Isamu Hokuto

Digynic triploid infant surviving for 46 days

We report on a triploid infant who survived for 46 days. She had severe intrauterine growth retardation, relative macrocephaly, and a small, noncystic placenta, which are manifestations compatible with type II phenotype. Cultured amniotic fluid cells, skin fibroblasts, cord blood, and peripheral blood lymphocytes all showed a nonmosaic 69,XXX karyotype. Analysis of chromosomal heteromorphisms and microsatellite DNA polymorphisms in the infant and her parents indicated that the extra haploid set in the infant resulted from nondisjunction at maternal second meiosis. Postzygotic, mitotic nondisjunction was ruled out because of the presence of both homozygous and heterozygous markers of maternal origin. A search of the literature demonstrated five triploid infants, including the girl we described, who survived 4 weeks or more, and the parental origin of whose triploidy was studied: four were digynic and one was diandric. These findings support the notion that type II triploids are digynic in parental origin and that they survive longer than type I, diandric triploids.

Functional hemispheric specialization in processing phonemic and prosodic auditory changes in neonates

This study focuses on the early cerebral base of speech perception by examining functional lateralization in neonates for processing segmental and suprasegmental features of speech. For this purpose, auditory evoked responses of full-term neonates to phonemic and prosodic contrasts were measured in their temporal area and part of the frontal and parietal areas using near-infrared spectroscopy (NIRS). Stimuli used here were phonemic contrast /itta/ and /itte/ and prosodic contrast of declarative and interrogative forms /itta/ and /itta?/. The results showed clear hemodynamic responses to both phonemic and prosodic changes in the temporal areas and part of the parietal and frontal regions. In particular, significantly higher hemoglobin (Hb) changes were observed for the prosodic change in the right temporal area than for that in the left one, whereas Hb responses to the vowel change were similarly elicited in bilateral temporal areas. However, Hb responses to the vowel contrast were asymmetrical in the parietal area (around supra marginal gyrus), with stronger activation in the left. These results suggest a specialized function of the right hemisphere in prosody processing, which is already present in neonates. The parietal activities during phonemic processing were discussed in relation to verbal-auditory short-term memory. On the basis of this study and previous studies on older infants, the developmental process of functional lateralization from birth to 2 years of age for vowel and prosody was summarized.

Intrauterine MRI with single-shot fast-spin echo imaging showed different signal intensities in hypoplastic lungs.

Abstract Ultrasonography is used for the prenatal diagnosis of hypoplastic lungs. However, ultrasound poses problems because of difficulties in getting the entire lung in perspective and the results depend on the skill of the examiner. When the alveolar formation of the fetal lung is retarded, the fetus is predicted to show an altered density on MRI using an SSFSE sequence due to a varied amount of alveolar lung fluid. We present a case of twins who showed a marked difference in signal intensity of the lung on MRI, which was useful for predicting the fetal pathophysiology. Intrauterine MRI provides the possibility of diagnosing hypoplastic lungs prenatally.

Iridic and retinal coloboma associated with prenatal methimazole exposure

Michihiko Aramaki, IsamuHokuto, TadashiMatsumoto, Hitoshi Ishimoto,Makoto Inoue, Tokuhiro Kimura, Yo-ichi Oikawa, Kazushige Ikeda, Yasunori Yoshimura, Takao Takahashi, and Kenjiro Kosaki* Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan Department of Obstetrics, Keio University School of Medicine, Tokyo, Japan Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan Department of Pathology, Keio University School of Medicine, Tokyo, Japan Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

A congenital anterior diaphragmatic hernia with massive pericardial effusion requiring neither emergency pericardiocentesis nor operation. A case report and review of the literature.

