Clinical characteristics of seizures associated with viral gastroenteritis in children.

OBJECTIVE: We analyzed the clinical features of seizures during gastroenteritis in children by comparing the norovirus and rotavirus pathogen, and the impact of fever, if present, during the seizure episodes. METHODS: Retrospective analysis was performed on 293 consecutive pediatric patients admitted with viral gastroenteritis to Osaka General Hospital between November 2007 and May 2009. Eighteen patients developed seizures, 12 of whom were positive for norovirus and six for rotavirus, as revealed by antigen detection. Of these 18 seizure patients, eight presented without fever (the aFS group) and 10 presented with febrile episodes (FS group). RESULTS: Seizure patients in the rotavirus group (83%) were more likely to be febrile than those in the norovirus group (58%). Compared with the aFS group, 90% of patients in the FS group presented seizures at an early stage of gastroenteritis. The frequency of clustered seizures in the FS group was considerably higher than that of febrile seizures in general and was also as high as that of "convulsions with mild gastroenteritis (CwG)". All seizure patients, whether febrile or afebrile, presented with generalized tonic clonic seizures (GTCS), complex partial seizures (CPS), or both. Diazepam (DZP) was less effective and carbamazepine (CBZ) was completely effective for the cessation of seizures in the FS group, similar to the drug response observed in CwG. CONCLUSIONS: The causative pathogen (norovirus or rotavirus) affected the frequency of febrile episodes during gastroenteritis, but fever had little effect on the clinical features of seizures. However, seizures occurred earlier during gastroenteritis in the FS group. On the whole, the clinical features of febrile seizures during viral gastroenteritis may closely resemble those of "convulsions with mild gastroenteritis" (CwG) than those of febrile seizures in general with respect to the frequency of clustered seizures and the antiepileptic drug responses and may have a pathogenic mechanism distinct from those of febrile seizures due to other causes.

Neurodegenerative central nervous system disease as late sequelae of Langerhans cell histiocytosis. Report from the Japan LCH Study Group.

Clinical features, brain magnetic resonance imaging findings and EDSS scores of 11 patients with neurodegenerative central nervous system Langerhans cell histiocytosis were analyzed in Japan. All patients initially had multi-system-type Langerhans cell histiocytosis; 8 at 1-2 years of age and 3 at a later age. Neurodegenerative central nervous system Langerhans cell histiocytosis disease developed after a median time interval of 3.9 years from initial diagnosis. With a median follow-up of 4.5 years, 6 patients showed progression of disease with an EDSS score >3. This study demonstrates the importance of early detection of neurodegenerative central nervous system Langerhans cell histiocytosis by brain magnetic resonance imaging, particularly in the follow-up of patients who developed multi-system-type Langerhans cell histiocytosis in early infancy.

Treatment with candesartan combined with angiotensin-converting enzyme inhibitor for immunosuppressive treatment-resistant nephrotic syndrome after allogeneic stem cell transplantation.

Most cases of nephrotic syndrome following stem cell transplantation (SCT) occur 6 months after SCT. The patients are treated with immunosuppressive therapies; however, in some cases treatment is not effective. We used enalapril, an angiotensin-converting enzyme inhibitor (ACEI) and candesartan, an angiotensin II receptor blocker (ARB), for the control of proteinuria in a case of immunosuppressive treatment (IST)-resistant nephrotic syndrome. A 15-year-old boy with acute lymphoblastic leukemia underwent allogeneic peripheral blood SCT from a completely HLA-matched sibling after completion of a conditioning regimen composed of 12-Gy doses of total-body irradiation, 600 mg/m2 thiotepa, and 140 mg/m2 melphalan. Twenty-eight months after SCT, minimal-change nephrotic syndrome was diagnosed on the basis of biopsy findings. Although neither cyclosporine (trough level, 100-150 ng/mL) nor corticosteroid was effective, proteinuria disappeared 2 months after the beginning of treatment with tacrolimus (trough level, 13-20 ng/mL), and remission was maintained for 23 months. Nephrotic syndrome recurred, however, and was resistant to tacrolimus. Findings at the second renal biopsy revealed membranous nephropathy. An ARB (candesartan, 4 mg/ day) in combination with an ACEI (enalapril, 5 mg/day) was started. Proteinuria improved within 2 weeks. We suggest that ARB combined with ACEI can be used to control proteinuria in patients with IST-resistant nephrotic syndrome after SCT.

The kinetics of immune reconstitution after cord blood transplantation and selected CD34+ stem cell transplantation in children: comparison with bone marrow transplantation.

