Exogenous artificial surfactants and their use in France]

The composition of endogenous surfactant and different types of exogenous surfactant available have been reviewed. The current European multicentre prospective trials with exogenous artificial surfactant in which France is involved have been described.     

Clinical impact of vancomycin heteroresistance in staphylococcal strains involved in neonatal sepsis: Discussion of a case report

Heteroresistance to vancomycin (HRV) represents a decreased susceptibility to vancomycin and is frequently observed in multidrug-resistant coagulase-negative staphylococci. The clinical significance of such heteroresistance is controversial, but several failures of vancomycin therapy have been related to HRV, especially in the neonatal population. Here we report the case of a preterm neonate, born at 26 weeks of gestation, who developed sepsis due to a multidrug-resistant HRV Staphylococcus capitis isolate. Bacteremia persisted despite adequate vancomycin serum concentration and catheter removal. The patient finally recovered after replacing vancomycin by linezolid. Through this case report, we would like to alert clinicians of the potential clinical impact of HRV and to discuss the lack of therapeutic alternatives in neonates.     

Human defensin alpha-1 causes Trypanosoma cruzi membrane pore formation and induces DNA fragmentation, which leads to trypanosome destruction

Human defensins play a fundamental role in the initiation of innate immune responses to some microbial pathogens. Here we show that human defensin alpha-1 displays a trypanocidal role against Trypanosoma cruzi, the causative agent of Chagas' disease. The toxicity of human defensin alpha-1 against T. cruzi is mediated by membrane pore formation and the induction of nuclear and mitochondrial DNA fragmentation, leading to trypanosome destruction. Exposure of trypomastigote and amastigote forms of T. cruzi to defensin alpha-1 significantly reduced parasite viability in a peptide concentration-dependent and saturable manner. The toxicity of defensin alpha-1 against T. cruzi is blocked by anti-defensin alpha-1 immunoglobulin G. Electron microscopic analysis of trypomastigotes exposed to defensin alpha-1 revealed pore formation in the cellular and flagellar membranes, membrane disorganization, and blebbing as well as cytoplasmic vacuolization. Furthermore, human defensin alpha-1 enters the trypanosome when membrane pores are present and is associated with later intracellular damage. Trypanosome membrane depolarization abolished the toxicity of defensin alpha-1 against the parasite. Preincubation of trypomastigotes with defensin alpha-1 followed by exposure to human epithelial cells significantly reduced T. cruzi infection in these cells. Thus, human defensin alpha-1 is an innate immune molecule that causes severe toxicity to T. cruzi and plays an important role in reducing cellular infection. This is the first report showing that human defensin alpha-1 causes membrane pore formation in a human parasite, leading to trypanosome destruction.     

Differential T-cell responses of semi-immune and susceptible malaria subjects to in silico predicted and synthetic peptides of Plasmodium falciparum

Malaria remains a public health hazard in tropical countries as a consequence of the rise and spread of drug and insecticide resistances; hence the need for a vaccine with widespread application. Protective immunity to malaria is known to be mediated by both antibody and cellular immune responses, though characterization of the latter has been less extensive. The aim of the present investigation was to identify novel T-cell epitopes that may contribute to naturally acquired immune responses against malaria. Using the Microsoft software, Epitome™ T-cell peptide epitopes on 19 Plasmodium falciparum proteins in the Plasmodium Database (www.plasmodb.org.PlasmoDB 9.0) were predicted in-silico. The peptides were synthesized and used to stimulate peripheral blood mononuclear cells (PBMCs) in 14 semi-immune and 21 malaria susceptible subjects for interferon-gamma (IFN-γ) production ex-vivo. The level of IFN-γ production, a marker of T-cell responses, was measured by ELISPOT assay in semi-immune subjects (SIS) and frequently sick subjects (FSS) from an endemic zone with perennial malaria transmission. Of the 19 proteins studied, 17 yielded 27 pools (189 peptides), which were reactive with the subjects’ PBMCs when tested for IFN-γ production, taking a stimulation index (SI) of ≥2 as a cutoff point for a positive response. There were 10 reactive peptide pools (constituting eight protein loci) with an SI of 10 or greater. Of the 19 proteins studied, two were known vaccine candidates (MSP-8 and SSP2/TRAP), which reacted both with SIS and FSS. Similarly the hypothetical proteins (PFF1030w, PFE0795c, PFD0880w, PFC0065c and PF10_0052) also reacted strongly with both SIS and FSS making them attractive for further characterization as mediators of protective immunity and/or pathogenesis.     

