Ryuzo Higuchi

Plasma angiotensin II concentrations in the early neonatal period

Background: There have been only a few reports on the renin-angiotensin system in low birthweight infants; in particular, plasma angiotensin II concentrations have not been studied. Aim: To investigate plasma angiotensin II concentrations in early neonatal infants including low birthweight infants. Methods: Forty six patients were studied, of whom 14 weighed not less than 2500 g (normal birth weight), 16 weighed less than 2500 g but not less than 1500 g (moderately low birth weight), and 16 weighed less than 1500 g (very low birth weight). Blood samples were collected twice, on day 0 and day 7. Angiotensin II concentration was assayed using an enzyme immunoassay kit with a microplate. Results: Geometric means of angiotensin II concentrations on day 7 were 19 pg/ml in the normal birthweight group, 28 pg/ml in the moderately low birthweight group, and 76 pg/ml in the very low birthweight group. The concentrations on day 7 in the very low birthweight group were significantly higher than those in the normal birthweight and moderately low birthweight groups (p  =  0.005, p  =  0.031). There were significant correlations between angiotensin II concentration on day 7 and gestational age (rs  =  −0.4, p  =  0.007) and birth weight (rs  =  −0.36, p  =  0.016). Conclusions: Specific physiological conditions associated with a very low birth weight are thought to be responsible for the increased concentration of angiotensin II on day 7. It is necessary to measure angiotensin II concentration for a longer period after birth and study the factors that could influence it.

Correlation between echocardiographic superior vena cava flow and short-term outcome in infants with asphyxia

OBJECTIVES To assess the relationship between superior vena cava (SVC) flow and short-term outcome in infants with perinatal asphyxia. METHODS Infants in sequence born after more than 35 weeks of gestation who had been hospitalized at the NICU and normal neonatal wards of Wakayama Medical University between May 2005 and September 2010 were recruited for this observational cohort study. The study eligibility criterion was the presence of perinatal asphyxia, as evidenced by abnormal fetal heart rate monitoring and an Apgar score of 7 or less at 1 min or need for resuscitation using positive pressure ventilation. SVC flow was measured in the first three days of life by Doppler echocardiography as described by Kluckow and Evans. Short-term outcome was defined as poor if MRI demonstrated bilateral lesions of the basal ganglia and thalamus and/or multicystic encephalomalacia due to hypoxic ischemia. RESULTS In the head cooling group, SVC flow in infants with a good outcome was lower than that in infants with a poor outcome at 12h (36.9±7.7 vs. 113.4±42.4 ml/kg/min (p=0.01)), 24h (75.2±25.3 vs. 155.6±45.7 ml/kg/min (p=0.03)), and 48 h (92.5±34.2 vs. 161.1±46.7 ml/kg/min (p=0.04)) after birth. SVC flow decreased promptly after introduction of head cooling in infants who had a good outcome, whereas it increased gradually after head cooling in those who had a poor outcome. CONCLUSION We speculate that regulation of brain circulation is disrupted in infants with asphyxia who show a poor outcome.

Early Features in Neuroimaging of Two Siblings With Molybdenum Cofactor Deficiency

We report the features of neuroimaging within 24 hours after birth in 2 siblings with molybdenum cofactor deficiency. The first sibling was delivered by emergency cesarean section because of fetal distress and showed pedaling and crawling seizures soon after birth. Brain ultrasound revealed subcortical multicystic lesions in the frontal white matter, and brain MRI at 4 hours after birth showed restricted diffusion in the entire cortex, except for the area adjacent to the subcortical cysts. The second sibling was delivered by elective cesarean section. Cystic lesions were seen in the frontal white matter on ultrasound, and brain MRI showed low signal intensity on T1-weighted image and high signal intensity on T2-weighted image in bifrontal white matter within 24 hours after birth, at which time the infant sucked sluggishly. Clonic spasm appeared at 29 hours after birth. The corpus callosum could not be seen clearly on ultrasound or MRI in both infants. Cortical atrophy and white matter cystic lesions spread to the entire hemisphere and resulted in severe brain atrophy within ∼1 month in both infants. Subcortical multicystic lesions on ultrasound and a cortex with nonuniform, widespread, restricted diffusion on diffusion-weighted images are early features of neuroimaging in patients with molybdenum cofactor deficiency type A.

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan

Background : This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan.

Adverse perinatal and neonatal outcomes in patients with chronic abruption–oligohydramnios sequence

Chronic abruption–oligohydramnios sequence (CAOS) is a clinical condition with lasting vaginal bleeding and oligohydramnios because of chronic placental abruption, which seems to cause preterm labor and neonatal chronic lung disease (CLD). This prompted us to explore the correlation between perinatal/neonatal outcomes and CAOS.

Increased level/dose ratio of amphotericin‐B in premature infants with renal failure

We introduced continuous intravenous infusion of amphotericin‐B (AMPH‐B) to extremely low birth‐weight (ELBW) infants (< 1000 g) with or without renal failure as a single agent for treating definite or probable systemic candidiasis. The species of Candida isolated from blood or tracheal aspirate or urine were C. albicans in seven infants, C. glablata in two, C. tropicalis in one and C. parapsilosis in one. The minimal inhibitory concentrations (MIC) of AMPH‐B required against these isolates were less than 0.2 μg/mL except for that against one strain of C. albicans (0.78 μg/mL). Serum AMPH‐B levels were 0.31‐0.78 (0.51 ± 0.14) μg/mL when doses of 0.2‐0.55 (0.32 ± 0.11) mg/kg per day were being administered. The serum level was higher than the MIC of each isolate in all but one infant who died of disseminated intravascular coagulation and Candida pneumonia. Another infant died of congenital heart disease. The other nine infants survived. The serum level showed no correlation with the daily dose. The ratio of the serum level to the daily dose (L/D ratio) showed a significant correlation to serum creatinine (r = 0.787) and the linear regression curve followed the equation: L/D ratio = 0.223 x serum creatinine + 1.11 (P < 0.01). Few adverse effects due to AMPH‐B were noted. Our data may give a simple reference to serum AMPH‐B levels during continuous intravenous infusion from the dose and the serum creatinine level.

