g Factor of the

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |µ|=2.31(14)µ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

The successful treatment of rapidly progressive idiopathic membranoproliferative glomerulo-nephritis Type 1 in a 4-year-old male pediatric patient.

A multivariate analysis [4] revealed that the presence of crescent formation on initial biopsy irrespective of type of membranoproliferative glomerulonephritis (MPGN) was independently associated not only with end-stage renal disease but also with post-transplantation recurrence. In this study, we reported on a 4-year-old male pediatric patient requiring hemodialysis due to rapidly progressive idiopathic MPGN Type 1 with severe nephrotic syndrome and extensive cellular crescent formation on initial biopsy. The patient had been treated intravenously (i.v.) with 9 pulses of methylprednisolone, followed by daily prednisolone, resulting in the withdrawal of dialysis within 1 month. However, since active lesions in the second renal biopsy such as cellular crescents still remained and nephrotic range proteinuria had persisted for more than 2 months, the patient received additional 3 i.v. pulses of methylprednisolone, followed by combinations of alternate-day prednisolone, mizoribine, dipyridamole and warfarin, which lead to complete remission in a short-period of time. The patient has been off the combination therapy for 10 months because the third biopsy prior to the termination of this regimen showed decreased inflammatory activity. There is currently no established protocol for children with crescentic MPGN due to a rarity of its clinicopathological presentation. This case report indicates that early treatment with multiple pulses of methylprednisolone followed by the short-term combination therapy may be of benefit for children with rapidly progressive idiopathic MPGN Type 1, even when both diffuse crescentic changes and nephrotic syndrome are present at onset.

Mycophenolate mofetil therapy for childhood-onset steroid dependent nephrotic syndrome after long-term cyclosporine: extended experience in a single center.

BACKGROUND: Mycophenolate mofetil (MMF) is being used increasingly in children with steroid-dependent nephrotic syndrome (SDNS). However, there is limited information on the optimal therapeutic range for mycophenolic acid (MPA), the active metabolite of MMF, in these patients. METHODS: 26 patients with SDNS (mean age 13.1 years, 19 with minimal change disease and 7 with focal segmental glomerulosclerosis) who had received MMF for at least 6 months after longterm cyclosporine (CsA, mean 56 months) at Saitama Children's Medical Center between September 2002 and August 2008 were analyzed. MMF was introduced at an initial dose of 250 mg/12 h, adjusted to maintain target predose MPA at greater than 2 microg/ml (maximum 1 g twice daily) gradually over 4 weeks. After the introduction of MMF, the dosages of both CsA and prednisolone (PSL) were tapered off if possible. RESULTS: The mean MMF dose required was 34 +/- 6 mg/kg, which maintained the mean predose MPA levels of 3.1 mg/ml. In 26 patients, treatment with MMF for a mean follow-up period of 19 months (range 7 - 42), resulted in a reduction of the mean PSL dose from 0.33 +/- 0.23 to 0.17 +/- 0.11 mg/kg per day (p < 0.01) and mean CsA dose from 3.2 +/- 1.7 to 1.3 +/- 1.8 mg/kg per day (p < 0.01). The mean 12-monthly relapse rates decreased from 2.5 +/- 1.4 to 0.8 +/- 1.2 episodes (p < 0.01). In 20 patients treated with MMF (77%), the dose of PSL and/or CsA was successfully tapered with a reduction in the relapse rates. In 6 patients, however, CsA therapy was reintroduced or its dose was increased because of treatment failure. The patients whose average predose MPA levels were less than 3 microg/ml were significantly likely to have treatment failure (p < 0.05). 2 patients reduced the MMF dosage because of anemia or herpes labialis. However, no severe gastrointestinal discomfort was seen in any patients. Despite long-term CsA therapy, marked tubulointerstitial fibrosis developed during MMF therapy in surveillance biopsies of only one of these five patients. CONCLUSIONS: Therapy with MMF based on the predose MPA levels can be a less toxic alternative to CsA or in some cases a useful additional medication to allow for a reduction in the CsA and/or PSL dosage.

Is single-daily low-dose cyclosporine therapy really effective in children with idiopathic frequent-relapsing nephrotic syndrome?

