Knockout of hyaluronidase Spam1 reduces age-related bone and cartilage changes in mouse knee.

OBJECTIVE: To investigate the role of Spam1 hyaluronidase in age-related bone and cartilage changes in the mouse knee. DESIGN: Spam1-/- and WT mice were euthanised at different ages from 10 to 52 weeks. The right hindlimbs were dissected, scanned with peripheral Quantitative Computed Tomography (pQCT) and then decalcified for histological analysis (modified Mankin score). In other mice, cartilages of both tibiae were sampled at 10, 30 and 52 weeks of age for RNA extraction and qPCR analysis. We assessed the expression of hyaluronidases Hyal1 and Hyal2, hyaluronan synthase HAS2, extracellular matrix proteases Mmp13 and Adamts-5, and type 2 collagen. RESULTS: Spam1-/- mice did not exhibit specific morphological characters up to 52 weeks of age. From 20 weeks, the proximal tibia of Spam1-/- mice had a significantly lower bone mineral density than WT mice. At 52 weeks, the modified Mankin score was significantly lower in Spam1-/- than WT mice. Spam1-/- chondrocytes expressed significantly less Hyal2 than WT ones at all ages and less Mmp13 at 52 weeks. Through all the experiment, the Hyal1 expression of Spam1-/- chondrocytes remained similar as that of WT chondrocytes. CONCLUSION: Spam1 knockout reduced significantly cartilage degradation in mouse knee whereas the chondrocyte expression of Hyal 1, Hyal 2 and Mmp13 was modified, suggesting a role of this hyaluronidase in cartilage metabolism.

Abrogation by subsequent feeding of antibody response including IgE, in parenterally immunized mice.

We have investigated the possibility of oral administration of ovalbumin (OVA) to prevent a secondary antibody response and interrupt reaginic antibody production. Repeated feeding seems necessary for both. Quality of results was dependent on the number of ingestions. Differences in abrogation of antibody response between mice strains were observed. Best results were obtained with AKR mice, good suppression was seen in C3H strain, and inconsistent results were obtained with DBA/2. 10 OVA oral doses were necessary to prevent a secondary antibody response in parenterally immunized mice, but 4 doses interrupted reaginic production in sensitized AKR mice. These results demonstrate that antigen feeding can prevent a secondary antibody response and interrupt reaginic antibody production.

The Development and Initial Validation of the Child Perceived Discrimination Questionnaire.

Perceived discrimination can affect psychological and physical health, starting in childhood. Yet, the measures that exist for measuring perceived discrimination among children have methodological limitations and structural/theoretical inconsistencies. The Child Perceived Discrimination Questionnaire (CPDQ) fills the gaps of the current measures by assessing two dimensions of everyday discrimination from both child and adult sources. To assess the reliability and validity of the CPDQ, we examined data from 163 participants, aged 9-11, 52.15% female, 57.67% Black. Results indicated that the CPDQ has good to excellent internal consistency and provided preliminary support for an a priori hypothesized factor structure. The CPDQ also discriminated between different race groups and demonstrated construct validity. Future research should seek additional evidence of reliability and validity for the CPDQ, though this preliminary evidence suggests that the CPDQ is appropriate for assessing perceived discrimination in children.

Cancer mortality in a synthetic spinning plant in Besançon, France.

