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Respiratory failure is one of the most common and critical problems in pediatric wards. Assessments by chest X-rays (CXRs) are common and prevalent for determining the cause of respiratory failure in children. However, CXRs can be misinterpretated. Some patients may require further evaluation with other tools, such as chest computed tomography (CCT). Lung ultrasound (LUS) has proven useful for detecting lung abnormalities with respiratory failure in adults, but its usefulness in children is still not clear. We present a series of eight children who were admitted in a tertiary children's hospital. Each child underwent CXR, CCT, and LUS. In seven of eight cases, both LUS and CCT were able to detect abnormal findings. However, the radiological findings in CXRs were not sufficient. These cases included children with pleural effusion that was comorbid with consolidation, or cases with substantial consolidation that required thoracentesis or proper physical therapy. Key messages LUS can be beneficial for evaluating children with respiratory failure that are admitted in pediatric intensive care unit (PICU) and may contribute towards appropriate therapy for children. How to cite this article Fukuhara S, Yamaguchi Y et al. Lung Ultrasound in Children with Acute Respiratory Failure: Comparison between Chest X-ray, Chest Computed Tomography, and Lung Ultrasound: A Case Series. Indian J of Crit Care Med 2019;23(2):95-98.

Several studies describing the diurnal occurrence of febrile seizures have reported greater seizure frequency early or late in the evening relative to midnight or early morning. However, no articles have reported on the diurnal occurrence of complex febrile seizure. Moreover, no studies have addressed the relationship between seizure severity and diurnal occurrence. We retrospectively evaluated complex febrile seizures in 462 children needing hospitalization, and investigated the relationship between severity and diurnal occurrence according to four categorized time periods (morning, afternoon, evening, and night). Our study showed that complex febrile seizures occurred most often in the evening, peaking around 18:00 (18:00-18:59), and least often at night (02:00-02:59). In addition, the frequency with which patients developed status epilepticus or needed anticonvulsant treatments was also lower during the night. However, the seizure duration and the proportion of the patients who needed anticonvulsant treatment were the same among the four time periods. Furthermore, we compared three subclasses (repeated episodes of convulsions, focal seizures, and prolonged seizures (≧15min)), two of the complex features (focal seizures and prolonged seizures), and all complex features among the four time periods. However, they were the same among the four time periods. Taken together, our data indicate that although the severity of seizures was stable over a 24-hour period, the occurrence of seizures in our cohort of pediatric patients with complex febrile seizures requiring hospitalization was highest in the evening and lowest at night.

Background In the intensive care unit, the use of continuous electroencephalography (cEEG) in children with altered mental status often results in the detection of non-convulsive seizures (NCS). Children with influenza can occasionally display altered mental status, but the prevalence of NCS in children with influenza with altered mental status is yet to be determined. This study determined the prevalence of NCS in pediatric patients with altered mental status associated with influenza A(H1N1)pdm09 infection. Methods We retrospectively reviewed admissions to the pediatric intensive care unit between September 2009 and February 2010 and confirmed the presence of NCS on cEEG in children with influenza A(H1N1)pdm09 and with altered mental status. Results Of the 15 patients (aged 41−159 months old), NCS was identified on cEEG in five children (33%). Conclusions Approximately one-third of the children infected with influenza A(H1N1)pdm09 with altered mental status had NCS. Further research is needed to determine if the detection and management of NCS improve outcome in these children.

The optimal timing of decompressive craniectomy in pediatric patients after presentation with malignant middle cerebral artery infarction is unknown. We report herein the case of a previously healthy 6-year-old Japanese girl who had good outcome after emergency decompressive craniectomy 116 h after malignant middle cerebral artery infarction. This case suggests that the timing of decompressive craniectomy can be delayed until deterioration of neurological findings and, compared with adults, a more prolonged time course for surgical intervention might be acceptable.

Background Children who present with seizure and/or impaired consciousness accompanied by fever without known etiology (SICF) may be diagnosed with either acute encephalopathy (AE) or febrile seizure (FS). Although approximately 5% of AE cases are fatal, it is difficult to identify fatal cases among children with SICF, which are often critical by the time of diagnosis. Thus, early prediction of outcomes for children with SICF, prior to diagnosis, may help to reduce mortality associated with AE. The aim of the present study was to identify clinical and laboratory risk factors for mortality acquired within 6 h of onset among children with SICF. Methods We retrospectively reviewed the medical records of children who had been admitted to Kobe Children’s Hospital (Kobe, Japan) with SICF between October 2002 and September 2015. We compared clinical and laboratory characteristics acquired within 6 h of onset and outcomes between survivors and non-survivors using univariate and multivariate analyses. Results The survivor and non-survivor groups included 659 and nine patients, respectively. All patients in the non-survivor group received a final diagnosis of AE. Univariate analysis revealed significant differences between the groups with regard to seizure duration and the following laboratory parameters: aspartate transaminase (AST), alanine aminotransferase, lactate dehydrogenase, sodium, and lactate. The multivariate analysis identified AST as a significant independent factor associated with mortality. Conclusions Elevation of AST within 6 h of onset is independently correlated with mortality in children with SICF. Our result may elucidate earlier intervention for patients with high risk of mortality.

