Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates.

AIM: Less invasive surfactant administration (LISA) can avoid tracheal intubation for neonatal respiratory distress syndrome, but can be painful because it requires laryngoscopy. The aim of this study was to assess the efficacy and tolerance of intravenous atropine plus ketamine administration before LISA. METHODS: We conducted a prospective observational study of all premature infants hospitalised in our French neonatal intensive care unit treated with LISA between March 2015 and March 2016. Ketamine was titrated by 0.5 mg/kg increments. The technical conditions, pain scores, emergent intubations and vital signs were collected and analysed. RESULTS: Values are reported as medians (interquartile ranges). We included 29 patients with a gestational age of 29.6 (28.6-30.9) weeks and birth weight of 1290 (945-1600) grams. Technical conditions were satisfying for 24 infants (83%). The Faceless Acute Neonatal Pain Scale score was 2 (2-4); seven infants (24%) required tracheal intubation before LISA could be performed; 17 (59%) had a pulse oxymetry value under 80% that lasted more than 60 seconds. Heart rate and mean arterial blood pressure transiently increased. CONCLUSION: Atropine plus ketamine before LISA resulted in low pain scores and stable haemodynamic parameters, but prolonged desaturations or apnoea leading to tracheal intubation were frequently observed.

Automated early warning system for the surveillance of Salmonella isolated in the agro-food chain in France.

Non-typhic Salmonella is one of the major bacterial pathogens that cause foodborne infections as well as economic losses for the food production industry. There is therefore a need to improve early detection to prevent the emergence and spread of Salmonella within the agro-food chain. The passive laboratory-based surveillance system of the Salmonella network has been integrated into the French Food Safety Agency's working plan. The objective of this study was to evaluate the ability of this network to detect unusual Salmonella contamination as early as possible in the agro-food chain. Three statistical methods were used to detect unusual events from the time-series of counts. After an experimental period of more than 1 year, this approach detected several unusual events linked to contamination in the agro-food chain that were confirmed in a timely manner at national or regional levels. This evaluation also reinforced the position of the Salmonella network as an integral part of the national public health surveillance system.

OASIS: an assessment tool of epidemiological surveillance systems in animal health and food safety.

The purpose of this study was to develop a standardized tool for the assessment of surveillance systems on zoonoses and animal diseases. We reviewed three existing methods and combined them to develop a semi-quantitative assessment tool associating their strengths and providing a standardized way to display multilevel results. We developed a set of 78 assessment criteria divided into ten sections, representing the functional parts of a surveillance system. Each criterion was given a score according to the prescription of a scoring guide. Three graphical assessment outputs were generated using a specific combination of the scores. Output 1 is a general overview through a series of pie charts synthesizing the scores of each section. Output 2 is a histogram representing the quality of eight critical control points. Output 3 is a radar chart representing the level reached by ten system attributes. This tool was applied on five surveillance networks.

Nationwide outbreak of Salmonella enterica serotype 4,12:i:- infections in France, linked to dried pork sausage, March-May 2010.

In May 2010, a nationwide excess of infections with the specific monophasic variant Salmonella enterica serotype 4,12:i:- was investigated in France. Subtyping with multilocus variable number of tandem repeats analysis revealed a distinct epidemic strain within this excess. Epidemiological investigations identified a dried pork sausage sold by a particular chain of supermarkets as the likely vehicle of transmission. The suspected batches have been withdrawn and recalled.

Milk fermented with yogurt cultures and Lactobacillus casei compared with yogurt and gelled milk: influence on intestinal microflora in healthy infants.

Ingestion of fermented dairy products induces changes in the equilibrium and metabolism of the intestinal microflora and may thus exert a healthful influence on the host. We compared the effects of consumption of a traditional yogurt, a milk fermented with yogurt cultures and Lactobacillus casei (YC), and a nonfermented gelled milk on the fecal microflora of healthy infants. Thirty-nine infants aged 10-18 mo were randomly assigned to one of three groups in which they received 125 g/d of one of the three products for 1 mo. The following indexes were not modified during the supplementation period or for 1 wk after the end of supplementation: total number of anaerobes, bifidobacteria, bacteroides, and enterobacteria; pH; water content; concentrations of acetate, butyrate, propionate, and lactate; and bacterial enzyme activity of beta-galactosidase and alpha-glucosidase. In contrast, in the yogurt group the number of enterococci in fecal samples increased (P < 0.05), whereas the percentage of branched-chain and long-chain fatty acids, which are markers of proteolytic fermentation, decreased (P < 0.05). In the YC group, the percentage of children with > 6 log10 colony-forming units lactobacilli/g feces increased (P < 0.05), whereas the potentially harmful enzyme activity of beta-glucuronidase and beta-glucosidase decreased (P < 0.05). These decreases were particularly marked in those infants in the YC group in whom activity of the enzymes was initially unusually high.

