Diffusion-weighted MRI for early diagnosis of neonatal herpes simplex encephalitis.

AIM: To determine the early changes and evolutions of brain diffusion-weighted imaging (DWI), and analyze prognostic factors of the early changes among patients with neonatal herpes simplex encephalitis (NHSE). METHOD: We selected patients who developed encephalitis by 28 d after birth; had herpes simplex infection; and who underwent magnetic resonance imaging, including DWI, ⩽7 d of symptom onset. Thirty-two DWI scans between 0 and 28 d after onset in 13 patients and the clinical data were recruited. The distribution, evolution of the lesions, and neurological outcome were analyzed. RESULTS: DWI frequently showed multiple cortical lesions in both hemispheres in the early period and both hemispheres on DWI (8/9 scans at ⩽48 h, 7/7 patients). As time from onset increased, the cortical lesions tended to coincide with subcortical white matter lesions beneath the initial cortical lesions (p<0.01). Lesions from the cortex extended to the subcortical white matter in 7 patients. Deep cerebral lesions, involving basal ganglia, internal capsules, thalamus, were also found in 9 patients ⩽7 d of onset. The distributions of deep cerebral lesions (none/unilateral/bilateral) ⩽7 d of onset showed significant correlations with neurological prognoses (gross motor functions: p<0.01; developmental or intellectual quotient scores: p<0.01). INTERPRETATION: Cortical lesions were main findings of DWI in NHSE in the early period. Bilateral deep cerebral lesions ⩽7 d were highly indicative of poor motor and cognitive outcomes.

A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase domain of the insulin receptor gene complicated by medullary sponge kidney.

Rabson-Mendenhall syndrome (RMS) is a genetic disorder characterized by severe insulin resistance and somatic characteristics. Recombinant insulin-like growth factor 1 (r-IGF-1) is used to treat RMS, as the IGF-1 and insulin receptors share homology. However, the effect of r-IGF-1 varies in patients and it is difficult to manage metabolic status appropriately in r-IGF-1 resistant cases. We report a Japanese boy with RMS who showed resistance to r-IGF-1 therapy and a novel mutation in the insulin receptor in the tyrosine kinase domain. Mutations in this region disturb tyrosine kinase catalytic activity in IGF-1 receptors as a result of dominant negative effects. We consider this mutation to be the cause of resistance to r-IGF-1. The patient also exhibited radiographical features of medullary sponge kidney and had severe nephrocalcinosis and hypokalemia, indicating Bartter syndrome. However, analysis revealed no mutations in the responsible genes and the etiology of the renal abnormalities therefore remains unknown.

Interleukin-6 polymorphism and bronchopulmonary dysplasia risk in very low-birthweight infants.

BACKGROUND: The aim of the present study was to evaluate the role of interleukin (IL)-6-634 polymorphism in neonatal disorders such as bronchopulmonary dysplasia (BPD) and periventricular leukomalacia (PVL) in very low-birthweight (VLBW) infants. METHODS: This prospective cohort study included 202 infants (gestational age at birth, 23-34 weeks; birthweight, 500-1499 g). Genotypic analysis (polymerase chain reaction-restriction fragment length polymorphism) was performed with DNA extracted from whole-blood samples. RESULTS: Genotype distribution (66.8% CC, 28.2% CG, 5.0% GG) was similar to that in the adult Japanese population. BPD occurred in 85 infants (42.1%) among 202 VLBW infants. The duration of O(2) therapy in infants with CG/GG genotypes was significantly longer than that in infants with the CC genotype (CG/GG vs CC: 40.3 ± 52.2 days vs 28.4 ± 32.6 days, P < 0.05), but the prevalence of BPD was not associated with the CG/GG genotype (CG/GG, 40.0%; CC, 46.3%, P= 0.24). Infants with CG/GG genotypes were more likely to have received postnatal corticosteroid therapy for BPD than those with the CC genotype (CG/GG vs CC: 20.9% vs 11.1%, P = 0.05). PVL occurred in six infants (3.0%). There was no significant difference in the prevalence of PVL among IL-6-634 polymorphisms (CG/GG, 3.0%; CC, 3.0%, P = 0.65). CONCLUSIONS: IL-6-634 polymorphism is associated with duration of oxygen therapy in VLBW infants. This suggests that the IL-6-634 polymorphism G allele is an aggravating factor of BPD. IL-6-634 polymorphism is not associated with PVL.

Cytochemical analysis of storage materials in cultured skin fibroblasts from patients with I-cell disease.

BACKGROUND: In cultured fibroblasts from I-cell disease patients the transport of many lysosomal enzymes is defective, and affected cells contain inclusion bodies filled with undegraded substrates. However, the contents of these inclusion bodies have not been well characterized yet. We attempted to identify accumulated substances in cultured I-cell disease fibroblasts cytochemically. METHODS: Cultured fibroblasts from I-cell disease patients were double-stained with a monoclonal antibody to lysosome-associated membrane protein-1 (LAMP-1) and that to GM2 ganglioside, or a series of lectins that specifically bind to sugar moieties. RESULTS: The patients' cells were granularly stained with the antibody to GM2 ganglioside and the lectins including Maakia amurensis, Datura stramonium, and concanavalin A. Their localization was coincident with that of LAMP-1. CONCLUSIONS: GM2 ganglioside and various kinds of glycoconjugates having sialic acidalpha2-3galactose, galactosebeta1-4N-acetylglucosamine and mannose residues accumulate in enlarged lysosomes in I-cell disease fibroblasts.

Factors affecting short-term mortality in very low birth weight infants in Japan.

No epidemiological surveys have examined risk factors related to the death of very low birth weight infants (VLBWIs) in Japan. The objectives of this study were to examine the death rate and fatalities related to complications among VLBWIs, and to analyze factors possibly determining the death of VLBWIs. The subjects of this study were 811 VLBWIs admitted to the Neonatal Care Center of Niigata City General Hospital between April 1987 and March 2003. We obtained information on gender, birth weight, gestational age, Apgar scores, single/multiple pregnancy, postnatal transfer, mode of delivery, complications and outcome (alive or deceased) at the time of discharge from medical records. Of the 811 infants, 98 died prior to discharge (12.1%). Logistic regression analysis showed that independent risk factors for death of VLBWIs were male gender (relative risk [RR]: 2.0), low birth weight (RR: 0.56), necrotizing enterocolitis (RR: 58.0), pulmonary hypoplasia (RR: 37.8), chromosomal abnormalities (RR: 36.3), congenital heart diseases (RR: 9.8), persistent fetal circulation (RR: 9.6), neonatal asphyxia (RR: 6.3) and sepsis (RR: 4.4). The risk for death rises 1.8-fold if birth weight decreases by 100 g. A very high risk of perinatal death is associated with necrotizing enterocolitis, pulmonary hypoplasia or chromosomal abnormalities. The risk of death due to congenital heart diseases or neonatal asphyxia is relatively lower, but the incidences of these two disorders are high (8% and 6%, respectively). From the viewpoint of prophylactic treatment aimed at reducing the death rate of VLBWIs, measures to increase birth weight are of primary importance. Furthermore, early treatment and improved perinatal management of congenital heart diseases and neonatal asphyxia are anticipated to reduce the overall death rate of VLBWIs.