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Background: While cardiovascular risks associated with high level of ionizing radiation are well-established, long-term effects of low and medium levels of exposure, between 0 and 5 gray (Gy), on the cardiovascular system are debated., Methods: Available literature was reviewed considering various populations, such as survivors of atomic bombs, nuclear workers, Chernobyl liquidators, radiologists and radiological technologists and patients exposed for medical reasons., Results: A significant increased risk of cardiovascular diseases associated with low doses of ionizing radiation was observed in 13 studies among the 27 analyzed. The ischemic heart diseases risk was detailed in 16 studies and seven of them showed a significant increase. The cerebrovascular risk was significantly increased in five studies among the 12 considered., Conclusion: Some epidemiological and experimental data are clearly in favour of an increased cardiovascular risk associated with exposure to low doses. However, given the multifactorial origin of cardiovascular diseases and the lack of a clear pathophysiologic mechanism, epidemiological results have to be carefully interpreted. Further research should be conducted in this area.

Objective: The goal was to analyze the relationship between changes in serum sodium levels during the first month of life and impaired functional outcomes at 2 years of age for very preterm infants., Methods: All very preterm infants who were born at <33 weeks of gestation between January 1, 2003, and July 31, 2004, were hospitalized in the NICU, and survived to discharge were included in this study. Changes in serum sodium levels were measured, and infants were evaluated at corrected age of 2 years., Results: The analysis involved 237 patients, for whom 3927 serum sodium determinations were performed during the first month of life. We defined 3 tertiles of changes in serum sodium levels. A total of 84 infants demonstrated small changes in serum sodium levels (<8 mEq/ L), 86 demonstrated large changes (8 -13 mEq/L), and 67 demonstrated very large changes (13 mEq/L). The reference group was represented by the first tertile. At 2 years of age, large and very large changes in serum sodium levels were significantly associated with risk of impaired functional outcomes, after adjustment for gestational age and perinatal and neonatal hospitalization characteristics (large changes: odds ratio: 3.5 [95% confidence interval: 1.1-11.8]; P = .04; very large changes: odds ratio: 5.1 [95% confidence interval: 1.3-13.6]; P = .02)., Conclusions: Although large and very large changes in serum sodium levels may simply reflect the severity of illness and/or the quality of care, a causal relationship with outcomes cannot be excluded. Cautious fluid and electrolyte management is recommended for very premature infants.

The clinical course of cystic fibrosis (CF) varies considerably among patients carrying the same CF-causing gene mutation. Additional genetic modifiers may contribute to this variability. As airway inflammation is a key component of CF pathophysiology, we investigated whether major cytokine variants represent such modifiers in young CF patients. We tested 13 polymorphisms in 8 genes that play a key role in the inflammatory response: tumor necrosis factor, lymphotoxin alpha, interleukin (IL) 1B, IL1 receptor antagonist, IL6, IL8, IL10 and transforming growth factor beta 1 (TGFB1), for an association with lung disease progression and nutritional status in 329 CF patients. Variants in the TGFB1 gene at position +869T/C demonstrated a significant association with lung function decline. A less pronounced rate of decline in forced expiratory volume in 1 sec (FEV(1)) and forced vital capacity (FVC) were observed in patients heterozygous for TGFB1 +869 (+869CT), when compared to patients carrying either TGFB1 +869TT or +869CC genotypes. These findings support the concept that TGFB1 gene variants appear to be important genetic modifiers of lung disease progression in CF., ((c) 2008 Wiley-Liss, Inc.)

We present a so-called lidar and almucantar (LidAlm) algorithm that combines information provided by standard elastic backscatter lidar (i.e., calibrated attenuated backscatter coefficient profile at one or two wavelengths) and sunphotometer AERONET inversion of almucantar like measurements (i.e., column-integrated aerosol size distribution and refractive index). The purpose of the LidAlm technique is to characterize the atmospheric column by its different aerosol layers. These layers may be distinct or partially mixed, and they may contain different aerosol species (e.g., urban, desert, or biomass burning aerosols). The LidAlm synergetic technique provides the extinction and backscatter coefficient profiles, particle size distributions, and backscatter-to-extinction ratios for each aerosol layer. We present the LidAlm procedure and sensitivity studies. The applications are illustrated with examples of actual atmospheric conditions encountered in the Paris area.

