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Biomedical subjects

Antoine Flahault

Publications and source records attributed to Antoine Flahault.

At least 37 records · Page 2Linked to original sources

Ischemic preconditioning modulates the expression of several genes, leading to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion.

Ischemia triggers an inflammatory response that precipitates cell death during reperfusion. Several studies have shown that tissues are protected by ischemic preconditioning (IP) consisting of 10 min of ischemia followed by 10 min of reperfusion just before ischemia. The molecular basis of this protective effect is poorly understood. We used cDNA arrays (20K) to compare global gene expression in liver biopsies from living human liver donors who underwent IP (n=7) or not (n=7) just before liver devascularization. Microarray data were analyzed using pairedt test with a type I error rate fixed at alpha = 2.5 10(6) (Bonferroni correction). We found that 60 genes were differentially expressed (36 over- and 24 underexpressed in preconditioning group). After IP, the most significantly overexpressed gene was IL-1Ra. This was confirmed by immunoblotting. Differentially expressed were genes involved in apoptosis (NOD2, ephrin-A1, and calpain) and in the carbohydrate metabolism. A significant increase in the amount of the anti-apoptotic protein Bcl-2 in preconditioned livers but no change in the cleavage of procaspase-3, -8, and -9 was observed. We also observed an increase in the amount in the inducible nitric oxide synthase. Therefore, the benefits of IP may be associated with the overproduction of IL-1Ra, Bcl-2, and NO countering the proinflammatory and proapoptotic effects generated during ischemia-reperfusion.

Adult↗

The clinical characteristics of HIV-infected patients receiving dialysis in France between 1997 and 2002.

BACKGROUND: In 1997, 0.38% of dialysis patients in France were infected by human immunodeficiency virus (HIV). No prevalence data were available in France since the widespread introduction of highly active antiretroviral therapy. METHODS: This was a cross-sectional epidemiologic survey. A questionnaire was sent to all French dialysis centers in July 2002. The centers that did not respond were sent 3 additional mailing reminders. Finally, the nonresponding centers were called early in 2004. RESULTS: Of the 27,577 patients on hemodialysis and 587 patients on peritoneal dialysis, 190 patients (0.67%) were infected by HIV. HIV-associated nephropathy was the cause of renal failure in 39.8% patients. Mean age was 44.6 +/- 10.9 years, the mean duration of dialysis was 4.9 +/- 5.9 years, the mean known duration of HIV infection was 8.9 +/- 5.6 years. Eighty-two percent of patients received antiretroviral therapy (ART). Fifty-eight percent of ART-treated patients had an undetectable HIV plasma viral load with a median CD4+ T-cell count 303/mm(3). CONCLUSION: The prevalence of HIV infection among French dialysis patients was 0.67% in late 2002, a 79% increase since 1997. Possible reasons for this large increase include increased access to dialysis, better general status of HIV dialysis patients, and increasing proportion of patients originating from Africa and the Caribbean. The current efficacy of ART makes renal transplantation a realistic option for these young patients.

AIDS-Associated Nephropathy↗

Risk perception of the "mad cow disease" in France: determinants and consequences.

Since 1996, when bovine spongiform encephalopathy (BSE) was assessed as a possible human transmissible disease, a variant of Creutzfeldt-Jakob disease (vCJD), French people have entered into a long period of fear and avoidance of beef and bovine byproducts, which produced an unprecedented collapse in the beef market. This article deals with the perceived risk of the "mad cow disease" (MCD) in the French general population. Two surveys were conducted on a representative sample of the adult population, the first one in 2000 during the peak of the crisis and the second one 13 months later in a quieter period. The main assumption we made was that changes in beef consumption are strongly related to the perceived risk of MCD, which we defined as people's cognitive and affective responses to hazard. Our objective was to identify the determinants and consequences of this perceived risk and to compare them in different sociopolitical contexts. The results issued from a bivariate and multivariate analysis show that: (i) the distribution of most of the variables significantly related to the perceived risk identified in the first survey had changed in the second survey, in relation with the reduction of worry and the resumption of national beef consumption; (ii) the propensity for self-protection through avoiding or ceasing beef eating was more related to feelings of worry than to subjective vCJD risk assessments; and (iii) the main determinant of less avoidance to beef products was the preference for beef, a feeling identified prior to emergence of the risk of MCD, remaining unchanged in various contexts.

Adult↗

ICPCview: visualizing the International Classification of Primary Care.

