Shinichi Haruki

A randomized study of two long-course prednisolone regimens for nephrotic syndrome in children

BACKGROUND Long-course prednisolone regimens have been shown to be more effective than short-course regimens in sustaining remission of nephrotic syndrome in children. However, the most beneficial approach among the long-course regimens remains unknown. METHODS Seventy-three children with new-onset nephrotic syndrome were allocated at random to the two long-course regimens and followed up for 2 years. Group A was administered prednisolone at a daily dose of 60 mg/m2 for 6 weeks, followed by an alternate-day dose of 40 mg/m2 for 6 weeks (the long daily regimen). Group B was administered the same daily dose for 4 weeks, followed by an alternate-day dose of 60 mg/m2 for 4 weeks, and doses were tapered by 10 mg/m2 every 4 weeks (the long alternate-day regimen). RESULTS Group B had a lower incidence of corticosteroid toxicities than group A during the initial treatment. Kaplan-Meier analysis of the sustained remission rate of the two treatment groups showed a marginally significant difference (P = 0.069) and showed a significant difference when patients were stratified for age of disease onset (P = 0.048). In a subgroup of younger children (<4 years at onset), group B had a greater rate of sustained remission (P < 0.01) and fewer children with frequent relapses (P < 0.05) than group A, whereas in older children (> or =4 years at onset), both groups had similar good sustained remission rates. CONCLUSION These findings collectively indicate that the long alternate-day regimen may be more beneficial, with less corticosteroid toxicities, than the long daily regimen, and children with younger age at disease onset may be susceptible to relapse and especially benefit from the long alternate-day regimen for sustaining remission of the disease.

Evaluation of variability of proteinuria indices

We compared several indices of proteinuria, namely protein concentration, hourly protein excretion rate (Up/h) and protein/creatinine ratio (Up/Ucr) in single voided urine samples as well as 24 h-urinary protein excretion (24 h-Up), in 44 children, aged 4–16 years, with varying degrees of urinary protein excretion. We found an excellent correlation between Up/h and Up/Ucr in early morning samples. These two indices in early morning samples had excellent correlation with 24 h-Up, comparable to those in any other urine sample of the day. Among daytime samples, Up/h varied widely, in contrast to Up/Ucr, which had significantly less variability. We analysed six early morning and six bedtime samples from 39 of these subjects, and found smaller coefficients of variation for individual patients indices in morning samples. Up/h was more variable than Up/Ucr, especially in bedtime samples. Urinary protein concentration had a poorer correlation with 24 h-Up and was more variable than any other index. We conclude that the Up/Ucr in early morning samples, which has the advantages both of simplicity and low day-to-day variability in a given patient, is a superior index of proteinuria.

Renal Handling of Albumin and Beta-2-Microglobulin in Neonates

Urinary albumin and beta 2-microglobulin (B2M) were measured during the neonatal period. Urinary albumin decreased postnatally in term neonates, while it remained almost constant in preterm neonates. Urinary B2M showed a peak level on day 7 both in term and preterm neonates. There was some trend towards higher levels of albumin and B2M with decreasing gestation, showing that glomerular permeability increases and proximal tubular protein reabsorption decreases with increasing degrees of prematurity. In sick preterms who were depressed at birth and had respiratory failure, both parameters were elevated during the first 2 weeks, indicating the presence of glomerular and tubular damage in this period. The changes in B2M with gestation or clinical condition were more pronounced than those in albumin.

Evaluation of proximal tubular function in preterm infants by urinary α1‐microglobulin

α1‐Microglobulin is a low molecular weight protein that is relatively stable in urine of low pH. There have been few reports on urinary α1‐microglobulin (U‐A1M) excretion in preterm infants. This study was designed to establish the ranges for U‐A1M in clinically stable preterm infants and to investigate changes observed in sick preterm infants. We measured U‐A1M and urinary β2‐microglobulin (U‐B2M) levels at 1, 4, 7, 14, 28 and 90 days after birth in stable preterm infants (Group 1) and sick preterm infants who were depressed at birth and required immediate resuscitation (Group 2). In Group 1 infants, both parameters were high during the first 28 days and appeared to decline thereafter. U‐A1M in Group 2 infants was only significantly increased compared with Group 1 on day 1, as was U‐B2M. On each day of the study, U‐A1M had significant positive correlations with U‐B2M for all the infants studied. The changes of the two parameters observed in Group 1 probably reflect postnatal evolution of proximal tubular function in stable preterm infants. A comparison of groups 1 and 2 shows a high prevalence of acute tubular injury at birth in sick infants and also suggests that U‐A1M as well as U‐B2M may be a sensitive index for detecting acute tubular damage and for following its course in preterm infants.

