Expositions médicamenteuses pendant la grossesse: une approche différenciée [Drug exposure during pregnancy: a differentiated approach].

Numerous drug exposures do occur unintentionally at the beginning of pregnancy. On the other hand, pursuing drug treatment may be necessary in women who wish to be pregnant. In these situations risk evaluation has to be done in a precise and differentiated manner, taking into account at the same time the risk for the fetus and maternal health. Teratovigilance services are able to give a thorough information enabling to avoid unwarranted drug arrests or pregnancy terminations. In return, physician's catamnesis about the outcome of the pregnancy exposed to one or several therapeutic agents will increase the bulk of knowledge health professionals and pregnant women have at their disposal.

Respiratory effects of an exposure to wheat dust among grain workers and farmers: a longitudinal study

OBJECTIVES: Agriculture is considered one of the occupations most at risk of acute or chronic respiratory problems. The aim of our study was to determine from which level of exposure to organic dust the respiratory function is chronically affected in workers involved in wheat grain or straw manipulation and to test if some of these working populations can recover their respiratory function after an exposure decrease. METHOD: 87 workers exposed to wheat dust: farmers, harvesters, silo workers and livestock farmers and 62 non exposed workers, were included into a longitudinal study comprising two visits at a six months interval with lung function measurements and symptom questionnaires. Cumulative and mean exposure to wheat dust were generated from detailed work history of each worker and a task-exposure matrix based on task-specific exposure measurements. Immunoglobulins (IgG and IgE) specific of the most frequent microorganisms in wheat dust have been determined. RESULTS: FEV1 decreased significantly with the cumulative exposure and mean exposure levels. The estimated decrease was close to 200 mL per year of high exposure, which corresponds roughly to levels of wheat dust higher than 10 mg/m(3). Peak expiratory flow and several acute symptoms correlate with recent exposure level. Recovery of the respiratory function six months after exposure to wheat dust and evolution of exposure indicators in workers blood (IgG and IgE) will be discussed. CONCLUSIONS: These results show a chronic effect of exposure to wheat dust on bronchial obstruction. Short term effects and reversibility will be assessed using the full study results.

Assessment of diesel exhaust particulate exposure and surface characteristics in association with levels of oxidative stress biomarkers

Exposure to PM10 and PM2.5 (particulate matter with aerodynamic diameter smaller than 10 μm and 2.5 μm, respectively) is associated with a range of adverse health effects, including cancer, pulmonary and cardiovascular diseases. Surface characteristics (chemical reactivity, surface area) are considered of prime importance to understand the mechanisms which lead to harmful effects. A hypothetical mechanism to explain these adverse effects is the ability of components (organics, metal ions) adsorbed on these particles to generate Reactive Oxygen Species (ROS), and thereby to cause oxidative stress in biological systems (Donaldson et al., 2003). ROS can attack almost any cellular structure, like DNA or cellular membrane, leading to the formation of a wide variety of degradation products which can be used as a biomarker of oxidative stress. The aim of the present research project is to test whether there is a correlation between the exposure to Diesel Exhaust Particulate (DEP) and the oxidative stress status. For that purpose, a survey has been conducted in real occupational situations where workers were exposed to DEP (bus depots). Different exposure variables have been considered: - particulate number, size distribution and surface area (SMPS); - particulate mass - PM2.5 and PM4 (gravimetry); - elemental and organic carbon (coulometry); - total adsorbed heavy metals - iron, copper, manganese (atomic adsorption); - surface functional groups present on aerosols (Knudsen flow reactor). Several biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and several aldehydes) have been determined either in urine or serum of volunteers. Results obtained during the sampling campaign in several bus depots indicated that the occupational exposure to particulates in these places was rather low (40-50 μg/m3 for PM4). Bimodal size distributions were generally observed (5 μm and <1 μm). Surface characteristics of PM4 varied strongly, depending on the bus depot. They were usually characterized by high carbonyl and low acidic sites content. Among the different biomarkers which have been analyzed within the framework of this study, mean urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly (p<0.05) during two consecutive days of exposure for non-smoker workers. On the other hand, no statistically significant differences were observed for serum levels of hexanal, nonanal and 4- hydroxy-nonenal (p>0.05). Biomarkers levels will be compared to exposure variables to gain a better understanding of the relation between the particulate characteristics and the formation of ROS by-products. This project is financed by the Swiss State Secretariat for Education and Research. It is conducted within the framework of the COST Action 633 "Particulate Matter - Properties Related to Health Effects".