This paper proposes a method to visualize the semantic content of data bases where the medical information is coded with the International Classification of Primary Care. The main idea is the identification of a pixel with a code and the conversion of all the data associated with these into an image the ICPCview. The method proceeds in two step, defining the reference frame and using this reference frame to visualize data. The reference frame is built by using a sign/diagnosis binary criterion, a seventeen category nosological criterion and an age ordinal criterion. The results are visualization of the signs and diagnosis of the ICPC according to gender, age and time period of the year. A limitation of the method lies in the fact that the result depends on the chosen reference frame. Further work has to be done with various reference frames and data. However the main point is that, when both the reference set of the image and of the mind of the user are built, the method is powerful at extracting the hidden content of a very large amount of data.

Databases, Factual↗

Association of influenza epidemics with global climate variability.

The reasons for the seasonality and annual changes in the impact of influenza epidemics remain poorly understood. We investigated the covariations between a major component of climate, namely the El Niño Southern Oscillation (ENSO), and indicators of the impact of influenza, as measured by morbidity, excess mortality and viral subtypes collected in France during the period 1971-2002. We show that both the circulating subtype and the magnitude of ENSO are associated with the impact of influenza epidemics. Recognition of this association could lead to better understanding of the mechanisms of emergence of influenza epidemics.

Analysis of Variance↗

Could measuring of perceived risk among general practitioners have helped anticipate the French BSE crisis?

In October of 2000, a second BSE crisis caught French public authorities unprepared and caused a collapse in beef consumption as well as considerable political turmoil. Data collected between May and July, 2000, among a group of general practitioners (GPs), while national consumption of beef was back to pre-BSE levels, paradoxically showed high latent risk perception, suggesting a new crisis was possible or likely.

Animals↗

Increased serum maternal levels of the HER2 oncoprotein p105 ectodomain in preeclampsia.

HER2/ERBB2 protein is a 185 kDa transmembrane growth factor receptor whose extracellular domain, a 105 kDa fragment (p105), can be released from cell surfaces by proteolytic cleavage. The aim of our study was to compare serum p105 concentrations in normal and pathological pregnancies and to determine whether any correlation exists between preeclampsia and p105 levels. Serum p105 was assayed in 96 non-pregnant women and 89 pregnant women (26 normotensive, 14 normotensive with a history of preeclampsia or fetal hypotrophy, 10 with chronic hypertension, 10 with gestational hypertension and 29 with preeclampsia). Median serum p105 levels (median; 95% confidence interval) were higher in the preeclampsia group (13.9 microg/l; 12.8-16.1 microg/l) than in the normotensive (11.7 microg/l; 10.6-13.3 microg/l; p < 0.05) or non-pregnant groups (9.3 microg/l; 8.9-9.6 microg/l; p < 0.001). There were no significant differences between the other pregnancy groups. In the normotensive group, serum p105 was correlated with the number of gestations (r = 0.46; p < 0.05), parity (r = 0.39; p < 0.05) and placenta weight (r = 0.61; p < 0.05). In preeclamptic women, serum p105 correlated with parity (r = 0.46; p < 0.05). Serum p105 concentrations above 11.9 microg/l were associated with a high odds ratio (OR) for onset of preeclampsia (after adjustment for parity OR = 9.0; 95% CI = 2.3-36.0; p < 0.005). Preeclampsia is associated with increased serum p105 concentrations, which may be related to increased fetomaternal cell traffic.

Adult↗

Influenza epidemics in the United States, France, and Australia, 1972-1997.

Influenza epidemics occur once a year during the winter in temperate areas. Little is known about the similarities between epidemics at different locations. We have analyzed pneumonia and influenza deaths from 1972 to 1997 in the United States, France, and Australia to examine the correlation over space and time between the three countries. We found a high correlation in both areas between France and the United States (correlation in impact, Spearman's r= 0.76, p < 0.001, and test for synchrony in timing of epidemics, p < 0.001). We did not find a similar correlation between the United States and Australia or between France and Australia, when considering a systematic half-year lead or delay of influenza epidemics in Australia as compared with those in the United States or France. These results support a high correlation at the hemisphere level and suggest that the global interhemispheric circulation of epidemics follows an irregular pathway with recurrent changes in the leading hemisphere.

Australia↗

Suicide and attempted suicide in France: results of a general practice sentinel network, 1999-2001.