Chronic progressive external ophthalmoplegia with ragged-red fibers: clinical, morphological and genetic investigations in 43 patients.

The evaluation of the severity of progressive external ophthalmoplegia (PEO) with ragged-red fibers in muscle, at the onset of the disease, when PEO is most often the only presenting symptom, is a difficult problem in neurological practice. In order to address that issue, we have performed a comparative analysis of the clinical, morphological and molecular characteristics of 43 patients affected with that form of ocular myopathy. Quantification of mitochondrial accumulation was performed with an image analysis application on muscle sections stained with succinate dehydrogenase histochemical reaction. The proportion of muscle fibres appearing as cytochrome c oxidase deficient was used as an index of the muscle-energy defect. Muscle mitochondrial DNA deletions were detected, localized and quantitated by Southern blot analysis. Point mutations were screened in five transfer RNA genes in the mtDNA (tRNA(Leucine (UUR)), tRNA(Lysine), tRNA(Glutamine), tRNA(Isoleucine) and tRNA(Formylmethionine)) by a denaturing gradient gel electrophoresis technique. This investigation confirmed the high frequency of mtDNA deletions or point mutations in PEO. At the onset of the disease, no clinical, morphological or molecular features could predict whether PEO would remain isolated or become part of a more severe multisystem disease. However, patients with mtDNA deletions were characterized by more severe ophthalmoplegia of earlier onset. Their muscle alterations were roughly parallel in severity to the proportion of deleted mtDNA molecules in muscle. Patients with a multitissular disease and mtDNA deletions were always sporadic cases and their clinical presentation was, most often, closely related to Kearns Sayre syndrome.

Phenotype-karyotype correlations in dup(18q): report of a case and review.

We report on a case of dup(18q) due to de novo translocation 46,XX,-21,t(18;21)(18qter----cen----21qter). The patient had many characteristic signs of full trisomy 18 except for internal organ malformations and early death. We review the phenotype-karyotype correlations between full trisomy 18 and dup(18q) and discuss the possibility of the existence of "critical zone(s)" at the proximal or/and distal region of 18q responsible for most signs of trisomy 18, such as congenital heart defect and early death.

Continuous tracheal gas insufflation enables a volume reduction strategy in hyaline membrane disease: technical aspects and clinical results.

OBJECTIVE: Instrumental dead space wash-out can be used to improve carbon dioxide clearance. The aim of this study was to define, using a bench test, an optimal protocol for long-term use, and to assess the efficacy of this technique in neonates. DESIGN: A bench test with an artificial lung model, and an observational prospective study. Dead space wash-out was performed by continuous tracheal gas insufflation (CTGI), via six capillaries molded in the wall of a specially designed endotracheal tube, in 30 preterm neonates with hyaline membrane disease. SETTING: Neonatal intensive care unit of a regional hospital. RESULTS: The bench test study showed that a CTGI flow of 0.5 l/ min had the optimal efficacy-to-side-effect ratio, resulting in a maximal or submaximal efficacy (93 to 100%) without a marked increase in tracheal and CTGI circuit pressures. In the 30 newborns, 15 min of CTGI induced a significant fall in arterial carbon dioxide tension (PaCO2), from 45 +/- 7 to 35 +/- 5 mmHg (p = 0.0001), and in 14 patients allowed a reduction in the gradient between Peack inspirating pressure and positive end-expiratory pressure from 20.8 +/- 4.6 to 14.4 +/- 3.7 cmH2O (p < 0.0001) while keeping the transcutaneous partial pressure of carbon dioxide constant. As predicted by the bench test, the decrease in PaCO2 induced by CTGI correlated well with PaCO2 values before CTGI (r = 0.58, p < 0.002) and with instrumental dead space-to-tidal volume ratio (r = 0.54, p < 0.005). CONCLUSION: CTGI may be a useful adjunct to conventional ventilation in preterm neonates with respiratory disease, enabling an increase in CO2 clearance or a reduction in ventilatory pressure.

