Kenichiro Kaneko

Detection of rotavirus in cerebrospinal fluid and blood of patients with convulsions and gastroenteritis by means of the reverse transcription polymerase chain reaction

Rotavirus RNA was detected in the blood and cerebrospinal fluid from eight Japanese children with convulsions and gastroenteritis in the acute stage by means of the reverse transcription polymerase chain reaction. This may suggest that rotavirus invades the central nervous system through blood vessels.

Haplotype-phenotype correlation in Fukuyama congenital muscular dystrophy

In typical Fukuyama congenital muscular dystrophy (FCMD), peak motor function is usually only unassisted sitting or sliding on the buttocks, though a few patients are able to walk at some point. However, a few patients have a severe phenotype and never acquire head control. In addition, it is clinically difficult to differentiate this severe FCMD from Walker-Warburg syndrome (WWS) or from muscle-eye-brain disease (MEBD). In order to establish a genotype-phenotype correlation, we performed haplotype analysis using microsatellite markers closest to the FCMD gene (FCMD) in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 propositi with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder (A-F) haplotype whereas the other 2 were heterozygous for the haplotype. In the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmological abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype are heterozygous for the A-F haplotype, and the other one homozygous for the haplotype. We confirmed that at least one chromosome in each of the 56 FCMD patients has the A-F haplotype. The rate of heterozygosity for the A-F haplotypes was significantly higher in severe cases than in typical or mild cases (P < 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. Thus, the present study yielded molecular genetic evidence of a broad clinical spectrum in FCMD.

Th1/Th2 balance in childhood idiopathic nephrotic syndrome.

AIMS In view of the conflicting evidence of helper T cell type 1 (Th1) or type 2 (Th2) pattern of cytokine synthesis in childhood idiopathic nephrotic syndrome (INS) this study examined the balance of Th1 and Th2 which are characterized by intracellular cytokine production of interferon-gamma (IFNgamma) and interleukin-4 (IL-4), respectively. SUBJECTS AND METHODS Sixteen children with steroid-sensitive INS (mean age 9.0 years) were included in this study, together with 15 healthy normal children (mean age 7.9 years) for the control group. Intracellular production of both IFNgamma and IL-4 in helper T cell (CD4+ cell) was investigated by a 3-color flow cytometry. RESULTS The cross-sectional data showed no significant differences of percentages of Th0 (IFNgamma+ IL-4+ CD4+ cell), Th1 (IFNgamma+ lL-4- CD4+ cell) and Th2 (IFNgamma- IL-4+ CD4+ cell) in CD4+ cells (p > 0.05). The Th1/Th2 ratio during nephrotic relapse did not differ from those during nephrotic remission and in normal healthy children (p > 0.05). CONCLUSION We conclude that there is no significant skew of Th1/Th2 balance in childhood INS and that the cardinal immunological abnormality does not lie in helper T cells but in other cells, such as suppressor/cytotoxic T cells, natural killer cells or monocytes/macrophage. To clarify the pathogenesis of INS, comprehensive studies for these cells would be worthwhile.

Kawasaki disease followed by haemophagocytic syndrome

Sir: Ohga et al. [6] reported the development of haemophagocytic syndrome (HPS) in an infant during the recurrent evolution of Kawasaki disease (KD). We have recently seen a similar course of this rare association. A 1-year-old Japanese girl was admitted to our hospital with a nonexudative conjunctival injection, a polymorphous rash, and fever for 3 days. The perinatal period and past medical history were unremarkable. On admission, blood hyperleucocytosis and increased C-reactive protein (CRP) prompted treatment with antibiotics, acetylsalicyclic acid, and dipyridamole because of the possibility of a streptococcal infection. Nevertheless, fever persisted with redness of the pharynx and cervical adenopathy; when indurated oedema of hands and feet became manifest, the diagnosis of KD was made. She was given 200 mg/kg of intravenous immunoglobulin (IVIG) on days 11, 12, and 13 after admission. Although afebrile up to day 18 (see Table 1) she developed again fever afterwards, up to 40.6°C on day 24, with at the same time recurrence of skin rash, conjunctival injection, and cervical lymphadenopathy. Marked hepatosplenomegaly appeared. Blood demonstrated again hyperleucocytosis and increased levels of CRP Fig. 1 Bone marrow smear of the patient (Wright-Giemsa Stain). Arrow indicates a haemophagocytic histiocyte

Effectiveness of lidocaine infusion for status epilepticus in childhood: A retrospective multi-institutional study in Japan

