[Congenital myasthenic syndromes in childhood: Drug therapeutic strategies]. / Syndromes myasthéniques congénitaux de l'enfant : stratégies thérapeutiques médicamenteuses.

Congenital myasthenia syndromes (CMS) are a group of genetic disorders responsible for neuromuscular junction dysfunction. Usually beginning before 2 years of age, they are revealed by fatigability and muscle weakness, especially after stress, and often prevent the child's normal development. Over recent years, major advances in therapeutic strategies have been made following the discovery of numerous mutations responsible for CMS and the understanding of their pathogenic role. Here we report a pediatric CMS case caused by a mutation of the ɛ subunit of the acetylcholine receptor. The initial treatment with acetylcholinesterase inhibitor rapidly showed its limits in terms of both effectiveness and tolerance. The association with 3.4 diaminopyridine (DAP), a new drug available to treat such conditions, has transformed the motor outcome of our patient and allowed psychomotor development. In addition to 3.4 DAP, other molecules adapted to other types of CMS are now available. Three major groups of CMS can be distinguished depending on whether the deficit is at the presynaptic, synaptic, or postsynaptic level of the neuromuscular junction. Depending on the type of CMS, therapeutic management may include acetylcholinesterase inhibitors, 3.4 DAP, fluoxetine, quinidine sulfate, or ephedrine. With the case report, we provide a recent review of the literature on such new therapeutic options, their indications and restrictions, their mechanism of action, and prescription modalities. Knowing the precise CMS type and the appropriate therapeutic options available is essential for the proper management of such chronic and severe but relatively treatable childhood disorders.

[Neuroprotection with hypothermia for hypoxic ischemic encephalopathy in term newborn: review of the learning]. / Neuroprotection par hypothermie lors des encéphalopathies anoxo-ischémiques du nouveau-né à terme: état des connaissances.

The hypothermia treatment for neonatal hypoxic ischemic encephalopathy is a concept revisited for more than 10 years. With this strategy, animal studies have shown an 80% reduction of brain damage. Conditions for the practice of hypothermia, to obtain neuroprotection, have been described in these studies: rapidity of the onset of cooling after the hypoxic ischemic event, prolonged duration during several hours, ability to obtain neuroprotection with two methods of cooling, selective head cooling or whole body hypothermia. Pilot studies in human newborns have demonstrated the feasibility of these strategies without immediate adverse effects. Two large randomised trials have been conducted in 2005 to test the efficacy. Only with the strategy of whole body cooling, the incidence of poor outcome at 18 months (death or severe disability) was statistically decreased (44% versus 66% in the control group). This reduction seems especially significant in the sub group of intermediate severity (48% versus 66%), whereas severe forms (Grade III in the Sarnat and Sarnat classification) were probably not ameliorated with this treatment. Now, the major problem is to determine the best indications for hypothermia with an early and precise assessment of the grade of the encephalopathy.

[Early management of infants born to mothers with meconium-stained amniotic fluid: a survey in French delivery rooms]. / Prise en charge précoce des enfants nés avec un liquide méconial: enquête dans les maternités françaises.

UNLABELLED: The meconium aspiration syndrome is the first cause of respiratory distress in full term newborns. At birth, management includes systematical oropharyngeal suctioning, before and after shoulders delivery, followed by tracheal suction. During last 10 years, many trials were published which discuss again the value of this strategy. AIM: To assess practices of the current management of births with a meconial amniotic liquid in the French maternities. METHODS: Observational survey by written questionnaires sent to the 617 French maternities. RESULTS: The rate of answers was of 54.3%. The incidence of the births presenting a meconial amniotic fluid was of 8.2%, complicated of meconium aspiration syndrome in 4.7%. In case of birth with presence of a meconial amniotic liquid, half of the maternities resorted systematically to oropharyngeal suctioning before shoulders delivery. A glottis exposition under laryngoscopy was practiced of principle for half of the newborn. Tracheal suctioning was achieved systematically in a quarter of the establishments. These techniques, with the exception of suctioning before clearing of the shoulders, were especially been achieved in a systematic way in the maternities of I and II A levels. CONCLUSION: This survey shows the necessity of harmonization of the practices in France for the management of the births with a meconial amniotic liquid.

