[HTLV and "donating" milk]. / HTLV-1 et don de lait maternel.

In France, the screening for human T-cell leukemia/ lymphoma virus type 1 and 2 (HTLV-1 and HTLV-2) during the donation of human milk has been carried out from 1992 with the application of the circular DGS 24 November 1992. The screening for antibodies against these viruses is regulated and done systematically during every donation of milk. Breast feeding being the main mode of transmission of the HTLV-1, the last ministerial decree of 25 August 2010 has made the screening test compulsory for the anonymous donation and for the personalized donation (of a mother for her own child) from all women including those affected by the infection. The milk delivered by milk banks is pasteurized (62.5 °C for 30 minutes) before freezing at -18 °C, which inactivates the pathogens. This double means of prevention of the transmission of the HTLV-1 paradoxically seems disproportionate in the absence of any precautionary measure in the case of direct breast-feeding and the use of mother's raw milk. Indeed, in most neonatal intensive care units in maternity hospitals, unpasteurized milk is administered to the neonates without any systematic preliminary testing of the serological HTLV-1 status of the mother. An increased sensitization of the community of the obstetricians, midwives and neonatologists by the Association of the Milk Banks of France (ADLF) and the Société de pathologie exotique could address the issue of screening for HTLV-1 in "donated" milk and breast-feeding.

[Toxoplasmosis in pregnancy: Practical Management]. / Toxoplasmose pendant la grossesse : proposition actuelle de prise en charge pratique.

The burden of congenital toxoplasmosis has become small in France today, in particular as a result of timely therapy for pregnant women, fetuses and newborns. Thus, the French screening and prevention program has been evaluated and recently confirmed despite a decline over time in the incidence of toxoplasmosis. Serological diagnosis of maternal seroconversion is usually simple but can be difficult when the first trimester test shows the presence of IgM, requiring referral to an expert laboratory. Woman with confirmed seroconversion should be referred quickly to an expert center, which will decide with her on treatment and antenatal diagnosis. Although the level of proof is moderate, there is a body of evidence in favor of active prophylactic prenatal treatment started as early as possible (ideally within 3 weeks of seroconversion) to reduce the risk of maternal-fetal transmission, as well as symptoms in children. The recommended therapies to prevent maternal-fetal transmission are: (1) spiramycin in case of maternal infection before 14 gestational weeks; (2) pyrimethamine and sulfadiazine (P-S) with folinic acid in case of maternal infection at 14 WG or more. Amniocentesis is recommended to guide prenatal and neonatal care. If fetal infection is diagnosed by PCR on amniotic fluid, therapy with P-S should be initiated as early as possible or continued in order reduce the risk of damage to the brain or eyes. Further research is required to validate new approaches to preventing congenital toxoplasmosis.

Human percutaneous absorption of a direct hair dye comparing in vitro and in vivo results: implications for safety assessment and animal testing.

Although in vitro skin absorption studies often detect small residues of applied test material in the epidermis/dermis, it is uncertain whether the residue is within the living skin. We studied the dermal absorption of a hair dye hydroxyanthraquinone-aminopropyl methyl morpholinium methosulphate (HAM) in human skin in vivo and in vitro. In vivo, skin (back and scalp) received 0.5% HAM in a commercial formulation at 20microg/cm2 After 0.5 or 48h, skin was tape stripped, followed by cyanoacrylate biopsies (CAB). Sebum from scalp sites was collected for 48h. In vitro, skin was treated with 20mg/cm2 dye for 0.5h, penetration determined after 24h. In vivo, at 0.5h, total recovery (back) was 0.67microg/cm2 (tape strips+CAB). Fluorescence microscopy showed HAM in the hair follicle openings (HFO). At 0.5h, scalp tape strips contained 1.80microg/cm2, HFO 0.82microg/cm2. At 48h, HFO contained 0.21microg/cm2, sebum 0.80microg/cm2. In vivo, skin residues were in the non-living skin and eliminated via desquamation and sebum secretion. In vitro, the SC contained 1.50microg/cm2, epidermis/dermis 0.86microg/cm2, receptor fluid<0.04microg/cm2, a total of 0.90microg/cm2 was considered to be bioavailable. In vitro epidermis/dermis residues were nearly identical to those located in non-living skin in vivo. In conclusion, in vitro percutaneous penetration studies may produce seemingly bioavailable material , which raises the need for a Threshold of Skin Absorption (TSA) addressing a negligible dermal absorption in order to avoid unnecessary in vivo toxicity studies on substances that produce no significant human systemic exposure.

