In utero and lactational exposure to vinclozolin and genistein induces genomic changes in the rat mammary gland.

Exposure to low doses of environmental estrogens such as bisphenol A and genistein (G) alters mammary gland development. The effects of environmental anti-androgens, such as the fungicide vinclozolin (V), on mammary gland morphogenesis are unknown. We previously reported that perinatal exposure to G, V, and the GV combination causes histological changes in the mammary gland during the peripubertal period, suggesting alterations to the peripubertal hormone response. We now investigate whether perinatal exposure to these compounds alters the gene expression profiles of the developing glands to identify the dysregulated signaling pathways and the underlying mechanisms. G, V, or GV (1 mg/kg body weight per day) was added to diet of Wistar rats, from conception to weaning; female offspring mammary glands were collected at postnatal days (PNDs) 35 and 50. Genes displaying differential expression and belonging to different functional categories were validated by quantitative PCR and immunocytochemistry. At PND35, G had little effect; the slight changes noted were in genes related to morphogenesis. The changes following exposure to V concerned the functional categories associated with development (Cldn1, Krt17, and Sprr1a), carbohydrate metabolism, and steroidogenesis. The GV mixture upregulated genes (Krt17, Pvalb, and Tnni2) involved in muscle development, indicating effects on myoepithelial cells during mammary gland morphogenesis. Importantly, at PND50, cycling females exposed to GV showed an increase in the expression of genes (Csn2, Wap, and Elf5) related to differentiation, consistent with the previously reported abnormal lobuloalveolar development previously described. Thus, perinatal exposure to GV alters the mammary gland hormone response differently at PND35 (puberty) and in animals with established cycles.

[Gender differences in premature mortality and avoidable deaths]. / Disparités de mortalité "prématurée" selon le sexe et causes de décès "évitables"

OBJECTIVE: This paper aims to describe and to analyse disparities between men and women for "premature" mortality rates (deaths before 65 year-old). The study is particularly focused on "avoidable" causes of death. These types of deaths are greatly related to risk behaviours such as alcohol abuse, tobacco abuse or dangerous driving. Taking account of these indicators ("premature" and "avoidable" mortality) enables to study health status discrepancies by gender and to characterize specific public health issues in France including high rates of "premature" mortality and risk behaviours. METHODS: The analysis is based on exhaustive mortality data from 1980 to 1999 supplied by the Centre for epidemiology of medical causes of death (CepiDc-INSERM). Specific causes of death closely related to risk behaviours are classified as "avoidable": lung and upper airways cancers, cirrhosis, alcoholic psychosis, traffic accidents, aids and suicide. The contribution of these categories in the global male overmortality was assessed according to different demographic and geographic characteristics. RESULTS: Within "premature" mortality, males experience greater burden of "avoidable" mortality (sex-ratio: 4 versus 2). The gender differences are mainly due to injuries and suicides in the younger age groups and to tobacco and alcohol-related cancers (lung and upper airways) in the 45-64 years age group. The recent decline in "premature" mortality sex-ratio is explained by an increase of these two cancers for females. Among european countries, the French male overmortality is especially marked and mainly attributable to "avoidable" causes of death. CONCLUSION: "Avoidable" and "premature" mortality provide useful tools for the follow-up of health status in France particularly because of high risk behaviours and prevention inadequacy. Reducing gender discrepancies will depend mainly on public health policies in terms of primary prevention.

[Quality of suicide mortality data]. / La qualité des données de mortalité sur le suicide.

