ml were considered as unreported smokers and excluded from the study. Winter PM(2.5) exposures were lower in Athens (geometric mean 39.7 microg/m(3)) than Halkida (geometric mean 56.2 microg/m(3)) (P<0.001), while there was no significant location difference during the summer (Athens: geometric mean 32.3 microg/m(3), Halkida: geometric mean 32.9 microg/m(3); P=0.79). On the other hand, PAH exposures (sum of the eight carcinogenic PAHs) were significantly higher in Athens than in Halkida during the winter (Athens: geometric mean 8.26 ng/m(3), Halkida: geometric mean 5.80 ng/m(3); P<0.001) as well as during the summer (Athens: geometric mean 4.44 ng/m(3), Halkida: geometric mean 1.48 ng/m(3); P<0.001). There was a significant difference in the profile of the PAH exposures at the two locations, the proportion of lighter PAH (benzo[a]anthracene, chrysene [CHRYS], benzo[k]fluoranthene, and benzo[b]fluoranthene) being higher, and that of heavier PAH (benzo[ghi]perylene [BPer] and indeno[1,2,3,cd]pyrene) lower, in Halkida than in Athens, regardless of season. This difference appeared to be related to individual exposure to environmental tobacco smoke (ETS), as indicated by (a) the correlation at the individual level between the CHRYS/BPer ratio and declared time of recent exposure to ETS as well as plasma cotinine levels, especially during the winter; (b) the parallel variation of the mean levels of all three markers (declared ETS exposure, cotinine levels, CHRYS/BPer ratio) among three subgroups of subjects (Athens subjects who had lowest levels of all three markers; Halkida subjects other than those living in the institute campus area; and Halkida subjects living in the institute campus area who had the highest levels of all three markers). This demonstrates that ETS can have a distinctive effect on the PAH exposure profile of subjects exposed to relatively low levels of urban air pollution.

Age at menarche in relation to adult height: the EPIC study.

In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age.

Risk factors for childhood poisoning: a case-control study in Greece.

OBJECTIVES: To identify child or family related risk factors for unintentional childhood poisoning in Greece and to explore whether product specific poisonings might have special features that make them amenable to preventive interventions. SETTING: A case-control study was undertaken in Athens, Greece in 1995. Cases were 100 consecutive children brought with poisoning to the emergency clinics of the two university affiliated children's hospitals. For every case two age, gender, and hospital matched controls were chosen from among children brought to the outpatient clinics of these hospitals on the same date. METHODS: All children and their guardians were interviewed by the same person using a standard questionnaire that covered demographic, socioeconomic, behavioral, and past injury characteristics. Information was also obtained concerning type and conditions of poisoning for cases. Statistical analysis was undertaken by modeling the data using conditional logistic regression. RESULTS: Socioeconomic factors were not important risk indicators in these data but children living with other than both parents were at increased risk (odds ratio (OR) = 4.7, p = 0.08), as were children with a history of previous poisoning that required medical care (OR = 5.1, p = 0.05). Unintentional poisonings caused by chewing or swallowing cigarettes were concentrated in families where both parents were smokers. CONCLUSIONS: Absence of a parent appears to be associated with increased likelihood of childhood poisoning. The importance of product accessibility is underlined by the concentration of tobacco poisoning among children of parents who were both smokers. In the cultural context of this study, sociodemographic factors do not appear to represent demonstrable risk factors. Instead, control of childhood poisoning should be concentrated on safe packaging, storage, and disposal of potentially hazardous products.

Diet during pregnancy in relation to birthweight in healthy singletons.