OBJECTIVES: To assess the mortality of a cohort of workers in a synthetic textile spinning plant and to evaluate the relationship between mortality from lung, liver and bladder cancer and the processes or the products used. METHODS: The study population consisted of male workers present for at least 6 months in the plant from 1968 to 1984. The cohort was followed until 1999. Vital status and the causes of death were determined by consulting national registries. The population of the Franche-Comté region was used for comparison. In total, 17 groups of exposure were assessed by the industrial hygienist, based on the consensus of an expert group that determined the exposure levels of each job to selected occupational hazards. Each worker was assigned to one or several groups, according to his occupational history. Confounding factors could not be assessed. Standardised mortality ratios (SMR) and 95% bilateral confidence intervals were calculated based on an assumed Poisson distribution of the number of cases to compare the plant mortality and the population mortality. Internal analyses were performed with Cox models in order to assess the risks of death related to the various exposures. RESULTS: In the whole cohort, mortality from all malignant neoplasms was lower than expected, but this was not significant. All the estimated SMRs were lower than or close to 1. The "hot -line fitters" (RR = 2.13; n = 9; 1.06 to 4.29) and the "fibre-drawing workers" (RR = 1.83; n = 20;1.09 to 3.07) experienced a statistically significant excess in mortality from lung cancer. A slightly elevated but not significant risk of death related to lung cancer (RR = 1.5; n = 41; 0.8 to 2.7) was observed in the groups with the highest exposure to mineral fibres. A statistically significant increase in cancer deaths was observed for workers with high exposure to dust (higher intensity: RR = 1.42; n = 79; 1.06 to 1.89). CONCLUSION: Some findings, mainly of lung cancer, justify further exploration in other plants in this industry.

Road mobility and the risk of road traffic accident as a driver. The impact of medical conditions and life events.

STUDY OBJECTIVE: We conducted a longitudinal investigation of the impact of self-reported life events and medical conditions on changes in road mobility on the wheel between 2000 and 2002 in order to assess whether these changes would affect the risk of road traffic accident (RTA). METHODS: Data are from a cohort of workers and retirees from the French national gas and electricity companies (the Gazel cohort). In the present study, 10,483 participants were included (7843 men aged 51-61 years and 2640 women aged 46-61 years, in 2000). The link between mobility and the risk of RTA was approximated using data on RTA number during lifetime and reported mobility in 2000. We then compared changes in road mobility between 2000 and 2002 resulting from life events and medical conditions reported to have occurred in the year 2001 or changed when compared to year 2000. We also compared road mobilities in 2000 in order to assess any pre-existing differences before life events and medical conditions. This led to estimation of the effect of road mobility changes on the risk of RTA. RESULTS: Changes in road mobility associated with life events and medical conditions were only found among men. These changes in road mobility were minimal. Ensuing changes in the risk of RTA were estimated to be small (odds-ratios ranged from 0.94 to 1.01). The only life events found to be associated with increased road mobility was an important purchase. Hospitalization, serious RTA, and retiring were associated with reduced road mobility. Concerning medical conditions, men who reported cataract, angina pectoris, diabetes, anxiety and stress, sleep disorder, and depression decreased their road mobility. CONCLUSION: We found no or moderate changes in road mobility resulting from life events and medical conditions, suggesting that results from previous published studies that assessed the impact of life events or medical conditions on RTA were not jeopardized by improper adjustment for road mobility.

Marital status and risk of Alzheimer's disease: a French population-based cohort study.

OBJECTIVE: To analyze the relationship between marital status and risk of AD or dementia. METHODS: This study was carried out from the Personnes Agées QUID (PAQUID) cohort, an epidemiologic study on normal and pathologic aging after age 65 years. The PAQUID cohort began in 1988. Individuals were followed up at 1, 3, and 5 years, with an active detection of dementia. Marital status was divided into four categories: widowed, never married, divorced or separated, and the reference category, married or cohabitant. The longitudinal relationship between marital status and risk of incident AD or dementia was analyzed by a Cox model with delayed entry. RESULTS: Among the 3,675 individuals initially not demented, 2,106 were married or cohabitants, 1,287 were widowers, 179 were never married, and 103 were divorced or separated. Among the 2,881 individuals reevaluated at least once for the risk of dementia during the 5-year follow-up, 190 incident cases of dementia were identified, including 140 with AD. The relative risks (RRs) of dementia (RR = 1.91, p = 0.018) and of AD (RR = 2.68, p<0.001) were increased for the never-married individuals compared with those who were married or cohabitants. This excess of risk was specifically associated with AD. Adjustment for other risk factors of dementia (education, wine consumption), or for factors reflecting social environment, leisure activities, and depression, did not modify the risk of AD for never-married individuals (RR = 2.31, p = 0.02). CONCLUSIONS: We confirmed an association between marital status and AD, with an excess risk observed among never-married individuals. This association may provide clues about the pathogenesis of AD.