Background: Fosphenytoin (IPHT) and continuous intravenous midazolam (cMDL) had commonly been used as second-line treatments for pediatric status epilepticus (SE) in Japan. However, there is no comparative study of these two treatments. Methods: We included consecutive children who I) were admitted to Kobe Children's Hospital because of convulsion with fever and 2) were treated with either fPHT or cMDL as second-line treatment for convulsive SE lasting for longer than 30 min. We compared, between the fPHT and cMDL groups, the proportion of barbiturate coma therapy (BCT), incomplete recovery of consciousness, mechanical ventilation, and inotropic agents. Results: The proportion of BCT was not significantly different between the two groups (48.7% [20/41] in fPHT and 35.3% [29/82] in cMDL, p = 0.17). The prevalence of incomplete recovery of consciousness, mechanical ventilation, and inotropic agents was not different between the two groups. After excluding 49 patients treated with BCT, incomplete recovery of consciousness 6 h and 12 h after onset was more frequent in the cMDL group than in the IPHT group (71.7% vs. 33.3%, p

Background The aim of this study was to identify predictors of neurologic damage in children with febrile seizures or altered consciousness within 6 h of seizure onset. Methods The present study included 86 children (age range, 4–159 months old), who fulfilled the diagnostic criteria for complex febrile seizures on admission between October 2002 and November 2008. Using the Pediatric Cerebral Performance Category Scale (PCPC), the children were classified into two groups: poor outcome (PCPC = 2–6) and good outcome (PCPC = 1). Clinical profiles and laboratory findings were compared between the groups. Results Of the 86 children, 17 fell into the poor outcome and 69 into the good outcome group. Using univariate analysis, three early risk factors for poor outcome were identified: (i) consciousness disturbance or hemiplegia at 6 h from onset; (ii) refractory status epilepticus; and (iii) elevation of aspartate aminotransferase to >90 IU/L within 6 h of onset. Using these criteria, children in the poor outcome group were identified with a 94% sensitivity and 67% specificity rate (odds ratio, 36.6; 95% confidence interval: 4.87–1560). During the study period, the inpatients who met the criteria for acute encephalopathy also fell into the poor outcome group. Conclusions The development of neurologic damage in children with complex febrile seizures can be predicted within 6 h of onset, using the identified risk factors. The authors propose an assumption of severe febrile seizures (SFS) in children who fulfill these risk factors. Using SFS as an inclusion criterion, an interventional study for acute encephalopathy can be designed.

Central nervous system involvement in hemophagocytic lymphohistiocytosis (HLH) is associated with a poor outcome. For such patients, it is unknown whether more aggressive therapies, such as intrathecal methotrexate or hydrocortisone, are inevitably required. We present a very rare case of 3-year-old Japanese girl who developed mild encephalitis/encephalopathy with a reversible splenial lesion, accompanied by Epstein-Barr virus-associated HLH, and review previous similar reports. Our case and previous reports suggest that mild encephalitis/encephalopathy with a reversible splenial lesion accompanied by Epstein-Barr virus-associated HLH has a relatively good prognosis, even in the absence of intrathecal treatments.

Background The time-dependent changes that occur in children after acute encephalopathy are not clearly understood. Therefore, we assessed changes in brain function after suspected acute encephalopathy over time. Methods We created a database of children admitted to the pediatric intensive care unit at Kobe Children’s Hospital because of convulsions or impaired consciousness with fever between 2002 and 2013. Clinical courses and outcomes were reviewed and patients who met the following criteria were included in the study: (1) 6 months to 15 years of age, (2) no neurological abnormality before onset, (3) treated for suspected acute encephalopathy, and (4) followed after 1 (0–2) month and 12 (10–17) months of onset. Outcomes were assessed using the Pediatric Cerebral Performance Category (PCPC) scale, with a score of 1 representing normal performance; 2, mild disability; 3, moderate disability; 4, severe disability; 5, vegetative state; and 6, brain death. Results A total of 78 children (32 male) with a median (range) age at onset of 20 (6–172) months were enrolled. Fifty-one cases scored 1 on the PCPC, 13 scored 2, three scored 3, five scored 4, one scored 5, and five cases scored 6 at discharge. Whereas seven of the 13 cases that scored a 2 on the PCPC recovered normal brain function after 12 months, none of the nine cases that scored a 3–5 on the PCPC recovered normal function. Conclusions Our findings suggest moderate to severe disability caused by acute encephalopathy had lasting consequences on brain function, whereas mild disability might result in improved function.

BACKGROUND In the neonatal intensive care unit (NICU), hemodynamics in very low-birthweight infants are generally examined for oxygen saturation (SpO2), heart rate, respiration rate, and blood pressure. The present study examined how changes in cerebral circulation in preterm infants can be evaluated by the SpO2 monitoring method with near infrared spectroscopy (NIRS) to detect the cerebral circulation. METHODS The study was conducted in 11 low-birthweight neonates with a mean weight of 1252 g (940-1948 g), mean post-conceptional age of 28.9 weeks (28-31 weeks) and in whom a total of 145 apneic episodes were examined. Changes in cerebral circulation at the apneic attack were evaluated by two parameters of Delta HbD ( micro mol/L) for reduction in cerebral oxygenation and Delta cHb (mL/100 g brain) for variation in cerebral blood volume using the near infrared spectroscopy (NIRS). RESULTS There was a tendency for a reduction in cerebral oxygenation and a change in cerebral blood volume as SpO2 was reduced. In the event of apneic attacks where SpO2 was reduced to