We have investigated the relationship between consumption of food groups and intake of energy-generating macronutrients on the one hand, and birthweight on the other among apparently healthy singleton, term babies. Three hundred and sixty-eight women who delivered in six maternity clinics in two Greek cities during specified days over an 8-month period completed a 190-item, interviewer-administered, validated, semiquantitative food frequency questionnaire. Study participants also provided information on sociodemographic, reproductive and lifestyle variables. Data were analysed using multiple regression modelling. Nutritional variables were energy-adjusted, and non-nutritional correlates of birthweight were accounted for. The analysis revealed most of the established non-nutritional associations of birthweight -- an indication of study validity. Among food groups, meat and meat products and fish and sea food were suggestively associated with increased birthweight (two tailed P-values 0.08 and 0.16, respectively). Among energy-generating nutrients, monounsaturated fat was positively associated with birthweight and significantly so in several of the models. We consider our findings are considered as compatible with hypotheses linking fish and meat intake to fetal growth and as indicative of a positive association between intake of monounsaturated fat and birthweight.

The association of fat and other macronutrients with breast cancer: a case-control study from Greece.

The Greek diet is characterized by a high total fat but low saturated fat intake. In a hospital-based case-control study of female breast cancer conducted in Athens (1989-91), 820 patients with confirmed cancer of the breast were compared with 795 orthopaedic patient controls and 753 hospital visitor controls, matched to the cases by age and interviewer. Diet was ascertained through a semiquantitative food frequency questionnaire; macronutrient intakes were estimated from the nutrient content of a selected typical portion size for each specified food item, summed for all items. Logistic regression was used to analyse the data, controlling for demographic and reproductive risk factors for breast cancer as well as for total energy intake and mutual confounding influences among nutrients. There was no significant or suggestive association of total protein, total fat, categories of fat or total carbohydrates with breast cancer risk. Thus, the mutually adjusted relative risk per quintile and (in parenthesis) 95% confidence interval were: for protein, 1.06 (0.94-1.20); saturated fat, 0.99 (0.89-1.11); monounsaturated fat, 0.97 (0.88-1.07), polyunsaturated fat, 1.05 (0.97-1.13); and total carbohydrates, 1.03 (0.94-1.12). In alternative analytical approaches only total protein appeared to be positively associated to the occurrence of breast cancer with some consistency, but the results were far from statistically significant. These findings do not support a role for fat or other energy-generating nutrients in the aetiology of breast cancer.

Biomarkers of genotoxicity of air pollution (the AULIS project): bulky DNA adducts in subjects with moderate to low exposures to airborne polycyclic aromatic hydrocarbons and their relationship to environmental tobacco smoke and other parameters.

The levels of bulky DNA adducts were measured by (32)P-post-labelling in lymphocytes of 194 non-smoking students living in the city of Athens and the region of Halkida, Greece, once in the winter and again in the following summer. Personal exposures to particulate-bound polycyclic aromatic hydrocarbons (PAH) were significantly higher in Athens subjects during both seasons. There was hardly any diagonal radioactive zone in the pattern of DNA adducts observed. Highest adduct levels were observed in a sub-group of subjects living in or near the Halkida Institute campus, which was located in rural surroundings with a minimal burden of urban air pollution. The remaining Halkida subjects had intermediate levels, while Athens subjects showed the lowest levels. This trend, which was observed over both monitoring seasons, consistently paralleled the variation in three markers of exposure to environmental tobacco smoke (ETS), namely (i) declared times of exposure to ETS during the 24 h prior to blood donation, (ii) plasma cotinine levels and (iii) chrysene/benzo[g,h,i]perylene ratios in the profile of personal PAH exposure. Furthermore, among the Halkida campus area subjects (but not the remaining subjects) positive correlations were observed between DNA adducts and (i) measured personal exposures to chrysene or benzo[a]pyrene, (ii) time of declared ETS exposure and (iii) chrysene/benzo[g,h,i] perylene ratios. These correlations suggest that, for a group suffering minimal exposure to urban air pollution, exposure to ETS was a significant determinant of the observed DNA damage. Gender had a consistent and significant effect on adduct levels (males having higher levels), which remained significant even after multiple regression analysis. Habitual consumption of roasted meat was significantly associated with an enhancement of adduct levels and the effect was strengthened when only individuals unexposed to ETS were taken into consideration. No significant effects were observed for other dietary parameters or factors reflecting exposure to air pollution.