The continuous surveillance of suicide and attempted suicide cases was added to the tasks of the French Sentinel Network of General Practitioners (GPs) in 1999. In 2001, 9700 suicides were estimated to have occurred and an estimated 61 500 attempted suicide cases were diagnosed by GPs, representing approximately 40% of cases nationwide. The majority of suicide and attempted suicide cases involved women (67%) and 43% of all cases involved patients aged 25-44 years. The fatality rate increased with age. About 80% of GPs complied with the current recommendation to refer patients who had attempted suicide to hospital.

Adolescent↗

[Anticancer drugs use evaluation: limits of the approved labeling].

A practice survey was performed in Tenon hospital on 396 consecutive patients treated for solid tumors during 4 weeks in november 2002. 33% of anticancer drugs were off label used. The wording heterogeneity of the different anticancer drugs approved labeling and the lack of anticancer drugs in a number of cancers can explain those results. On one hand, randomised comparative clinical trial, considered as the best level of evidence to obtain a label used, is not always possible in cancerology, especially for rare tumors. One the other hand, pharmaceutical firm are not obliged to asked a label used for an anticancer drugs in spite of high level of evidence. So, label used can not be the own references for anticancer drugs prescribing, therapeutic advanced can be realised and disseminated before their taking into account in the label used.

Antineoplastic Agents↗

Risk factors of influenza transmission in households.

BACKGROUND: Influenza transmission in households is a subject of renewed interest, as the vaccination of children is currently under debate and antiviral treatments have been approved for prophylactic use. AIMS: To quantify the risk factors of influenza transmission in households. DESIGN OF STUDY: A prospective study conducted during the 1999 to 2000 winter season in France. SETTING: Nine hundred and forty-six households where a member, the index patient, had visited their general practitioner (GP) because of an influenza-like illness were enrolled in the study. Five hundred and ten of the index patients tested positive for influenza A (subtype H3N2). A standardised daily questionnaire allowed for identification of secondary cases of influenza among their household contacts, who were followed-up for 15 days. Of the 395 (77%) households that completed the questionnaire, we selected 279 where no additional cases had occurred on the day of the index patient's visit to the GP. METHODS: Secondary cases of influenza were those household contacts who had developed clinical influenza within 5 days of the disease onset in the index patient. Hazard ratios for individual clinical and demographic characteristics of the contact and their index patient were derived from a Cox regression model. RESULTS: Overall in the 279 households, 131 (24.1%) secondary cases occurred among the 543 household contacts. There was an increased risk of influenza transmission in preschool contacts (hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.09 to 3.26) as compared with school-age and adult contacts. There was also an increased risk in contacts exposed to preschool index patients (HR = 1.93, 95% CI = 1.09 to 3.42) and school-age index patients (HR = 1.68, 95% CI = 1.07 to 2.65), compared with those exposed to adult index cases. No other factor was associated with transmission of the disease. CONCLUSION: Our results support the major role of children in the dissemination of influenza in households. Vaccination of children or prophylaxis with neuraminidase inhibitors would prevent, respectively, 32-38% and 21-41% of secondary cases caused by exposure to a sick child in the household.

Adolescent↗

Management of acute asthma exacerbations by general practitioners: a cross-sectional observational survey.

BACKGROUND: General practitioners (GPs) have a central place in the management of asthma, particularly in the context of acute exacerbations. AIM: To evaluate the management of asthma exacerbations by GPs, and to investigate the ability of risk factors for near fatal asthma to predict the severity of asthma attacks in the community. DESIGN OF STUDY: A 1-month multicentre cross-sectional survey. SETTING: One thousand and ninety-four GPs of the French Sentinel Network were contacted; 365 responded. METHOD: Asthma exacerbations were classified according to severity at presentation. Univariate and multivariate analyses were performed by logistic regression to identify those factors associated with severe exacerbations. RESULTS: Exacerbations were described in 219 patients with asthma. Over half (54%) of exacerbations were severe. Peak expiratory flow was recorded during the consultation in 55% of patients who were more than 5 years old. beta(2) agonists were prescribed to 93% of patients, systemic corticosteroids to 71%, and antibiotics to 64%. Only 42% of patients had a written action plan for self-management of exacerbations. Risk factors for near fatal asthma, identified in 26% of patients, were not significantly associated with severe asthma exacerbations. Short duration of exacerbation before consultation (<3 hours) was associated with an increase in relative risk of severe exacerbation of 3.38, 95% confidence intervals (CIs) = 1.19 to 9.61, compared with duration of >3 hours. CONCLUSION: Risk factors for near fatal asthma identified in previous studies were not predictive of a severe exacerbation in general practice, with the exception of short duration of exacerbation before consultation. This suggests that new methods to predict risk in the outpatient settings should be developed.