Severe resistance to insulin and insulin-like growth factor-I in cells from a patient with leprechaunism as a result of two mutations in the tyrosine kinase domain of the insulin receptor.

We studied the biological properties of insulin receptors (IRs) and insulin-like growth factor-I (IGF-I) receptors in cultured fibroblasts from a patient with leprechaunism (leprechaun Par-1). Patient cells displayed normal insulin binding capacity and affinity. Basal in vivo autophosphorylation and in vitro exogenous kinase activity of patient IRs were elevated twofold to threefold compared with control receptors, and insulin had no further effect on these processes. Moreover, patient IRs were unable to promote the stimulation of metabolic and mitogenic pathways. IR substrate-1 (IRS-1) and mitogen-activated protein (MAP) kinase tyrosine phosphorylation and glycogen and DNA synthesis were not increased in the basal state in patient fibroblasts and were also insensitive to the stimulatory effect of insulin. As for IGF-I, although binding and receptor kinase activity were normal, the ability to stimulate glycogen and DNA synthesis was altered in patient cells. Two mutant alleles of the IR gene were detected by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. The maternal allele contained a point mutation in exon 18 encoding the tryptophan-for-arginine substitution at position 1092, and the paternal allele had a point mutation in exon 20 substituting lysine for glutamic acid at codon 1179. Thereby, leprechaun Par-1 was a compound heterozygote for two missense mutations located in the IR beta-subunit. The present investigation provides the first evidence that leprechaunism can be causally related to structural alterations in the tyrosine kinase domain of the IR. These alterations result in severe impairment of insulin and IGF-I action.

[Progressive external ophthalmoplegia of mitochondrial origin: contribution of morphological and molecular studies]. / Ophtalmoplégies externes progressives d'origine mitochondriale: apport des investigations morphologiques et moléculaires.

We performed a comparative analysis of the clinical, morphological and molecular characteristics of 62 patients affected with progressive external ophthalmoplegia with ragged-red fibres in muscle. Twenty-seven patients had only muscular disease, and 35 had a multisystemic disease with neurological, cardiac, sensory, or endocrine symptoms. Quantitation of mitochondrial accumulation and numbering of cytochrome c oxidase deficient muscle fibres were done in 43 patients. Muscle mitochondrial DNA deletions were detected, quantitated and localised by Southern Blot analysis. Point mutations were screened in five mitochondrial DNA transfer RNA genes by denaturing gradient gel electrophoresis technique. This study further emphasized the relationships between progressive external ophthalmoplegia and mitochondrial DNA mutations that were present in 46/62 patients (40 deletions, 4 h point mutations in the tRNA leucine gene and 2 further families with maternal inheritance but no mutation identified to-date). Family history was positive in 12 patients: 4 with a maternally inherited disease (2 of whom had an identified mitochondrial DNA mutation), and 4 with an autosomal dominant inherited disease, none of which was associated with multiple mitochondrial DNA deletions. Interestingly, 2 of our patients with an identified mitochondrial DNA mutation appeared as sporadic cases. No morphological or molecular parameters was correlated with the tissular extension of the disease. However, mitochondrial DNA deletions were significantly associated with ocular symptoms which had an earlier onset and were more severe. Clinical features of the patients with a multisystemic disease and a mitochondrial DNA deletion were essentially related to Kearns-Sayre syndrome. In particular, a cardiac conduction defect was present in 12 patients out of 18 with a multisystemic disease associated with a mitochondrial DNA deletion; it was never encountered in 17 patients with a multisystemic disease but no mitochondrial DNA deletion.

[Psychologic management of extreme prematurity]. / Prise en charge psychique de l'extrême prématurité.

The ongoing progress in neonatal intensive care is modifying the psychic context of prematurity for all the partners, infants as well as parents and physicians. Comfort and prognosis of preterm infants have much improved. Since newborns under 24 weeks of gestational age are now surviving, they spend approximately half the duration of pregnancy out of the maternal uterus. All the psychological issues of such an early separation have to be considered, including the developmental outcome of a sensorial environment which is quite different from the intra-uterine one. Research has been developing in this field. The cooperation between neonatalogists and psychologists has been profitable to parents. Problems linked to the separation, such as difficulty in representing the infant, are no more frequent owing to the attention paid to the mother-child bond and subsequent early contacts. What is forward now is the impact of an hyper technical world of intensive care on the parents, and of the strange aspect of the tiny baby surrounded by engines and tubes. Such an overpresence of reality often results in a reaction of traumatic daziness among parents. The cooperation of the whole staff is necessary for the resumption of an imaginary process of psychic functioning. Finally, the survival of very-low-birth-weight infants confronts the neonatalogists with some delicate ethical questions. Psychiatrists and psychologists might have an important part to play in aiding the profession in its sorting out of these ethical issues.

