A European survey on biobanks: trends and issues.

Biobanks have recently gained great significance for research and personalised medicine, being recognised as a crucial infrastructure. At the same time, the widely varied practices in biobanking may also pose a barrier to cross-border research and collaboration by limiting access to samples and data. Nevertheless, the extent of the actual activities and the impact of the level of networking and harmonisation have not been fully assessed. To address these issues and to obtain missing knowledge on the extent of biobanking in Europe, the Institute for Prospective Technological Studies (IPTS) of the European Commission's Joint Research Centre, in collaboration with the European Science and Technology Observatory (ESTO), conducted a survey among European biobanks. In total, 126 biobanks from 23 countries responded to the survey. Most of them are small or medium-sized public collections set up either for population-based or disease-specific research purposes. The survey indicated a limited networking among the infrastructures. The large majority of them are stand-alone collections and only about half indicated to have a policy for cross-border sharing of samples. Yet, scientific collaborations based on the use of each biobank appear to be prominent. Significant variability was found in terms of consent requirements and related procedures as well as for privacy and data protection issues among the biobanks surveyed. To help promote networking of biobanks and thus maximise public health benefits, at least some degree of harmonisation should be achieved.

Immunolocalization of the prostaglandin E2 receptor subtypes in human bone tissue: differences in foetal, adult normal, osteoporotic and pagetic bone.

PGE(2) is an important mediator of bone metabolism, but the precise localization of its receptors in human bone remains unknown. The present study used specific antibodies against EP(1), EP(2), EP(3) and EP(4) receptors for immunolocalization in normal, osteoporotic and pagetic human adult bone and in human foetal bone. No labelling was obtained for the EP(1) and EP(2) receptors. The EP(3) receptor was detected in foetal osteoclasts, osteoblasts and osteocytes, but only in osteoclasts and some osteoblasts from adult bone. The EP(4) receptor was detected in foetal osteoclasts, osteoblasts and osteocytes and in adult osteoclasts and osteoblasts, but not in adult osteocytes. Our results show differences in PGE(2) receptor expression in foetal and adult human bone but no difference in adult normal compared to pathologic bone. Finally, these results show that the distribution of EP receptors in human osteoblasts in bone corresponds in part to what we recently described in human osteoblasts in culture.

Immunohistochemical localization of the prostacyclin receptor (IP) human bone.

Prostacyclin (PGI(2)) is an important mediator implicated in bone metabolism. Among the natural prostaglandins it is the most potent inhibitor of bone resorption and mediates bone modelling and remodelling induced by strain changes. The effects of prostacyclin depend on its interaction with a specific receptor (IP). Despite its well documented effects on bone the localization and distribution of the IP receptor in human bone remain unknown. The present study used specific antipeptide antibodies to IP receptor for immunolocalization of the IP receptor in normal, osteoporotic and Pagetic human adult bone and in human fetal bone. The IP receptor was detected in fetal and adult osteoclasts and osteoblasts. Fetal osteocytes also expressed IP receptor but not adult osteocytes. Interestingly, the expression of IP receptor in adult osteoblasts was gradually lost as these cells were trapped in the matrix and became osteocytes. The IP receptor showed a perinuclear distribution within the cells, but in multinuclear osteoclasts not all nuclei were positive. Our results showed differences in IP receptor expression in fetal and adult human bone and, in adult bone, with the differentiation of osteoblasts into osteocytes. They also showed that there is no difference on the expression of prostacyclin receptors in Pagetic, osteoporotic and normal human bone, and they confirm the presence of the IP receptor in human osteoblasts as had been demonstrated by our previous study with human osteoblasts in culture.

Environmental pesticide exposure as a risk factor for Alzheimer's disease: a case-control study.

The aim of this study was to evaluate the influence of pesticide exposure on the development of Alzheimer's disease (AD), taking into account the potentially confounding factors (genetic, occupational exposure, and sociodemographic). The 1924 study participants (>70 years old) were randomly selected in the Saguenay-Lac Saint-Jean region (Quebec, Canada). The AD diagnosis was established in three steps according to recognized criteria. Sixty-eight cases were paired with a nondemented control for age (+/-2 years) and sex. Structured questionnaires addressed to subjects and proxy respondents allowed a description of the sociodemographic characteristics, lifestyle characteristics, and residential, occupational, familial, and medical histories. Assessment of environmental exposure to pesticides was based on residential histories and the agriculture census histories of Statistics Canada (1971-1991) for herbicide and insecticide spraying in the area. Statistical analyses were performed with a logistic regression, adjusting for potential confounding factors. The results failed to show a significant risk of AD with an exposure to herbicides, insecticides, and pesticides. However, future investigations are needed to establish more precisely the identification, measurement, mobility, and bioavailability of neurotoxic pesticide residues in relation to AD.

Aluminum forms in drinking water and risk of Alzheimer's disease.