Traffic ticket fixing and driving behaviours in a large French working population.

STUDY OBJECTIVE: The use of connections who have the authority to cancel penalties related to traffic violations seems to be very frequent in France. This study aimed at describing risk taking driving behaviours associated in France with using connections to have traffic tickets cancelled (ticket fixing). DESIGN: Retrospective study on driving behaviour and road safety conducted between March and December 2001 within a cohort of French employees. SETTING: France. PARTICIPANTS: Employees of the French national utility company who have been followed up since 1989. The sample comprises 10 594 men aged 53-63 years and 3258 women aged 48-63 in 2001. MAIN RESULTS: One third of the men and one fifth of the women reported that they had had a ticket fixed at some time. Those who reported having tickets fixed were more likely than the others to report high driving speeds (adjusted odds ratios (aOR) were 1.24, 1.52, and 1.66 in built up areas, on rural roads, and on motorways respectively), to report driving while under the influence (aOR = 1.39), and to report risky use of cellular phone while driving (aOR = 1.83). In addition, participants who reported having tickets fixed were more likely to have had at least one serious road traffic accident in the past 11 years (aOR = 1.21). CONCLUSIONS: Indulgence and the use of connections are common practices in France. These results suggest that it is to confer a feeling of impunity that jeopardises efforts to combat unsafe driving. Abolition of these traditions is essential to ensure the credibility of preventive and repressive measures.

Orosomucoid: a mortality risk factor in elderly people living in the community?

AIM: We explored the value of variables relating to inflammation and nutrition as a prognostic factors for mortality in an elderly community-dwelling population. METHODS: We measured plasma levels of orosomucoid, C-reactive protein (CRP), albumin, and transthyretin, and the body mass index (BMI) of 245 subjects aged 65 to 95 living in the community (PAQUID study). The risk of death was analyzed two, four and six years after blood sampling by use of the Cox proportional hazards model with delayed entry. A survival curve was generated by the Kaplan-Meier method. RESULTS: Multivariate analysis--including sex, BMI, and plasma levels of albumin, transthyretin orosomucoid and CRP levels--showed that orosomucoid in the highest quartile (>0.88 g/L) was the strongest predictor of mortality two years after blood sampling [relative risk (RR)=7.4; 95% interval confidence (IC) 2.2-24.6; P<0.1]; the association remained significant four and six years after blood sampling [RR=2.5; 95%IC 1.2-5.2 and RR=1.9; 95%IC 1.0-3.4 respectively, P<0.05]. Orosomucoid levels above 1 g/L (the most accurate threshold for prediction of mortality) were associated with a strong increase in the risk of death two years [RR=12.3; 95%IC 4.3-35.0; P<0.001], four years [RR=6.9; 95%IC 3.3-14.7; P<0.001], and six years [RR=4.4; 95%IC 2.3-8.5; P<0.001) after blood sampling. CONCLUSION: These results further underline the association between systemic inflammation and mortality. They may help us to identify of high-risk subpopulations of elderly subjects so we can employ prevention strategies.

[Differences between males and females in traffic accident risk in France]. / Différences entre les hommes et les femmes face au risque routier.

BACKGROUND: In France 7,720 people were killed in traffic accidents in 2001, 75% of which were men; the number of injured people is estimated at 153,945, of which 65% were men. The objective of the study is to describe differences between males and females regarding accidents, and to explain the main reasons for these differences. METHODS: Analysis is conducted from both national police data (2001) and data from the Rhone medical road accident trauma Register (1996-2001). RESULTS: The male/female incidence rate is 3.1 for mortality (95% CI: 3.0-3.3) and 1.7 for morbidity (95% CI: 1.7-1.8). Two-wheel motorised vehicle accidents are very specific to males, which explains part of this overrepresentation. The fatality rate and the severe injuries rate among survivors are higher for males. This is true for every main user group (car users, motorised two-wheelers, cyclists, pedestrians) after adjusting for accident circumstances and age of casualties. Males are more severely injured for all body regions and have more often severe after-effects. CONCLUSIONS: This paper shows the mechanisms leading to this unfavourable outcome for men. They correspond to differences in the number of trips, in the choice of road transport types, and moreover to differences in risk-taking behaviours. Underlying these behaviours, deep-rooted, strong and rather invariant differences between genders are to be found in the values associated with risk-taking on the road.