[Physiopathological approach and antenatal diagnosis of diabetes mellitus insulin resistant: apropos of a case with leprechaunism]. / Approche physiopathologique et diagnostic anténatal du diabète insulinorésistant: à propos d'un cas de lepréchaunisme.

BACKGROUND: Leprechaunism is characterized by severe intrauterine growth retardation, elfin-like face, relatively large hands, feet and genitalia and abnormal skin with hypertrichosis, acanthosis nigricans and low subcutaneous fat. The insulin receptors have multiple defects. CASE REPORT: A boy was born after cesarean section at the 35th week of gestation because of intrauterine growth retardation: weight: 930 g; height: 36 cm; head circumference: 27 cm. He had trigonocephaly, coarse features and hyperkeratosis. Ultrasonography confirmed the presence of a ventricular septal defect detected during pregnancy. Hyperglucosemia (3 g/l) was associated with insulinemia above 350 mU/l; his C-peptide concentration was above 20 ng/ml. The patient was given intravenous insulin, up to 2,500 U/kg/d. He died at the age of 95 days, weighing 1500 g, with persistent hyperglucosemia and cholestasis. Postmortem examination showed adrenal and thymus hypoplasia and hyperplasia of pancreatic islet cells. Molecular biology studies showed that this patient was heterozygotic for two mutations, one in exon 20 inherited from his father, the other in exon 18 inherited from his mother; both mutations are associated with tyrosine-kinase activity of the insulin receptor. These results will be used for antenatal diagnosis in any future pregnancy. CONCLUSION: Molecular biology can indicate specific defects in the insulin receptor. It may also allow antenatal diagnosis in some families.

[The incidence of prescriptions without marketing product license in a neonatal intensive care unit]. / Incidence des prescriptions hors autorisation de mise sur le marché en réanimation néonatale.

UNLABELLED: Most of the drugs prescribed in pediatric units have no product licence. The lack of clinical studies in children and appropriate drug formulations decrease their safety. The lack of a legal framework makes the prescriber insecure. Even if the debate is not recent, few studies have been carried out in this field. The aim of the present study was to evaluate the rate of prescriptions of unlicensed and off-label drugs in a neonatal intensive care unit. PATIENTS AND METHODS: The present study was carried out in our neonatal intensive care unit, from January 12 to February 12, 1998. Forty babies aged 0 to 128 days were included (90% newborns), with a gestational age between 25 to 40 weeks (88% were premature, with a birth weight lower than 1000 g). RESULTS: Two hundred and fifty-seven prescriptions were administered with 55 different types of drugs during this period. Ten percent of the prescribed drugs had no product licence. Sixty-two percent were off-label for premature infants and 64% for newborns: 90% due to age, 9.3% due to dose and 0.7% to method of administration. No therapeutic alternatives to these prescriptions were found among the few available licensed drugs. CONCLUSION: The prescriptions of unlicensed and off-label drugs in neonatal intensive care units are daily and repeated events. The prescribers are usually not aware of the exact status of the drug and do not realize neither he importance of the problem nor the legal and potential consequences. The lack of pediatric clinical studies is to a large extent responsible for the absence of drug registration in pediatrics. The pharmaceutical industry has few incentives to develop the pediatric product licences.

[Video recording of newborn resuscitation in the delivery room: technique and advantages]. / Enregistrement vidéo de situations réelles de réanimation en salle de naissance: technique et avantages.

An extreme attentiveness is mandatory when caring about extremely-low-gestational-age neonates at birth because of their innate vulnerability. The interventions performed during resuscitation of these infants may have direct influence on the immediate survival and also on long-term morbidity. Although stressfull, each resuscitation step is crucial and needs to be precise, fast and harmless. In order to determine our compliance to the international guidelines and to assess our neonatal performances in delivery room, we used a Mobotix camera to record all resuscitations of extremely-low-gestational-age neonates during the decisive first minutes of life. Neonatal medical and nursing staff agreed to be recorded. Our local ethics committee approved that videotaping neonatal resuscitation is an audit of clinical practice and thus does not require informed consent. During debriefing sessions, we reviewed the videotaped recordings, which allowed us to identify frequent deviations from the international guidelines and to re-educate and improve performance. The most frequent errors we recognized were errors of hygiene, not re-evaluating oxygen titration and airway obstruction during mask ventilation. We observed team behaviour and coordination during resuscitation and focused on quality of care. We believe that this method may be very effective as a teaching tool.