Background: This study aims to determine the effect of differently positioned infant car seats on cardio­respiratory parameters in healthy full-term newborns. Methods: We examined 15 healthy term newborns for respiratory compromise due to normal restraint in a recommended infant car seat. There are currently two types of car seats available in Japan: a chair-shaped car seat and a bed-shaped car seat. Using a sleep apnea recorder, we simultaneously monitored heart rate, percutaneous oxygen saturation, chest impedance and nasal airflow in infants placed in each of the car seats and also placed in the supine position on a nursery cot. Episodes of oxygen desaturation below 95% and longer than 10 s (mild desaturation) and below 90% longer and than 10 s (moderate desaturation) were evaluated over 30 min observation period. Results: The amount of time infants spent in a sleep state was significantly longer in the car seats than it was on the cot (P = 0.0015 for bed-shaped, P = 0.0012 for chair-shaped) and there was no difference in this measure between the two types of car safety seats. Mean of oxygen saturation with the chair-shaped car seat (95.8%) was significantly lower than that with the bed-shaped car seat (98.8%) (P = 0.0008). Newborn infants laid on the cot showed no episodes of desaturation. Newborn infants placed in the chair-shaped car seat had significantly more episodes of mild desaturation (mean, 7.33 times in nine of 15 infants), whereas in the bed-shaped seat observed only once each in two infants (P = 0.008). Moderate desaturation was observed in four of 15 infants in the chair-shaped car seat, whereas not observed in the bed-shaped car seat (P = 0.068). Conclusion: The results suggest that prior to discharge the degree of oxygen desaturation that occurs when an infant is placed in a chair-style car seat should be checked.

ObjectivesThis study aimed to verify the screening performance of our clinical prediction rule for neurological sequelae due to acute encephalopathy (NSAE-CPR), which previously identified the following three variables as predictive of poor outcomes: (1) refractory status epilepticus; (2) consciousness disturbance and/or hemiplegia at 6 hours from onset and (3) aspartate aminotransferase >90 IU/L within 6 hours of onset.DesignMedical community-based multicentre retrospective cohort study.SettingSix regional hospitals in Harima and one tertiary centre in Kobe, Japan, from 2008 to 2012.ParticipantsWe enrolled a total of 1612 patients aged Primary outcome measuresUnivariate and multivariate analyses were performed to determine the association between each of the three predictor variables and poor AE outcome (Pediatric Cerebral Performance Category score ≥2). Receiver operating characteristic curve (ROC) analysis was also performed to assess the screening performance of the NSAE-CPR.ResultsThe ROC analysis identified at least one of the three predictive variables as an optimal cut-off point, with an area under the curve of 0.915 (95% CI 0.825 to 1.000). The sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and Matthews correlation coefficient were 0.867, 0.954, 0.149, 0.999, 18.704, 0.140 and 0.349, respectively.ConclusionsOur findings indicate that the NSAE-CPR can be used for the screening and identification of patients with poor outcomes due to acute encephalopathy within 6 hours of onset.

Background: The aim of the present study was to evaluate the value of an end-tidal carbon monoxide corrected for inhaled carbon monoxide concentration (ETCOc) at the early neonatal period. The value would be useful for predicting subsequent hyperbilirubinemia in non-hemolytic full-term infants. Methods: The ETCOc levels were measured every 6 h during the first 72 h of life in healthy, full-term, non-hemolytic, newborn Japanese infants using a breath carbon monoxide analyzer. The ETCOc levels in hyperbilirubinemic infants were compared with those in non-hyperbilirubinemic infants. Hyperbilirubinemia was defined as the level of the peak total serum bilirubin concentration (TBC) greater than or equal to 257 μmol/L (15.0 mg/dL). The ETCOc measurement for predicting subsequent hyperbilirubinemia was evaluated with a receiver–operating characteristic (ROC) curve. Results: Fifty-one infants were enrolled in the study. Seven of the 51 infants developed hyperbilirubinemia. The ETCOc levels in non-hyperbilirubinemic infants were decreased in the first 72 h after birth. However, those in the hyperbilirubinemic infants were not decreased significantly, and were higher than those in non-hyperbilirubinemic infants at 42, 48, 54 and 66 h of age. The ETCOc level at 42 h of age was the most predictive of subsequent hyperbilirubinemia by ROC analysis. At the cut-off level of 1.8 μL/L (p.p.m.), the sensitivity, the specificity, the positive predictive value and negative predictive value were 86, 80, 40 and 97%, respectively. Conclusion: Increased ETCOc level in the early neonatal period is associated with subsequent hyperbilirubinemia, even in infants without hemolytic disease. The ETCOc measurement may be useful as a screening test for predicting hyperbilirubinemia without hemolytic diseases.