Abstract All previously reported cases of anterior diaphragmatic hernia with massive pericardial effusion were treated by pericardiocentesis and radical surgery during the early neonatal period. However, we initially followed the course of our patient in the neonatal period. Subsequently, elective surgery was performed at 70 days of age. Including our case, cardiac tamponade has not been observed in any previously reported cases of congenital anterior diaphragmatic hernia with massive pericardial effusion. Conclusion: Emergency pericardiocentesis and surgery are not always required immediately after birth, even when the presence of this condition is suspected by prenatal diagnosis. Our observation may be beneficial to preterm low birth weight infants with this condition.

Cyclin E enhances P53-mediated transactivation

Plasmids expressing G1 and G2 cyclins were introduced into the Saos‐2 cell system monitoring p53‐mediated transactivation [(1993) Oncogene 8, 543]. Cyclin E, but not other cyclins, enhanced the p53‐mediated transactivation about 2‐fold. Co‐transfection of a CDK2 expression plasmid caused a 30% increase in the extent of the p53‐mediated transactivation. Moreover, the transfected p53 protein became phosphorylated coordinately with the enhanced transactivation. The close correlation between transactivation and p53 phosphorylation suggests that phosphorylation is involved in positive regulation for the transactivation by p53.

Usefulness of measurement of urinary N-terminal pro-brain natriuretic peptide in neonatal period

N-terminal pro-brain natriuretic peptide (NT-proBNP) is an N-terminal peptide dissociated from proBNP when BNP is generated from proBNP. Its molecular size is about 8500 kDa, and it has no physical activity. It is a sensitive marker for the early diagnosis and evaluation of heart failure, as its blood level increases from a mild stage of cardiac dysfunction. Serum NT-proBNP in childhood was reported by Schwachtgen. Some references have investigated the usefulness of urinary NT-proBNP, however, it is still very controversial. We measured the serum and urinary NT-proBNP levels in neonates, and evaluated their correlation and the usefulness of urinary NT-proBNP. The 36 serum and urine samples were collected at the age of 0–25 days from 9 neonates with a birthweight of 659–3330 g (median: 2864 g), who were born at 25–41 (median: 37) weeks’ gestation at Keio University Hospital between October 2007 and June 2008. Each NT-proBNP concentration was determined by ElectroChemi-Luminescence Immunoassay using modular analytics (Roche Diagnostics Co. Ltd, Tokyo, Japan). The serum and urinary sample needed is just 200 mL, and it takes about 20 min for analysis. Neonates who showed severe neonatal asphyxia, congenital heart disease, congenital malformation, or chromosomal anomaly were excluded. Urine samples were collected within 2 h before or after blood collection. Written informed consent was obtained from the neonates’ parents prior to the study. Serum level of NT-proBNP was in agreement with the normal range in the neonatal period reported by Schwachtgen. A significant correlation with a coefficient of determination of 0.548 was observed in the regression equation obtained by the least squares method between the serum and urinary NT-proBNP levels. The serum and urinary level of NT-proBNP was not normally distributed in each group. Furthermore, a low level of NT-proBNP was frequently observed, and we evaluated these data with a natural logarithm. As shown in Figure 1, similar significant correlation with a coefficient of determination of 0.703 was observed by the same method. NT-proBNP is considered to be excreted primarily via the kidney, and its metabolic routes via the muscle, liver, etc., have also been reported in adults. However, in neonates, the metabolic route via the muscle or liver may be negligible because of the small muscle mass and immature metabolic function of the liver. Blood samples cannot be collected in sufficient amounts from neonates, such as premature infants. The results of this study suggest that the cardiac load can be evaluated non-invasively according to the trend of changes in the urinary NT-proBNP level in neonates, especially extremely low-birthweight infants.

An ultra premature baby of 290 g birth weight needed more than 500 mg/kg of calcium and phosphorus daily

Ultrapremature babies accompanied by intrauterine growth retardation may require supplemental calcium and phosphorus far above the recommended doses.