[Fetal toxicity of angiotensin-II receptor antagonists]. / Toxicité foetale du candesartan.

We report a case of a newborn with an oligohydramnios, acute renal failure and ossification abnormalities. The role of maternal treatment of essential hypertension by angiotensin-II receptor antagonists is discussed in regard to the literature and pathophysiological data.

[Metoclopramide and neonatal methaemoglobinemia]. / Métoclopramide et méthémoglobinémie néonatale.

We report the case of a five-day-old newborn with cyanosis. After exclusion of pulmonary and cardiac illness, methaemoglobinemia was diagnosed. Cyanosis is the first symptom of methaemoglobinaemia. Numerous causes of methaemoglobinemia have been described, with congenital and acquired forms, which are the most frequent. We discuss here the clinical features, diagnosis, and treatment of acquired methaemoglobinaemia in newborns with special emphasis on forms secondary to metoclopramide toxicity.

The safety and efficacy of nitric oxide therapy in premature infants.

OBJECTIVES: To assess the safety-efficacy balance of low-dose inhaled nitric oxide (iNO) in hypoxemic premature infants because no sustained beneficial effect has been demonstrated clearly and there are concerns about side effects. STUDY DESIGN: Eight hundred and sixty infants <32 weeks were randomized at birth to receive 5 ppm iNO or placebo when they presented with hypoxemic respiratory failure (HRF) defined by a requirement for mechanical ventilation, fraction of inspired oxygen (FIO 2 ) >40%, and arterio-alveolar ratio in oxygen (aAO 2 ) <0.22. The primary end point was intact survival at 28 days of age. RESULTS: Sixty-one of 415 infants presented with HRF and were compared with 84 of 445 controls who presented with HRF. There was no difference in the primary end point (61.4% in infants [23% with HRF who were treated with iNO] vs 61.1% in controls [21.4% in controls with HRF]; P = .943). For the infants with HRF who were treated with iNO, there was no significant difference from controls for intraventricular hemorrhage (IVH) (6% vs 7%), necrotizing enterocolitis (8% vs 6 %), or patent ductus arteriosus (PDA) (34% vs 37%). Compared with nonhypoxemic infants, the risk of bronchopulmonary displasia (BPD) increased significantly in HRF controls (OR = 3.264 [CI 1.461-7.292]) but not in infants with HRF who were treated with iNO (OR = 1.626 [CI 0.633-4.178]). CONCLUSIONS: iNO appears to be safe in premature infants but did not lead to a significant improvement in intact survival on day 28.

Spread of Stenotrophomonas maltophilia colonization in a pediatric intensive care unit detected by monitoring tracheal bacterial carriage and molecular typing.

In our pediatric intensive care unit in Tours (France), intubated and ventilated inpatients are systematically monitored for tracheal bacterial colonization twice a week. This led us to detect five patients colonized with Stenotrophomonas maltophilia over a 4-month period. Molecular typing of the isolates using random amplified polymorphism DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) confirmed that four of the five isolates were genetically related. The strict isolation of carriers and improvements in hygiene measures stopped the spread. This systematic strategy prevented pulmonary nosocomial infections or allowed their early detection. Moreover, it has made it possible to assess the efficiency of care practices continuously.

Comparison of fecal flora following administration of two antibiotic protocols for suspected maternofetal infection.

Two protocols are used by French neonatologists for the treatment of suspected maternofetal infection (SMFI). Three groups of premature and term neonates were included to study the impact of antibiotics on fecal flora: 10 infants with SMFI treated with amoxicillin and netilmicin (group BI), 10 infants with SMFI treated with amoxicillin, cefotoxime and netilmicin (group TRI) and 10 infants without antibiotic therapy as controls (group C). Group BI samples were colonized with Klebsiella oxytoca and Escherichia coli resistant to amoxicillin and by Eneterococcus faecium and coagulase-negative staphylococci. In group TRI biodiversity of the intestinal flora was low, with rapid growth of staphyloccoci and occurrence of Candida spp. These modifications of the intestinal flora should encourage us to use antibiotic treatment as targeted as possible.