We evaluated the usefulness of intravenous lidocaine therapy for managing of status epilepticus (SE) during childhood in a retrospective multi-institutional study. Questionnaires were sent to 28 hospitals concerning patients admitted for SE who were managed with lidocaine, assessing patient characteristics, treatment protocols and efficacy. In 279 treated patients, 261 SE occurrences at ages between 1 month and 15 years were analyzed. SE was classified as showing continuous, clustered, or frequently repeated seizures. Considering efficacy and side effects in combination, the usefulness of lidocaine was classified into six categories: extremely useful, useful, slightly useful, not useful, associated with deterioration, or unevaluated. In 148 SE cases (56.7%), lidocaine was rated as useful or extremely useful. Multivariate analysis indicated lidocaine was to be useful in SE with clustered and frequently repeated seizures, and SE attributable to certain acute illnesses, such as convulsions with mild gastroenteritis. Efficacy was poor when SE caused by central nervous system (CNS) infectious disease. Standard doses (approximately 2mg/kg as a bolus, 2mg/kg/h as maintenance) produced better outcomes than lower or higher doses. Poor responders to the initial bolus injection of lidocaine were less likely to respond to subsequent continuous infusion than good initial responders. We recommend lidocaine for use in SE with clustered or frequently repeated seizures, and in SE associated with benign infantile convulsion and convulsions with mild gastroenteritis. Lidocaine should be initiated with a bolus of 2mg/kg. If SE is arrested by the bolus, continuous maintenance infusion should follow; treatment should proceed to different measures when SE shows a poor response to the initial bolus of lidocaine.

Carbamazepine-induced thrombocytopenia and leucopenia complicated by Henoch-Schönlein purpura symptoms

A rare case of carbamazepine-induced leucopenia and thrombocytopenia complicated by Henoch-Schönlein purpura (HSP) symptoms is presented. Laboratory findings suggested that leucopenia and thrombocytopenia could be due to bone marrow suppression and HSP symptoms to an allergic reaction to carbamazepine. To the best of our knowledge this is the first report that carbamazepine may cause haematological disorders associated with symptoms of HSP by different mechanisms at the same time in the same patient.

Urine-based enzyme-linked immunosorbent assay for the detection of Helicobacter pylori antibodies in children

Objective:  Recent studies of urine‐based enzyme‐linked immunosorbent assays (ELISA) for detection of antibody to Helicobacter pylori (H. pylori) have already shown high sensitivity and specificity in adults. The diagnostic accuracy of these assays in children was investigated.

Abnormal contralateral kidney in unilateral multicystic dysplastic kidney disease

We performed a retrospective study of infants with unilateral multicystic dysplastic kidney (MCDK) in order to investigate the associated urological abnormalities. We examined the records of seven patients, in five of whom a diagnosis had been made prenatally using ultrasonography. Our investigation focused on the associated urological abnormalities, particularly on the contralateral side, and the results of voiding cystourethrography (VCUG). Four of the seven patients (57%) had urological abnormalities other than MCDK: three exhibited vesicoureteral reflux (VUR) of the contralateral side including one patient who also had an ipsilateral ectopic ureter, and the fourth patient had a ureterocele of the ipsilateral side. The results indicate that contralateral VUR, was the most common abnormality associated with MCDK. Two infants had high-grade VUR and underwent anti-reflux surgery soon after the diagnosis. Both have remained free of recurrent urinary tract infection.

The fluctuations of neuron-specific enolase (NSE) levels of cerebrospinal fluid during bacterial meningitis: the relationship between the fluctuations of NSE levels and neurological complications or outcome.

Neuron‐specific enolase (NSE) is one of the glycolytic enzymes distributed exclusively in neurons. It was measured serially in the cerebrospinal fluid (CSF) of 10 children with bacterial meningitis during the illness using radio‐immunoassay.

Risk of exacerbation of hyponatremia with standard maintenance fluid regimens

Sirs, We read with interest the article entitled “Simplified treatment strategies to fluid therapy in diarrhea” by Assadi and Copelovitch in this journal [1] and would like to draw attention to the risk of iatrogenic exacerbation of hyponatremia when the formula for maintenance fluid requirements recommended by Assadi and Copelovitch is applied. They postulated that 100 ml of water, 3 mEq Na, 2 mEq K, and 2 mEq Cl should be given to children for each 100 kcal of energy expenditure according to the recommendations of Holliday and Segar [2]. Based on this theory, it is concluded that 5% dextrose in 0.25% NaCl with 20 mEq/l KCl is suitable for maintenance therapy. Moritz and Ayus [3] and Halberthal et al. [4], however, recently postulated independently that iatrogenic hyponatremia with fatal outcome may develop in children when hypotonic solutions, such as 0.25% NaCl, are infused as maintenance fluid therapy. They speculated that a considerable number of children with common pediatric diseases suffer from hyponatremia due to syndrome of inappropriate secretion of antidiuretic hormone (SIADH) because there are many non-osmotic stimuli for ADH release in sick children [4]; e.g., hyponatremia has been reported in 52% of children with febrile convulsions [5] and 33% of children with respiratory syncytial virus bronchiolitis [6]. Therefore, exacerbation of hyponatremia with a fatal outcome may occur if 5% dextrose in 0.25% saline with 20 mEq/l KCl is infused in children. Thus, we should pay attention to the risk of exacerbation of hyponatremia in sick children with standard fluid regimens, and maintenance therapy should be reconsidered. Our case review confirmed that more than half of children with febrile convulsions and 15% of children without fever developed hyponatremia on admission (Table 1). Most fit the criteria of SIADH [7]. From these findings, we are currently investigating whether acetated Ringer’s solution containing 130 mEq/l Na and 4 mEq/l K with reduced volume (two-thirds the standard maintenance fluid regimens of Holliday and Segar [2]) might be suitable for maintenance therapy for children with common pediatric diseases, in which hyponatremia due to SIADH is observed rather frequently.