L-citrulline Prevents Alveolar and Vascular Derangement in a Rat Model of Moderate Hyperoxia-induced Lung Injury

Background

Moderate normobaric hyperoxia causes alveolar and vascular lung derangement in the newborn rat. Endogenous nitric oxide (NO), which promotes lung growth, is produced from the metabolism of l-arginine to l-citrulline in endothelial cells. We investigated whether administering l-citrulline by raising the serum levels of l-arginine and enhancing NO endogenous synthesis attenuates moderate hyperoxia-induced lung injury.

Methods

Newborn rats were exposed to FiO₂?=?0.6 or room air for 14?days to induce lung derangement and then were administered l-citrulline or a vehicle (sham). Lung histopathology was studied with morphometric features. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for analysis. Lung vascular endothelial growth factor (VEGF), nitric oxide synthase (eNOS), and matrix metalloproteinase 2 (MMP2) gene and protein expressions were assessed.

Results

Serum l-arginine rose in the L-citr?+?hyperoxia group (p?=?0.05), as well as the Von Willebrand factor stained vessels count (p?=?0.0008). Lung VEGF immune staining, localized on endothelial cells, was weaker in the sections under hyperoxia than the l-citr?+?hyperoxia and room air groups. This pattern was comparable with the VEGF gene and protein expression profiles. Mean alveolar size increased in the untreated hyperoxia and sham-treated groups compared with the groups reared in room air or treated with l-citrulline under exposure to hyperoxia (p?=?0.0001). Lung VEGF and eNOS increased in the l-citrulline-treated rats, though this treatment did not change MMP2 gene expression but regulated the MMP2 active protein, which rose in BALF (p?=?0.003).

Conclusions

We conclude that administering l-citrulline proved effective in improving alveolar and vascular growth in a model of oxygen-induced pulmonary damage, suggesting better lung growth and matrix regulation than in untreated groups.     

The psychological impact of cryptic chromosomal abnormalities diagnosis announcement

This qualitative study aims to describe the psychological impact of the diagnosis announcement of pathogenic Copy Number Variations (pCNVs). We performed semi-structured interviews of 60 parents of 41 affected children and 5 geneticists who announced the diagnoses. The diagnosis of the best characterized microdeletion syndromes, often defined by patronymic names (e.g. Williams syndrome), is generally made on a clinical basis by geneticists and confirmed by fluorescence in situ hybridization analysis. Chromosomal microarray, on the contrary, can allow the disclosure of rare pCNVs named after cytogenetic formulas, with poorly known clinical consequences: this makes doctors feel less confident with these diagnosis announcements. The disclosure of pCNVs named after cytogenetic formulas does not facilitate the parental mental representation of the disease, leading some parents to call into question the genotype-phenotype correlation or the very notion of a diagnosis. The announcement of inherited pCNVs can increase the feeling of parental guilt; the disclosure of de novo pCNVs can induce a feeling of “breakage” in the mental representation of the parent-child vertical transmission. In conclusion, our study shows that the disclosure of pCNVs has a significant psychological impact: a multidisciplinary approach to the diagnosis announcement, including a psychological support, should be systematically warranted.     

Étude comparative de dix sujets SDF fréquentant un centre d’hébergement d’urgence et de dix sujets SDF vivant uniquement dans la rue : acceptation et refus de l’hébergement d’urgence

Objectives

The last decades have seen an increasing number of homeless people (SDF) in Western societies. Public authorities have developed a solid assist device to treat this “homeless problem” by creating emergency shelter. Generally, this type of accommodation does not set any condition of admission and answers an immediate need of safekeeping of the person. Yet many homeless people refuse emergency shelter, even in winter. They prefer to sleep outside in extreme conditions. The purpose of this article is to help understanding the refusal and the acceptance of emergency accommodation for the homeless population.

Patients/materials and methods

In this study, a group of ten homeless subjects using emergency shelter (CHU) is compared to a group of ten homeless subjects who are refusing the emergency shelter and living only on the streets. To each subject, a semi-structured interview, an evaluation of the HAD scale (Zigmond AS and Snaith RP, 1983) and one of the self-esteem scale are conducted (Rosenberg, 1969). The analysis of data, collected during research interviews, will be completed with the statistical analysis of the results of the scale's test. Thereby we will highlight the similarities and the differences explaining the denial or the approval of emergency shelter.

Results

The common point between these two groups of subjects is the following: each of them has a traumatic or painful past. These subjects experienced many failures, dropouts, deficiencies which have seriously disrupted and affected them. The accumulation of chronic and traumatic life events made that the most recent event is identified by these subjects as the cause of their homeless situation. Survive from day to day involves a constant acting out in the street space, reflecting an impossible psychic crystallization or development. These two groups of subjects differ mainly in their ways of understanding their homeless situation. Thus, the acceptance/refusal of emergency shelter refers to an acceptance/refusal of the homeless identity, a fitting/misfitting to the homeless conditions, an acceptance/refusal of assistance, and acceptance/rejection of the collective space. In quantitative terms, there is a link between anxiety/depression and the denial of emergency shelter. Subjects refusing emergency shelter have a depression level significantly higher (10.3 against 7.1) and anxiety level significantly lower (11 against 14.1) than subjects users of emergency shelter.

Conclusions

This study allows us to consider the denial of accommodation of the homeless as a will not to passively suffer from their situation of social exclusion. Those homeless subjects voluntarily maintain a difficult lifestyle causing a greater psychological suffering than the ones using emergency shelter, and this not to settle in their situation. At the opposite, regular users find in emergency shelter a social frame and some new benchmarks. This leads to a relief and to a lower mental suffering that promote an over-adaptation of their living conditions.     