We describe a case of a young child who lived in Hong Kong who presented with a severe epilepticus status after a return flight to Paris. Routine laboratory tests failed to establish a cause. Upon further questioning, the parents reported that the nanny had given an abdominal massage to the child with an unlabelled solution reported to have anti-flatulence effects. Toxicological analysis of this solution revealed the presence of camphor. Although the highly toxic effects of camphor have long been established, the present case illustrates that camphor continues to be a source of paediatric exposure. This case highlights the importance of systematic questioning and recalls the extreme danger associated with camphor even when administered transcutaneously.

Objective: To analyse the effect of external radiation exposure on the mortality of French nuclear workers., Methods: A cohort of 29 204 workers employed between 1950 and 1994 at the French Atomic Energy Commission (Commissariat à l'Energie Atomique (CEA)) or at the General Company of Nuclear Fuel (COmpagnie GEnérale des MAtières nucléaires (Cogema, now Areva NC)) was followed up for an average of 17.8 years. Standardised mortality ratios (SMRs) were computed with reference to French mortality rates. Dose-effect relationship were analysed through trend tests and Poisson regression, with linear and log-linear models., Results: The mean exposure to X and gamma radiation was 8.3 mSv (16.9 mSv for exposed worker population). A total of 1842 deaths occurred between 1968 and 1994. A healthy worker effect was observed, the number of deaths in the cohort being 59% of the number expected from national mortality statistics. Among the 21 main cancer sites studied, a statistically significant excess was observed only for skin melanoma, and an excess of borderline statistical significance was observed for multiple myeloma. A dose-effect relationship was observed for leukaemia after exclusion of chronic lymphoid leukaemia (CLL). The relative risk observed for non-CLL leukaemia, n = 20, was 4.1 per 100 mSv (90% CI 1.4 to 12.2), linear model and 2.2 per 100 mSv (90% CI 1.2 to 3.3), log-linear model. Significant dose-effect relationship were also observed for causes of deaths associated with alcohol consumption: mouth and pharynx cancer, cirrhosis and alcoholic psychosis and external causes of death., Conclusion: The risk of leukaemia increases with increasing exposure to external radiation; this is consistent with published results on other nuclear workers cohorts.

Objectives: To assess the prognosis of newborn infants with refractory hypoxemia who required extracorporeal membrane oxygenation (ECMO)., Methods: Eighty-nine newborn infants treated by ECMO during more than 24 hours over a 8-year period (1996-2003) were included in this observational cohort study with a 9-month and 24-month evaluation., Results: Respiratory failure mainly resulted from meconium aspiration syndrome (MAS, 43%), congenital diaphragmatic hernia (CDH, 15%) and sepsis (15%). Overall survival at hospital discharge was 67%. Infants with MAS had the best survival rate (82%) and those with CDH had the worst (46%). Of the remaining 60 survivors, 53% remained oxygen dependent at 28 days and 33% at 45 days. At the age of 2 years, only 1 infant remained oxygen dependent (but did not required oxygen at 3 years) and only 3 infants had significant neurodevelopmental problems. CDH group was associated with a prolonged duration in supplementary oxygen (P<0.001) and a prolonged duration for tube feeding (P=0.01) as compared with other diagnoses. Regarding neurologic outcome, CDH infants had the poorer neurological acquisition rate at 9 months but a very good evolution by the time of the 24-month evaluation., Conclusions: Morbidity in ECMO survivors is low considering the severity of illness in the newborn period, mainly related to pulmonary and feeding dysfunctions during the first months, in particular for the CDH group. Outcome at the age of 2 years of CDH infants is most often favourable regarding growth and neurodevelopmental evolution.

Unlabelled: Tracheal intubation is a painful procedure commonly used in the neonatal intensive care units and in the delivery rooms. It can be complicated by changes in vital signs., Objective: To ascertain the use of sedatives and/or analgesics before tracheal intubation in French neonatal intensive care units and delivery rooms., Methods: A survey by questionnaire sent to 58 neonatal intensive care units and 58 maternities., Results: We obtained 46 responses (79,3%) from the neonatal intensive care units and 38 (65,5%) from the delivery rooms. In neonatal intensive care units, 74% of the newborns received a sedative and/or an analgesic before being intubated, and 60% of the units had specific written guidelines. Opioïds and benzodiazepines were the main drugs used. In the delivery rooms, sedatives or analgesics were only used in 21% of the centres., Conclusion: The use of sedation-analgesia seems to improve in neonatology but is still insufficient in the delivery rooms. The development of specific guidelines and a best learning about the different drugs are necessary.