Improvement of the experimental setup for skin absorption screening studies with reconstructed skin EPISKIN.

Percutaneous penetration studies are usually performed in human skin samples set up in a Franz cell device. The ability to perform these studies may depend on the availability of skin samples. Reconstructed skin models are an interesting alternative to overcome such limitations but are less easily mounted in diffusion cell devices. Previous data showed that EPISKIN was a highly performing model to carry out such studies. However, the setup in a PermeGear cell device is time consuming and therefore unsuitable for screening purposes. Another approach could be using EPISKIN in its cell culture insert. The aim of this study was to compare cutaneous penetration of chemicals applied to EPISKIN samples in a PermeGear cell versus in their own insert. Eight chemicals having widely different chemical structures and penetration potentials were studied. Six test chemicals showed a similar penetration level in both devices. Using the PermeGear cell device, the penetration level was overestimated for the other 2 tested chemicals. The results demonstrated that percutaneous studies with EPISKIN samples could be easily performed using the insert setup. The EPISKIN model has been greatly improved in the recent years and it is now possible to develop screening tests for the evaluation of skin penetration with a higher reliability.

[Congenital cytomegalovirus infection manifesting as neonatal respiratory distress in an HIV-exposed uninfected newborn]. / Pneumopathie congénitale à cytomégalovirus chez un nouveau-né à terme né de mère séropositive pour le VIH.

BACKGROUND: Cytomegalovirus (CMV) is one of the most common intrauterine infections, affecting approximately 1% of all live births. There are few reports on congenital CMV infections manifesting as isolated pneumonitis. CASE REPORT: We report a case of congenital CMV with neonatal respiratory distress affecting an HIV-exposed uninfected infant. This infant required noninvasive ventilation beginning within the first 15min of life. The initial chest X-ray showed diffuse bilateral ground-glass opacifications. Bacterial infection, meconium aspiration and hyaline membrane disease were excluded. Salivary quantitative CMV PCR was positive (2,342,261IU/mL) and serum viral load for CMV was low (476IU/mL). Bronchoalveolar lavage (BAL) performed on day 12 for quantitative CMV PCR was significantly positive (1,045,942IU/mL). Intravenous ganciclovir treatment was started on day 14 (7.5mg/kg/12h) for 2 weeks and oral valganciclovir (15mg/kg/12h) was given for 4 weeks afterwards. Ventilatory support was stopped on day 18. HIV serum viral load was negative on day 30. DISCUSSION: Congenital CMV infection can present as isolated pneumonitis with persistent neonatal respiratory symptoms, emphysematous lung disease, or persistent pulmonary hypertension. If this diagnosis is suspected, and even if CMV viremia remains low, BAL with quantitative CMV PCR must be performed to ascertain the diagnosis and indicate antiviral treatment. HIV-exposed uninfected infants have higher rates of congenital CMV infection when the mother's CD4 rate is<200/mm3. Most cases of CMV transmission in HIV-exposed uninfected infants have occurred by maternal endogenous reactivation or reinfection.

[Hyaline membrane disease in full-term neonates]. / Maladie des membranes hyalines chez le nouveau-né à terme.