Background: In the present study, we investigated the effect of dexamethasone (DEX) therapy on extubation and pulmonary function in patients with chronic lung disease (CLD) who required long-term mechanical ventilation. In addition, we compared the effects of DEX therapy among CLD types. Methods: Twenty-two CLD patients who were ventilator dependent for 28 days or longer received DEX therapy for the purposes of extubation. A tapering dose of DEX, starting from 0.5 mg/kg per day, was administered for 7 days. Pulmonary function was measured at initiation of administration and 4 days after initiation. We evaluated static respiratory system compliance (Crs) and static respiratory system resistance (Rrs) adjusted by bodyweight. Chronic lung disease types were categorized according to the classification of the Ministry of Health and Welfare Research Project. We compared the effect of DEX therapy among CLD types. Results: Dexamethasone therapy was started at a mean (±SD) 45±11 days after birth and 32.1±1.3 weeks of postconceptional age in infants with a mean bodyweight of 939±153 g. After DEX therapy, extubation was successful in all 22 patients. Following DEX administration, Crs was significantly increased from 0.69±0.13 to 1.17±0.21 mL/cm H2O per kg. In contrast, Rrs did not show any clear changes. Comparing CLD types, no difference was observed for Crs and Rrs in each disease type. Conclusions: Dexamethasone was administered to CLD patients requiring long-term mechanical ventilation for the purposes of extubation and extubation was successful in all patients. It was found that Crs was increased in all patients following DEX, regardless of CLD type. The increase in Crs following DEX administration may have been related to successful extubation.

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. Methods: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. Results: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1500 g and 39 infants weighed more than 2500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. Conclusions: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

In the intensive care unit, the use of continuous electroencephalography (cEEG) in children with altered mental status often results in the detection of non-convulsive seizures (NCS). Children with influenza can occasionally display altered mental status, but the prevalence of NCS in children with influenza with altered mental status is yet to be determined. This study determined the prevalence of NCS in pediatric patients with altered mental status associated with influenza A(H1N1)pdm09 infection.We retrospectively reviewed admissions to the pediatric intensive care unit between September 2009 and February 2010 and confirmed the presence of NCS on cEEG in children with influenza A(H1N1)pdm09 and with altered mental status.Of the 15 patients (aged 41-159 months old), NCS was identified on cEEG in five children (33%).Approximately one-third of the children infected with influenza A(H1N1)pdm09 with altered mental status had NCS. Further research is needed to determine if the detection and management of NCS improve outcome in these children.

In order to clarify the difficulties which handicapped people experienced in the Hanshin-Awaji earthquake disaster, 678 families with handicapped children were studied 1.5 months after the earthquake. All the students who were enrolled in this study were going to some type of school or training classes for handicapped children in January 1995. The study was completed between 1 and 10 March. The questionnaires which were designed for this study consisted of three parts: the difficulties which the families were faced with, their requirements for social and medical services and the symptoms and reactions of their children after the earthquake. A total of 466 answers were obtained from their parents. The kinds of difficulties differed between the families of mentally retarded children and those of the physically handicapped. While many parents with physically handicapped children desired better medical information or materials, many parents with mentally retarded children wanted better care services for their children. Physical and psychological effects of the earthquake were only temporary in most cases. However, some of the handicapped children were still suffering from such reactions as of 10 March. From the results of our study it became evident that a systematic relief program for these handicapped people should be established. The relief program should include the distribution of information regarding medical and social services. Psychological reactions such as panic, excitement and suppression of mental activity were still observed in some handicapped children on 10 March. Further observation will therefore be necessary.

The aim of this study was to identify predictors of neurologic damage in children with febrile seizures or altered consciousness within 6 h of seizure onset.The present study included 86 children (age range, 4-159 months old), who fulfilled the diagnostic criteria for complex febrile seizures on admission between October 2002 and November 2008. Using the Pediatric Cerebral Performance Category Scale (PCPC), the children were classified into two groups: poor outcome (PCPC = 2-6) and good outcome (PCPC = 1). Clinical profiles and laboratory findings were compared between the groups.Of the 86 children, 17 fell into the poor outcome and 69 into the good outcome group. Using univariate analysis, three early risk factors for poor outcome were identified: (i) consciousness disturbance or hemiplegia at 6 h from onset; (ii) refractory status epilepticus; and (iii) elevation of aspartate aminotransferase to90 IU/L within 6 h of onset. Using these criteria, children in the poor outcome group were identified with a 94% sensitivity and 67% specificity rate (odds ratio, 36.6; 95% confidence interval: 4.87-1560). During the study period, the inpatients who met the criteria for acute encephalopathy also fell into the poor outcome group.The development of neurologic damage in children with complex febrile seizures can be predicted within 6 h of onset, using the identified risk factors. The authors propose an assumption of severe febrile seizures (SFS) in children who fulfill these risk factors. Using SFS as an inclusion criterion, an interventional study for acute encephalopathy can be designed.

Two types of mefenamic acid (MA) suppositories were prepared, one with Vosco®, an oleaginous base (Vosco suppository) and another with polyethylene glycol (PEG), a watersoluble base (PEG suppository). The crystallinities of MA in the Vosco and PEG suppositories, the in vitro release behaviors of MA from them, and the pharmacokinetics of MA following their rectal administarations to healthy volunteers were respectively compared. X-ray diffractometry revealed that MA in the Vosco suppository was mainly dispersed in a crystal form, whereas MA in the PEG suppository was disseminated in the amorphous state, with the in vitro release of MA from the PEG suppository being faster. MA in the Vosco or PEG suppository was chemically stable, and the in vitro release behavior of MA from each suppository did not change after storage for 2 months at 5°C. The serum MA maximum concentration (Cmax) and the time to reach Cmax after rectal administration of the PEG suppository appeared to be respectively higher and to be shorter than those of the Vosco suppository. The areas under the serum MA concentration-time curves (AUCs) from zero time to 8 h for the Vosco and PEG suppositories were 3.2 and 4.1 μg·h/ml, respectively, and their values were not significantly different. It was concluded that the PEG suppository presented a faster release characteristic of MA than did the Vosco suppository and that the serum MA concentration profiles arising after administration of these suppositories reflected their release characteristics.