Purpose: To determine whether minimal residual disease (MRD) measured by Wilms' tumor gene 1 (WT1) expression is a prognostic marker in pediatric acute myeloid leukemia (AML), we quantified WT1 transcript by real-time quantitative-polymerase chain reaction in 92 AML at diagnosis and during follow-up., Patients and Methods: Patients (median age, 6 years; cytogenetics, favorable 27%, intermediate 59%, poor 13%) were treated between 1995 and 2002 and enrolled in Leucémie aiguë Myéloblastique Enfant (LAME) 89/91, LAME 99 pilot study and Acute Promyelocytic Leukemia French collaborative protocols. With a median follow-up of 26 months, event-free survival was 56% with a standard deviation (SD) of 5% and overall survival of 62.5% with an SD of 6%. WT1 copy number was normalized by TATA box binding protein gene transcripts and expressed as WT1/TBP x 1,000 ratio. Median WT1 ratio in normal patient controls was 12 (range, 0 to 57). A level over two SD than normal bone marrow controls (ie, WT1 ratio > 50), was considered as significant overexpression., Results: At diagnosis, WT1 overexpression was detected in 78% of patients (72 of 92 patients; median copy ratio, 2231). The WT1 values were significantly higher (P = .01) in favorable cytogenetics and lower (P < .0001) in M5-FAB subtype, 11q23 rearrangements (P < .001), and infants (P = .003) and demonstrate a strong correlation with fusion transcript AML1-ETO, PML-RARalpha expression. After induction treatment, WT1 ratio was analyzed in 46 of 72 patients and found above 50 in nine of 36 patients and five of 25 patients at D35-50 and 3 to 5 months, respectively. WT1 ratio > 50 after induction is an independent prognostic risk factor of relapse (P = .002) and death (P = .02)., Conclusion: WT1 quantification is an informative molecular marker for MRD in pediatric AML and is now performed as prospective analysis in ELAM02 protocol.

Evidence of the benefits of screening for breast cancer using mammography after the age of 50 is considered sufficient. Information on the determinants of compliance to the recommendations on mammography is needed to identify women to which public health messages should be specifically addressed and also to interpret results from epidemiological data in which some breast cancer cases are detected through screening programmes and others are not. The general characteristics and dietary data of French women participating in the E3N cohort study were analysed. Odds ratios of the frequency of non-compliance to recommendations on breast cancer screening were computed in women over and under the age of 50. Non-compliant women over 50 (i.e. never attenders) had a poorer access to physicians and poorer health with regard to specific risk factors even after adjustment for age and educational level. Women who were used to referring to gynaecologists early in life were better attenders later on. Logically, women under 50 who were over-screened, as compared to public health recommendations, had the opposite characteristics. Public health recommendations should be designed specifically according to targeted subgroups of women. Determinants of attendance for screening should be kept in mind in the interpretation of epidemiological studies in which some cases may be over-screened and others not.

Cystic fibrosis is the most common lethal autosomal recessive disease among the Caucasian population. It is caused by defects in the CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator). Although over 1600 disease-causing mutations in the CFTR gene have been described, the highly variable disease phenotype in cystic fibrosis cannot be explained on the basis of this gene alone. Both the environment and other non-CFTR genes are likely to be important. The increased understanding of pathophysiological processes in the cystic fibrosis lung has led to several studies on genes in these pathways. One of the major aims of such studies is to produce targets for novel drug developments.

Recent evidence suggests that genetic polymorphisms that affect the production of interleukin (IL)-10 may play a role in the response to pathogens in cystic fibrosis (CF). The present study was designed to investigate a possible association between alleles carried at position -1082 in the promoter region of the IL-10 gene and clinical data on 378 patients with CF. After adjustment for potential confounding variables, a significant relationship was found between the -1082GG genotype and both colonization with Aspergillus fumigatus and allergic bronchopulmonary aspergillosis. In addition, higher serum levels of IL-10 were observed in patients colonized with A. fumigatus. These results suggest that polymorphisms in the promoter region of the IL-10 gene may influence the host response to A. fumigatus in the context of CF.