[Study of correlations between antibiotics prescriptions and guidelines in a neonatal intensive care unit]. / Etude de la corrélation entre les prescriptions d'antibiotiques et les recommandations dans une unité de soins intensifs néonatals.

UNLABELLED: The increasing use of wide spectrum antibiotics has been reported to be associated with a greater prevalence of multi-resistant bacteria. OBJECTIVES: The aims of this study were to survey the use of antibiotics and to evaluate the correlations between patterns of prescription of antibiotics and prescription guidelines in a neonatal intensive care unit. MATERIAL AND METHODS: In this 6-month study, all newborns admitted to the NICU and treated with antibiotics were included. Data regarding criteria of antibiotic prescription, length of treatment, and criteria of withdrawing treatment were collected. The correlation between prescriptions and guidelines was evaluated a posteriori by a non-prescriber physician. One hundred and sixteen newborns were included, of whom nine had received antibiotics on more than one occasion. Mean gestational age was 33.5 weeks. In 82% of cases, the reason for hospitalisation was respiratory distress syndrome. RESULTS: Patients received systemic antibiotics for primary infection (78%), nosocomial infection (17%) and postsurgical prophylaxis (5%). Suspected foeto-maternal infections (SFMI) were the dominant features of primary infection (96%). In 49% of cases, suspected infection was not proven and justified withdrawal of treatment within 3 days. Sixty percent of nosocomial infections occurred in newborns with gestational ages of less than 28 weeks. Bacterial criteria were decision-making factors only in nosocomial infections. An absence of observance of guidelines occurred in 9% of treated newborns, and in most cases involved excessive length of treatment. CONCLUSION: These results show: (1) the majority of antibiotic prescriptions were for not proven SMFI; (2) a low rate of nosocomial infections; (3) the predominance of nosocomial infections in premature newborns; (4) less than 10% of non-observance of guidelines. It appears necessary to develop more precise guidelines to limit antibiotic use and to evaluate them regularly.

mRNA D(2) dopaminergic receptor expression after hypoxia-ischemia in rat immature brain.

Previous studies have shown a reduction of dopaminergic D(2) receptors (D(2)R) in the striatum after hypoxia-ischemia in newborn rats. We show here an early and transient reduction of mRNA D(2)R in nonatrophic brains following hypoxia-ischemia. The left carotid artery of P7 rats was ligated followed by hypoxia for 2 h. The rats were sacrificed after 24 h, 48 h and 14 days. D(2)R mRNA was studied by in situ hybridization, the cell number by conventional histology, and neuronal and astrocyte differentiation by immunohistochemistry. A 20% reduction of striatal mRNA D(2)R occurred 24 h after hypoxia-ischemia, whereas no reduction was observed after 48 h and 14 days. There were no differences in total cell number and in the expression of neuronal (MAP-1, MAP-2) and astrocyte (GFAP) markers between both brain hemispheres nor between control and hypoxia-ischemia animals. The early decrease in mRNA D(2)R could explain the delayed reduced D(2)R after neonatal hypoxia-ischemia.

Prospective randomized multicenter comparison of high-frequency oscillatory ventilation and conventional ventilation in preterm infants of less than 30 weeks with respiratory distress syndrome.

BACKGROUND: Early use of high-frequency ventilation and exogenous surfactant is proposed as the optimal mode of ventilatory support in infants with respiratory distress syndrome. In very premature infants, we tested the hypothesis that high-frequency versus conventional ventilation could decrease exogenous surfactant requirements and improve pulmonary outcome, without altering the complication rate, including that of severe intraventricular hemorrhage. METHODS: Preterm infants with a postmenstrual age of 24 to 29 weeks, presenting with respiratory distress syndrome were randomly assigned to high-frequency oscillatory ventilation (lung volume recruitment strategy) or conventional ventilation. RESULTS: Two hundred seventy-three infants were enrolled. One hundred fifty-three had a postmenstrual age of 24 to 27 weeks, and 143 had a birth weight /=2 instillations of exogenous surfactant (30% vs 62%; odds ratio:.27; 95% confidence interval:.16-.44) and no difference in pulmonary outcome. The incidence of severe intraventricular hemorrhage was 24% in the high-frequency group and 14% in the conventional ventilation group (adjusted odds ratio: 1.50; 95% confidence interval:.68-3.30). CONCLUSION: Early use of high-frequency oscillatory ventilation in very premature infants decreases exogenous surfactant requirements, does not improve the pulmonary outcome, and may be associated with an increased incidence of severe intraventricular hemorrhage.