[Palliative care in the neonatal period. Part one: general considerations]. / Réflexions et propositions autour des soins palliatifs en période néonatale : 1(re) partie considérations générales.

In France, the law dated 22 April 2005 required that all practitioners offer palliative care to patients as an alternative to unreasonable obstinacy. The practical development of palliative care during the neonatal period is not easy, even though obstetricians and neonatologists have always been aware of the ethical necessity of comfort in the dying newborn. The decision leading to palliative care begins with the recognition of patent or potential unreasonable obstinacy, followed by withdrawing treatment and technical support, and finally a palliative care plan is drawn up with the medical team and the parents.

[Evidence versus experience in neonatal practice: the example of extremely premature infants]. / Niveaux de preuves versus pratiques cliniques: l'exemple de l'extrême prématurité

We focused on current nutritional and ventilation strategies of extremely preterm infants and reviewed the evidence and the practical experience in four French neonatal intensive care units. The recommendations from reviews and the local clinical guidelines were compared and were overall in agreement. We wanted then to evaluate if different ventilatory and nutritional styles existed between four French intensive neonatal units, and if these approaches had an effect on short term outcomes. 399 infants delivered at a gestational age <28 weeks between January 2005 and December 2006 were retrospectively studied (unit I = 141, unit II = 97, unit III = 85, unit IV = 76). Data were collected from birth to discharge. The study groups were similar with regard to gestational age, birth weight, gender, prenatal steroids, rate of inborn. There were significant differences in ventilatory and nutritional strategies between the units. Incidence of NEC, IVH grade 3-4 and PVL were similar between the units. Mortality rate during the hospitalization stay was 14.9 %, 35.0 %, 29.4 % and 29 % (p<0.05). A national database would be useful to analyse differences in strategies and long term outcomes.

Disseminated bronchoalveolar keratinocyte plugs in severe neonatal congenital lamellar ichthyosis.

We present here a case of congenital lamellar ichthyosis responsible for neonatal death immediately after delivery due to obstruction by bonchoalveolar keratinocyte plugs. The main interest of this case was to confirm in utero amniotic fluid movement into the distal airways by fetal breathing or gasping.

Efficacy of dead-space washout in mechanically ventilated premature newborns.

The prosthetic dead space makes a significant contribution to the total dead space in low-birth-weight premature newborns receiving artificial ventilation in response to respiratory distress. Use of an endotracheal tube with capillaries molded into the tube wall enables washout of the dead space without insertion of a tracheal catheter. In 10 premature newborns (mean gestational age, 27.5 +/- 2.2 wk; mean weight, 890 +/- 260 g) receiving continuous positive-pressure ventilation (Paw = 12.7 +/- 1.8 cm H2O; FIO2 = 39 +/- 17%), tracheal gas insufflation (TGI) for CO2 washout was conducted using this technique. The flow of tracheal insufflation (0.5 L/min) was derived from the inspiratory line of the ventilator circuit and blown into the trachea. Intratracheal pressures showed little or no TGI-related modification ( < 1 cm H2O). A control system enabled TGI discontinuation in the event of a pressure rise. At constant ventilation pressure, PaCO2 decreased by 12.1 +/- 5.9 mm Hg (delta PaCO2 = -26 +/- 12%) under TGI, whereas PaO2 remained unchanged. While maintaining PaCO2 constant, peak inspiratory pressure (PIP) was decreased by 5.4 +/- 1.7 cm H2O (delta PIP = -22.0 +/- 8.3%). TGI showed immediate efficacy (PCO2 reduction of at least 5 mm Hg) in nine of the 10 newborns who then received chronic TGI (14 to 138 h). TGI appears to be an effective method, suitable for long-term clinical application, enabling a reduction in the aggressive nature of conventional ventilation.

[Spontaneous perforation of the bile ducts]. / Perforation spontanée des voies biliaires.

Spontaneous perforation of the extra-hepatic bile ducts in infancy is rare and of unknown etiology. Its finding at laparotomy in a 2 month-old premature with artificial ventilation allows to underline that the diagnosis may be difficult and may necessitate ultrasonography and even hepatobiliary scintigraphy.