The objective of this study was to assess the relation between long-term exposure to different aluminum (Al) forms in drinking water and Alzheimer's disease (AD). The study participants were selected from a random sample of the elderly population (> or = 70 years of age) of the Saguenay-Lac-Saint-Jean region (Quebec). Sixty-eight cases of Alzheimer's disease diagnosed according to recognized criteria were paired for age (+/-2 years) and sex with nondemented controls. Aluminum speciation was assessed using established standard analytical protocols along with quality control procedures. Exposure to Al forms (total Al, total dissolved Al, monomeric organic Al, monomeric inorganic Al, polymeric Al, Al(3+), AlOH, AlF, AlH(3)SiO(2+)(4), AlSO(4)) in drinking water was estimated by juxtaposing the subject's residential history with the physicochemical data of the municipalities. The markers of long-term exposures (1945 to onset) to Al forms in drinking water were not significantly associated with AD. On the other hand, after adjustment for education level, presence of family cases, and ApoE varepsilon4 allele, exposure to organic monomeric aluminum estimated at the onset of the disease was associated with AD (odds ratio 2.67; 95% CI 1.04-6.90). On average, the exposure estimated at the onset had been stable for 44 years. Our results confirm prime the importance of estimation of Al speciation and consideration of genetic characteristics in the assessment of the association between aluminum exposure and Alzheimer's disease.

Markers of infection, breast-feeding and childhood acute lymphoblastic leukaemia.

Infections are suspected to play a role in the aetiology of childhood leukaemia. In 1989-95, we evaluated the relation between childhood acute lymphoblastic leukaemia and pre- and postnatal markers of exposure to infection, as well as breast-feeding. A population-based case-control study was carried out in certain regions of Québec, Canada, in 1989-95 including 491 incident cases diagnosed between 1980 and 1993 and aged between 0 and 9 years. An identical number of healthy controls matched for age, sex and region of residence at the date of diagnosis was included. Having older siblings, mother's use of antibiotics during pregnancy, and being born second or later were all associated with increased risk of leukaemia while early day-care attendance (odds ratio (OR) = 0.49; 95% CI 0.31-0.77), and breast-feeding (OR = 0.68; 95% CI 0.49-0.95) were significantly protective. A marker of population mixing was not a risk factor. When including all variables defining family structure in a model, having older siblings at time of diagnosis was a risk factor among children diagnosed before 4 years of age (OR = 4.54; 95% CI 2.27-9.07) whereas having older siblings in the first year of life was protective among children diagnosed at 4 years of age or later (OR = 0.46; 95% CI 0.22-0.97).

A genealogical study of Alzheimer disease in the Saguenay region of Quebec.

We performed an analysis of inbreeding and kinship among the ascending genealogies of 205 autopsy-confirmed Alzheimer disease (AD) subjects recruited in the Saguenay area of Québec. We hypothesized that if some traits pertaining to the disease were determined by inherited factors, and if the corresponding genes were not too frequent in the population, it might be possible to detect some clusters of patients related to common ancestors and presenting a level of kinship and/or inbreeding higher than is observed in the unaffected population of the same age. In view of the heterogeneity of the disease, we also verified if some of the factors investigated could be associated more specifically with subsets of cases based on age of onset and on apolipoprotein E (APOE) genotype. Results were compared with those obtained on 205 controls matched for gender, place and year of birth. We found that late-onset AD cases with an APOE-epsilon 4 were significantly more inbred than controls and that this increase was explained by the high level of inbreeding of a few cases whose parents were related at the first-cousin level. This could possibly indicate the implication of a recessive element in a small subset of AD cases in the Saguenay population. We also found that late-onset epsilon 4+ cases were significantly more closely related among themselves than with controls. This increase in kinship may be attributable to the presence of the epsilon 4 allele or to some other unidentified genetic factor possibly acting in conjunction with APOE-epsilon 4.

Maternal work during pregnancy and the risks of delivering a small-for-gestational-age or preterm infant.

OBJECTIVE: The objective of this study was to assess the relation of some maternal job characteristics to the risks of delivering a small-for-gestational-age or preterm infant. METHODS: Altogether 4390 women who lived in Quebec City, Canada, and the surrounding area, and who gave birth between January and October 1989 to a singleton liveborn neonate were included. Information on gestational age at delivery, job characteristics, nonoccupational physical activities, and several potential confounders was obtained in a telephone interview a few weeks after the delivery. Birthweight was recorded from the birth certificate. RESULTS: The risk of having a small-for-gestational-age infant (birthweight lower than the 10th percentile for gestational age and gender) was increased among the women who worked at least 6 h a day in a standing position. The adjusted odds ratios (OR) were 1.00, 1.13 [95% confidence interval (95% CI) 0.83-1.55], and 1.42 (95% CI 1.02-1.95) for the women working in a standing position < 3, 3-5, and > or = 6 h a day, respectively. The risk for a small-for-gestational-age infant also slightly increased as the gestational age at work cessation increased. A modest increment in the risk of delivering preterm (OR, 1.45, 95% CI 0.84-2.49) was observed for the women working regularly in the evening or at night. Physical effort, lifting heavy objects, and long workhours were not related to either a small-for-gestational-age or a preterm infant. CONCLUSIONS: The results indicate that prolonged standing and working late into pregnancy may increase the risk of delivering a small-for-gestational-age infant, whereas regular evening or night work may be a risk factor for preterm birth.