[Mortality in a pediatric hospital. Six-year retrospective study]. / Mortalité dans un hôpital pédiatrique. Etude rétrospective sur six ans.

AIMS: To define the characteristics of patients dying in a pediatric hospital, including causes and modes of death. PATIENTS AND METHODS: This retrospective, descriptive, epidemiologic study was performed between 1 January 1990 and 31 December 1995. All patients who died in the hospital between these dates were included. Patients already dead on arrival (sudden infant death syndrome, children deceased during their transport), and those whose hospital records could not be found, were excluded. RESULTS: A total of 375 children were studied, including 195 neonates. The sex ratio was 1.3. Ninety-one percent of deaths took place in three departments: intensive care, neurosurgery-neurology and oncology. Median duration of hospitalization was three days. The most common causes of deaths were accidents, neurologic diseases (particularly among neonates) and tumours. Analysis of modes of death revealed that 41.1% occurred following unsuccessful resuscitation, 38.8% were the result of withdrawal of life-support or a 'do not resuscitate' order and 21.6% resulted from brain death. Evolution of modes of death over the six years showed a reduction of cases with unsuccessful resuscitation, an increase in decisions of 'do not resuscitate' orders and withdrawal of life-support and no change in rates of brain death. Organs were made available for transplantation from 12 of the 81 children with brain death (14.8%). CONCLUSION: Accidents were the most common cause of death. The distribution of deaths showed a clear increase in withdrawal or withholding of life-support care, relying on ethical decisions, which are more frequent than some years ago.

Consequences of pulmonary inflations (sighs) on cerebral haemodynamics in neonates ventilated by high-frequency oscillation.

High-frequency oscillation (HFO) is a technique frequently used in neonatal resuscitation, but which has yet to be evaluated. The use of intrathoracic pressures may have an effect on the cerebral circulation of immature neonates. The aim of this study was to examine the variations in cerebral blood velocity and oxygenation during brief pulmonary inflations (sighs), by focusing on alveolar recruitment. In this prospective study performed in 13 intubated and ventilated neonates (alpha = 5%; 1-beta = 80%), mean blood velocity and Doppler Resistance Index were measured, and variations in chromophores concentrations were evaluated by near infrared spectroscopy. Brief inflations at 4 cm H2O above the mean regulated intra-thoracic pressure did not cause any variation in the parameters measured. An explanation for this discordance with animal studies may be the level of pressure chosen, which could be more appropriate for the pulmonary compliance of neonates.

Congenital neonatal myotonic dystrophy with persistent pulmonary hypertension and coma: a difficult diagnosis.

The fulminant forms of congenital myotonic dystrophy, which rapidly lead to death, are difficult to diagnose. The case described illustrates the roles of persistent pulmonary hypertension in such a fatal form.

Kainate-induced apoptotic cell death in hippocampal neurons.

We have examined the role apoptosis plays in epileptic brain damage using intra-amygdaloid injection of kainate. With the silver staining technique of Gallyas, argyrophylic (dying) neurons were observed, a few hours after the injection, in the amygdala and in the vulnerable pyramidal neurons of the hippocampal CA3 region. In both areas, cell death has apoptotic features, including: (i) nuclear chromatin condensation and marginalization with light and electron microscopy; (ii) DNA fragmentation with a typical ladder pattern on agarose gel electrophoresis; (iii) positive nuclear labelling with a selective in situ DNA fragmentation staining method. Combined in situ DNA labelling and silver staining showed that the DNA fragmentation occurred in dying neurons. CA1 or granule cells which do not degenerate following intra-amygdaloid injection of kainate were not stained with the in situ DNA labelling or the argyrophylic technique. Administration of diazepam blocked the kainate-induced seizures and prevented DNA fragmentation in CA3 but not in the amygdala. Therefore, apoptosis contributes to the local and distant damage induced by kainate.