[Relation between global cognitive performance and dependency evaluated by the AGGIR scale]. / Relation entre performances cognitives globales et dépendance évaluée par la grille AGGIR.

BACKGROUND: The aim of the present study was to investigate the relation between cognitive performances and dependency state according to the AGGIR model, the national standardized instrument determining the attribution of the "Prestation Spécifique Dépendance" (PSD) in France. METHOD: The sample of the study comprised 1,052 subjects aged 73 and over seen at the 8-year follow-up of the Paquid cohort. The "Autonomie Gérontologie Groupes Iso-Ressources" (AG-GIR) model relies on the assessment of eight measures of disability and two additional measures of intellectual coherence and orientation. The model results in a classification of six Iso-Resources Groups (GIR), only the subjects from GIR 1, 2 or 3 being potential beneficiaries of the PSD. RESULTS: The percentage of completely independent subjects (GIR 6) was 85% and only 6.1% were dependent according to the level of the attribution of the PSD (GIR 1 to 3). Among these subjects, 57.8% had been diagnosed as cases of dementia. Conversely, less than half of the cases of dementia were not potential beneficiaries of the PSD. Cognitive performances assessed by the Mini Mental State Examination (MMSE), were associated to a risk of dependency with an odds ratio of 1.4 for the subjects who lost one point on the MMSE (95% CI: 1.3-1.5, p < 0.001). Even when dementia was not diagnosed, low cognitive performances and dyspnea were the main factors of the dependency classification according to the AGGIR model. CONCLUSIONS: This study confirms the relationship between cognitive performances and dependency assessed by the AGGIR model. However the model seems to lack sensitivity for taking into account functional impairment associated with dementia. Consideration of Instrumental Activities of Daily Living in the classification procedure could improve the satisfaction of the needs of these subjects.

Determinants of chronic bronchitis prevalence in an elderly sample from south-west of France.

This paper attempts to estimate by means of a cross-sectional study in subjects aged 65 yrs and over the determinants of the prevalence of chronic bronchitis according to age, gender, smoking history, educational level, former occupation and associated morbidity. Data were examined from the third year of a cohort (Personnes àgêes QUID (PAQUID)) and concerned 2,406 subjects. Identification of chronic bronchitis was based on a direct question asking for the presence of phlegm on most days during at least 3 months per year for at least the two previous years. Of the sample, 13% reported chronic bronchitis (20% of males, and 8% of females). A multivariate analysis was performed and showed that chronic bronchitis was linked to sex, smoking history and professional category. Independent of these factors, asthma history and digitalic drug therapy were also closely associated to chronic bronchitis. These results underline the long-term effect of smoking and occupation on chronic bronchitis, and also illustrate the strong association with asthma and cardiac morbidity over 65 yrs of age.

[Normative data for the MMSE, the Benton visual retention test, the Isaacs's set test, the digit symbol substitution test and the Zazzo's cancellation task in subjects over the age 70: results from the PAQUID Study]. / Normes pour le MMSE, le test de rétention visuelle de Benton, le set test d'Isaacs, le sous-test des codes de la WAIS et le test de barrage de Zazzo chez des sujets âgés de 70 ans et plus: données de la cohorte PAQUID.

UNLABELLED: Introduction. The aim of this study was to produce norms for the Mini-Mental State Examination, the Benton visual retention test, Isaacs's set test, the digit symbol substitution test and Zazzo's cancellation task (short 8-line version), in elderly people. METHODS: Data was collected in a representative sample of 1780 subjects aged 70 years and older, followed-up for five years after inclusion in the PAQUID study. Only individuals who did not have characteristics likely to alter their cognitive performance were considered. RESULTS: Descriptive statistics (median, tenth percentile, first and third quartile) were used to define gender-, age- and education-specific norms. CONCLUSIONS: These norms can be used by clinicians to interpret a patient's performance on several widely used cognitive tests according to the scores obtained by individuals of the same age, gender and educational level.

