Serial hemodynamic assessment using Doppler echocardiography in a fetus with left ventricular aneurysm presented as fetal hydrops.

A 22-week fetus presented with a large left ventricular aneurysm, 24 × 21 × 18 mm in size, detected by abnormal four-chamber view, and severe fetal hydrops with pericardial effusion, ascites and skin edema. The aneurysm was thin-walled, hypokinetic, and had enlarged with gestational age, causing compression of the lung. Although the left ventricular function had progressively impaired as expressed by increase in Tei index, hydrops had resolved by 32 weeks of gestation, probably because of maternal digoxin therapy and successful compensation by the right ventricle, as represented by retrograde blood flow in the distal aortic arch via the patent arterial duct. Because of the significant risk of severe cardiorespiratory failure, we transported the mother to a neonatal cardiac surgical center at 38 weeks of gestation. Indeed, the baby showed severe cardiopulmonary failure after birth, showing 100% of cardiothoracic ratio on the chest X-ray film, but was saved by the successful Dor procedure, including surgical resection of the aneurysm at 10 h of life. In this case, serial echocardiographic evaluation can allow us to monitor the hemodynamics and lead to successful postnatal management.

Determinants of outcomes following acute child encephalopathy and encephalitis: pivotal effect of early and delayed cooling.

BACKGROUND: Acute encephalopathy/encephalitis is one of the most important causatives of mortality and neurological deficit during childhood. The aim of this retrospective observational study was to investigate clinical variables and therapeutic options associated with the outcome of children with acute encephalopathy/encephalitis. METHODS: Relationships between the clinical information at admission and the neurological outcome evaluated using Pediatric Cerebral Performance Category Scale (PCPC) at 12 months after admission were assessed in 43 patients who were treated at 10 Japanese paediatric intensive care units. RESULTS: Sixteen patients were cared for at normothermia, whereas mild hypothermia was applied to 27 children. In univariate analysis, ages ≤ 18 months, marked elevation in serum lactate dehydrogenase (LD) and aspartate transaminase, diagnosis of either acute necrotising encephalopathy or haemorrhagic shock and encephalopathy syndrome and longer hypothermic periods were associated with increased risks of death or severe neurological deficit, whereas hypothermia showed pivotal effects: the outcome of children cooled after 12 h of diagnosis was statistically invariant with normothermic children, but was significantly worse compared with children cooled ≤ 12 h. In multivariate analysis, younger ages and elevated serum LD were associated with adverse outcomes, whereas early initiation of cooling was related to favourable outcomes. For normothermic children, PCPC scores were dependent on the computed tomographic findings suggestive of cerebral oedema, serum LD levels and Glasgow Coma Scale at admission. For hypothermic children, PCPC scores depended on longer delays in cooling initiation. CONCLUSION: Without therapeutic hypothermia, the outcome of children was determined by variables suggestive of the severity of encephalopathy/encephalitis at admission. Hypothermia may have pivotal impacts on the outcome of children according to the timing of cooling initiation following acute encephalopathy/encephalitis.

Therapeutic hypothermia can be induced and maintained using either commercial water bottles or a "phase changing material" mattress in a newborn piglet model.

BACKGROUND: Therapeutic hypothermia, a safe and effective treatment for neonatal encephalopathy in an intensive care setting, is not available in low-resource settings. Aims/ METHODS: To assess two low-tech, low-cost cooling devices for use in low-resource settings: (i) commercially available water bottles filled with tepid water (25 degrees C); (ii) a mattress made of phase changing material (PCM) with a melting point of 32 degrees C (PCM works as a heat buffer at this temperature). Eleven anaesthetised newborn piglets were studied following transient hypoxia-ischaemia. The cooling device was applied 2-26 h after hypoxia-ischaemia with a target rectal temperature (T(rectal)) of 33-34 degrees C. T(rectal) undershoot was adjusted using cotton blankets; the cooling device was renewed when T(rectal) rose above 35 degrees C. T(rectal) data during cooling were dichotomised (within or without target) to assess: (a) the total period within the target T(rectal) range; (b) the stability and fluctuation of T(rectal) during cooling. RESULTS: Therapeutic hypothermia was achieved with both water bottles (n = 5) and the PCM mattress (n = 6). The mean (SD) time to reach target T(rectal) was 1.8 (0.5) h with water bottles and 1.9 (0.3) h with PCM. PCM cooling led to a longer period within the target T(rectal) range (p<0.01) and more stable cooling (p<0.05). Water bottle cooling required device renewal (in four out of five piglets). CONCLUSION: Simple, low-tech cooling devices can induce and maintain therapeutic hypothermia effectively in a porcine model of neonatal encephalopathy, although frequent fine tuning by adjusting the number of blankets insulating the piglet was required to maintain a stable temperature. PCM may induce more stable cooling compared with water bottles.

