Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders.

In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl-)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2-18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.

[The role of immunosuppressive agents in Kawasaki disease: a discussion of two cases]. / Place des immunosuppresseurs dans les formes évoluées de maladie de Kawasaki : à propos de deux cas avec atteinte cardiaque sévère.

INTRODUCTION: Kawasaki disease (KD) is the most common cause of acquired heart disease in developed countries. Ten percent of patients with KD develop coronary aneurism. Ten percent of patients treated with intravenous immunoglobulin (IgIV) have persistent coronary dilatations, which sustains the search for new therapies. We describe 2 cases of refractory KD and discuss the therapeutic options. CLINICAL REPORT: A 3-year-old child and a 3-month-old infant had refractory KD. Both were treated with IgIV and corticosteroids. They both had persistent fever and major coronary artery dilatation. The first patient received a treatment with acetyl-salicylic-acid (ACA) only. The second received an immuno-therapy with an anti-TNF-α agent. Fever and inflammatory symptoms disappeared within 12h in the second case. Coronary artery aneurisms worsened during the first month and then stabilized. The first child had fever and inflammatory symptoms for a longer duration, but coronary artery dilatations stabilized and disappeared with no additional treatment than ACA. DISCUSSION AND CONCLUSION: TNF-α is known to be one of the inflammatory factors involved in KD disease. Anti-TNF-α agents have been tested in treatment of refractory KD. In one of the cases reported herein, this therapy was not effective on coronary artery aneurism. More studies are needed to define the optimal treatment of refractory KD.

Familial 18 centromere variant resulting in difficulties in interpreting prenatal interphase FISH.

We report here on a familial case of centromeric heteromorphism of chromosome 18 detected by prenatal interphase fluorescence in situ hybridization (FISH) analysis transmitted by the mother to her fetus, and resulting in complete loss of one 18 signal. The prenatal diagnosis was performed by interphase FISH (AneuVysion probe set, and LSI DiGeorge 22q11.2 kit) because of the presence of an isolated fetal cardiac abnormality, and was first difficult to interpret: only one centromeric 18 signal was detectable on prenatal interphase nuclei, along with one signal for the Y and one for the X chromosome. The LSI DiGeorge 22q11.2 kit also showed the absence of one TUPLE 1 signal on all examined nuclei. In fact, the FISH performed on maternal buccal smear displayed the same absence of one chromosome 18 centromeric signal, combined with the presence of two TUPLE1 signals. All these results led to the diagnosis of an isolated 22q11.2 fetal microdeletion that was confirmed on metaphases spreads. This case illustrates once again that the locus specific (LSI) probes are more effective than the alpha centromeric probes for interphase analysis. The development of high-quality LSI probes for chromosomes 18, X and Y could avoid the misinterpretation of prenatal interphase FISH leading to numerous additional and expensive investigations.

Burden of infant bronchiolitis: data from a hospital network.

In France, surveillance of bronchiolitis is based on a pilot network of hospital emergency departments. The study was a 1-year observational study (2007-2008) carried out in a central region of metropolitan France. The hospitalization rate for bronchiolitis was 17.7/1000 children aged <1 year and the estimated prevalence of bronchiolitis ranged from 17.7% to 34.4% in children aged <1 year. Such a network constitutes a valuable tool to estimate the dynamic and the burden of infant bronchiolitis.

Direct genotyping of cytomegalovirus envelope glycoproteins from toddler's saliva samples.