Septo-optic dysplasia with infantile spasms

A 21-month-old boy with septo-optic dysplasia and infantile spasms is reported. Eighteen hours after birth he had generalized convulsions, dyspnea, and hypoglycemia which were followed by recurrent clonic seizures despite administration of phenobarbital and valproic acid. At 16 months of age he had hypoglycemia and apnea attacks during varicella infection. At 19 months of age left hemiconvulsions and left hemiparesis occurred; his mental and motor development, which had been delayed but progressive, deteriorated. Tonic spasms appeared at 21 months of age and electroencephalography revealed multifocal spikes. At 27 months of age electroencephalography disclosed hypsarrhythmia. Cranial computed tomography depicted brain atrophy, right microphthalmia, and intact septum pellucidum. Magnetic resonance imaging demonstrated hypoplasia of the corpus callosum and a small pituitary gland. Coloboma of the right optic disc was detected. Physical examination revealed short stature, left hemiparesis, micropenis, and cryptorchidism. Endocrinologic loading tests revealed hypofunction of the hypophysial anterior lobe.

Tay-Sachs Disease with Altered β-Hexosaniinidase B: A New Variant?

Summary: A 2.5-year-old Japanese girl who showed signs and symptoms compatible with classic Tay-Sachs disease and had altered β-hexosaminidase B and I1 as well as completely deficient β-hexosaminidase A activity is reported herein.Heat treatment of the patients serum and leukocyte samples showed the existence of 13.5–27.3% and 35.7% of the heat-labile component of β-hexosaminidase, respectively, such is usually considered to correspond to β-hexosaminidase A. The absence of β-hexosaminidase A activity was confirmed by DEAE-cellulose column chromatography and cellulose acetate paper electrophoresis. The patients serum β-hexosaminidase also contained a significant amount of acid pH-labile components. The effects of buffer concentrations on the activities of total and heat-labile components of the serum β-hexosaminidase of the patient differed from those of the control subjects.Heat treatment of the each component of serum β-hexosaminidase which had been separated by DEAE-cellulose column chromatography showed that β-hexosaminidase B and I1 in the serum from this patient were heat labile as compared with those from the control subjects, and the other component I2 was less heat labile at 50° for 3 h.There were no differences in the km values of β-hexosaminidase B, I1, and I2 for the synthetic substrate 4-methylumbeIli-feryl N-acetyl-β-D-glucosaminide before and after heat treatment at 50° for 3 h among the reported patient, another patient with classic Tay-Sachs disease, and a normal infant.Speculation: In prenatal diagnosis of such patients as reported herein, it will be necessary to confirm the absence of β-hexosaminidase A in amniotic fluid and/or amniotic fluid cells by methods other than the heat-inactivation method, e.g., electrophoresis or ion-exchange column chromatography.

Atypical Epstein-Barr virus infection associated with Gianotti-Crosti syndrome and Bell's palsy.

typical infectious mononucleosis (IM),1 a number of studies has been done to reveal various clinical patterns of Epstein–Barr virus (EBV) infection and to clarify its pathophysiological role. Within such a subgroup, which does not usually exhibit typical clinical features of IM, a number of EBV-associated neurological disorders has also been reported.2 These are meningoencephalitis, encephalomyelitis, Guillain–Barre syndrome, cerebellar ataxia and cranial and peripheral neuropathies. The incidence of such disorders with or after EBV infection has been estimated to be from 0.37 to 26.5%.3 However, there have been only a few reports that mention the involvement of EBV in transient facial nerve palsy (Bell’s palsy) in infancy.4,5 Other than the typical skin rash in IM, a variety of reactive dermatoses in association with EBV have also been reported: erythema nodosum, erythema annulare centrifugum, acute pityriasis lichenoides and Gianotti– Crosti syndrome (GCS).6 Gianotti–Crosti syndrome affects mainly children and is characterized by a papular rash, localized on cheeks, extremities and buttocks, lymphadenopathy and anicteric acute hepatitis.7 Although GCS may be caused by several viral and bacterial infections, a few reports have argued the possibility of EBV involvement in GCS.8 There have been no reports, to our knowledge, in which both GCS and Bell’s palsy have occurred simultaneously. We present a clinical picture of a 20month-old Japanese boy, who showed a possible EBV infection followed by both GCS and Bell’s palsy concurrently. Case report

Comparative Study between 18-and 16-Gauge Needle Automated Renal Biopsy under Orthogonal Ultrasound Guidance in Children

Comparative Study between 18-and 16-Gauge Needle Automated Renal Biopsy under Orthogonal Ultrasound Guidance in Children S. Shinya Tsuchida M. Masahiro Hiraoka C. Chikahide Hori H. Hirokazu Tsukahara S. Shinichi Haruki S. Shuhe Hayashi S. Shinichi Fujisawa Y. Yukuo Konishi M. Masakatsu Sudo Fukui Medical School, Fukui Prefectural Hospital, Fukui Red Cross Hospital, Fukui, and Fujisawa Clinic, Shiga, Japan

Leukotriene B4 production in children with steroid-responsive nephrotic syndrome

Leukotriene B4 (LTB4) production in polymorphonuclear leucocytes (PMN) was examined in ten children with steroid-responsive nephrotic syndrome (SRNS) before, during, and after steroid administration. Comparison of LTB4 production was made in 14 children with non-inflammatory disease who were not receiving steroid therapy. No significant change was noted in PMN LTB4 biosynthesis in children with SRNS throughout any phase of the disease. Furthermore, there was no significant difference in LTB4 biosynthesis in PMN between SRNS patients before steroid therapy and patients with non-inflammatory disease. These findings suggest that inhibition of LTB4 production is not involved in the mechanism underlying steroid action in SRNS.