Endothelial dysfunction in MELAS improved by l-arginine supplementation.

The authors evaluated endothelial function in patients with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke) by flow-mediated vasodilation (FMD) and found a significant decrease vs controls. Two years of supplementation with oral l-arginine, a nitric oxide precursor, significantly improved endothelial function to control levels and was harmonized with the normalized plasma levels of l-arginine in patients. l-Arginine therapy improved endothelial dysfunction and showed promise in treating strokelike episodes in MELAS.

Serum sodium levels in patients with Kawasaki disease.

The purpose of this study was to assess the hypothesis that lower serum sodium levels are associated with cardiovascular sequelae in patients with Kawasaki disease (KD). We used the database of the 16th nationwide survey of KD in Japan. We investigated the distribution of serum sodium levels and the relationship between serum sodium levels and cardiovascular sequelae. Of the reported cases, serum sodium levels were reported in 13,569 patients (89%). The proportion of patients with serum sodium levels 130 mEq/L or less, was greater in complete cases than in incomplete cases. The proportion of patients with serum sodium levels 130 mEq/L or less was increased with age. The largest proportion of patients with serum sodium levels 130 mEq/L or less was found in the category of 3-5 days since onset of illness. A serum sodium of level 135 mEq/L or less was an independent risk factor for cardiovascular sequelae (odds ratio, 1.79, 95% confidence interval, 1.42-2.26). Among patients with KD, there are significant differences in serum sodium levels between diagnostic categories, age, and days since the onset of illness. The sodium level may be a simple predictor of cardiovascular sequelae.

Perinatal bile acid metabolism: analysis of urinary unsaturated ketonic bile acids in preterm and full-term infants.

AIM: To compare urinary concentrations of unsaturated ketonic bile acids in preterm and full-term infants. METHODS: Urinary unsaturated ketonic bile acids were determined using gas chromatography-mass spectrometry. RESULTS: Urinary concentrations of total bile acids in early preterm infants (of less than 29wk gestational age) exceeded concentrations in late preterm (between 30 and 37 wk) and full-term infants (between 38 and 41 wk; p < 0.01). The percentage of ketonic bile acids (7alpha, 12alpha-dihydroxy-3-oxo-4-cholenoic acid and 7alpha-hydroxy-3-oxo-4-cholenoic acid) among total urinary bile acids in full-term infants (20.2 +/- 14.1%) was higher than that in early preterm infants (8.94 +/- 8.1%; p < 0.05). The percentage of unsaturated bile acids (3beta-hydroxy-delta5-bile acids) among total bile acids in urine did not differ greatly between groups. CONCLUSION: The percentage of 3-oxo-delta4 bile acids among total bile acids in urine gradually increased from early to late preterm infants, while healthy full-term infants excreted large amounts of 3-oxo-delta4 bile acids in urine at delivery.

Enlarged bronchial arteries in a fetus with transposition of the great arteries and intact ventricular septum.

Enlarged bronchial arteries are associated in some patients with transposition of the great arteries and intact ventricular septum. The etiology of these enlarged bronchial arteries is not yet known. In this report, we describe a case of TGA/IVS in which enlarged bronchial arteries were demonstrated from the prenatal period. The arteriogram at one year after arterial switch repair demonstrated enlarged bronchial arteries. This prenatal information may be useful for deciding on a strategy for postnatal treatment and counseling the family members.

Soluble forms of the selectin family in children with Kawasaki disease: prediction for coronary artery lesions.

