Kazuo Okuyama

A multicenter randomized trial of high frequency oscillatory ventilation as compared with conventional mechanical ventilation in preterm infants with respiratory failure

A multicenter randomised trial was conducted in nine neonatal centers in Japan to re-evaluate the safety and the efficacy of high frequency oscillatory ventilation using the piston type oscillator (Hummingbird) in the treatment of respiratory failure in preterm infants weighing between 750 and 2000 g at birth. A total of 92 infants were enrolled in the study. Forty-six infants were allocated to high frequency oscillatory ventilation and 46 infants to conventional mechanical ventilation. There were no differences in sex, birth weight, gestation and Apgar score between groups. The study was begun 2.0 +/- 1.6 h (mean +/- S.D.) after birth in the high frequency oscillation group and 1.7 +/- 1.5 h after birth in the conventional mechanical ventilation group. The absence of intraventricular hemorrhage was confirmed by echography in all cases before beginning ventilation. Mortality was similar in high frequency oscillatory ventilation and conventional mechanical ventilation (0 and 2%). The incidence of intraventricular hemorrhage was also similar in the high frequency and conventional mechanical ventilation groups (15 and 13% overall; 4 and 2% in grades III and IV, respectively). Nine percent of the infants in high frequency oscillatory ventilation and 13% in conventional mechanical ventilation developed bronchopulmonary dysplasia, but the difference was not significant. The frequency of air leaks was also equal in both groups. Periventricular leukomalacia was detected in 9% of infants on conventional mechanical ventilation and 2% on high frequency oscillation, but the difference was not significant. Mean airway pressure was significantly higher in the high frequency oscillatory ventilation group and the infants on high frequency oscillation showed a significantly higher arterial to alveolar oxygen tension ratio after 6 h of treatment. These results suggest that high frequency oscillatory ventilation does not increase the risk of severe complications such as air leaks, intraventricular hemorrhage or periventricular leukomalacia when it is used by experienced neonatologists. Indeed high frequency oscillatory ventilation helps provide better oxygenation with higher mean airway pressure without increasing the risk of bronchopulmonary dysplasia and severe complications such as air leaks and intraventricular hemorrhage.

Central nervous system disease in a child with primary Sjögren syndrome.

A 9-year-old girl had hemiparesis, and a diagnosis of primary Sjögren syndrome was made. The neurologic dysfunction was multifocal, involving both the brain and spinal cord, and was recurrent; the findings mimicked multiple sclerosis. Corticosteroid treatment during episodes of acute neurologic dysfunction appeared to be beneficial.

The site of 1α,25-dihydroxyvitamin D3 production in pregnancy

Metabolism of 25-hydroxyvitamin D3 (25-OH-D3) in pregnancy was investigated invitro in New Zealand White rabbits fed a rabbit chow. Kidney homogenates from pregnant mothers and fetuses were separately incubated with [3H]-25-OH-D3. The homogenates from fetuses produced significant amounts of [3H]-1α,25-dihydroxyvitamin D3 [1α,25-(OH)2-D3] from its precursor, while those from mothers predominantly produced [3H]-24,25-dihydroxyvitamin D3 [24,25-(OH)2-D3]. The identity of the radioactive metabolites produced from [3H]-25-OH-D3 was established by periodate cleavage and comigration with synthetic 1α,25-(OH)2-D3 or 24,25-(OH)2-D3 on high pressure liquid chromatography. These results clearly indicate that the fetal kidney is at least one of the sites of 1α,25-(OH)2-D3 synthesis in pregnancy.

Postnatal reference growth curves for very low birth weight infants

To construct standard growth curves for Japanese infants of very low birth weight (VLBW) with birth weights of 500-1499 g, we reviewed longitudinal data provided by 54 neonatal intensive care units in Japan. A total of 382 surviving singleton infants, appropriate for gestational age infants, and who were free of neurological sequelae at more than 2.5 years of age, were enrolled. Growth curves, including body weight, head circumference and body length were generated for four ranges of birth weight: 500-749 g, 750-999 g, 1000-1249 g, and 1250-1499 g. When compared with previously published growth data from western countries, Japanese infants of VLBW showed greater weight loss, regained birth weight more slowly, and exhibited smaller average gains in weight, head circumference, and body length. The growth curves reported in western countries may not be useful as reference standards of early postnatal growth in Japan. The new growth curves are a more accurate reflection of current in-hospital growth trends in Japan.