The present study compares immune reconstitution after allogeneic cord blood transplantation (CBT) and CD34+ stem cell transplantation (CD34-SCT) with that after bone marrow transplantation (BMT). Eighty-eight children who underwent CBT (20 patients), BMT (58), and CD34-SCT (10) were enrolled, and lymphocytes and T-, B-, and natural killer-lymphocyte subsets were monitored for more than 5 years after transplantation. CBT recipients showed significant ircreases in (1) total lymphocyte counts (P < .001), (2) CD4+/CD8+ cell ratios (P < .01), (3) CD4+ and CD4+CD45RA+ cells (P < .001), (4) CD8+CD11b+ cells (P < .001), and (5) CD19+ and CD19+CD5+ cells (P < .0001) and marked decreases in the frequencies of CD8+ and CD8+CD11b- cells (P < .0001). CD34-SCT recipients showed lower lymphocyte counts in the first 6 months and an emergence of lymphocyte and CD4+CD45RA+ cells at approximately 9 months and 1 year. Both CBT and CD34-SCT recipients showed increased frequencies of CD56+ cells at 1 month (CD34-SCT versus BMT, P < .001) but decreased frequencies after 6 months (CBT versus BMT, P < .001). Lymphoproliferative responses to exogenous interleukin 2 were constantly lower in CBT and CD34-SCT recipients than in BMT recipients. These results suggest that the delay in immune reconstitution after CBT in the early phase was mainly qualitative and related to the immaturity of cells, whereas the delay in CD34-SCT was mainly quantitative in the first several months.

High incidence of human herpesvirus 6 infection with a high viral load in cord blood stem cell transplant recipients.

Human herpesvirus 6 (HHV-6) infection in recipients of cord blood stem cell transplants (CBSCTs) was estimated by semiquantitative and real-time quantitative polymerase chain reaction (PCR) and reverse-transcription PCR. Of the CBSCT recipients, 7 (70%) of 10 had active HHV-6 infection after transplantation, and all 7 were inferred from their age to have already had a primary infection. Because HHV-6 DNA is seldom detected in cord blood, these cases were considered likely to represent reactivation. In contrast, the 3 patients without HHV-6 infection were all believed to be naive regarding HHV-6 primary infection because of their age and the results of PCR assays given before the transplantation procedure. The incidence of HHV-6 infection after transplantation was significantly higher (P <.05) than after bone marrow (BM) transplantation and peripheral blood stem cell (PBSC) transplantation, when recipients without primary HHV-6 infection prior to transplantation were excluded (CBSCT, 100%; BMT/PBSCT, 56.3%). Real-time PCR revealed a higher level of viral DNA in the peripheral blood mononuclear cells from CBSCT recipients than from BMT/PBSCT recipients or patients with exanthem subitum (P <.05). HHV-6 mRNA of the U79/80 gene was also detected by reverse-transcription PCR in all analyzed patients with HHV-6 infection. Its detection was correlated with the emergence of viral DNA in the plasma and symptoms such as fever and rash. Thus, HHV-6 infection was more frequent and the viral load was higher in CBSCT recipients with prior primary infection.

Establishment of a monosomy 7 leukemia cell line, MONO-7, with a ras gene mutation.

A monosomy 7 leukemia cell line, designated MONO-7, was established from the peripheral blood of a patient with monosomy 7 acute myelocytic leukemia (French-American-British classification M0). The cells were cultured continuously for more than 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. The cell line exhibits an unclassified appearance. Cytochemically, alpha-naphthol-acetate esterase and myeloperoxidase are negative. Immunophenotypically, the cell line expresses CD33, CD13, CD56, CD34, CD38, HLA-DR, and CD45, but lacks T and B cell-associated antigens. Karyotypic analysis of the cell line showed only 45,XY,-7. Analysis of the N-ras gene mutation demonstrated identical mutations in fresh leukemic cells and the MONO-7 cell line. Clonal rearrangements of the immunoglobulin heavy-chain gene, T-cell receptor beta-chain gene, or T-cell receptor gamma-chain gene were not found in DNA extracted from MONO-7 cells. The growth of MONO-7 cells in vitro was stimulated by recombinant human granulocyte-macrophage colony-stimulating factor or interleukin 3. To our knowledge, this is the first report of the establishment of a cell line with the karyotype 45,XY,-7 without any other abnormality and with a ras gene mutation.

Establishment of a Monosomy 7 Leukemia Cell Line, MONO-7, With aras Gene Mutation.

A monosomy 7 leukemia cell line, designated MONO-7, was established from the peripheral blood of a patient with monosomy 7 acute myelocytic leukemia (French-American-British classification M0). The cells were cultured continuously for more than 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. The cell line exhibits an unclassified appearance. Cytochemically, α-naphthol-acetate esterase and myeloperoxidase are negative. Immunophenotypi-cally, the cell line expresses CD33, CD13, CD56, CD34, CD38, HLA-DR, and CD45, but lacks T and B cell-associated antigens. Karyotypic analysis of the cell line showed only 45,XY,-7. Analysis of the N-ras gene mutation demonstrated identical mutations in fresh leukemic cells and the MONO-7 cell line. Clonal rearrangements of the immunoglobulin heavy-chain gene, T-cell receptor ß-chain gene, or T-cell receptor γ-chain gene were not found in DNA extracted from MONO-7 cells. The growth of MONO-7 cells in vitro was stimulated by recombinant human granulocyte-macrophage colony-stimulating factor or interleukin 3. To our knowledge, this is the first report of the establishment of a cell line with the karyotype 45,XY,-7 with-out any other abnormality and with a ras gene mutation.