Unlabelled: The objective of this study was to describe the characteristics of children who required mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) support for respiratory syncytial virus (RSV) bronchiolitis, and to identify risk factors associated with disease severity assessed by duration of MV, mortality and need for ECMO. Ventilated children under 1 year of age admitted for bronchiolitis were retrospectively studied over the 8-year period 1996-2003. The study population included 151 children. Of these, 38.4% were born prematurely and 8.6% had bronchopulmonary dysplasia (BPD). The mean age at initiation of MV was 61 days (+/-63 days). Infants were ventilated for a mean of 7.8 days (+/-7.5 days). Multivariate analysis revealed that prolonged duration of MV (>6 days, median value) was significantly associated with low gestational age ( P =0.02 for the group <32 weeks), requirement of neonatal oxygen supplementation ( P =0.03), BPD ( P =0.02) and positive tracheal aspiration culture ( P =0.004), in particular for Haemophilus influenzae ( P =0.03). Fourteen infants required ECMO with a mean period of MV before ECMO of 3.9 days (+/-4.5 days). Amongst these infants, the frequency of BPD was significantly higher as compared with the others ( P =0.001). Four infants died (survival rate 71.4%). The mean duration of ECMO for survivors was 12.1 days (+/-3.3 days)., Conclusion: The data suggest that gestational age, requirement of neonatal oxygen supplementation, bronchopulmonary dysplasia and tracheal colonisation with Haemophilus influenzae are correlated with prolonged mechanical ventilation in children with bronchiolitis. Only bronchopulmonary dysplasia was associated with a need for extracorporeal membrane oxygenation that may provide lifesaving support in infants refractory to conventional management.

Objectives: Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF., Methods: Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a cohort of 146 children with CF by PCR-based methods. Pulmonary function, assessed by spirometric measures of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), was analysed in children at the age of 9., Results: No association between spirometric measurements, and GSTM1, GSTP1 or GSTT1 genotypes was found. As compared with patients homozygous for GSTM3*A allele, CF children carrying the GSTM3*B allele displayed a significant better lung function, assessed by both mean values of FEV1 and of FVC (respectively P = 0.01 and P = 0.002). These correlations remained significant after adjustment for potential confounding factors (respectively adjusted P = 0.008 and P = 0.002) and also in subgroups of CF patients who carry the deltaF508 CFTR mutation. Haplotype analysis of GSTM3 in combination with GSTM1 indicated that the positive impact of GSTM3*B allele on pulmonary performances was barely influenced by the GSTM1 genotypes of CF children., Conclusions: These data provide the first evidence suggesting that polymorphism of the GSTM3 gene contributes to clinical severity in CF, which may have prognostic significance and could prompt to start a more targeted therapy in young patients with CF., (Copyright 2004 Lippincott Williams & Wilkins)

Unlabelled: Over the last decade, several new therapies including exogenous surfactant therapy, inhaled nitric oxide and high-frequency ventilation have become available for the treatment of neonatal pulmonary failure. The aim of this retrospective study was to evaluate to what extent these modalities have impacted the use of neonatal extracorporeal membrane oxygenation at our institution and to discuss the role of ECMO in 2003 in the management of newborn infants with refractory hypoxemia., Population and Methods: Two hundred and twenty six newborn infants treated by ECMO before 15 days of life and during more than 24 h in our intensive care unit were retrospectively included from two time periods (group 1: 1988-1993 and group 2: 1996-2003)., Results: As compared with the first group, the number of newborns supported by ECMO in the second group has clearly diminished and their severity has increased. Overall survival rate was 80% in the first group and 69% in the second group. Meconium aspiration syndrome remains the major indication for ECMO (44%). Pulmonary sequelae, assessed by bronchopulmonary dysplasia rate (41%) are more frequent that neurologic sequelae (4.8%)., Conclusion: ECMO remains an useful technique in the management of newborn infants with refractory hypoxemia, with a consideration to institute ECMO early in order to increase survival rate.

Liver disease in patients with cystic fibrosis (CF) is inconstant and has not yet been clearly related to any specific risk factor. While the expression of cystic fibrosis transmembrane conductance regulator (CFTR) is restricted to the biliary epithelium in the liver, recent findings indicate that CFTR modulates reduced glutathione (GSH) transport and that CFTR dysfunction creates an imbalance in the antioxidant defense. Among liver detoxifying enzymes, the glutathione S-transferases (GSTs) play a key role in the protection against oxidative stress. Because oxidative injury contributes to the development of liver disease, we hypothesized that 2 members of the GST superfamily, GSTM1 and GSTP1, which are expressed in the biliary epithelium, could influence the hepatic status in patients with CF. The potential impact of GSTM1 and GSTP1 gene polymorphisms was assessed in 106 children with CF (mean age, 11.5 years). Based on polymerase chain reaction/restriction fragment length polymorphism analysis, we found that the frequency of GSTP1-Ile(105)/Ile(105) genotype was significantly higher in patients with CF with liver disease than in those without (P <.03). Among the youngest patients, aged 6 years, GSTP1-Ile(105)/Ile(105) genotype was associated with a 8-fold increase in the risk of liver disease compared with other GSTP1 genotypes (P =.002). No association between the GSTM1 genotype and liver status was documented. In conclusion, GSTP1-Ile(105)-encoding allele contributes to hepatic dysfunction in CF. Identification of this polymorphism may have prognostic value and prompt early treatment in patients with CF with an increased risk of liver disease.

