A 5‐HT2A/2C receptor agonist, 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane,mitigates developmental neurotoxicity of ethanol to serotonergic neurons

Prenatal ethanol exposure causes the reduction of serotonergic (5‐HTergic) neurons in the midbrain raphe nuclei. In the present study, we examined whether an activation of signaling via 5‐HT_2A and 5‐HT_2C receptors during the fetal period is able to prevent the reduction of 5‐HTergic neurons induced by prenatal ethanol exposure. Pregnant Sprague–Dawley rats were given a liquid diet containing 2.5 to 5.0% (w/v) ethanol on gestational days (GDs) 10 to 20 (Et). As a pair‐fed control, other pregnant rats were fed the same liquid diet except that the ethanol was replaced by isocaloric sucrose (Pf). Each Et and Pf group was subdivided into two groups; one of the groups was treated with 1 mg/kg (i.p.) of 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOI), an agonist for 5‐HT_2A/2C receptors, during GDs 13 to 19 (Et‐DOI or Pf‐DOI), and another was injected with saline vehicle only (Et‐Sal or Pf‐Sal). Their fetuses were removed by cesarean section on GD 19 or 20, and fetal brains were collected. An immunohistological examination of 5‐HTergic neurons in the fetuses on embryonic day 20 using an antibody against tryptophan hydroxylase revealed that the number of 5‐HTergic neurons in the midbrain raphe nuclei was significantly reduced in the Et‐Sal fetuses compared to that of the Pf‐Sal and Pf‐DOI fetuses, whereas there were no significant differences between Et‐DOI and each Pf control. Thus, we concluded that the reduction of 5‐HTergic neurons that resulted in prenatal ethanol exposure could be alleviated by the enhancement of signaling via 5‐HT_2A/2C receptors during the fetal period.     

Neonatal cholestasis and glucose‐6‐P‐dehydrogenase deficiency

We report a Caucasian neonate with chronic non‐spherocytic hemolytic anemia due to a class I G6PD deficiency. A novel mutation missense mutation in exon eight of the G6PD gene was detected (c.827C>T p.Pro276Leu). Bilirubin peaked on day 5 at 24 mg/dl with a conjugated bilirubin of 17 mg/dl. Jaundice resolved within 4 weeks. A detailed work‐up failed to reveal other specific factors contributing to cholestasis. Severe hemolytic disease of the newborn may cause cholestasis even in the absence of associated primary hepato‐biliary disease. Pediatr Blood Cancer 2010;54:758–760. © 2010 Wiley‐Liss, Inc.     

Self‐esteem in 6‐ to 16‐year‐olds with monosymptomatic nocturnal enuresis

Aim: Childhood nocturnal enuresis (NE) and incontinence has been shown to be associated with increased behavioural problems and reduced self‐esteem (SE) in Western populations. The impact on Asian children, however, is not known. This study investigates the relationship between SE and monosymptomatic NE in Malaysian children aged 6 to 16 years. Method: Children with wetting frequency of at least 4 out of 14 nights were recruited with controls matched for age, gender and race. SE scores were obtained using the ‘I Think I Am’ questionnaire for five domains: body image, talents and skills, psychological well‐being, relationship with family and relationship with others. Results: A total of 126 children were recruited; 22 enuretics aged 6–9 years and their matched controls (Group1) and 41 enuretics aged 10–16 years and their matched controls (Group 2). SE scores were similar between the enuretic and controls in Group 1, whereas in Group 2, enuretics had significantly lower scores (P < 0.05) in ‘body image’, ‘relationship with others’ and total SE scores. This difference was more pronounced among girls, adolescents and those who wet more than 10/14 nights. Conclusion: The SE of Malaysian children with monosymptomatic NE aged 10 years and above is significantly lower than their peers. This effect is seen particularly among girls, adolescents and those with frequent wetting. In the light of these findings, the ‘wait and see’ approach by the Malaysian medical profession is no longer appropriate. Treatment should begin before the age of 10 years.     

Hereditary spherocytosis diagnosed with the eosin‐5′‐maleimide binding test

We describe three cases of hereditary spherocytosis (HS) diagnosed using the eosin‐5′‐maleimide (EMA) binding test and discuss the relevance of the EMA binding test. In Japan, this test is not widely used because the prevalence of HS is low. This test is a valuable screening test for the diagnosis of HS.     

Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome

There are no proven safe and effective therapies for children who develop life‐threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS‐CoV‐2, but has theoretical risks.We present the first report of CP in children with life‐threatening coronavirus disease 2019 (COVID‐19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody‐dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.     

Effect of 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin suggests abnormal palate development after palatal fusion

Mouse embryos exposed to 2,3,7,8‐tetrachloridedibenzo‐p‐dioxin (TCDD) develop cleft palates and hydronephrosis. Cleft palates occur after TCDD exposure due to contact and/or fusion failure. We investigated whether cleft palate can be induced by dissociation of the palatine process after fusion. Pregnant mice on gestational day (GD) 12 were randomly divided into two groups: one group was administered through gastric tubes one dose of olive oil (control group) and the other group was administered one dose of TCDD diluted with olive oil, both at a dose of 40 µg/kg body weight. Embryos were removed by cesarean section from pregnant mice during the palatal formation stage (GD 13–18) and the palatal form was observed using a stereoscopic microscope. In TCDD‐exposed embryos, palatal fusion was observed on GD 14, 15 and 16 and the incidence of cleft palate was 100% on GD 18. Fusion rates were 17.5 ± 15.2% and 12.4 ± 11.8% on GD 15 and 16, respectively. Some palates from the TCDD‐exposed mouse embryos showed clearly developed cleft palate after fusion of the lateral palatine processes during palatal formation. A mass of cells, which were chiefly epithelial in the fused palates was observed in the TCDD‐exposed mouse embryos. A decrease in E‐cadherin expression was observed in this mass of cells, indicating its involvement in the development of cleft palate.     

Cat‐scratch disease with severe pleuritis in a 6‐year‐old girl

We present the case of a 6‐year‐old girl with cat‐scratch disease (CSD), who developed severe pleuritis without lymphadenitis. Bartonella henselae DNA was detected on real‐time polymerase chain reaction (PCR) analysis of whole blood. This is the first report of CSD diagnosed on real‐time PCR using whole blood.     

Trends in the off‐label use of β‐blockers in pediatric patients

The use of US Food and Drug Administration (FDA)‐approved drugs for the treatment of an unapproved indication or in an unapproved age group, or at doses or route of administration not indicated on the label is known as off‐label use. Off‐label use may be beneficial in circumstances when the standard‐of‐care treatment has failed, and/or no other FDA‐approved medications are available for a particular condition. In pediatric patients, off‐label use may increase the risk of adverse events as pharmacokinetic and pharmacodynamic data are limited in children. Approximately 73% of off‐label drugs currently prescribed for various conditions do not have sufficient scientific evidence for safety and efficacy. For example, β‐blockers are a class of drugs with FDA‐approval for very few indications in pediatrics but are commonly used for various off‐label indications. Interestingly, the proportion of off‐label use of β‐blockers in adults is at about 52% (66.2 million) of the total number of β‐blockers prescribed. The frequency of off‐label use of β‐blockers in children is also high with limited data on the indications as well as safety and efficacy. We present trends in off‐label use of β‐blockers in children to discuss drug safety and efficacy and include recommendations for pediatric providers.