Iron supplementation in preterm infants treated with erythropoietin]

Anemia in premature infants can be prevented by prophylactic treatment with recombinant human erythroprotein (r-huEPO). r-HuEPO as been used for a long time in patients with end-stage renal failure. The main factor which can limit r-HuEPO efficiency is limited iron bioavailability. Adapted iron supplementation is needed when preterm infants receive r-HuEPO in order to avoid the depletion of iron stores. Oral iron supplementation is simple but indigestibility is frequent. Furthermore, the intestinal absorption and utilization of oral iron is limited. Parenteral iron supplementation is possible in infants who are very pre-term as they are parenterally fed during the first weeks of life. There are various preparations of intravenous iron with different physicochemical properties. Toxicity and side-effects of parenteral iron preparations depend on these properties. Two parenteral iron preparations are available in France: iron-saccharate (Venofer) and iron-dextrin (Maltofer). Iron delivery and possible side-effects of these preparations are different and need to be considered before use in preterm infants.     

Value of plasma fibronectin in pediatric intensive care

This work was undertaken to demonstrate the pathophysiologic and prognostic value of plasma fibronectin measurement in critically ill children. Fibronectin was measured by laser-nephelometry in 25 children (group 1) whose ages ranged from 1 month to 12 years (mean: 13.8 months). All presented with severe infections. The control group consisted of 16 children with various benign disorders, whose ages ranged from 3 months to 13 years (mean: 3.6 years). Fibronectin plasma levels in group 1 (mean: 0.16 g/l +/- 0.08) and in the control group (mean: 0.28 +/- 0.10) were significantly different (alpha less than 0.001). The initial concentration and the kinetics of this protein during evolution seem to have a good diagnostic and prognostic value in severe infections in children.     

Perinatal care regionalization and acceptability by professionals in France

BACKGROUND: For twenty years, most of industrial countries developed recommendations on regionalization of perinatal care. Perinatal regionalization is particularly aimed at improving morbidity and mortality outcomes of low birth weight newborns by transferring pregnant women to the maternity units having a medical or neonatal environment suited to the risks incurred by mothers or babies. Perinatal regionalization cannot be effective without being well accepted by the majority of professionals. The objectives of this study were then to identify professionals'expectations and objections to perinatal regionalisation and to compare them from a professional group to another one. METHODS: Professionals of 3 French perinatal networks were under consideration: the Rh?ne, the Auvergne and the Gard-Lozère networks. The study included two stages: 1) a psychosociological qualitative study, based on professionals'interviews, aimed at identifying main concerns of professionals and developing a questionnaire; then 2) an epidemiological quantitative study, using this questionnaire within French networks. In the questionnaire, 8 dimensions explored the professionals'views: constraints related to regulation aspects and to the setting up of maternity units care levels, risk of loss of professionals' competence and prestige, consequences on medical practices, on inter-professional relationship, on work organization and financial aspects, and related to the new role of 'private practice'professionals, legal consequences. RESULTS: The response rate of the epidemiological study was 80%. The results permitted to construct 8 dimension scores describing the reasons of poor acceptability of regionalization. After taking into account the age, the sex, the network and the juridical status of the institution, the study revealed a significant poorer acceptability of regionalization by most of medical specialty groups (anesthetists, obstetricians, midwives and "private practice" professionals) compared with neonatologists, or by "private" professionals (professionals working in private clinics and "private practice" professionals) compared with professionals working in university or community hospitals. The study described also network setting up conditions related to its functioning. CONCLUSION: By identifying clearly professionals 'objections and expectations, this study should facilitate improvement in the organization of studied perinatal networks.