BACKGROUND: The polymorphism of genes encoding CMV envelope protein is used for strain classification and may influence pathogenesis and/or infectivity. CMV genotyping is usually based on sequencing or acrylamide gel-RFLP, but these methods are not suited to rapid screening of large populations. OBJECTIVES: We developed a high-throughput method to analyze CMV strains diversity and to detect multiple-strain infection in a large population of toddlers (six daycare centers (DCC) and an emergency unit (EU)). METHODS: We developed a new PCR-RFLP method coupled with capillary electrophoresis fragment detection for UL55-gB, UL75-gH and UL73-gN genotyping. To detect gB recombinants, gpUL55 typing was applied to two variable zones (NTerminal and central). We applied this method to 212 CMV-positive saliva samples and controlled the results by direct sequencing of PCR products. RESULTS: We identified 112 strains, that fell into eight groups in UL55-gB, two groups in UL75-gH, and seven groups in UL73-gN. The 79 samples from the emergency unit contained 30 strains, 28 children harboring 2 strains. The samples (n=133) from the six daycare centers contained respectively 4, 1, 6, 1 and 11 strains. Fifteen percent of strains were UL55-gB recombinants. CONCLUSION: Our new method can simultaneously determine gB, gH and gN genotypes and offers more precise classification of CMV strains than previous RFLP-based methods. This could constitute the basis for a new classification, particularly in UL55-gB. Easy direct identification of multiple strains and recombinants in pathological samples could facilitate large epidemiologic studies.

[Slow ventricular tachycardia presenting in the antenatal period]. / Tachycardie ventriculaire lente de révélation anténatale.

The authors report two cases of slow ventricular tachycardia presenting in the antenatal period. One foetus had anasarca at 38 weeks' gestation. After birth, improved myocardial function contributed to the rapid resorption of the effusions. The other case was well tolerated in the foetal and neonatal periods. In both cases, Holter ECG recorded an intermittent ventricular arrhythmia with salvos of sustained ventricular tachycardia with a maximum rate of 185/min, only 10% higher than the underlying sinus rhythm, disappearing on acceleration of the sinus rhythm. The aetiological investigation was negative. Therapeutic abstention was supported by the spontaneously favourable outcome after 3 and 5 months. Slow ventricular tachycardia or accelerated idioventricular rhythms are usually considered to be benign but the case with foetal anasarca suggests that they should be carefully followed up in the neonatal period. In the absence of a consensus on management, therapeutic abstention implies regular cardiological examination until the arrhythmia has disappeared.

Identical chromosome imbalance in two siblings born to a mother with a double reciprocal translocation.

We report the case of a woman who carried two reciprocal translocations. Her karyotype was 46,XX,t(3;12)(q12;q21)(4;17)(p14;p13). She had two children, a phenotypically normal daughter (karyotype (46,XX,t(3;12)(q12;q21)) and a son with partial 4p trisomy (karyotype 46,XY,t(3;12) (q12;q21),-17,+maternal der(17)). She was pregnant with a female fetus who had the same karyotype as her son. She also reported a history of two spontaneous abortions. This viable recurrent abnormality was due to the maternal (4;17) translocation with meiotic segregation type 2:2 adjacent 1. In this case of the two reciprocal translocations carried by the mother, one led to imbalances, whereas the other remained balanced in the viable offspring.

[Concentration of amoxicillin in neonates after infusion to the mother during labor]. / Concentration d'amoxicilline chez le nouveau-né après perfusion de la mère durant le travail.

Amoxicillin is effective against S. agalactiae (MIC 50 = 0.03 mg/l). Neonatal prophylaxis of GBS infection had already been studied but very few data are available regarding pharmacokinetic of these antibiotics. In this study, 58 pregnant women with GBS colonisation and/or with epidemiologic risk factors received intrapartum antibiotic infusion at the beginning of the labor (1 g amoxicillin every 6 hours until the delivery). At delivery, cord blood and gastric fluid were taken in delay from 0.5 to 6 hours after the beginning of the infusion. Dosages were done in triplicate with a microbiological method using Bacillus subtilis ATCC 6633 as test strain. In cord blood amoxicillin appeared as early as the first half hour. Concentration were from 5 to 7 mg/l between 1 hour and 4 hours after the beginning of the infusion, and from 3 to 4 mg/l after 4 hours. In gastric fluid, concentrations obtained were over 1 mg/l after 1.5 hour and over 3 mg/l after 2.5 hours with good efficiency even after the sixth hour. The protocol using a slow intrapartum amoxicillin infusion (1 g) gave concentrations in gastric fluid and cord blood over S. agalactiae MIC.

[Maternal motivation for choice of feeding method]. / Motivations maternelles pour le choix du mode d'allaitement.