OBJECTIVES: Evaluation of the consequences of preplanned delivery near term on the neonatal respiratory distress syndrome and its mechanism of occurrence. PATIENTS AND METHODS: During five years, full-term infants (> or =37 weeks gestational age) admitted in the Institut de Puericulture de Paris, with a well characterized hyaline membrane disease, were included in a retrospective study. RESULTS: During this period, 97 full-term neonates with respiratory distress syndrome were hospitalized in the neonatal intensive care unit. The diagnosis of hyaline membrane disease was made in view of clinical and radiological criteria. The study of mode of delivery has shown a high frequency of pre-planned delivery: 54% caesarean and 24% vaginal delivery. A high-risk of occurrence of hyaline membrane disease was identified around 37 weeks gestational age in the case of preplanned delivery. CONCLUSION: Preplanned delivery near 37 weeks gestational age may increase the risk of occurrence of hyaline membrane disease in full-term neonates.

Toxicity of extracellular proteins from Diplodia seriata and Neofusicoccum parvum involved in grapevine Botryosphaeria dieback.

Botryosphaeria dieback, esca and Eutypa dieback are three economic major grapevine trunk diseases that cause severe yield reduction in vineyards worldwide. The frequency of disease symptoms has increased considerably over the past decade, and no efficient treatment is currently available to control these diseases. The different fungi associated with grapevine trunk diseases mainly induce necrotic wood and characteristic foliar symptoms. In this context, fungi virulence factors and host invasion are not well understood. We hypothesise that extracellular proteins produced by Diplodia seriata and Neofusicoccum parvum, two causal agents associated with Botryosphaeria dieback, are virulence factors responsible for the pathogenicity. In our previous work, we demonstrated that the total extracellular compounds produced by N. parvum induced more necrosis on Chardonnay calli and triggered a different defence gene expression pattern than those produced by D. seriata. Furthermore, this aggressiveness was not clearly correlated with the production of mellein, a characteristic phytotoxin of Botryosphaeriaceae, in our in vitro calli model. To characterise other potential virulence factors and to understand the mechanisms of host invasion by the fungus, we evaluated the profile, quantity and the impact of extracellular proteins produced by these fungi on Vitis vinifera calli necrosis and defence gene expression. Our results reveal that, under the same conditions, N. parvum produces more extracellular proteins and in higher concentrations than D. seriata. With Vitis vinifera cv. Chardonnay cells, we showed that equivalent concentrations of proteins secreted by N. parvum were more aggressive than those of D. seriata in producing necrosis and that they clearly induced more grapevine defence genes.

The coordination of mental health services at the neighborhood level.

The neighborhood health center is becoming a major locus of mental health care delivery. Because of their strategic position at the neighborhood level, mental health care systems in the comprehensive health center locus have been able to develop linkages with both general health and community mental health systems to provide a broad continuum of coordinated health and mental health care. Four models identified in a survey of 19 neighborhood mental health programs are described. The authors suggest that persistent problems in coordination of care between neighborhood mental health and other caregiving systems would be considerably alleviated by a fiscal reimbursement scheme that rewarded integration rather than fragmentation of care.

Tobacco cells contain a protein, immunologically related to the neutrophil small G protein Rac2 and involved in elicitor-induced oxidative burst.

Suspension-cultured cells of Nicotiana tabacum generated active oxygen species (AOS) when they were treated with the proteinaceous elicitor, cryptogein. This response was blocked by diphenylene iodonium, an inhibitor of the neutrophil NADPH oxidase. When microsomal extracts of tobacco cells were probed with an antibody directed against the human small G protein Rac2, two immunoreactive proteins were detected at 18.5 and 20.5 kDa. The same experiment performed with cytosolic extracts of tobacco cells led to the observation of a strong immunoreactive protein at 21.5 kDa only in the cryptogein-treated cells. The appearance of this cytosolic protein was related to the production of AOS by the elicited cells. These results provide evidence for the possible involvement of small G proteins, homologous to the neutrophil Rac2 protein, in the regulation of the elicitor-induced oxidative burst in plant.