BACKGROUND: A recent study on renal transplant patients has shown that a single dose of cyclosporine (CsA) has added the advantage of decreasing dosages and adverse effects, while maintaining graft function. However, the efficacy of this regimen in children with idiopathic frequent-relapsing nephrotic syndrome (NS) remains controversial. METHODS: 20 children with steroid-dependent NS or CsA-dependent NS (18 with minimal change disease, MCD and 2 with focal segmental glomerulosclerosis, FSGS) were enrolled in this prospective study. CsA was commenced at 1.5 â 2 mg/kg, given as a single daily dose before breakfast, and the dose was adjusted to reach 2 hours post-dose CsA levels (C2) of 600 - 800 ng/ml. RESULTS: In 9 out of 18 patients with MCD, treatment with single-daily CsA for a median of 13 months (range 7 - 21) resulted in a reduction of mean minimum prednisolone (PSL) dose from 1.1 A+/- 0.55 to 0.04 A+/- 0.09 mg/kg on alternate days (p < 0.01), and the median relapse rate from 1.3 (1.1 - 2.5) to 0 (0 - 0.2) episodes/6 months (p < 0.01). Of them, PSL could be weaned off in 7 patients (4 of 6 with steroid-dependent NS, only 3 of 14 with CsA-dependent NS) without relapse of NS while on this therapy. However, 11 out of 20 were considered to have treatment failure: 1 with steroid-dependent NS and 10 with CsA-dependent NS. In 2 patients having FSGS, this method showed no beneficial effects. In 18 patients with MCD, relapse free ratio on single-daily CsA therapy was significantly higher in patients whose average C2 levels were greater than 700 ng/ml (p < 0.05). CONCLUSIONS: Our experience demonstrates that single-daily low-dose CsA therapy maintaining C2 levels greater than 700 ng/ml may be effective in children with steroid-dependent NS or MCD, with no relapse. In contrast, the usefulness of this regimen in children with CsA-dependent NS appears to be limited.

Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome.

BACKGROUND: Cyclosporine A (CsA) has been widely used in children with steroid dependent and steroid resistant nephrotic syndrome (NS) because of its efficacy in relieving these patients from systemic side effects of steroids. However, its long term use is controversial, since chronic CsA induced nephropathy (CsAN) may develop in a considerable number of patients. AIMS AND METHODS: In order to clarify the risk factors for the development of CsAN, the clinical characteristics of children with steroid dependent or steroid resistant NS taking CsA (target blood trough levels 50-150 ng/ml) for more than six months, managed at a single centre, were retrospectively analysed. RESULTS: Thirteen of 30 children (24 boys and 6 girls) taking CsA (mean duration 43 months, range 6-144) had CsAN defined as the presence of CsA associated arteriopathy with or without striped tubulointerstitial lesions. The multivariate analysis revealed that CsA treatment for more than 36 months and an age younger than 5 years at the start of CsA treatment were independent risk factors for the development of CsAN. The univariate analysis also showed that patients with CsAN had more frequent relapses during CsA treatment than those without CsAN. CONCLUSION: An alternative treatment should be seriously considered after a 36 month administration of CsA in order to prevent CsAN. Data also suggest that CsA treatment in children younger than 5 years should be avoided if possible.

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.

Angiotensin converting enzyme gene polymorphism in primary vesicoureteral reflux.

We studied the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene in 78 patients with primary vesicoureteral reflux (VUR), and examined renal function by dimercaptosuccinate (DMSA) renoscintigraphy and diethylenetriamine-penta-acetic acid (DTPA) renogram in each genotype. Patients were classified into three genotypes according to the ACE gene I/D polymorphisms: 32 in II genotype, 36 in ID, and 10 in DD. The incidence of presumably congenital unilateral small kidneys was high in DD patients (70%). Glomerular filtration rate obtained from DTPA renogram was 120.7+/-35.7 ml/min (expressed as mean+/-SD) in II genotype, 111.7+/-33.3 in ID, and 88.0+/-18.0 in DD. The total quantitative DMSA tracer uptake of both kidneys was also low in patients with the D allele. This study shows that the D allele of ACE gene is closely related to small congenital kidneys with refluxing ureters in patients with primary VUR, and in accordance with previous reports, this allele is also related to the progression of reflux nephropathy.