Final diagnosis in patients with congenital cystic lung disease detected by fetal ultrasonography

Recently, congenital cystic lung diseases have frequently been detected before birth by fetal ultrasonography. The purpose of this study was to retrospectively evaluate the final diagnosis in patients diagnosed with congenital cystic lung disease by fetal ultrasonography. The study population comprised those babies delivered at Keio University Hospital between February 1996 and May 2008 who were found to have congenital cystic lung disease in utero. Fetal lung hypoplasia was defined according to the ratio of the fetal lung volume determined by fetal magnetic resonance imaging to the fetal body weight estimated by fetal ultrasonography. The subjects underwent chest radiography at birth and 1, 4, 7, and 10 months after birth and chest contrast-enhanced computed tomography (CT) 1 week and 10 months after birth. After bronchoscopy, bronchography, and angiography were performed 12 months after birth, a lobectomy was performed. The final diagnosis was made according to the clinical course, as well as the findings obtained by imaging techniques, and histopathological findings. Congenital cystic lung disease was detected in 25 infants during the study period. The prenatal and final diagnoses are shown in Figure 1 and Table 1. A prenatal diagnosis of congenital cystic adenomatoid malformation (CCAM) was made for all 17 patients that survived after birth; however, the final diagnoses were CCAM in six patients, bronchial atresia in eight and extralobar sequestration in three. Eight infants died before the 33 week of pregnancy; this includes the aborted cases (Fig. 1*). Of these eight fetuses, congenital cystic lung disease was complicated by hydrops fetalis in three and pulmonary hypoplasia in five. Of those with hydrops fetalis, fetal thoracoamniotic shunting was performed in two, but both were prematurely delivered and died soon after birth. None of the surviving infants had hydrops fetalis. Of the 17 infants delivered after 36 weeks of pregnancy, transient tachypnea of the newborn (TTN) was noted in one, but all others remained asymptomatic throughout the neonatal period with no mortality. In these 17 infants the prenatal diagnosis was CCAM in all cases. Two infants developed pneumonia within 1 year after birth, and the final diagnosis was CCAM type II in both. One further infant experienced two episodes of pneumonia and 14 underwent surgery without developing respiratory infections. In this study, the cystic lesions showed progressive regression in 10 infants (three with CCAM, five with bronchial atresia, and two with extralobar sequestration) but did not disappear completely in any of them. The cystic lesions showed progressive enlargement in three patients who died in the early neonatal period. In addition to lung hypoplasia and hydrops fetalis, progressive enlargement of the cystic lesion is considered to be a factor that exacerbates the prognosis. There have been few reports which describe outcomes of prenatally diagnosed cystic lung disease according to determined protocol. Congenital cystic lung diseases detected by fetal ultrasonography are often prenatally diagnosed as CCAM, but the final diagnosis of bronchial atresia was more frequent than that of CCAM among the survivors in this study. Postnatal bronchoscopy together with contrast-enhanced CT seems important for accurate diagnosis. In this study, a lobectomy to include the lesion was performed 12 months after birth. The indications and timing of surgery require further evaluation.

Metabolic acidosis due to continuous drainage of massive chylous pleural effusion in two neonates

