Lipoperoxidation of lung lipids in rats exposed to nitrogen dioxide.

Absorption spectra characteristic of diene conjugation and typical for peroxidized polyenoic fatty acids can be induced in rat lung lipids after the rats have been exposed to a scant amount of nitrogen dioxide (1 part per million) for 4 hours. The peroxidative changes do not occur immediately but appear to reach a maximum between 24 and 48 hours after exposure. The prooxidant effect of this atmospheric pollutant in rat lung lipids may be partially prevented by prior treatment of the animal with large doses of alpha-tocopherol.

Borna disease virus and mental health: a cross-sectional study.

BACKGROUND: Borna disease is an infectious neurological disease of horses, sheep and possibly other animals. A role for Borna disease virus (BDV) in human neurological and psychiatric illness has been proposed, but this hypothesis remains controversial. AIM: To investigate the epidemiology of BDV in UK farming communities. DESIGN: Retrospective cohort study. METHODS: We measured the seroprevalence of BDV in the PHLS Farm Cohort, a representative sample of those employed in agriculture in the UK, and investigated the clinical significance of our findings by comparing the prevalence of symptoms of neurotic psychopathology in those found seropositive and seronegative. RESULTS: Seroprevalence was 2.3% (95%CI 1.3- 4.0%) in 1994, 3.1% in 1996 (95%CI 1.9-5.0%) and 2.6% in 1999 (95%CI 1.5%-4.6%). Those living or working on livestock farms had higher seroprevalence (2.6%) than those on mixed (2.3%) or arable (1.6%) farms, but this was not statistically significant. Exposure to horses, sheep and cats did not increase risk of seropositivity. Seropositives were no more likely to report symptoms of psychiatric morbidity. DISCUSSION: UK farming populations appear to be exposed to Borna disease virus. However, we found no evidence that exposure to BDV was associated with morbidity in this healthy occupational cohort.

Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans.

Endogenous oestradiol is strongly associated with breast cancer risk but its determinants are poorly understood. To test the hypothesis that vegetarians have lower plasma oestradiol and higher sex hormone-binding globulin (SHBG) than meat-eaters we assayed samples from 640 premenopausal women (153 meat-eaters, 382 vegetarians, 105 vegans) and 457 post-menopausal women (223 meat-eaters, 196 vegetarians, 38 vegans). Vegetarians and vegans had lower mean body mass indices (BMI) and lower plasma cholesterol concentrations than meat-eaters, but there were no statistically significant differences between meat-eaters, vegetarians and vegans in pre- or post-menopausal plasma concentrations of oestradiol or SHBG. Before adjusting for BMI there were small differences in the direction expected, with the vegetarians and vegans having higher SHBG and lower oestradiol (more noticeable amongst post-menopausal women) than the meat-eaters. These small differences were essentially eliminated by adjusting for BMI. Thus this study implies that the relatively low BMI of vegetarians and vegans does cause small changes in SHBG and in post-menopausal oestradiol, but that the composition of vegetarian diets may not have any additional effects on these hormones.

Thinking life is not worth living. A population survey of Great Britain.

BACKGROUND: "Saving lives: our healthier nation" includes a target to reduce the death rate from suicide. Thoughts of suicide and feeling life is not worth living might be the first step in a pathway that can end in completed suicide. This study aims to identify factors associated with feeling life is not worth living amongst the household population of Great Britain, and to assess the strength of these associations after taking account of an individual's level of psychiatric morbidity. METHODS: The 1993 OPCS National Psychiatric Morbidity Surveys of Great Britain assessed psychiatric morbidity using the Revised Clinical Interview Schedule amongst a stratified, clustered probability sample of 9830 subjects representative of the British private household population aged 16-64. RESULTS: Of the sample 0.8 % (95 % CI 0.6 %-1 %) had thoughts of suicide in the week before interview and 3.1 % (95 % CI 2.7 %-3.5 %) reported thoughts of life not worth living in the week before interview. Psychiatric morbidity was most strongly associated with such thoughts. Ethnicity, marital status and low social support were strongly associated with such thoughts after adjusting for age, sex and psychiatric morbidity. CONCLUSIONS: Reducing psychiatric morbidity in the population as a whole might also decrease the frequency of suicidal thoughts. Policies which improve social support at a population level might also have a large impact on prevalence of suicidal thoughts.

Endogenous estrogen and postmenopausal breast cancer: a quantitative review.

This paper systematically reviews the results from epidemiologic studies investigating the hypothesis that breast cancer risk in postmenopausal women increases with increasing concentrations of estradiol in blood and with increasing urinary estrogen excretion rates. Data from 29 epidemiologic studies of endogenous hormones and postmenopausal breast cancer were used. The ratio of the average estrogen concentration in the women with breast cancer to that in the women without breast cancer (and its 95 percent confidence interval [CI]) was calculated for each study, and the results were summarized by calculating weighted averages of the log ratios. In six prospective studies of serum estradiol concentration, 329 women who subsequently developed breast cancer had, overall, a 15 percent (CI = 6-24 percent, P = 0.0003) higher mean concentration of estradiol in their blood than the 1,105 women who remained free of cancer. The results of these prospective studies did not differ significantly from each other (chi2 for heterogeneity = 8.7; degrees of freedom = 5; P > 0.1). Similar differences in mean estrogen levels were seen in the case-control studies which reported either estradiol concentrations in the blood or urinary estrogen excretion. However, the case-control studies showed significant heterogeneity among their results. The data from the prospective studies strongly suggest that breast cancer risk in postmenopausal women is associated with relatively high concentrations of endogenous estradiol.

