Neonatal rebound hyperkalemia associated with ritodrine alone : a case report

Background: Betamimetics have been used for tocolysis extensively in the past, and one of them, ritodrine is widely used in Japan. Various adverse events have been reported for this agent, including newborn hypoglycemia and hypokalemia, as well as maternal hypokalemia and rebound hyperkalemia; however, cases of neonatal rebound hyperkalemia are not described in the literature. Case presentation: A male infant born at 36 weeks of gestation by cesarean section at a local maternity clinic suddenly entered cardiopulmonary arrest with ventricular tachycardia and fibrillation due to hyperkalemia (K+, 8.7 mmol/L). No monitoring, examination of blood electrolyte levels, or infusions had been performed prior to this event. Maternal infusion of ritodrine (maximum dose, 170 μg/min) had been performed for 7 weeks prior to cesarean section. After resuscitation combined with calcium gluconate, the infant died at 4 months old due to serious respiratory failure accompanied by acute lung injury following shock. No cause of hyperkalemia other than rebound hyperkalemia associated with ritodrine was identified. Conclusions: This case report serves as a warning regarding the potential risk of neonatal rebound hyperkalemia in association with maternal long-term ritodrine administration

Effective treatment of a 13-year-old boy with steroid-dependent ocular myasthenia gravis using tacrolimus

Over the past several years, tacrolimus has attracted attention as a new therapeutic drug for myasthenia gravis (MG), but few reports have considered its use for MG in pediatric patients, and most of these have focused on severe systemic MG. In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis. He first showed symptoms of ocular MG at age 2 years 3 months. At age 13 years, he was receiving PSL (3.75 mg/day), but the symptoms of ocular MG recurred. We increased the dosage of oral PSL up to 30 mg/day, and three courses of mPSL pulse therapy were applied, but these therapies had only limited effect, and his symptoms worsened. Tacrolimus was started at 0.4mg/day (0.011mg/kg/day), and every two weeks the dose was gradually increased by 0.2mg/day. His symptoms of MG began to improve three weeks after the initial administration of tacrolimus. Approximately three months after the start of tacrolimus administration, PSL was discontinued. Currently, at one year and four months after the start of tacrolimus administration, while slight ptosis is observed in the evening, it does not influence his daily life, and his condition remains comparable to that when he stopped taking PSL. No adverse effects of tacrolimus have been recognized. In pediatric patients with steroid-dependent ocular MG without thymectomy, tacrolimus may be a safe and effective alternative to steroid and thymectomy

Novel large deletion involving EVC and EVC2 in Ellis–van Creveld syndrome

Ellis–van Creveld syndrome is an autosomal recessive skeletal dysplasia that is characterized by thoracic hypoplasia, polydactyly, oral abnormalities, and congenital heart disease. It is caused by pathogenic variants in the EVC or EVC2 genes. We report a case of a newborn with a compound heterozygous variant comprising NM_147127.5: c.1991dup:[p.Lys665Glufs*10] in the EVC2 gene and a novel large deletion involving exon 1 in EVC and exons 1–7 in EVC2

Urinary angiotensinogen during renal development in neonates

Background All components of the renin-angiotensin system (RAS) are abundantly synthesized in the developing kidney, suggesting that the RAS plays an important role in renal development. To examine this system in human neonates, we measured urinary angiotensinogen levels in preterm and full-term neonates, and examined the relationship between urinary angiotensinogen levels and gestational age. Methods Urine and plasma samples were collected from 20 preterm and 18 full-term neonates at birth. Angiotensinogen levels were measured using enzyme-linked immunosorbent assay. Results Plasma angiotensinogen concentrations were not increased in preterm neonates compared to that in full-term neonates (P = 0.7288). However, the urinary angiotensinogen-to-creatinine ratio was significantly higher in preterm neonates compared to that in full-term neonates (P = 0.0011). Importantly, the urinary angiotensinogen-to-creatinine ratio dropped significantly with increasing gestational age (P = 0.0010), whereas the plasma angiotensinogen concentration was not correlated with gestational age (P = 0.7814). Conclusions These results suggest that urinary angiotensinogen levels may indicate the involvement of intrarenal RAS activation in prenatal renal development

Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells

Phosphoinositide 3-kinase (PI3K) negatively regulates Toll-like receptor (TLR)–mediated interleukin-12 (IL-12) expression in dendritic cells (DCs). We show here that 2 signaling pathways downstream of PI3K, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 (GSK3), differentially regulate the expression of IL-12 in lipopolysaccharide (LPS)–stimulated DCs. Rapamycin, an inhibitor of mTOR, enhanced IL-12 production in LPS-stimulated DCs, whereas the activation of mTOR by lentivirus-mediated transduction of a constitutively active form of Rheb suppressed the production of IL-12. The inhibition of protein secretion or deletion of IL-10 cancelled the effect of rapamycin, indicating that mTOR regulates IL-12 expression through an autocrine action of IL-10. In contrast, GSK3 positively regulates IL-12 production through an IL-10–independent pathway. Rapamycin-treated DCs enhanced Th1 induction in vitro compared with untreated DCs. LiCl, an inhibitor of GSK3, suppressed a Th1 response on Leishmania major infection in vivo. These results suggest that mTOR and GSK3 pathways regulate the Th1/Th2 balance though the regulation of IL-12 expression in DCs. The signaling pathway downstream of PI3K would be a good target to modulate the Th1/Th2 balance in immune responses in vivo