Nutrient balance, metabolic response, and bone growth in VLBW infants fed fortified human milk

The effects of fortification of preterm human milk were evaluated by comparing two groups of very low birth weight infants (birth weight < or = 1300 g, gestational age < or = 30 weeks): six fed preterm human milk fortified with a commercially available protein-mineral supplement (protein 0.7 g/dl, calcium 90 mg/dl, phosphorus 45 mg/dl) and seven fed unfortified preterm human milk. Nitrogen and energy balance studies were performed at an average age of 56 postnatal days. Nitrogen retention in the fortified group (348.2 +/- 70.5 mg/kg/day) was significantly greater than that in the unfortified group (196.0 +/- 50.0 mg/kg/day) and similar to that of fetuses of comparable gestational age. Energy stored by the two groups did not differ. At age 8 weeks, the infants in the fortified group had higher serum protein, higher serum albumin, and better mineral status (higher serum calcium and phosphorus and lower alkaline phosphatase and renal tubular reabsorption of phosphate). The bone density and width of the distal third radius, as measured by X-ray microdensitometry, were greater in the fortified group than in the unfortified group 12 weeks after birth. These results suggest that the supplement corrects any nutritional inadequacies of preterm human milk for very low birth weight infants.

Fortified preterm human milk for very low birth weight infants

We studied the nutritional effects of two types of human milk fortifiers for very low birth weight infants. These studies suggest that fortified human milk provides nutritional advantages for very low birth weight infants. However, providing calcium and phosphorus with supplementation is necessary for the improvement of bone density.

Intracranial vessels with color doppler echoencephalography in infants

A technique for imaging of the intracranial vessels in infants was described, which used high resolution, commercially available, color Doppler ultrasonography (real-time two-dimensional Doppler). On 12 normal infants, serial scans were obtained in sagittal, coronal, and axial plains. A large number of intracranial arteries and veins could be clearly demonstrated in real-time, including anterior cerebral artery, pericallosal artery, middle cerebral artery, posterior cerebral artery, basilar artery, communicating artery, internal cerebral vein, inferior and superior sagittal sinuses, great cerebral vein, straight sinus, occipital sinus and transverse sinus. In conclusion, color Doppler examination is useful in the detection of vessels in infants and in the measurement of intracranial blood flow velocity.

Monitoring of immature rabbit brain during hypoxia with near-infrared spectroscopy

Continuous monitoring of the cerebral blood flow, oxyhemoglobin, deoxyhemoglobin, total hemoglobin, oxidized cytochrome a, a3, and tissue pH during prolonged CO2 or N2 loading in 2-week-old rabbits was performed by near-infrared spectroscopy, the thermocouple method, and a tissue pH meter. Near-infrared spectroscopy demonstrated decreases in oxyhemoglobin and oxidized cytochrome a, a3 and increases in deoxyhemoglobin and total hemoglobin in the early stage within 5 min, which gradually lessened with time on both 10% concentration of inspired O2 with CO2 and N2. CBF increased with venous retention in the early stage and then slowly decreased in parallel with blood pressure and oxidized cytochrome a, a3 on abolition of autoregulation. These changes were more remarkable during the 10% concentration of inspired O2 with CO2 than N2 which may be caused by marked acidosis and hypotension associated with hypercarbia. Oxidized cytochrome a, a3, however, demonstrated a gradual decrease in 10% concentration of inspired O2 with N2 rather than CO2; therefore, the continuous monitorings demonstrated hemodynamic and oxygenation changes despite the same extent of prolonged hypoxic loading. These changes in prolonged hypoxic conditions may occur in human intrapartum asphyxia which develops into postnatal hypoxic-ischemic encephalopathy.

Ventriculitis in infants: Diagnosis by color doppler flow imaging

A color Doppler flow imaging technique was used to study the dynamics of cerebrospinal fluid (CSF) in infants with meningitis. Eight infants with bacterial meningitis (6) or aseptic meningitis (2) were studied with color Doppler imaging of CSF flow for a total of 18 times. In 2 infants with bacterial meningitis, Doppler sonograms of CSF flow were obtained in the aqueduct during the acute stage. The CSF flow demonstrated a to-and-fro motion which was synchronized with cardiac pulsations and respiration. The detection of CSF flow on color Doppler flow imaging in the aqueduct may indicate the existence of ventriculitis. Color Doppler flow imaging is useful for the evaluation of CSF flow dynamics in infants.

Evaluation of bone density in newborn infants by computed X-ray densitometry

We evaluated bone density in term and preterm infants using computed x-ray densitometry, which permits measurement of bone density with minimal disturbance to the infants in their incubators. Bone density, bone width, and bone length of the right radius were determined in 155 infants of appropriate weights for their gestational ages (23 to 41 weeks). A curve for intrauterine bone growth was extrapolated from these data. The mean coefficients of variations for variabilities for intra- and interobserver error for all measurements were < 3.5%. In 18 infants, measurements of the right forearm were obtained in two positions to confirm the validity of densitometric measurements. The mean coefficients of variation were 3.42% for bone density, 3.48% for bone width, and 0.21% for bone length. Bone density was significantly correlated with gestational age (r = 0.924) and birth weight (r = 0.921). Bone width and length were also correlated with gestational age (r = 0.866 and 0.937) and birth weight (r = 0.878 and 0.954). Our results suggest that computed x-ray densitometry is a useful method for evaluation of bone density in preterm infants, including those in an intensive care environment.