Signs of asphyxia at birth and risk of schizophrenia. Population-based case-control study.

BACKGROUND: Previous research has found an association between obstetric complications and schizophrenia, but in many studies the sample size was limited, and no assessment of specific exposures was possible. AIMS: To assess the role of different complications, and in particular to distinguish between disordered foetal development and hypoxia at birth. METHOD: From the Stockholm County In-Patient Register and community registers, we identified 524 cases of schizophrenia and 1043 controls, matched for age, gender, hospital and parish of birth. Data on obstetric complications were obtained from birth records. RESULTS: There was a strong association between signs of asphyxia at birth and schizophrenia (OR 4.4; 95% C11.9-10.3) after adjustment for other obstetric complications, maternal history of psychotic illness and social class. CONCLUSIONS: Signs of asphyxia at birth are associated with an increased risk of schizophrenia in adults.

Obstetric complications and risk of schizophrenia. Effect of gender, age at diagnosis and maternal history of psychosis.

BACKGROUND: Obstetric complications have been studied frequently as possible risk factors for schizophrenia. AIMS: To test the hypotheses that individual obstetric complications are most strongly associated with an increased risk of schizophrenia in males, in patients with an early age at first diagnosis and in subjects with a maternal history of psychosis. METHOD: Cases of schizophrenia diagnosed between January 1971 and June 1994 were identified in the Stockholm County In-Patient Register. Controls were matched on age, gender, hospital of birth and parish of birth. Obstetric data were recorded blind to case-control status for 524 cases and 1043 controls. RESULTS: This study did not find any large or consistent effect of gender, age at diagnosis or maternal history of psychosis on the risk of schizophrenia associated with individual complications. CONCLUSIONS: Future studies should examine these effects using a much larger sample that includes patients with schizophrenia and control subjects whose genetic risk of schizophrenia has been assessed accurately.

Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom).

OBJECTIVE: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer. METHODS: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance. RESULTS: SHBG decreased with increasing body mass index and increasing waist-hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women. CONCLUSIONS: Certain factors such as obesity and perhaps waist-hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.

Pregnancy and menstrual hormone levels in mothers of twins compared to mothers of singletons.

This study examined the hormonal differences between premenopausal mothers of twins and other premenopausal parous women during and after pregnancy. Serum concentrations of oestradiol and testosterone between 6 and 20 weeks of gestation were measured for 11 mothers of twins and 115 mothers of singletons selected from the controls in a case-control study of cryptorchidism. Serum concentrations of oestradiol, progesterone, testosterone, follicle stimulating hormone and sex hormone-binding globulin during the menstrual cycle were measured for 25 mothers of twins and 38 mothers of singletons recruited as a part of a prospective study of breast cancer risk. During pregnancy, women carrying twins had a 58% higher geometric mean oestradiol concentration (p = 0.02) and a 50% higher testosterone concentration (p = 0.03) than women carrying singletons. Women who had previously had twins demonstrated a 49% higher mean concentration of follicle stimulating hormone (p = 0.02) and a 42% higher concentration of sex hormone-binding globulin (p = 0.03) than women who had singletons only, but no significant differences in oestradiol, progesterone and testosterone concentrations. The increased concentrations of follicle stimulating hormone during the menstrual cycle of mothers of twins, which has also been reported in two previous studies suggests that follicle stimulating hormone level may be an important determinant of dizygotic twinning.

Social, biological and reproductive characteristics of mothers of twins: implications for breast cancer risk.

The biological, social and reproductive characteristics of women who have had twins were compared with those of other parous women using questionnaire data gathered for a prospective cohort study of women aged 35 and over on the island of Guernsey. Data for 97 mothers of twins and 4026 other parous women were available for analysis. The two groups were similar in height, first degree family history of breast cancer, use of hormone replacement therapy or other hormones, age at menarche, length of menstrual cycle and age at first and last birth. The mothers of twins were slightly heavier, more likely to smoke and consume more caffeine, less likely to have used oral contraceptives in the past, slightly younger when reaching the menopause and had a larger number of pregnancies. Adjustment for age did not alter these results. This study does not provide evidence that mothers of twins differ markedly from other parous women across a range of characteristics that might be associated with twinning or associated with breast cancer risk.

A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey.