Exhaled breath condensate as a matrix for combustion-based nanoparticle exposure and health effect evaluation

Health assessment and medical surveillance of workers exposed to combustion nanoparticles are challenging. The aim was to evaluate the feasibility of using exhaled breath condensate (EBC) from healthy volunteers for (1) assessing the lung deposited dose of combustion nanoparticles and (2) determining the resulting oxidative stress by measuring hydrogen peroxide (H2O2) and malondialdehyde (MDA). Methods: Fifteen healthy nonsmoker volunteers were exposed to three different levels of sidestream cigarette smoke under controlled conditions. EBC was repeatedly collected before, during, and 1 and 2 hr after exposure. Exposure variables were measured by direct reading instruments and by active sampling. The different EBC samples were analyzed for particle number concentration (light-scattering-based method) and for selected compounds considered oxidative stress markers. Results: Subjects were exposed to an average airborne concentration up to 4.3×10(5) particles/cm(3) (average geometric size ∼60-80 nm). Up to 10×10(8) particles/mL could be measured in the collected EBC with a broad size distribution (50(th) percentile ∼160 nm), but these biological concentrations were not related to the exposure level of cigarette smoke particles. Although H2O2 and MDA concentrations in EBC increased during exposure, only H2O2 showed a transient normalization 1 hr after exposure and increased afterward. In contrast, MDA levels stayed elevated during the 2 hr post exposure. Conclusions: The use of diffusion light scattering for particle counting proved to be sufficiently sensitive to detect objects in EBC, but lacked the specificity for carbonaceous tobacco smoke particles. Our results suggest two phases of oxidation markers in EBC: first, the initial deposition of particles and gases in the lung lining liquid, and later the start of oxidative stress with associated cell membrane damage. Future studies should extend the follow-up time and should remove gases or particles from the air to allow differentiation between the different sources of H2O2 and MDA.

Prolonged fluconazole exposure leads to a shift to Candida species with decreased susceptibility in breakthrough candidemia: prospective survey of the Fungal Infection Network of Switzerland

Objectives: To compare the clinical characteristics, species distribution and antifungal susceptibility of Candida bloodstream isolates (BSI) in breakthrough (BTC) vs. non-breakthrough candidemia (NBTC) and to study the effect of prolonged vs. short fluconazole (F) exposure in BTC.Methods: Candida BSI were prospectively collected during 2004- 2006 from 27 hospitals (seven university, 20 affiliated) of the FUNGINOS network. Susceptibility to F, voriconazole (V) and caspofungin (C) was tested in the FUNGINOS mycology reference laboratory by microtitre broth dilution method with the Sensititre YeastOneTM test panel. Clinical data were collected using standardized CRFs. BTC was defined as occurring during antifungal treatment/prophylaxis of at least three days duration prior to the candidemia. Susceptibility of BSI was defined according to 2010/2011 CLSI clinical breakpoints.Results: Out of 567 candidemia episodes, 550 Candida BSI were available. Of these, 43 (7.6%) were from BTC (37/43, 86% were isolated after F exposure). 38 BTC (88.4%) and 315 NBTC (55.6%) occurred in university hospitals (P < 0.001). The majority of patients developing BTC were immunocompromised: higher proportions of haematological malignancies (62.8% in BTC vs. 47.1% in NBTC, P < 0.001), neutropenia (37.2% vs. 11.8%, P < 0.001), acute GvHD (14% vs. 0.2%, P < 0.001), immunosuppressive drugs (74.4% vs. 7.8%, P < 0.001), and mucositis (32.6% vs. 2.3%, P < 0.001) were observed. Other differences between BTC and NBTC were higher proportions of patients with central venous catheters in the 2 weeks preceding candidemia (95.3% vs. 83.4%, P = 0.047) and receiving total parenteral nutrition (62.8% vs. 35.9%, P < 0.001), but a lower proportion of patients treated with gastric proton pump inhibitors (23.3% vs. 72.1%, P < 0.001). Overall mortality of BTC and NBTC was not different (34.9% vs. 31.7%, P = 0.73), while a trend to higher attributable mortality in BTC was found (13.9% vs. 6.9%, P = 0.12). Species identification showed a majority of C. albicans in both groups (51.2% in BTC vs. 62.9% in NBTC, P = 0.26), followed by C. glabrata (18.6% vs. 18.5%), C. tropicalis (2.3% vs. 6.3%) and C. parapsilosis (7.0% vs. 4.7%). Significantly more C. krusei were detected in BTC versus NBTC (11.6% vs. 1.6%, P = 0.002). The geometric mean MIC for F, V and C between BTC and NBTC isolates was not significantly different. However, in BTC there was a significant association between duration of F exposure and the Candida spp.: >10 days of F was associated with a significant shift from susceptible Candida spp. (C. albicans, C. parapsilosis, C. tropicalis, C. famata) to non-susceptible species (C. glabrata, C. krusei, C. norvegensis). Among 21 BTC episodes occurring after £10 days of F, 19% of the isolates were non-susceptible, in contrast to 68.7% in 16 BTC episodes occurring after >10 days of F (P = 0.003).Conclusions: Breakthrough candidemia occurred more often in immunocompromised hosts. Fluconazole administered for >10 days was associated with a shift to non-susceptible Candida spp.. Length of fluconazole exposure should be taken into consideration for the choice of empirical antifungal treatment.