Passive smoking during pregnancy and the risk of delivering a small-for-gestational-age infant.

The objective of this population-based study was to assess the association between environmental exposure to tobacco smoke during pregnancy and the risk of delivering a small-for-gestational-age (SGA) infant (< 10th percentile). A total of 4,644 nonsmoking women who lived in the Quebec City area and who gave birth between January and October 1989 to a singleton liveborn neonate were included in the analysis. Information on gestational age at delivery, maternal passive smoking at home and at work, and several potential confounders was obtained by a telephone interview with the mother a few weeks after delivery. Birth weight was abstracted from the birth certificate. Overall, passive smokers were at little or no higher risk of having a SGA infant than unexposed women (adjusted odds ratio = 1.09, 95% confidence interval (CI) 0.85-1.39). Passive exposure to tobacco smoke at home only was not related to SGA. However, small increments in risks were observed in women exposed to passive smoking at work only, and risks increased consistently with weekly duration, number of weeks, and intensity of exposure. When compared with unexposed mothers, women exposed to tobacco smoke in the workplace for 1-14, 15-34, and > or = 35 hours per week had adjusted odds ratios of 1.13 (95% CI 0.79-1.61), 1.17 (95% CI 0.73-1.87), and 1.36 (95% CI 0.91-2.09), respectively. This latter odds ratio was close to that observed among women who smoked actively 1-5 cigarettes per day. Although not conclusive, the results are compatible with the hypothesis that environmental exposure to tobacco smoke during pregnancy may be related to a modest increase in the risk of delivering a SGA infant.

Relation of caffeine intake during pregnancy to intrauterine growth retardation and preterm birth.

Whether caffeine intake during pregnancy is related to intrauterine growth retardation, low birth weight, and preterm birth remains unclear. The purpose of this population-based study is to assess these associations and to evaluate the interaction between caffeine intake and smoking. The study participants (n = 7,025) were women who lived in Quebec City, Canada, and the surrounding area who gave birth between January 1989 and October 1989 to a singleton liveborn neonate. Information on gestational age at delivery, caffeine intake (coffee, tea, chocolate, and colas) during pregnancy, and several potential confounders was obtained by telephone a few weeks after delivery. Birth weight was abstracted from the birth certificate. Caffeine consumption was associated with an increased risk of intrauterine growth retardation (birth weight less than the 10th percentile for sex and gestational age). For women whose average daily caffeine consumption was 0-10, 11-150, 151-300, or > 300 mg, the adjusted odds ratios for delivering a newborn with growth retardation were 1.00, 1.28 (95% confidence interval (CI) 1.04-1.59), 1.42 (95% CI 1.07-1.87), and 1.57 (95% CI 1.05-2.33), respectively. Caffeine intake, however, was not related to preterm delivery or low birth weight. We conclude that caffeine intake during pregnancy is a risk factor for intrauterine growth retardation.

Measurement precision of an olfactory perception threshold test for use in field studies.

Changes in olfactory function have been associated with workplace exposure to a variety of substances. In the workplace, smell can be particularly important, since it is commonly used to detect potentially hazardous situations or as an indicator of mask cartridge breakthrough. Sensitive quantitative measures of olfactory loss would be useful in epidemiological studies and workplace surveillance. The objective of the present study was to determine the reproducibility of an olfactory perception threshold test and variations with age, gender, and smoking status. The test was a standard olfactory kit (Olfactolab No. 11), including 18 serial dilutions of PM-carbinol, with an equal number of blanks. The forced choice method was used, with both tester and subject blinded as to which bottle contained the odorant. Olfactory perception threshold was recorded when the subject identified the same dilution three times. To assess reproducibility, testing was repeated four times over a period of 4 weeks, on the same weekday and the same time of day. Subjects (n = 63) ranged in age from 20 to 60 years (mean age: 39.7 +/- 12.5 years), 47.6% were women, 29.5% currently smoked, and 27.9% were former smokers. Results showed no inter-week differences in olfactory perception threshold (Analysis of variance for repeated measures: F = 0.59; p much greater than 0.05). Inter-class correlation for assessment of agreement of continuous variables was 0.76. Inter-week concordance of hyposmia showed fair to good agreement (0.55 greater than or equal to kappa less than or equal to 0.66). Three-way analysis of variance (ANOVA) revealed significant differences with respect to age category (F = 7.36; p less than 0.001) and current smoking status (F = 4.54; p less than 0.05), but not for gender (F = 2.32; p greater than 0.05). The multiple regression model with age and smoking as independent variables was highly significant (F = 13.03; p less than 0.001), explaining 28% of the variance; olfactory threshold increased 0.47 ds/year (t = 4.01; p less than 0.001) and 0.27 ds/cigarettes/day (t = 2.46; p less than 0.05). The findings of this study indicate that this test is reproducible and sensitive to expected changes with age and smoking status. It corresponds well to criteria for testing in the field and should be considered for studies characterizing olfactory functions and sensory loss among working populations.