Serum unbound bilirubin concentrations (UBC) and serum total bilirubin concentrations (TBC) were measured serially in 138 low birthweight (LBW) infants treated with phototherapy for non-hemolytic hyperbilirubinemia. We attempted to assign the suitable critical UBC levels for predicting bilirubin encephalopathy into two different birthweight groups: a very low birthweight (VLBW) group (birthweight < 1,500 g) and an LBW group (birthweight between 1,500 g and 2,499 g). Twelve infants were diagnosed as 'at risk' for kernicterus, of whom 11 had signs of acute bilirubin encephalopathy and received exchange transfusion. One VLBW infant had neurological sequelae at a 3 year follow-up, although exchange transfusion was not carried out because of low TBC. Sensitivity and specificity for predicting kernicterus were calculated at different UBC levels between 0.6 microgram/dl and 1.5 micrograms/dl and TBC levels between 8 mg/dl and 26 mg/dl. The receiver-operating characteristic (ROC) curves plotted for UBC as a predictor of kernicterus were clearly shifted up and to the left compared with the curves for TBC in the VLBW and LBW groups. Thus, the UBC measurement may well provide a more rational basis for evaluating the risk of kernicterus in LBW infants. The optimal cut-off points were derived from these curves. In the VLBW group, the sensitivity was 100% and the specificity was 96% for a UBC of 0.8 microgram/dl, and 80% and 64% for a TBC of 11 mg/dl. In the LBW group, the sensitivity was 100% and the specificity was 98% for a UBC of 1.0 microgram/dl and 71% and 78% for a TBC of 16 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and 1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (TCCA), both precursors of mutagenic N-nitroso compounds (N-nitrosamines, 1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid and 2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid), were detected in various food-stuffs, urine from healthy human subjects and human milk. A purification procedure, involving a chemically-bonded material followed by HPLC combined with fluorometric detection, was used for the quantitative determination of these compounds, allowing the separation of two diastereoisomers of MTCA. An HPLC and mass spectrometry method was also developed for their identification. Comparing the concentration of MTCA and TCCA in fermented products and raw materials suggested that tetrahydro-beta-carbolines may have been produced through fermentation or by condensation of tryptophan and acetaldehyde formed from ethanol added as a food preservative. This is the first report of excretion of tetrahydro-beta-carbolines in human urine and human milk. A comparison of the concentrations of tetrahydro-beta-carbolines in urine from human infants and human milk indicates that tetrahydro-beta-carbolines may be synthesized endogenously in humans. A possible pathway of tryptophan metabolism in plants and animals is presented.

Twenty hydrocephalic patients diagnosed in the third trimester of fetal life were evaluated and followed during a 7-year period. The factors affecting the prognosis, including the type of hydrocephalus, underlying conditions, associated anomalies, time of diagnosis and delivery, fetal period after diagnosis, head circumference and degree of ventriculomegaly at birth, and age at treatment, were comprehensively analyzed. The difference between final outcomes as assessed by developmental quotient (DQ) or intelligence quotient (IQ) were statistically tested with computation by means of STAX packages in an NEC 9801 VX. Hydrocephalus as an isolated defect occurred in six cases (30%), was associated with other central nervous system anomalies in nine (45%), and was secondary to intrauterine intraventricular hemorrhage or brain tumor in five (25%). The average age at the time of diagnosis was 33.9 weeks of gestation (range, 27-40 weeks). One fetus was treated by transabdominal cephalocentesis, but the majority of patients underwent ventriculoperitoneal shunt postnatally. The final IQ or DQ scores ranged from 20 to 120 (mean score, 50.6). The data analyses revealed that the only significant factor affecting outcome was the fetal period after diagnosis of hydrocephalus (r = -0.5076, p less than 0.01). Our data supports the fact that the results of an on-going hydrocephalic state may become irreversible during fetal life. It is emphasized that establishment of a more precise pathophysiological evaluation, and a less invasive but more reliable decompressive technique for fetal hydrocephalus, is urgent.