Cloning of Rac and Rho-GDI from tobacco using an heterologous two-hybrid screen.

To examine whether molecular similarities exist between the animal and plant Rho GTPase signaling pathways, we have developed a heterologous two-hybrid screening method. By this technique, we have cloned a cDNA encoding a tobacco Rac-like protein able to interact with a mammalian Rho-GDI. In a second screen this tobacco Rac was used as a bait and a tobacco homologue of Rho-GDI was identified. These results show that some components of the animal and plant Rac signaling pathways are similar enough to allow their interaction in an heterologous approach. Moreover these data suggest a similar regulation of Rho GTPases in animals and plants.

[Acute neonatal appendicitis in an inguinal hernia]. / Appendicite aiguë néonatale intra-herniaire.

UNLABELLED: Acute neonatal appendicitis is a rare surgical emergency. Prognosis depends on early diagnosis and management. CASE REPORT: A three and a half-month-old premature infant needed an urgent laparotomy because of an occlusive syndrome and sepsis with an inflammatory skin reaction. The per-operative diagnosis was suppurative acute appendicitis with local peritonitis, the appendix being strangulated into the inguinal hernia. DISCUSSION: Neonatal appendicitis represents 0.1% of all infantile appendicitis. Fifty percent of such cases occur in premature infants. Two clinical presentations exist, whose diagnosis is often made during surgery. The abdominal presentation (2/3 of the cases) can mimic necrotizing enterocolitis; the diagnosis is often late and evolution leads to diffuse peritonitis in the majority of the cases, while the mortality rate is higher than 50%. The intra-hernial presentation (1/3 of the cases), instead, is usually diagnosed and managed early due to the inguino-scrotal induration, while mortality rate is near zero. CONCLUSION: The high frequency of inguinal hernia in premature infants should not mask the risk for intra-hernial appendicitis. Inguino-scrotal inflammation should evoke the diagnosis. Prognosis depends on early and urgent surgical management.

[Cystic adenomatoid malformation of the lung revealed in a newborn infant by an image of a lung abscess]. / Malformation kystique adénomatoïde du poumon révélée chez un nouveau-né par une image d'abcès pulmonaire.

BACKGROUND: Cystic adenomatoid malformation, a rare pulmonary malformation, usually appears as a cystic mass, radiologically. It may be infected and confusion has also arisen in distinguishing it from pneumonia with pneumatoceles. CASE REPORTS: A full-term boy suffered from severe neonatal respiratory distress. Pregnancy had been uneventful despite the fact that his mother had insulin-dependent diabetes. Prenatal ultrasonographies did not reveal any abnormality. On day 2, X-rays showed a right pulmonary mass that appeared solid. The patient was treated for E Coli sepsis. Subsequently, the pulmonary mass became lacent, cystic, fluid-filled, resembling an abscess; the CT scan confirmed these features. As the lesion increased in volume, a limited resection was performed. Histologic examination showed adenomatoid proliferation of bronchiolar elements with formation of cysts and necrosis. CONCLUSION: Infection of cystic adenomatoid malformation may supervene the first days of life resulting in a lung abscess appearance.

[Erythropoietin administration to preterm infants: comparison between subcutaneous and intravenous route]. / Erytoropoïétine chez le nouveau-né: efficacité comparée des voies d'administration sous-cutanée et intraveineuse.