The associations between serum concentrations of oestradiol, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in post-menopausal women were investigated in a prospective study on the island of Guernsey. Sixty-one women who developed breast cancer an average of 7.8 years after blood collection were matched for age, year of blood collection and number of years post-menopausal with 179 control subjects. Women using exogenous hormones at the time of blood collection were excluded from the study. Women who subsequently developed breast cancer had a 29% higher geometric mean oestradiol concentration than control women (P = 0.004). The odds ratio for breast cancer in the top third compared with the lowest third of the oestradiol concentration distribution was 5.03 (95% confidence interval 2.02-12.49, P for trend < 0.001). Adjusting for testosterone and SHBG concentrations did not substantially alter the odds ratio for oestradiol. Although testosterone and SHBG concentrations were associated with breast cancer risk, the concentrations of these hormones were correlated with those of oestradiol; the associations were not statistically significant after adjusting for oestradiol concentration. These data provide evidence that serum oestradiol concentrations in post-menopausal women may have a substantial effect on breast cancer risk.

A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey.

The associations between serum concentrations of oestradiol, progesterone, testosterone and sex hormone-binding globulin (SHBG) and risk of breast cancer in premenopausal women were investigated in a prospective study of breast cancer on the island of Guernsey. Sixty-two women diagnosed with breast cancer an average of 8 years subsequent to blood collection were matched for day of menstrual cycle, age and year of blood collection with 182 control subjects. Cases had a 12% higher mean oestradiol concentration over the whole menstrual cycle (P = 0.17) with a large difference at mid-cycle (75% higher, P = 0.04). Differences between cases and control subjects in progesterone (luteal phase), testosterone and SHBG were small and not statistically significant: luteal phase progesterone 9% lower in cases, P = 0.64; testosterone 4% higher, P = 0.57; SHBG 8% higher, P = 0.24. The small difference in oestradiol concentration could be aetiologically important, but larger prospective studies are needed.

Mental health of British farmers.

AIMS: To estimate the prevalence of neurotic symptoms in a sample of British farmers, to investigate whether farming characteristics are associated with psychiatric morbidity, and to test the hypothesis that British farmers have a higher prevalence of depression and thoughts of life not worth living than the British household population. METHODS: A total of 425 farmers from Hereford, Norwich, and Preston completed the Revised Clinical Interview Schedule (CIS-R) by computer between March and July 1999. The comparison cohort consisted of 9830 private householders aged 16-64 from the Office of Population Censuses and Surveys National Psychiatric Morbidity Surveys of Great Britain carried out in 1993 in which the CIS-R was administered. All analyses used the commands developed specifically for survey data available in Stata version 6.0. RESULTS: Taking a threshold of an overall score of 12 or more on the CIS-R, only 6% of farmers reported clinically relevant psychiatric morbidity. Psychiatric morbidity was not significantly associated with farm type or size in this study. Farmers reported a lower prevalence of psychiatric morbidity than the general population but were more likely to report thinking that life is not worth living, particularly after the low prevalence of psychiatric morbidity had been taken into account (odds ratio 2.56, 95% CI 1.39 to 4.69). When restricting the comparison to only rural or semirural householders, this increased risk was even more pronounced (odds ratio 3.26, 95% CI 1.51 to 7.02). CONCLUSIONS: The relation between depression and suicidal ideation seems to be quite different among farmers and the general population and warrants further investigation. We have shown it is possible to measure mental health systematically in a sample of British farmers. This study should be repeated in the aftermath of the foot and mouth crisis.

Substantial linkage disequilibrium across the insulin-degrading enzyme locus but no association with late-onset Alzheimer's disease.

Insulin-degrading enzyme (IDE; insulysin; EC 3.4.24.56) is a 110-kDa neutral metallopeptidase that can degrade a number of peptides including beta-amyloid. The gene encoding IDE is located on chromosome 10 close to a region of linkage for late-onset Alzheimer's disease (LOAD) and thus is a functional and positional candidate for this disorder. We analysed all of the coding exons, untranslated regions and 1000 bp of 5'-flanking sequence of IDE by using denaturing high-performance liquid chromatography and sequencing. We detected eight single nucleotide polymorphisms (SNPs), three in the 5' flanking sequence and five in the coding sequence, of which three were found at lower than 5% frequency. None of them changed the amino acid sequence. We genotyped the five SNPs with allele frequencies of more than 5% in 133 Caucasian LOAD cases and 135 controls collected in the UK and 95 cases and 117 controls collected at the Mayo Clinic, Rochester, USA. Two of the SNPs were analysed in a further independent case-control sample (Washington University, St. Louis: 86 cases, 94 controls). No significant association was found with any individual SNP in any of the samples or with any haplotypes. Analysis of the marker D10S583, which maps 36 kb upstream of IDE, also failed to show association in 134 cases and 111 matched controls from the UK ( P=0.63). Strong linkage disequilibrium was detected between the five SNPs that spanned the whole of the 120-kb genomic region of IDE and one major and a number of minor haplotypes were detected in the populations studied. We conclude that IDE does not make a substantial contribution to the aetiology of LOAD and therefore cannot account for the linkage between LOAD and 10q.

Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND: Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS: We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS: Breast cancer risk increased with increasing BMI (P(trend) =.002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION: The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.