Acute Disease↗

[Anticancer drugs off label used of: what do the experts think about?].

Anticancer drugs off label used in Tenon hospital were analysed by a panel of 12 experts not working at Tenon hospital. They distinguished 3 groups of off-label prescribing according to scientific evidence, labelling anticancer drugs alternative in presence and patient's characteristics: justified off label used (62%), unjustified off label used (26%) and prescriptions for which no consensus had been reached between the experts (12%). Nineteen per cent of unjustified off label used had labelling alternative and 7% did not have anticancer drugs labelling alternative. Questions who experts had to answer to analyse drugs prescribing could be systematically asked when a chemotherapy is prescribed. It could allowed to take into account scientific, economic and ethical requirements. This method proposed by the local drug committee could be used to regulate economic resources and to justify financing of some expensive anticancer drugs.

Antineoplastic Agents↗

Prediction of the spread of influenza epidemics by the method of analogues.

This study was designed to examine the performance of a nonparametric forecasting method first developed in meteorology, the "method of analogues," in predicting influenza activity. This method uses vectors selected from historical influenza time series that match current activity. The authors applied it to forecasting the incidences of influenza-like illnesses (ILI) in France and in the country's 21 administrative regions, using a series of data for 938 consecutive weeks of ILI surveillance between 1984 and 2002, and compared the results with those for autoregressive models. For 1- to 10-week-ahead predictions, the correlation coefficients between the observed and forecasted regional incidences ranged from 0.81 to 0.66 for the method of analogues and from 0.73 to -0.09 for the autoregressive models (p < 0.001). Similar results were obtained for national incidence forecasts. From the results of this method, maps of influenza epidemic forecasts can be made in countries in which national and regional data are available.

Bias↗

Varicella in French adolescents and adults: individual risk assessment and cost-effectiveness of routine vaccination.

Age-specific force of varicella infection, hospitalisation and death rates in non-immune persons were calculated using an age-based mathematical model and national data for France. A cost-effectiveness model was then applied to hypothetical cohorts of persons aged 15-45 years with a negative or uncertain history of varicella. Vaccination strategies with and without prior serotesting, and healthcare payer perspective and societal perspective were considered. A sensitivity analysis was performed. Vaccination prevented more than one third of all varicella-related deaths. With serotesting, compared with no intervention, the cost per case avoided and per year of life saved for subjects aged 15 years were 335 and 55,100 Euro, respectively. When work-loss costs were also included, savings were associated with screening and vaccination of subjects less than 30 years old. Without serotesting, the costs raised markedly, with an almost identical effectiveness, resulting in an unfavourable incremental cost-effectiveness. Based on medical costs, routine serotesting and varicella vaccination for French adolescents and young adults with a negative or uncertain history of varicella affords health benefits at a cost comparable to those of other very expensive therapies considered worthwhile. From the societal perspective, such screening and vaccination might save costs.

Adolescent↗

Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression.

Tissue microarray technology enables the analysis of hundreds of specimens by arranging numerous 0.6-mm tissue core biopsy specimens into a single paraffin block. Validation studies are necessary to evaluate the representativeness of small disks taken from the original tissue. We validated the tissue microarray technology in colorectal carcinoma by analyzing the immunohistochemical expression of proteins involved in the two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors, hMLH1 and hMSH2 proteins for microsatellite instability (MSI) tumors. We compared in 30 colorectal carcinomas (15 MSI(-) and 15 MSI(+)), 8 microarrays disks, and the whole section of the block from which they were derived. Tumoral tissue was present in 95.7% of the microarray disks. The analysis of three disks per case was comparable to the analysis of the whole section in 99.6% (p53), 98.8% (hMLH1), and 99.2% (hMSH2) of cases. In the second part we applied the tissue microarray technology to 263 consecutive cases of colorectal carcinoma, sampled by three cores. We showed that 48.5% overexpressed p53 and 8.7% lost hMLH1 or hMSH2. Tissue microarray technology, validated in colorectal carcinoma, appears as a useful research tool for rapid analysis of the clinical interest of molecular alterations.

Adaptor Proteins, Signal Transducing↗

Is pertussis being considered as a cause of persistent cough among adults?

A study was conducted to determine the 1124 French Sentinel network general practitioners ability to consider pertussis as a cause of persistent cough among adults. Pertussis was rarely considered in the differential diagnosis of cough (6%). Factors associated with pertussis being considered included younger age, shorter cough duration, world health organization clinical definition for pertussis, and muscular chest pain.

Adult↗