OBJECTIVE: Our aim was to compare the effectiveness of a one-month treatment with recombinant human erythropoietine (rHuEpo) according to the administration route. METHODS: Retrospective study based on the data collection from medical files of 64 preterm infant hospitalized in the "institut de puériculture et de périnatalogie" (Paris) between January 13th, 2002 and April 13th, 2002. The first group (N =33) was treated by subcutaneous rHuEpo 750 IU/kg per week, in three injections by week, for one month. The second group (N =15) was treated by continuous infusion of rHuEpo in total parenteral nutrition 1050 IU/kg per week (30% augmentation to compensate the amount absorbed by the filter). The third group (N =16) received 750 IU/kg per week of rHuEpo in three direct intravenous injections. The effectiveness of rHuEpo was evaluated by the absolute reticulocyte count, the level of hemoglobin and the incidence of blood transfusion (multiple logistic analysis of variant and regression). RESULTS: The absolute reticulocyte count and hemoglobin level were significantly reduced after one month of treatment by continuous infusion of rHuEpo in total parenteral nutrition and direct intravenous injections compared with a one-month treatment by subcutaneous rHuEpo. Hemoglobine level were at 8.8 and 9.6 g/dl vs 10.3 g/dl (P =0.02) and absolute reticulocyte count at 123,000/mm3 and 190,000/mm3 vs 216,000/mm3 (p =0.001). The number of transfused infants was significantly increased with utilization of continuous (40%) and direct intravenous (75%) compared with those treated by subcutaneous route (21.2%) while the ferritin level and phlebotomy losses were not significantly different in the three groups. The number of blood transfusion was significantly linked to phlebotomy losses and administration route of rHuEpo. CONCLUSION: Our study tends to demonstrate that rHuEpo administered subcutaneously reduces significantly the number of transfusion in contrary to intravenous routes. Waiting for pilot study and new molecules, we recommend subcutaneous administration of rHuEpo to preterm infants 250 IU/kg three times weekly in the treatment of anemia of prematurity.

[Neonatal enterovirus myocarditis]. / Myocardite néonatale à entérovirus.

UNLABELLED: Enterovirus infections in neonates are difficult to diagnose. Diphasic pattern and possibly fatal myocarditis must be anticipated. CASE REPORT: A 14-day-old girl had presented a heart failure after an initial episode of gastroenteritis and supraventricular tachycardia. Investigation demonstrated global myocardial dysfunction. Diagnosis of neonatal enterovirus myocarditis was made by polymerase chain reaction detection of viral genome. Heart failure was controlled with medical treatment. CONCLUSION: Enterovirus myocarditis is typically a biphasic illness. Rapid diagnosis of enteroviral infection in neonatal period may be made by polymerase chain reaction detection of viral genome. There is anecdoctal evidence that immunoglobulin infusions may improve outcome.

[Treatment of subclinical congenital toxoplasmosis by sulfadiazine and pyrimethamine continuously during 1 year: apropos of 46 cases]. / Traitement de la toxoplasmose congénitale non sévère par sulfadiazine et pyriméthamine en continu pendant un an: à propos de 46 cas.

UNLABELLED: In France, most of children suffering from congenital toxoplasmosis have an infraclinic or moderate type at birth. This study aimed at evaluating, on the mid term, tolerance and results of postnatal treatment previously given in severe toxoplasmosis. METHODS: A retrospective study considered 46 children with a mild or moderate congenital toxoplasmosis treated over 12 months with sulfadiazine-pyrimethamine and treatment was completed since three months. RESULTS: Five children suffered from a lesion of chorioretinitis during treatment and two after. After a mean follow-up of 27.1 months, ten children (21.7% 95%CI [12.1-35.9]) had at least one ocular injury. Specific IgG titers and immune load were diminished to become almost non-existent at the end of the year of treatment (respectively p < 10(-5) and p = 0.0005). No thrombocytopenia was observed. Twenty-three children (50%) had at least one episode of neutropenia < 1000/mm3, 14 had only one, nine presented two or more installment. None was followed by an infection. CONCLUSION: This therapeutic pathway is more demanding but shorter than those usually offered when associating pyrimethamine-sulfadiazine. Yet, it does give identical result on the mid term. Longer follow-up is needed to appreciate. Active molecule on cysts should be introduced.

[Evaluation of neonatal care discharge practices: three years experience]. / Evaluation des pratiques autour de la sortie de néonatalogie: 3 ans d'expérience.