Wine consumption and dementia in the elderly: a prospective community study in the Bordeaux area.

Alcoholism is a possible cause of dementia, mainly through associated nutritional deficiencies and, rarely, through acute direct toxicity. However alcohol consumption was not found to be a risk factor in previous epidemiologic studies. We prospectively studied 3,777 community residents aged 65 and over, in the districts of Gironde and Dordogne. Average daily alcoholic consumption was recorded at baseline. Incident cases of dementia and Alzheimer's disease were screened at follow-up with explicit criteria. At 3 years, 2,273 subjects not demented at baseline were still available for follow-up. Wine was the only alcoholic beverage reported by more than 95 p. 100 of regular drinkers. In the 318 subjects drinking 3 to 4 standard glasses per day (> 250 and up to 500 ml), categorized as moderate drinkers, the crude odds ratio (OR) was 0.18 for incident dementia (p < 0.01) and 0.25 for Alzheimer's disease (p < 0.03), as compared to the 971 non-drinkers. After adjusting for age, sex, education, occupation, baseline MMSE and other possible confounders, the ORs were respectively 0.19 (p < 0.01) and 0.28 (p < 0.05). In the 922 mild drinkers (< 1 to 2 glasses per day) there was a negative association only with AD, after adjustment (OR = 0.55; p < 0.05). The inverse relationship between moderate wine drinking and incident dementia was explained neither by known predictors of dementia nor by medical, psychological or socio-familial factors. Considering also the well documented negative associations between moderate wine consumption and cardiovascular morbidity and mortality in this age group, it seems that there is no medical rationale to advise people over 65 to quit drinking wine moderately, as this habit carries no specific risk and may even be of some benefit for their health. Advising all elderly people to drink wine regularly for prevention of dementia would be however premature at this stage.

[Is it possible to improve sleep in children? A research on health education in nursery schools]. / Peut-on améliorer le sommeil des enfants? Une recherche en éducation pour la santé à l'école maternelle.

An educational project in nursery schools was carried out with the aim to improve children's sleep. Its effectiveness was tested in terms of awareness of families and length of sleep of children. The method was a prevention trial based on the random division of classes of 3-year old into two groups (intervention group and control group) comprising children enrolled in nursery schools in the Rhône region (France) in 1992. The project, lasting 2 years, relied on physicians from the community (Maternal, Child Health Service and School Health Service), their role being to mobilise the teaching teams, distribute specific teaching tools and raise awareness of families to respect the sleep patterns of children, during routine medical examinations. The study was carried out in 140 nursery schools with 1,500 children in each group. The evaluation was based on the application of a logistical regression model taking potentially confounding factors into account, and an analysis in sub-groups in order to demonstrate the effectiveness of intervention on particularly exposed groups. The results show: 1) the feasibility of such an intervention among nursery school children on a large scale, 2) the effectiveness of the action, with a reduction of the risk of "poor knowledge" among parents (OR = 0.76), particularly in urban areas, and a reduction in the risk "short nights" in the sub-group of children who had " little sleep at 3 years" in low social class families (OR = 0.50).

[Compliance in HIV infected adults. Study of opportunistic infection prophylaxis with cotrimoxazole in Ivory Coast]. / Observance chez les adultes infectés par le VIH. Etude d'une prophylaxie des infections opportunistes par le cotrimoxazole en Côte d'Ivoire.