Prevention of suicide is a public health priority in France. Indicators of suicide mortality have been widely used to describe epidemiological situations or to evaluate public health actions. It is therefore essential to examine the quality of suicide mortality data. The purpose of this work was to identify potential biases affecting the quality of such data and their comparability between different countries as well as to determine how they can affect conclusions. Potential biases were identified by studying the characteristics of the death certificate system and analyzing the international literature on data quality. The impact of biases was assessed by analyzing the causes of "concurrent" death with suicide in the official statistics (trauma and poisoning caused in an undetermined way concerning intention and unknown causes). The proportion of suicides listed as "concurrent" causes of death, estimated from specific surveys was extrapolated to official data. This method was also used to correct the international data. Practices concerning death certificates for violent deaths vary considerably from one country to another: type of certifying physician, frequency of medicolegal investigations, frequency of autopsies, suicide definition criteria, confidentiality regulations, religious and culture context. These practical differences lead to variability in undetermined and unknown causes. The corrections made on the mortality data after taking into account for these potential biases showed that the rate of suicide determined from official data is considerably underestimated, but that sociodemographic and geographic factors of suicide change little after correction. Likewise, the order by country was similar after taking into consideration concurrent causes. A reliable evaluation of the rate of suicide for a given country is of course important. However, it is possible to characterize populations at risk and analyze the determinants of suicidal behavior without necessarily recording all suicides, as long as the declaration bias is stable. Statistical analysis of death by suicide in France shows that, despite under-reporting, the principal sociodemographic and geographic features and trends over time can be considered as valid. A series of recommendations is proposed however to improve data quality and homogeneity for death certificate reporting. Designing operational criteria for deciding when to declare suicide as the cause of death would be helpful to guide physicians who report deaths. Classical autopsies could be completed by "psychological autopsies" with friends and family of the deceased. The death certificate form could be improved to include items for complementary information favoring or not suicide.

[Death due to drug addiction in Ile-de-France]. / Décès par toxicomanie en Ile-de-France.

The aim of a cooperative study, carried out by the Paris Forensic Medicine Institute and the French National Institute of Health and Medical Research (INSERM SC8) was to assess the number of drug addiction-related deaths occurring in the Paris region in 1990. There were 253 deaths including 92 in Paris and 161 in Paris suburbs. A large percentage of these deaths were not recorded in the National death statistics registry (only 36% of all the deaths and only 24% of the Paris deaths had been registered). The overall drug addiction mortality in the Paris region is 29.4 per million inhabitants and is highest among the 25-29 year age group. Rates decrease rapidly after 30 years of age and are extremely low after 40. Mortality is highest in unmarried men and in the inactive population with a wide variability according to site of residence. Rates are much higher in Paris than in the suburbs. For the 20-29 year population in Paris, drug addiction has an important impact on the mortality figures for the general population, causing 12% of all deaths. It is the third cause of death after AIDS and suicide.

[Suicide in Paris and Ile-de-France]. / Le suicide à Paris et en Ile-de-France.

A study carried out in collaboration between the Institute of Forensic Medicine of Paris and the INSERM (SC8) concerned all the suicide occurred in Paris region over 1990; 455 suicides in Paris and 1,229 in the suburbs of Paris (overall, 1,684 suicides observed in Paris area for the same period). For Paris city, the rate of suicide reaches 23.3 per 100,000 subjects. This frequency increases up to 40 years and falls after this age with a further rise between 75 and 85 years. Suicide represents 17% of the total mortality for adolescents and young adults living in Paris, with a large over-representation of males (277 males, 178 females). Suicide is more frequent before 45 years in Paris than in France but this tendency is reversed after 45 years. It represents the first cause of violent deaths among young population (15-34 years) living in Paris and is, after AIDS, the second cause of death. In Paris suburbs, it constitutes the second cause of mortality after traffic accidents. The mode of suicide in Paris is essentially poisoning, then hanging and jumping from high place. In contrast, outside Paris, the hanging is more frequently used than poisoning and firearms. The contribution of the Institute of Forensic Medicine of Paris is essential for the knowledge of these voluntary deaths, a large part of them being unknown in the National statistic of causes of death. This underestimation is extremely important: only 68% of the suicides are known by the Official Statistic in Paris region and 26% for Paris city.(ABSTRACT TRUNCATED AT 250 WORDS)

[Trends in mortality characteristics in Aids in France 1983-1990]. / Caractéristiques de l'évolution de la mortalité par SIDA en France de 1983 à 1990.

From 1983 to 1990, the number of AIDS deaths in France (8119 deaths overall), increased substnatially but the annual rate of progression has fallen since 1987 (+35% in 1990). The socio-demographic characteristics of the deaths remained quite steady with the exception of the proportion of subjects living in Paris which decreased. The proportion of AIDS deaths out of all deaths is still low for the entire population (5 deaths out of 1000 in 1990) but appears important in some sub-groups. In 1990, AIDS represents for the 25-34 years old group, 12 deaths out of 100 for males and 7 deaths out of 100 for females and for the 25-44 years old group, 15 deaths out of 100 for nonmarried males and 4 deaths out of 10 for males working in an information or artistic profession. Furthermore, it accounts, in 1989, for the third of the deaths of males between 25 and 44 years living in Paris. The analyse tends to show that there is not an important under-declaration of AIDS deaths in France.