Combined pharmacotherapy for nocturnal enuresis.

Nocturnal enuresis is a common childhood disorder. Tricyclic antidepressants and anticholinergic agents have been the well accepted pharmacological treatment for this disorder and are efficacious in 40-70% and 10-50% of cases, respectively. The present study was performed to evaluate the effect of a combined treatment of tricyclic antidepressant and an anticholinergic agent. Twenty-two children aged 6-12 years with primary monosymptomatic nocturnal enuresis who did not prefer to use a conditioning alarm were given a combined treatment of these drugs. After a control period of 1 month, each patient was treated for 6 months and then observed for 3 months. A 30-mg dose of amitriptyline or imipramine was given with either 2-4 mg oxybutinin or 10-20 mg propiverine. Efficacy was determined relative to the number of wet nights per week compared with the control period, with more than a 50% decrease in wet nights per week taken to indicate efficacy. The mean wet nights per week decreased from 6.1 to 1.7 (P<0.01), and efficacy was established in 20 patients (90.9%). Relapses occurred in 60.0% of patients during the follow-up period. No significant side effects were observed. The efficacy of the combined therapy in monosymptomatic nocturnal enuresis appears to be greater than that reported for either drug alone, and therefore can be a choice of treatment in order to motivate children with nocturnal enuresis.

Apoptosis of renal tubular cells in Shiga-toxin-mediated hemolytic uremic syndrome.

In order to clarify the mechanism of unusual renal tubular dysfunction seen in a child with Shiga toxin (Stx)-mediated hemolytic uremic syndrome (HUS), we studied the renal biopsy specimens for Stx binding and apoptosis of renal tubular cells. A 7-year-old boy with Stx-2-mediated HUS demonstrated extensive renal tubular damage characterized by nonoliguric acute renal failure, increased urinary tubular enzymes and defective urine-concentrating capacity. His renal biopsy specimens were analyzed for Stx binding and apoptotic cell death. Seven kidney tissue specimens obtained from patients without HUS served as controls. Detection of Stx binding to renal sections and apoptotic cells were performed using mouse monoclonal anti-Stx 2 antibody and the TUNEL method, respectively. Positive staining was observed predominantly in renal tubular cells, while the 7 kidney tissue specimens from control patients did not show positive staining. To the best of our knowledge, this is the first case to show Stx binding and apoptotic cell death in renal tubules on biopsy specimens obtained from a child with Stx-mediated HUS. In conclusion, this case suggests that vascular endothelial cells are not the sole nor the consistent target for Stx-mediated cell injury and that significant renal tubular damage other than glomerular damage might occur in some children with Stx-mediated HUS.

Non-lupus nephropathy associated with antiphospholipid antibodies.

Renal biopsy was performed in a 12-year-old girl with hematuria and proteinuria which was first detected at the age of 7, and the findings were the mesangial proliferative glomerulonephritis with IgG and C3 deposits. The routine blood examination for the biopsy disclosed the presence of the prolonged activated partial thromboplastin time and the biological false positive reaction in the syphilis test. These results led us to the further investigation, which revealed the presence of high titers of anticardiolipin antibodies. Since this girl presented no extra-renal symptoms of systemic lupus erythematosus (SLE) and had negative serologic tests for SLE, we hypothesize that her nephritis is closely related to antiphospholipid antibodies.

Renal amyloidosis in recessive dystrophic epidermolysis bullosa.