BACKGROUND: The compliance to a daily treatment for illimited duration and the factors that influence it have been rarely studied in sub-Saharian Africa. OBJECTIVE: Describe the compliance to prophylaxis with cotrimoxazole fort (one tablet per day) and its associated factors in patients infected by HIV participating in a clinical trial in Abidjan. METHOD: The tablets packed in individual blisters were provided every month, and the blisters were recuperated the following month. A global compliance ratio (GCR) was established for each patient (empty blisters at the end of the study/follow-up period during the study) and monthly compliance ratio [MCR] (empty blisters during a visit/time lapse since last visit). For each monthly visit foreseen in the protocol, a respect of the appointment ratio (RAR) was described (visits foreseen in the protocol respected that month/visits foreseen in the protocol). The association of GCR with the characteristics on inclusion was studied using logistic regression methods. RESULTS: 530 adults were followed-up for a mean of 10 months. The MCR and the RAR progressed in parallel, decreasing the first 5 months and stabilizing at around 0.80 for the RAR and 0.70 for the MCR. The mean GCR was of 0.77. Three hundred and nine patients (58%) were considered as compliant (0.80

The recent dramatic decline in road mortality in France: how drivers' attitudes towards road traffic safety changed between 2001 and 2004 in the GAZEL cohort.

A very significant decline in the number of road casualties has been observed recently in France, concomitantly with a dramatic increase in law enforcement. The aim of this study was (i) to assess changes in attitudes about road traffic accident (RTA) prevention initiatives in France from 2001 to 2004 and (ii) to identify factors associated with an increase in positive attitudes towards RTA prevention initiatives. In 2001 and 2004, 9216 participants reported their attitudes towards traffic safety using the same self-administered Driving Behaviour and Road Safety Questionnaire. Sociodemographic, psychological and behavioural data were also available. The mean change in scores analysis showed that support for relaxing existing regulations decreased significantly during this period, while support for heightened enforcement and stricter regulations showed some decrease but remained high overall, especially concerning blood alcohol content and speed controls. Multivariate analyses suggest that highly educated drivers changed their attitudes towards road safety regulations more than other categories. Our results suggest that increased traffic law enforcement measures led to increasing support for current restrictions. Even if support for additional traffic law enforcement began to wane slightly in 2004, a large part of our population remained in favour of strengthening law enforcement related to speeding and drunk driving.

Elevation of 3'5' cyclic adenosine monophosphate alters CD3 and CD25 antigens expression in activated T lymphocytes.

Modulation of CD3 molecules and expression of receptors for IL-2 (CD25) are pivotal events of lymphocyte activation and proliferation. Knowing the inhibitory effect of cAMP elevating agents on T lymphocyte activation, we investigated the effect of cholera toxin (CT) and dibutyryl cyclic AMP (dbcAMP) on the modulation of the CD3/Ti complex and on the appearance of the CD25 antigen on PHA-activated human lymphocytes. Cytofluorometry analysis of indirectly anti-CD3 labelled cells showed that CT accelerated the disappearance of CD3 molecules and slowed their reappearance. CT or dbcAMP inhibited the expression of CD25 antigen. In both cases, not only the relative number of CD3+ or CD25+ cells decreased, but the number of CD3 or CD25 antigens per cell as well. Exogenous rIL-2 did not reverse the inhibition of IL-2R expression by CT, showing that this effect is independent of the inhibition of IL-2 production already demonstrated. We conclude that augmenting cAMP levels might affect early steps of activation such as antigen receptor modulation, but do affect more profoundly late IL-2 dependent steps especially the autocrine IL-2 pathway of IL-2 receptor upregulation and the production of IL-2.

[An ELISA study of the intestinal and serum anti-LPS antibody response in BALB/c mice fed with various mutants of "Salmonella typhi-murium" (author's transl)]. / Etude, par la méthode ELISA, du titre des anticorps sériques et intestinaux anti-LPS chez la souris BALB/c vaccinée à l'aide de mutants "rough" et "smooth" de Salmonella typhi-murium.

The specific anti-LPS serum antibody response in BALB/c mice, before and after an oral booster with different non-pathogenic strains of Salmonella typhi-murium, was measured by an ELISA technique. Serum response to LPS was found to depend on the length of the LPS polysaccharide moiety in "rough" mutants. The M206 "smooth" mutant induced a less marked anti-LPS response. The immunogenicity of the polysaccharidic "core" appears to be modified by the O antigen. The specific antibody response in the gut only becomes marked following after booster of Ra, Rc and M206 mutants.