OBJECTIVES: This study purpose was to identify the advantages and limitations of our practice in planning newborns' discharge from the neonatal unit. We searched for appropriate actions to promote good family conditions and environment for infants being discharged from the neonatal unit. MATERIALS AND METHODS: During a six-month period in 1999, we interviewed 110 families whose infants were discharged from our units. All interviews were conducted by the same person using a semi-directive protocol to collect the parents' perceptions of their child's hospitalisation and discharge and their recall of the first days at home. Data were collected after a sufficient period of adaptation at home. Analysis of the interviews showed that different difficulties could be prevented. Based on these findings, we instituted different pluridisciplinary discharge group to review practices in September 2000. In 2002, the same type of survey was conducted to evaluate improvement. RESULTS: Discharge from the neonatal unit was affected by the parents' perceptions of hospitalization, their ability to anticipate, before announcement of the "medical" discharge, home life with their child and to imagine their own professional and familial network. CONCLUSION: The parents' abilities to elaborate a discharge plan all along their child's hospitalisation helps improve the newborn's arrival in the family.

[Mid and long-term neurological prognosis of preterm infants less than 28 weeks gestational age]. / Le pronostic neurologique à moyen et long terme des prématurés d'âge gestationnel inférieur à 28 semaines d'aménorrhée.

The study of the long-term outcome of extremely premature babies is specially difficult because data in the literature is very heterogeneous. Recruitment (inborn, outborn), type of obstetrical management, and criteria and means used for interrupting curative treatment have varied greatly. We present the outcome of 204 infants born before 28 weeks of gestation between 1992 and 1997. The minimal follow up is 6 years. 82 infants (40.2%) died during the neonatal period. Significantly associated with neonatal death were absence of prenatal steroid course, male gender, elevated lactic acid at birth, and occurrence of pulmonary complications. When major neurological lesions (ventricular hemorrage stage III or IV and kryptic leucomalacia) developed, most infants died following a decision to stop active treatment. Out of the 114 survivors, 17 (14.9%) developed cerebral palsy (CP) or a low IQ. 31 (27.2%) had minor disorders, 66 (57.9%) were completely normal. The predictive factors of CP were major brain lesions, elevated lactic acid at the time of birth and multiple pregnancy. We also detail the minor neurological sequelae, cognitive behavioral, and psychological disorders observed in this population of extremely premature children and discuss the need for early and continuous care for these high risk babies.

[Enteral nutrition for the preterm infant: which maternal milk supplement?]. / Nutrition entérale du préterme: quelle(s) supplémentation(s) pour le lait de femme?

Different types of human milks are given to preterm newborns (mother and bank milk). Their effect on neonatal growth is recalled. The usefulness and justification of dietetic supplements as well as appropriate quantities and practical aspects are discussed.

[Perinatal corticosteroid therapy: modalities, efficacy, consequences]. / Corticothérapie périnatale: modalités, efficacité, conséquences.

During perinatal period, corticosteroid treatment has two major indications: first antenatally to improve fetal maturity and then to treat postnatal bronchopulmonary dysplasia. Antenatal corticosteroid treatment is widely proved to be efficient in reducing hyaline membrane disease and perinatal mortality incidence. Moreover, it has positive effects on intraventricular hemorrhage incidence, on hemodynamic failure, on persistent patent ductus arteriosus and on necrotizing enterocolitis. Side-effects are few and mild considering expected benefits and they usually occurs after multiple courses. Contra-indications are rare. Bronchopulmonary dysplasia comes with early, important and prolonged inflammatory processes. Corticotherapy allows decreasing significantly length of mechanical ventilation and oxygenotherapy among ventilated premature infants diagnosed with bronchopulmonary dysplasia. In the meantime, acute side-effects are frequent and benefits on mortality rate and long term outcome are not obvious. Main concern remains on possible long-term deleterious consequences on growth, lung and central nervous system development. In this field, clinical data are still insufficient as animal experimentation data promote caution and search for a minimal efficient therapeutic pathway.