The airborne differential absorption lidar LEANDRE II, developed for profiling tropospheric water-vapor mixing ratios, is described. The emitter is a flash-lamp-pumped alexandrite laser, which operates in a double-pulse, dual-wavelength mode in the 727-736 nm spectral domain. Two 50-mJ successive on-line and off-line pulses with an output linewidth of 2.4 x 10(-2) cm(-1) and a spectral purity larger than 99.99% are emitted at a 50-mus time interval. The spectral positioning is controlled in real time by a wavemeter with an absolute accuracy of 5 x 10(-3) cm(-1). The receiver is a 30-cm aperture telescope with a 3.5-mrad field of view and a 1-nm filter bandwidth. These instrument characteristics are defined for measuring the water-vapor mixing ratio with an accuracy better than 0.5 g kg(-1) in the first 5 km of the atmosphere with a range resolution of 300 m, integration on 100 shots, and an instrumental systematic error of less than 2%. The sensitivity study and first results are presented in part II [Appl. Opt. 40, 3462-3475 (2001)].

The airborne lidar LEANDRE II, described in part I [Appl. Opt. 40, 3450-3461 (2001)], has been flown on the French Atmospheric Research Aircraft to perform lower-troposphere (0-3.5-km) measurements of the water-vapor mixing ratio. We present and discuss the method used for retrieval of the water-vapor mixing ratio and analyze systematic and random measurement errors in relation to instrument design and performance. The results of a series of test flights are presented. With a 0.8-km horizontal resolution and a 300-m vertical resolution, the standard deviation of the measurement error ranges from approximately 0.05 g kg(-1) at 3.5 km to 0.3-0.4 g kg(-1) near the ground, in agreement with the predicted random error. Comparisons with dew-point hygrometer measurements show a vertically averaged difference of ?0.15 g kg(-1), approximately equal to the observed water-vapor variability.

The Paris area is strongly urbanized and is exposed to atmospheric pollution events. To understand the chemical and physical processes that are taking place in this area it is necessary to describe correctly the atmospheric boundary-layer (ABL) dynamics and the ABL height evolution. During the winter of 1994-1995, within the framework of the Etude de la Couche Limite Atmosphérique en Agglomération Parisienne (ECLAP) experiment, the vertical structure of the ABL over Paris and its immediate suburbs was extensively documented by means of lidar measurements. We present methods suited for precise determination of the ABL structure's temporal evolution in a dynamic environment as complex as the Paris area. The purpose is to identify a method that can be used on a large set of lidar data. We compare commonly used methods that permit ABL height retrievals from backscatter lidar signals under different meteorological conditions. Incorrect tracking of the ABL depth's diurnal cycle caused by limitations in the methods is analyzed. The study uses four days of the ECLAP experiment characterized by different meteorological and synoptic conditions.

The time course of the unfolding characteristics of the protein moiety and of the thermotropic behavior of the core-located apolar lipids of highly homogeneous low-density lipoprotein (LDL) subspecies (d 1.030-1.040 g/mL) have been evaluated during transition metal- and azo radical-induced oxidation using differential scanning calorimetry. Apolipoprotein B100 (apo-B100) structure was highly sensitive to oxidative modification; indeed, a significant loss of thermal stability was observed at initial stages irrespective of whether oxidation was mediated by site-specific binding of copper ions or by free radicals generated during decomposition of azo compounds. Subsequently, thermal protein integrity was destroyed, as a result of potentially irreversible protein unfolding, cross-linking reactions, and aggregation. Our results suggest that even minimal oxidative modification of apo-B100 has a major impact on the stability of this large monomeric protein. By contrast, the core lipids, which consist primarily of cholesteryl esters and triglycerides and play a determinant role in the thermal transition occurring near physiological temperature, preserved features of an ordered arrangement even during propagation of lipid peroxidation.