There are two types of metabolic acidosis: one resulting from acid accumulation, and the other from HCO3 loss. The latter type is often associated with renal or intestinal HCO3 loss. We report two neonates who presented with metabolic acidosis due to continuous drainage of chylous pleural effusion and required sodium bicarbonate. Case 1: after normal pregnancy and threatened premature labor, baby 1 was born at 31 weeks 2 days of gestation with a birthweight of 1344 g. Because there was no spontaneous breathing, the child was put on a respirator. Bilateral pleural effusion gradually increased, and chest drainage was started at the age of 16 days. Because chylous pleural effusion fluctuated between 100 and 500 mL per day, physiological saline and albumin were given continuously to maintain the circulating plasma volume. The baby was diagnosed with congenital myotonic dystrophy, and the pleural effusion was considered associated with this condition. Octreotide and prednisolone were given to reduce the pleural effusion but no response was observed, and the baby died at the age of 126 days. Metabolic acidosis persisted throughout the clinical course. Arterial blood gas analysis before sodium bicarbonate was as follows: pH, 7.066; pCO2, 56.8 mmHg; base excess, -12.9 mEq/L; Na, 133 mEq/L; K, 5.2 mEq/L; Cl, 111 mEq/L; anion gap (AG), 9.9 mEq/L. Normal anion gap suggested that the metabolic acidosis was due to HCO3 loss. Stools were small in quantity, excluding the loss of HCO3 from the gastrointestinal tract. The urinary pH was 4.91 at a time when the serum pH was 7.03, 5.04 at a time when the serum pH was 7.38, excluding renal tubular acidosis. The dose of sodium bicarbonate required for pH adjustment changed with fluctuations in the amount of pleural effusion, suggesting HCO3 loss into the pleural effusion. It is not possible to measure HCO3 in the pleural effusion directly. Instead, we measured pH of the pleural effusion several times, and this was close to serum pH. For example, pH of pleural effusion was 6.992 at a time when the serum pH was 7.066, and 7.393 at a time when the serum pH was 7.336. We therefore estimated HCO3 loss assuming that HCO3 in the pleural effusion is the same as serum HCO3. The estimated HCO3 loss into the pleural effusion approximated the HCO3 dose given (Fig. 1a). Case 2: baby 2 developed pleural effusion from 30 weeks of gestation, and underwent thoracentesis with basket catheter placement. The infant was born at 33 weeks 4 days of gestation with a birthweight of 2055 g, and was placed on a respirator. Chest drainage for pleural effusion was started at the age of 2 days. Pleural effusion fluctuated between 100 and 500 mL per day, and the circulating plasma volume was adjusted with physiological saline, albumin, fresh frozen plasma (FFP), and gammaglobulin. At the age of 37 days or later, physiological saline was replaced with Lactated Ringer. The pleural effusion subsided after octreotide, thoracic duct ligation, and intrapleural infusions of autologous blood, and the baby was discharged at the age of 111 days. As in baby 1, metabolic acidosis with a normal anion gap was observed, requiring supplementation with sodium bicarbonate. Clinical and laboratory findings excluded HCO3 loss from the kidney or gastrointestinal tract. The estimated HCO3 loss into the pleural effusion approximated the HCO3 dose given (Fig. 1b). Metabolic acidosis with a normal anion gap is generally associated with HCO3 loss in the kidney or gastrointestinal tract. Siegler et al. reported that a 3-month-old infant with massive chylous pleural effusion resulting from postoperative thoracic duct injury presented with metabolic acidosis. The two infants reported here differed regarding the cause of chylous pleural effusion, the underlying disease, and the clinical course, but the clinical and laboratory findings suggest that the loss of HCO3 into the pleural effusion led to metabolic acidosis. We speculate that the continuous drainage of a large amount of chylous pleural effusion resulted in a reduction in plasma HCO3, and the circulating plasma volume was maintained with physiological saline and albumin, leading to dilutional metabolic acidosis. Baby 2 did not require sodium bicarbonate at the age of 23 days or later because of FFP use. At the age of 37 days or later, physiological saline was replaced with Lactated Ringer. This may have eliminated the need for sodium bicarbonate, but it was difficult to evaluate the effect of Lactated Ringer because of the decrease of pleural effusion. In the present study we estimated HCO3 loss to the pleural effusion by using serum HCO3, because serum pH always nearly equaled that of pleural effusion. But this does not mean that serum HCO3 concentration always equals that of the pleural effusion. This is a limitation of the study. It is hoped that a method to measure HCO3 concentration of the pleural effusion Correspondence: Emi Okishio, MD, Division of Neonatology, Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: e_oxy@yahoo.co.jp Received 22 January 2012; revised 6 June 2012; accepted 20 June 2012. bs_bs_banner