Biliary atresia (BA) is a rare disease, characterized by progressive and obliterative cholangiopathy, and is one of the major causes of secondary vitamin K deficiency in infancy. We describe 15 infants (10 female, 5 male) with BA, presenting with intracranial hemorrhage (ICH), including 10 subdural hemorrhages, 4 subarachnoid hemorrhages, 2 intraventricular hemorrhages, and 1 intraparenchymal hemorrhage. The age at onset of ICH ranged from 26 to 79 (mean 54.2) days. Eight patients underwent successful surgical evacuation of ICH, following administration of vitamin K. All 15 patients underwent Kasai portoenterostomy for BA 8–30 days after onset. During a mean follow-up period of 86.8 (range 2–352) months, 4 patients died of liver failure despite lack of neurological sequelae. Two patients underwent living-related donor and 1 patient living-unrelated donor liver transplantation. Only 2 patients suffered neurological signs and symptoms, including mental retardation and epilepsy, whereas 3 were noted to have temporary hemiparesis which recovered completely during the follow-up period. The possibility of BA should be considered in the treatment of ICH due to vitamin K deficiency, since it is reported to be one of the major causes of secondary vitamin K deficiency. Urgent surgical intervention for ICH can be performed successfully following sufficient administration of vitamin K or fresh frozen human plasma. Moreover, early performance of Kasai portoenterostomy is possible even for patients who have undergone craniotomy.

The serum bilirubin level of Japanese newborn infants in their first few days is significantly higher than that in Caucasian newborn infants, suggesting that there might be genetic risk factors for the development of neonatal hyperbilirubinemia in the Japanese population. Recently, it has been reported that a variant TATA box in the promoter region of the bilirubin UDP-glucuronosyltransferase 1 (UGT1A1) gene is associated with the development of neonatal hyperbilirubinemia. This finding led us to the idea that a mutation, glycine to arginine at codon 71 (G71R), in the coding region of the UGT1A1 gene can cause neonatal hyperbilirubinemia. In this study, we determined the genotypic distribution of the G71R mutation in 72 Japanese newborn infants: 23 infants with hyperbilirubinemia and 49 infants without hyperbilirubinemia. In the hyperbilirubinemia group, 15 of 23 newborn infants had the G71R mutation (3 homozygotes and 12 heterozygotes), whereas in the non-hyperbilirubinemia group 16 of 49 newborn infants had the G71R mutation (1 homozygote and 15 heterozygotes). Therefore, the G71R mutation was present significantly more frequently in the hyperbilirubinemia group than in the non-hyperbilirubinemia group. This finding strongly suggests that the presence of the G71R mutation contributes to the development of neonatal hyperbilirubinemia in the Japanese population.

The first known surviving case of acrania is presented. The patient was the first child of a 29-year-old Japanese woman. Fetal ventriculomegaly was documented in the 35th gestational week. Prenatal sonography and magnetic resonance imaging suggested hydrocephalus with a wide encephalomeningocele. The baby was born at 38 weeks of gestational age by vaginal delivery. The patient had no calvarium, but did have a complete skull base with a partial defect in the occipital scalp and an underlying dural defect. Subsequently, the patient underwent repair of the scalp defect. At 3 months of age, after hydrocephalus developed, a subduro-peritoneal shunt was placed because of cosmetic and nursing problems. His developmental quotient was 10 at 3 years.

The urinary excretion of cytomegalovirus (CMV) DNA, amplified by polymerase chain reaction using two pairs of primers for late antigen (LA) and major immediate-early antigen (MIE), and serum CMV IgM were examined in 85 pre-term infants (birth-weight less than 2000 g) on admission and monthly until 6 months after birth. Of these 85 infants, 27 had blood exchange transfusions (BET) and 28 had bolus blood transfusions two to nine times. Fifteen of 27 infants underwent BET with blood that had been filtered through Pall RC100 leukocyte removal filter; the other 12 with unfiltered blood. Neither urinary CMV DNA nor serum CMV-specific IgM was detected at birth in any of the 85 pre-term infants; during the first 6 months after birth urinary CMV DNA, for both MIE and LA, appeared in 22 of the 85 infants (25.9%) and CMV IgM was positive in 14 of the 85 (16.5%). Nine of the 12 (75%) infants who received BET of unfiltered blood showed a significantly higher prevalence of urinary CMV DNA compared to the infants in the other three groups (i.e., those who received no blood transfusion, those who had bolus blood transfusions, or those who received BET of filtered blood; P < 0.01 in each instance). In a logistic regression model, CMV DNA urinary excretion was significantly associated with the mode of blood transfusion (unfiltered BET), and the Odds ratio was 38.9 (95% confidence interval, 9.4-160). There was no significant association with other independent variables such as gender, mother's seropositivity, gestational age, birth-weight or delivery mode.(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify the preventive effects of glucocorticoid on perinatal hypoxic-ischemic (HI) brain damage, an experiment was carried out on 4-day-old rats pretreated for 4 consecutive days with 3 different regimens; namely, a low dose dexamethasone (Dex) (0.1 mg/kg/day), a high dose Dex (0.5 mg/kg/day), and a saline administration. On the 7th postnatal day, after ligation of the left common carotid artery, the rats were exposed to 8% oxygen and decapitated on the 10th, 14th, 21st and 28th postnatal days. Ligated side brain damage was observed in 75, 7 and 3% of the rats in the saline, low and high dose Dex groups, respectively. However, a high mortality rate (42%) was noted in the high dose Dex group. The cumulative number of animals with poor outcome (death or brain damage) was 49 (80%), 13 (33%) and 24 (44%) in the saline, low and high dose Dex groups, respectively. On the 10th and 14th postnatal days, the rats in both the Dex groups showed delayed neuronal maturation and myelination in the non-ligated side motor cortex, however, these maturational differences disappeared on the 21st postnatal days. Otherwise, the number of cortical cells in both the Dex groups were significantly lower than that in the saline group on the 28th postnatal days (P < 0.05 in each). These findings suggest that the pretreatment with Dex protects the developing brain from HI injury through the suppression of the neuronal maturation. However, a decreased number of cortical cells may give rise to psychomotor retardation later.