Impact of self-esteem on the relationship between orthodontic treatment need and oral health-related quality of life in 11- to 16-year-old children

The interest in the psychological aspects of orthodontic treatment increases, but a drawback of many studies is that the psychological characteristics of the children themselves are often ignored. One of these psychological attributes is self-esteem (SE), which is a relatively stable personal resource that might moderate the effects of conditions or events. The aim of this study was to investigate whether there is a relationship between orthodontic treatment need and oral health-related quality of life (OHRQoL) and whether this relationship is influenced by SE. This cross-sectional study comprised 223 children (113 boys and 110 girls) between 11 and 16 years of age (mean age 13.2 years), seeking orthodontic treatment. The OHRQoL was scored by the use of the Child Perception Questionnaire (CPQ(11-14)). The Dutch adaptation of the Harter's Self-Perception Profile was used to assess SE, and the Index of Orthodontic Treatment Need defined the need for treatment. Spearman correlations, Mann-Whitney U-tests, and regression models were used to analyze the data. There was a significant relationship between orthodontic treatment need and OHRQoL, and between SE and OHRQoL. No evidence was found that SE moderates the relationship between OHRQoL and treatment need.     

Use of short-acting beta2-agonists during pregnancy and the risk of pregnancy-induced hypertension

BACKGROUND: The effect of inhaled short-acting beta(2)-agonists (SABAs) on pregnancy outcome, especially hypertensive complications, is not well documented. After the finding of a possible protective association of inhaled SABAs with pregnancy-induced hypertension (PIH) in a previous study, we decided to further investigate their effect on this condition. OBJECTIVE: We sought to determine the effect of inhaled SABA use during pregnancy on the risk of PIH (gestational hypertension, preeclampsia, or eclampsia) in asthmatic women. METHODS: Three of Quebec's administrative databases were linked to constitute a cohort of asthmatic women who had at least 1 delivery between 1990 and 2000. A nested case-control study was performed using up to 10 control subjects matched to each case patient for the year of conception and gestational age. Statistical analyses considered 22 confounders. RESULTS: The cohort was composed of 3505 asthmatic women who had a total of 4593 pregnancies. Three hundred two patients with PIH and 3013 control subjects were identified. Compared with nonuse, inhaled SABA use during pregnancy was significantly associated with a reduced risk of PIH (adjusted rate ratios: >0-3 doses/week, 0.62 (95% CI, 0.44-0.87); > 3-10 doses/week, 0.51 (95% CI, 0.34-0.79); and >10 doses/week, 0.48 (95% CI, 0.30-0.75)). CONCLUSIONS: To our knowledge, this is the first study reporting that inhaled SABA use during pregnancy is associated with a reduced risk of PIH. Potential explanations include pharmacologic and physiological effects or residual confounding. CLINICAL IMPLICATIONS: These results increase the evidence about the safety of inhaled SABAs in this population, although they should not undervalue the importance of maintaining good control of asthma symptoms.     

CTX-M beta-lactamase-producing Escherichia coli in French hospitals: prevalence, molecular epidemiology, and risk factors

In 2004, 65 CTX-M-producing Escherichia coli isolates were collected from infected patients in four French hospitals. The blaCTX-M-15 genes were predominant. Pulsed-field gel electrophoresis highlighted a clonal propagation of CTX-M-15-producing strains belonging to phylogenetic group B2, notably in the community. The main risk factors for acquiring these isolates were urinary tract infections or the presence of a urinary catheter in diabetic or renal failure patients.     

Surgical management of lumbar spinal stenosis in patients over 80: is there an increased risk?

Neurosurgical Review - Management of lumbar spinal stenosis (LSS) represents the first cause of spinal surgery for the elderly and will increase with the aging population. Although the surgery...     

Covariate effects and population pharmacokinetics of lamivudine in HIV-infected children

Aim

Lamivudine is used as first line therapy in HIV-infected children. Yet, like many other paediatric drugs, its dose rationale has been based on limited clinical data, without thorough understanding of the effects of growth on drug disposition. Here we use lamivudine to show how a comprehensive population pharmacokinetic model can account for the influence of demographic covariates on exposure (i.e. AUC and C_max).

Methods

Data from three paediatric trials were used to describe the pharmacokinetics across the overall population. Modelling was based on a non-linear mixed effects approach. A stepwise procedure was used for covariate model building.

Results

A one compartment model with first order elimination best described the pharmacokinetics of lamivudine in children. The effect of weight on clearance (CL) and volume of distribution (V) was characterized by an exponential function, with exponents of 0.705 and 0.635, respectively. For a child with median body weight (17.6 kg), CL and V were 16.5 (95% CI 15.2, 17.7) l h⁻¹ and 46.0 (95% CI 42.4, 49.5) l, respectively. There were no differences between formulations (tablet and solution). The predicted AUC(0,12 h) after twice daily doses of 4 mg kg⁻¹ ranged from 4.44 mg l⁻¹ h for children <14 kg to 7.25 mg l⁻¹ h for children >30 kg.

Conclusions

The use of meta-analysis is critical to identify the correct covariate-parameter relationships, which must be assessed before a model is applied for predictive purposes (e.g. defining dosing recommendations for children). In contrast to prior modelling efforts, we show that the covariate distribution in the target population must be considered.