Rodriguez lethal acrofacial dysostosis syndrome with pulmonary hypoplasia

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Changes in Maternal and Child Health Outcomes After Introduction of a Helicopter into Perinatal Transportation in Japan

To examine the effect of perinatal helicopter transportation on maternal and child health. Helicopter transportation for the sparsely populated southern areas of Wakayama and Mie prefectures was introduced in June 2003. Maternal and child health statistics for 2000–2002 and 2004–2006 were compared between the south and north regions of the prefectures. There were 9 maternal transports from south Wakayama, 2 from north Wakayama, and 5 from south Mie in 2004–2006; and 13 neonatal transports from south Wakayama and 7 from north Wakayama during the same period. Decreases in neonatal and perinatal mortalities in 2004–2006 compared to 2000–2002 were greater in south Wakayama than in north Wakayama (−0.31 vs. −0.28, and −0.57 vs. −0.18, respectively); and greater in south Mie than in north Mie (−0.90 vs. −0.49, and −2.49 vs. −1.48, respectively). The changes in the number of maternal deaths between 2000–2002 and 2004–2006 were 0 in south Wakayama, 1 in north Wakayama, −2 in south Mie, and −1 in north Mie, with the greatest change occurring in south Mie. Use of a helicopter for perinatal transportation can possibly improve maternal and child health in sparsely populated areas far away from urban areas.

Neonatal tracheobiliary fistula diagnosed by MR cholangiopancreatography.

370 via a transverse upper abdominal incision. The esophageal hiatus was expanded and the remnant of the sac was mobilized from the FIGURE 1. Abdominal computed tomography image at a level below the diaphragm shows pneumobilia (arrows) and C ongenital bronchobiliary fistula, an uncommon malformation of the digestive tract, was first reported by Neuhauser et al (1) in 1952. The patient age distribution in previous case reports has ranged widely from infants to adults, despite the congenital nature of the anomaly. Here we report a Japanese neonatal case of tracheobiliary fistula that was diagnosed by bronchoscopy and magnetic resonance cholangiopancreatography.

DIAPHRAGMATIC HERNIA IN AN INFANT OF A DIABETIC MOTHER: AN UNUSUAL ASSOCIATION IN DIABETIC EMBRYOPATHY

A male infant, weighing 1250 g, was born at 32 weeks gestation. The mother was a 31-year-old Japanese, gravida 3, para 1, and the pregnancy had been complicated with insulin-dependent diabetes mellitus (IDDM), oligohydramnios and intrauterine growth retardation. Insulindependent diabetes mellitus (class B) developed in the mother at 23 years of age during her first pregnancy, which resulted in the stillbirth of an infant weighing 970 g at 29 weeks gestation. There was no specific description of congenital anomalies in the birth record. The mother spontaneously aborted twice thereafter. Three weeks after her last menstrual period, the mother complained of epigastric pain and discontinued insulin injections by her own volition. She was transferred to the emergency room 29 days after her last period due to loss of consciousness. On admission, she was semicomatose and showed diabetic ketoacidosis (blood sugar 35.4 mmol/L). Subcutaneous insulin injections were started again four times a day (54 units/day) and she soon recovered. Her hemaglobin (Hb) A1c increased from 7.9 to 8.6% and then decreased to 6.7% during her 1 month hospital stay, when she was found to be pregnant. From 13 weeks gestation, hypoglycemic episodes occurred once or twice a week, and she was admitted to our hospital at 19 weeks gestation because of threatened abortion, oligohydramnios and ‘brittle’-type IDDM. Continuous subcutaneous insulin infusions were started instead of four-times-a-day injections. At 32 weeks gestation, a preterm male infant was delivered by Cesarean section because of fetal distress and he had Apgar scores of 1 at 1 and 5 min. The baby was intubated but died at 11.5 h of age of respiratory failure. His birth weight of 1250 g was below the 1.9SD from the mean for 32 weeks gestation and his length was 31.5 cm (mean – 4.0SD) and his head circumference was 27.6 cm (mean –1.0SD). Physical examination of the infant revealed low-set ears, a flattened nose, a short neck, asymmetric thorax, undescended testes, absent anus, a reduction of the lower limbs, bilateral equinovarus and a preaxial polydactyly of the right great toe and a postaxial polydactyly in the right toe (Fig. 1). The urogenital raphe and anal pit were absent. The radiographic findings were right-sided CDH, scoliosis with left convexity at the lower thorax, fusion of the 8th and 9th right ribs and 10th and 11th right ribs, an absence of the right 12th rib, multiple vertebral anomalies (fused vertebrae and hemivertebrae) in the thoracolumbar spine, hypoplastic sacrum and dislocated hips (Fig. 2). The chromosome analysis revealed a normal 46XY karyotype with G banding. At autopsy, the right lung weighed 4.3 g and the left lung weighed 6.2 g. The ratio of lung weight to bodyweight was 0.82%, which indicates pulmonary hypoplasia. An atrial septal defect (ASD) with a diameter of 3 mm was found as an intracardiac anomaly. The colon was atretic at the end of sigmoid colon. The right kidney was absent and the left was small, multicystic and weighed 4.3 g. The testes, ureters and urinary bladder were absent.