BACKGROUND: Although it is known that renal amyloidosis may complicate several dermatoses, recessive dystrophic epidermolysis bullosa (RDEB) complicated by nephropathy has been thought to be rare. We, however, had seen a young adult with RDEB who died of renal failure due to systemic amyloidosis. OBJECTIVE: A retrospective study was performed in order to investigate the incidence and etiology of renal amyloidosis in RDEB. METHODS: Routine urinalysis, serum amyloid A protein (SAA) and creatinine levels were repeatedly determined in 11 patients with RDEB (mean age 17.7 years, range 5-28, 7 males, 4 females). Nephropathy was defined as the presence of both proteinuria and hematuria with red blood cell casts. RESULTS: Seven out of 9 generalized RDEB patients had nephropathy including 3 cases with end-stage renal disease (2 died within 2 years from the onset of nephropathy), while 2 patients with localized RDEB did not. Levels of SAA were significantly higher in patients with nephropathy than those in patients without nephropathy (p<0.05). CONCLUSION: Nephropathy is a common and serious complication of RDEB. Renal amyloidosis may play an important role in its etiology. We recommend that patients with RDEB should be periodically screened for nephropathy due to amyloidosis by urinalysis and measuring SAA levels.

[Studies on growth of verotoxin-producing Escherichia coli (VTEC) O157 in enrichment broth and minimal broth].

Growth of 10 strains of VTEC O157, which were isolated from faecal specimens, was evaluated in conventionally recommended enrichment broth media Trypticase soy broth (TSB) and Davis's Minimal Medium (DMM) at different temperatures. Five strains of VTEC O157 used in the test proliferated well in TSB and reached to 10(9) CFU/ml at 36 degrees C in 24 hours incubation and to the same population densities at 25 degrees C in 48 hours. Whereas in DMM at 36 degrees C there was no proliferation in 6 hours, but grew to 10(6) CFU/ml in 24 hours and 10(8) CFU/ml in 48 hours. Three strains of VTEC O157 tested at 25 degrees C grew to 1.52 x 10(4) CFU/ml in 24 hours, 1.67 x 10(8) CFU/ml in 48 hours and 6.80 x 10(8) CFU/ml in 72 hours. No proliferation was observed at 4 degrees C in 72 hours in growth TSB and DMM. The growth in glucose free DMM was found in 7 out of 10 strains, and 4 out of these 7 strains grew profusely to 10(5) CFU/ml in 48 hours. One out of 3 strains showed no proliferation but survived 72 hours postinoculation, decreasing from 179 CFU to 29 CFU in 100 microliters of medium. The other 2 strains became completely extinct in 48 hours after inoculation with 263 CFU and 2,420 CFU in 100 microliters of medium respectively. However, these 3 strains which showed no growth in glucose free DMM could proliferate in DMM containing 1/10 of the usual glucose concentration, at a rate depending on the concentration. In conclusion, it is suggested that the finding of increase of VTEC O157 in glucose free DMM would be a useful solution for the food poisoning problem caused by VTEC O157.

Bacterial contamination of ready-to-eat foods and fresh products in retail shops and food factories.

Raw vegetables cut for salad, cooked salad, cooked rice, boiled noodles, bean curd, and cooked Japanese foods were purchased in 27 retail shops in Tokyo. Intact vegetables before being processed and ready-to-eat fresh salad products were obtained from two food factories located in the suburbs of Tokyo. Two hundred thirty-eight retail samples, 137 samples of intact vegetables, and 159 samples of fresh products were examined for aerobic plate count (APC), coliforms, Escherichia coli, Listeria spp., Staphylococcus aureus, and Bacillus cereus. The APC of retail foods were 2.1 to 5.7 log CFU/g, and the range for the coliforms was 0.1 to 2.3 log CFU/g. The APC and coliform values showed that the raw vegetables cut for salad were the most heavily contaminated among the six kinds of ready-to-eat foods examined. Although L. monocytogenes was not detected, two samples of raw vegetables and five kinds of cooked foods yielded Listeria spp. S. aureus was detected in one sample of Japanese cooked food. The APC of the intact vegetables were 2.9 to 7.3 log CFU/g upon arrival and 2.2 to 7.2 log CFU/g after 3 days storage at 10 degrees C. The APC of the fresh products were 3.4 to 7.6 log CFU/g upon arrival and 4.7 to 8.7 log CFU/g after 3 days storage at 10 degrees C. The isolation rates for coliforms were 6.1 to 50% for intact vegetables and 50 to 66.7% for fresh products. E. coli was detected only in the fresh products. B. cereus was isolated from 20.1% (17 of 81) of the intact vegetables and 9.2% (8 of 87) of the fresh products.