To determine the effects of maternal administration of dexamethasone (DEX) and thyrotropin-releasing hormone (TRH) on fetal lung maturation, 16 pregnant rats were divided into the following four groups: 20 μg/kg TRH twice a day was given intraperitoneally to the TRH group rats, 0.5 mg/kg/day DEX to the DEX group and both DEX and TRH to the DEX + TRH group for 3 consecutive days from gestational day 17. The control rats were given an equivalent volume of saline. The pregnant rats were sacrificed on gestational day 20 and the fetal lungs were removed. The relative amounts of surfactant protein A (SP-A), B (SP-B) and C (SP-C) mRNAs were analyzed by Northern blotting and the total lung disaturated phosphatidylcholine (DSPC) contents were determined using an enzymatic method. The SP-B and -C mRNA and DSPC contents in the DEX and DEX + TRH groups were significantly higher than those in the control group, whereas the SP-A mRNA levels did not differ significantly among the four groups. The SP-B and -C mRNA and DSPC contents in the DEX and DEX + TRH groups did not differ significantly. These findings suggest that TRH has no effects on the regulation of surfactant protein mRNAs or DSPC contents in the fetal rat lung and has no additive effects when combined with DEX.

We conducted a prospective study to investigate perioperative changes in the production of superoxide anion (O2-) by neutrophils isolated from ten neonates between the ages of five and 16 days (N group) and ten infants ranging in age from one to ten months (I group). They underwent abdominal surgery under general anaesthesia with halothane and nitrous oxide in oxygen. The O2- production (speed and amount) was measured perioperatively using the cytochrome c reduction method. Both groups showed a decrease in the speed and amount of O2- production during and after surgery. The decrease in O2- production reached its lowest level three hours postoperatively or at the end of surgery in both groups. The O2- production in the I group returned to the basal value 48 hr postoperatively. In contrast, the O2- production in the N group was still lower 48 hr after surgery than before anaesthesia. Although the total amount of O2- production by neutrophils in one mL of peripheral blood remained unchanged in the I group, the total amount of O2- production in the N group decreased at the end of surgery and thereafter. These data indicate that even relatively minor abdominal surgery with halothane anaesthesia may be associated with perioperative neutrophil impairment in both neonates and infants. This impairment of neutrophil function in infants but not in neonates may be compensated by an increase in neutrophil numbers. It is possible that perioperative susceptibility of neonates to bacterial infections is attributable, at least in part, to the inhibition of O2- production in neutrophils by surgery and general anaesthesia.

MRI-Based White Matter Volumes and Motor Impairment in Preterm Infants with Spastic Cerebral Palsy

END-TIDAL CARBON MONOXIDE (ETCO) AND NONHEMOLYTIC HYPERBILIRUBINEMIA IN FULL-TERM INFANTS. † 1394

We investigated the activity and the content of copper and zinc-containing superoxide dismutase (SOD) and superoxide anion (O2-) production in polymorphonuclear leukocytes (PMN) from healthy term newborn infants, very low birth wt infants, and healthy adults. SOD activity in PMN was measured with nitroblue tetrazolium reduction assay on PAGE, and the SOD content in PMN was determined with an ELISA using a monoclonal antibody against human copper and zinc-containing SOD. The activity and the content of SOD in the term neonatal PMN and VLBW-infants' PMN were significantly lower than those in the adults' PMN (term newborn infants, 6.6 +/- 0.6 U/mg protein and 170.4 +/- 16.3 ng/mg protein, n = 10; VLBW infants, 6.8 +/- 0.9 and 173.0 +/- 16.2, n = 6; adults, 10.3 +/- 0.6 and 241.9 +/- 13.3, n = 10; values were expressed as mean +/- SEM). Both the phorbol myristate acetate- and the N-formyl-methionyl-leucyl-phenylalanine-induced O2- production rates of VLBW-infants' PMN were significantly higher than those of the term neonatal PMN. The phorbol myristate acetate-induced O2- production rate of the term neonatal PMN was significantly lower than that of the adults' PMN. The phorbol myristate acetate-induced H2O2 production rate of the term neonatal PMN was significantly lower than that of the adults' PMN. The conversion rate from O2- to H2O2 of the neonatal PMN was similar to that of the adults' PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

The usefulness of serum C-reactive protein (CRP) in the early detection of neonatal infection was studied using a special laser nephelometric apparatus (CRP-1), by which CRP concentrations could be quickly determined in the nursery, with only a small amount of serum (20 microL). Initial serum CRP concentrations of samples obtained from 90 infants suspected to have sepsis and/or meningitis were evaluated. Of the 90 infants, 25 showed culture-proven septicemia and/or bacterial meningitis, while 18 were considered to be infectious based on clinical signs and positive sepsis work-up even though cultures were negative. 47 infants had negative cultures and sepsis work-up and showed a favorable clinical courses. Statistical analysis for the evaluation of serum CRP at the level of one mg/dL was performed. False negative CRP was demonstrated in seven of 25 infants with culture-proven sepsis and/or meningitis (28%) and in 4 of 18 infants with other infections (22%). On the other hand, seven of 47 (15%) non-infected infants showed false positive results. The specificity and sensitivity of serum CRP determination were 85% and 74%, respectively, for all patients, and 85% and 72%, respectively, for patients with sepsis and/or meningitis. The sensitivity varied with the pathogens. We conclude that, while the initial CRP values alone are unsatisfactory for deciding the need for antibiotic therapy, CRP is useful in the early detection of neonatal infections, and its measurement by this new equipment should available in the nursery.