AIM: To investigate the relationship between the plasma levels of soluble forms of the selectin family and the incidence of coronary artery lesions (CALs) in patients with Kawasaki disease (KD). METHODS: Thirty-three patients with KD, including group A patients (n = 22) who had no CALs and group B patients (n = 11) who had CALs, as well as age-matched febrile (n = 10) and afebrile controls (n = 11), were studied. RESULTS: Peak plasma E-selectin levels (172.0 +/- 58.6 ng ml(-1)) occurred during the acute phase of KD, while peak plasma P-selectin levels (260.3 +/- 43.2 ng ml(-1)) occurred during the subacute phase of the illness (p<0.05). Plasma L-selectin levels (1757.3 +/- 244.3 ng ml(-1)) during the convalescent phase tended to be higher than in either the acute or the subacute phase (not significant). Before intravenous immunoglobulin treatment, the plasma levels of E- (225.1 +/- 46.8 ng ml(-1)) and P-selectin (259.4 +/- 76.2 ng ml(-1)) of patients with CALs (n = 11) were significantly higher than those of patients (n = 22) with no CALs (E-selectin, 131.6 +/- 36.9 ng ml(-1); P-selectin, 184.9 +/- 84.6 ng ml(-1); p < 0.05). When a plasma E-selectin value before immunoglobulin treatment of >184.7 ng ml(-1) was used as the cut-off point, the sensitivity and specificity for the incidence of CALs were 81.8% and 90.9%, respectively. These findings demonstrate the relationship between plasma levels of selectins and disease severity of Kawasaki vasculitis. CONCLUSION: Higher plasma levels of E-selectin may have potential as a predictor of the incidence of coronary artery lesions in Kawasaki disease patients.

Severe infantile measles encephalitis occurred three months after neonatal measles.

A 3-month-old girl who developed severe measles encephalitis after neonatal measles is reported. Her mother had measles when she was ten days old and she was admitted to our hospital with low grade fever, Koplik spot, and mild exanthema seventeen days after birth, and she recovered in 7 days without any complication. At three months of age, she was readmitted because of intractable seizures. The levels of IgM and IgG antibodies against measles in the cerebrospinal fluid were elevated. The measles virus genome, amplifying the region encoding the nucleocapsid protein, was detected from the brain specimen by reverse transcriptase-polymerase chain reaction. Magnetic resonance imaging showed a focal destructive lesion and diffuse cerebral atrophy. The electroencephalogram did not show periodic synchronous discharges. Although the neonatal measles was believed to be relatively mild in severity, the possible development of measles encephalitis should be carefully monitored in an infant who had neonatal measles.

Neurobiology and neurochemistry of Rett syndrome.

The current status of neurobiological and neurochemical research on Rett syndrome is reviewed, and correlations are developed with previously described neurophysiological, neuroimaging, neuropathological, and immunohistochemical changes. We review the abnormalities reported in the biogenic amine neurotransmitters/receptor systems, and of beta-phenylethylamine, an endogenous amine synthesized by the decarboxylation of phenylalanine in dopaminergic neurons of the nigrostriatal system. We also discuss the roles of other neurotransmitters, including beta-endorphin and substance P, and neurotrophic factors, including nerve growth factors. Recently, DNA mutations in the methyl-CpG binding protein 2, mapped to Xq28, have been identified in some patients with Rett syndrome. The multiple abnormalities in the various neurotransmitters/receptor systems explain the pervasive effects of Rett syndrome.

Reduced expression of neuropeptides can be related to respiratory disturbances in Rett syndrome.

We immunohistochemically examined neurotransmitter systems, which function in the brainstem and are involved in neuronal organization of respiration, in an autopsy brain from a patient with Rett syndrome (RS). Immunoreactivity (IR) for tyrosine hydroxylase, a functional marker for catecholaminergic neurons, was severely reduced in the locus ceruleus, while that for tryptophan hydroxylase involved in serotonin synthesis was spared in the raphe nuclei. In the brainstem, IR for substance P (SP) was reduced in the parabrachial complex and that for methionine-enkephalin (met-enk) was affected in the parabrachial, hypoglossal, dorsal vagal and solitary nuclei. In addition, expressions of these neuropeptides were also disturbed in the basal ganglia. A widespread altered expression of antagonistic neuropeptides, SP and met-enk, may be involved in the pathogenesis of RS, especially in its respiratory manifestation.

Mutation analysis of the methyl-CpG-binding protein 2 gene (MECP2) in Rett patients with preserved speech.

Genomic DNAs from 35 Japanese sporadic patients with Rett syndrome (RTT) were screened for DNA mutations in the entire coding region and exon-intron boundaries of methyl-CpG-binding protein 2 (MECP2). We detected mutations in 30 (85.7%) of 35 patients. Among these 35 RTT patients, five patients (14%) had the preserved speech variant of this disease. Four respective mutations (R133C, R306C, R294X, 2 base pair (bp) deletion) were found in these five patients. Two patients had the same missense mutation, R133C. The patients with the R133C mutation and one with frameshift mutation presented the relatively mild clinical presentation, and the R133C mutation was not found in any other patient without preserved speech. We confirmed that the preserved speech variant is one of the clinical phenotypes of RTT and is also caused by MECP2 mutation. We speculated that the clinical phenotype of patients with the R133C missense mutation might be mild.