We studied the different motivations mothers had for choosing a particular mode of nursing at the University Hospital in Limoges. An anonymous questionnaire was distributed to all mothers who hat delivered between January 1 and April 30, 1992. It was apparent that the medical team did little to promote breast-feeding or to counteract negative attitudes. The results of this study, together with a review of the literature were used to determine conditions for encouraging breast feeding.

Comparative effects of two topical antiseptics (chlorhexidine vs KMn04) on bacterial skin flora in atopic dermatitis.

In order to determine the efficacy and tolerance of two topical antiseptics, chlorhexidine vs KMn04 (diluted at 1:20,000), we compared their bacteriological and clinical effects in a randomized trial on 20 children with Atopic Dermatitis (AD) treated with topical steroids (desonide). After treatment, a clinical improvement was noted in the two groups, though without statistical differences. In vivo: Before treatment, Staphylococcus aureus (S.A.) density was high and predominant in both groups. After treatment, the decrease in S.A. was greater in the chlorhexidine group than in the KMn04 group, without significant difference. In vitro: At the clinical dilution used, there was a statistical difference (p < 0.05) between the number of killed bacteria in the chlorhexidine group (-3 log) and the number in the KMn04 group (-1 log). This study confirms the role and importance of the choice of a topical antiseptic in the treatment of AD.

[Neonatal pneumococcal septicemia]. / Septicémies néonatales à pneumocoque.

We report two cases of neonatal pneumococcal septicemia, including one fatal case in a 32-week-gestational-age premature infant. Neonatal pneumococcal septicemias account for less than 1% of all neonatal infections. Diagnosis is provided by simple and rapid methods for identifying pneumococci. Clinical features have little specificity (respiratory distress) and resemble those found in B streptococcus infections. The mother rarely exhibits symptoms at delivery. The severity of the prognosis is not related to resistance to the antimicrobial agents currently used in neonatal infections but to the infectivity of the organism itself and to the specific immunologic characteristics of premature neonates. The current use of amoxicillin and aminoglycosides in neonatal infections does not therefore need to be revised.

[Metabolic and cardiovascular effects of beta-blockers taken by the mother in newborn infants]. / Effets métaboliques et cardiovasculaires chez le nouveau-né des bêtabloquants pris par la mère.

The effects of beta-blockers administered to mothers with arterial hypertension were investigated in 38 neonates of varying gestational age and weight. During the first 48 hours of extra-uterine life, heart rate was continuously monitored and blood pressure and glycaemia were measured every 3 hours. Left ventricular function was studied by echocardiography on the first day post-partum, once again between the 5th and 10th days. Hypoglycaemia was observed in 42% of the neonates; 47% had one or several episodes of bradycardia and 2 had arterial hypotension. Most important, a significant improvement of left ventricular function was observed between the first and the 5th-10th days. This time-related change was not found in a control group. The cardiac dysfunction was more pronounced in neonates who had an episode of bradycardia, and although it is usually asymptomatic, it probably accounts for the fortunately rare cardiovascular collapses observed in some newborn babies.

[Value of continuous Doppler velocimetry for the diagnosis of patent ductus arteriosus]. / Intérêt de la vélocimétrie Doppler continu pour le diagnostic de la persistance du canal artériel.

A study of the curve of wave Doppler ultrasonography of 3 arterial axes (carotid, subclavian and femoral) was performed in 32 children in whom the diagnosis of patent ductus arteriosus was suspected. A continuous 8 MHz wave directional ultrasonic Doppler apparatus was used. At the level of subclavian and femoral arteries, patent ductus arteriosus is associated with a negative holodiastolic wave on the curve. At the carotid level, disappearance of the physiologic diastolic elevation may be the only change observed. Three groups were studied (1) 15 premature neonates with isolated murmur, (2) 15 premature neonates with respiratory distress and (3) 2 older children. In group 2, diagnosis of patent ductus arteriosus relies on clinical signs. A good correlation between Doppler and clinical data and/or TM ultrasonography was observed in 93% of cases.