Sera from 39 preterm and 35 full-term infants with hyperbilirubinemia, undergoing phototherapy continuously for 48 h, were assayed for unbound bilirubin by the peroxidase oxidation method. Assessment was done to determine the influence of therapeutic exposure to light on the serum unbound bilirubin concentrations in preterm and full-term infants. At 24 and 48 h after initiation of phototherapy, the unbound/total bilirubin ratios, as well, as the serum total and unbound bilirubin levels showed statistically significant declines of values in both preterm and full-term infants. It is concluded that, following phototherapy, the serum levels of unbound bilirubin decline more conspicuously than the decrease in serum total bilirubin levels.

To assess hemolysis in hyperbilirubinemic infants with ABO isoimmunization, we measured the carboxyhemoglobin (HbCO) concentrations in full-term infants with ABO isoimmunization during the first week of life. Two groups of infants, ABO compatible (n = 34) and ABO incompatible (n = 30), were further divided into two groups with and without hyperbilirubinemia. All the infants from ABO incompatible pregnancies showed a positive indirect Coombs' test. The groups with hyperbilirubinemia included infants with maximum serum total bilirubin levels about 15 mg/dL and infants treated by phototherapy or exchange transfusion. In the ABO incompatible infants, the HbCO levels in those with hyperbilirubinemia were significantly higher than in infants without hyperbilirubinemia during the first week after birth (p less than 0.01 at 24, 72, 120 hours after birth, respectively). The levels of HbCO in the ABO incompatible infants with hyperbilirubinemia were significantly higher compared with the levels in the ABO compatible infants with hyperbilirubinemia (p less than 0.05 at 24 hours, p less than 0.01 at 72 and 120 hours after birth, respectively). HbCO measurement may facilitate the early diagnosis of hemolytic disease and the prediction of jaundice caused by ABO isoimmunization.

To assess the interaction of bilirubin with albumin and to determine the site of bilirubin toxicity in cells, a study was made of the O2 production of neonatal neutrophils (PMNs) by two different stimulators: (1) concanavalin A (Con A) plus cytochalasin D (Cyt D), which acts on the cell surface, and (2) phorbol myristate acetate, which acts intracellularly. PMNs that had been separated from cord blood were incubated for 60 min at 37 °C in the solution with different molar ratios of bilirubin/albumin (unbound bilirubin, ranging from 0.35 to 3.92 μg/dl). The unbound bilirubin was determined by peroxidase oxidation method. A PMN viability of more than 96% was maintained after the incubation in each of solutions. The O2 production rate of PMNs stimulated by Con A plus Cyt D was inhibited in the presence of unbound bilirubin levels as low as 1.12 μg/dl, and the rate decreased as the levels of unbound bilirubin rose. The O2 production rate stimulated by Con A plus Cyt D was more remarkably inhibited than that by phorbol myristate acetate, which directly activates intracellular protein kinase C. These findings suggest that bilirubin toxicity to PMN can be shown at levels of unbound bilirubin as low as those in hyperbilirubinemic sera, and the critical site at which bilirubin exerts its toxicity is mainly in membrane level rather than on intracellular functions.

Bilirubin production, as indexed by serum carboxyhemoglobin (HbCOc), was studied in a group of normal term Japanese infants and Caucasian controls during the second to third day of life. Stringent entry criteria were employed in order to eliminate infants with hemolysis or other known causes of increased bilirubin production. The mean HbCOc of the Japanese infants (0.69 +/- 0.15% sat) was significantly higher than that of the Caucasian infant (0.58 +/- 0.17% sat). The serum total bilirubin was also significantly higher in Japanese infants (11.1 +/- 3.0 mg/dl versus 8.0 +/- 2.2 mg/dl). This difference may be attributable to environmental and/or genetic factors.

To assess the site of bilirubin toxicity to cells, we have studied O2− production of PMN by two different stimulators; con-canavalin A(ConA)+cytochalasin D(CytD) which acts on the cell surface, and phorbor myristate acetate(PMA) which acts intracellularly. PMNs separated from cord blood using LymphoprepR were incubated in the buffered solution(pH 7.4) with different molar ratios of bil/alb for 30 min. at 37°C. Using a special double beam photodetector, O2− was measured by an increase in the difference in the absorbance(550-540)nm, due to the reduction of ferri-cytochrome C. Unbound bilirubin(UB) was determined by automated peroxidase method(UB Analyzer). More than 96% viability of PMNs was maintained in each solutions. O2− production by ConA+CytD was inhibited more than that by PMA which directly activates intra-cellular protein kinase C as UB levels rose. These results suggest that the critical site at which bilirubin exerts its toxicity is mainly on cell surface receptor rather than on intracellular functions. The inhibitory action increased as UB rose.