Sources d'exposition aux phtalates dans une unité de soins néonatals [Phthalate exposure in the neonatal intensive care unit].

There are growing concerns on long-term health consequences, notably on fertility rates, of plasticizers such as phthalates. While di(2-ethylhexyl)phthalate (DEHP) is currently used in several medical devices, newborns in the neonatal intensive care unit are both more exposed and more vulnerable to DEHP. The objectives of this study were to identify, count, and describe possible sources of DEHP in a neonatal care unit. Our method consisted in the listing and the inspection of the information on packaging, complemented by contact with manufacturers when necessary. According to the results, 6% of all products and 10% of plastic products contained some DEHP; 71% of these involved respiratory support devices. A vast majority of the items showed no information on the content of DEHP. Further research is needed, particularly to determine the effects of such an early exposure and to study and develop safer alternatives.

Letter health consultation : Exposure to benzene from Equistar pyrolysis gasoline tank, Clinton, Iowa (2008)

The Iowa Department of Public Health (IDPH) has been asked by several citizens of Clinton, Iowa to evaluate potential health effects from exposure to benzene from an above ground tank located near a residential area. The above ground tank is managed by Equistar Chemicals, LP (Equistar) and is use to store pyrolysis gasoline prior to off-loading onto barges. The IDPH in cooperation with the Agency for Toxic Substances and Disease Registry (ATSDR) prepared this health consultation to review the air quality monitoring provided by Equistar and provide an evaluation of the health effects from exposure to benzene at the levels detected in ambient air near the tank. The information in this health consultation was current at the time of writing. Data that emerges later could alter this document’s conclusions and recommendations.

Sidebranching induced by external noise in solutal dendritic growth

We have studied sidebranching induced by fluctuations in dendritic growth. The amplitude of sidebranching induced by internal (equilibrium) concentration fluctuations in the case of solidification with solutal diffusion is computed. This amplitude turns out to be significantly smaller than values reported in previous experiments. The effects of other possible sources of fluctuations (of an external origin) are examined by introducing nonconserved noise in a phase-field model. This reproduces the characteristics of sidebranching found in experiments. Results also show that sidebranching induced by external noise is qualitatively similar to that of internal noise, and it is only distinguished by its amplitude.

Exposure to bioaerosols in poultry houses at different stages of fattening: use of real-time PCR for airborne bacterial quantification

Previous studies have demonstrated that poultry-house workers are exposed to very high levels of organic dust and consequently have an increased prevalence of adverse respiratory symptoms. However, the influence of the age of broilers, on bioaerosol concentrations has not been investigated. To evaluate the evolution of bioaerosol concentration during the fattening period, bioaerosol parameters (inhalable dust, endotoxin and bacteria) were measured in 12 poultry confinement buildings in Switzerland, at 3 different stages of the birds' growth; Samples of air taken from within the breathing zones of individual poultry-house employees as they caught the chickens ready to be transported for slaughter, were also analysed. Quantitative PCR (Q-PCR) was used to assess the quantity of total airborne bacteria and total airborne Staphylococcus species. Bioaerosol levels increased significantly during the fattening period of the chickens. During the task of catching mature birds, the mean inhalable dust concentration for a worker was 31 ± 4.7 mg/m3, and endotoxin concentration was 11'080 ± 3436 UE/m3 air, more than ten-fold higher than the Swiss occupational recommended value (1000 UE/m3). The mean exposure level of bird catchers to total bacteria and Staphylococcus species measured by Q-PCR is also very high, respectively reaching values of 72 (± 11) x107 cells/m3 air and 70 (± 16) x106/m3 air. It was concluded that in the absence of wearing protective breathing apparatus, chicken catchers in Switzerland risk exposure beyond recommended limits for all measured bioaerosol parameters. Moreover, the use of Q-PCR to estimate total and specific numbers of airborne bacteria is a promising tool for evaluating any modifications intended to improve the safety of current working practices.

Asymmetric stochastic switching driven by intrinsic molecular noise

Low-copy-number molecules are involved in many functions in cells. The intrinsic fluctuations of these numbers can enable stochastic switching between multiple steady states, inducing phenotypic variability. Herein we present a theoretical and computational study based on Master Equations and Fokker-Planck and Langevin descriptions of stochastic switching for a genetic circuit of autoactivation. We show that in this circuit the intrinsic fluctuations arising from low-copy numbers, which are inherently state-dependent, drive asymmetric switching. These theoretical results are consistent with experimental data that have been reported for the bistable system of the gallactose signaling network in yeast. Our study unravels that intrinsic fluctuations, while not required to describe bistability, are fundamental to understand stochastic switching and the dynamical relative stability of multiple states.