The objectives of this study are to clarify (1) the difference in demographic and clinical variables at initial presentation between acute and chronic idiopathic thrombocytopenic purpura (ITP), and (2) the prognostic factors of patients with chronic ITP. We conducted a retrospective analysis of 247 children with newly diagnosed ITP between April 1991 and March 2006 who visited one of the 12 hospitals belonging to the Kyoto University Pediatric Hematologic Study Group. 180 and 67 cases were classified as the acute type and as the chronic type, respectively. Older age, higher initial platelet count, positive medical history or concomitant medical diagnosis, the absence of preceding infection or vaccination, and the absence of an increase in immunoglobulin were risk factors for the chronicity. The prognostic factors in chronic ITP were evaluated in 53 patients after excluding patients receiving splenectomy or having insufficient follow-up data. The overall time required for 50% resolution in patients with chronic ITP was approximately 5.6 years. Age at presentation of less than 3 years and higher platelet counts at the time of chronic ITP diagnosis were good prognostic factors. On the other hand, gender, initial platelet counts, and preceding infection or vaccination were not associated with the prognosis.

Pediatric leukemia survivors in Japan experience equal or less fatigue compared with that of controls in different fatigue dimensions. Elucidation of underlying mechanisms of cancer-related fatigue including the differences of cultural background among different countries is necessary for future study of this issue.

We have previously reported that calcium ionophore A23187 differentially induces necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in HL60 cells, a promyelocytic leukemia cell line. Stimulation with VP16, however, induces typical apoptosis in both cell lines. Necrosis in CEM cells, characterized by cell shrinkage and clustering, began within 5 min of treatment. Swelling of the mitochondria, lumpy chromatin condensation and intact plasma membranes were evident by electron microscopy. These A23187-mediated changes in CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the mitochondrial Na(+)/Ca(2+) exchanger. The changes, however, were not affected by cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude within 1 min of treatment with 2 microM A23187. Intra-mitochondrial calcium increased with clonazepam pre-treatment alone in both CEM and HL60 cells. However, intra-mitochondrial calcium did not change drastically in response to A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam. A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction, which is independent of the mitochondrial permeability transition, but affected by intra-mitochondrial calcium, while HL60 cells lack these early changes. Differences in the responses to A23187 between these two cell lines might derive from differences in the susceptibility of the mitochondrial membrane to rapid increases in intra-cellular calcium.

The purpose of the present study is to clarify the effects of the administration of choline on the in vivo release and biosynthesis of acetylcholine (ACh) in the brain. For this purpose, the changes in the extracellular concentration of choline and ACh in the rat striatum following intracerebroventricular administration of choline were determined using brain microdialysis. We also determined changes in the tissue content of choline and ACh. When the striatum was dialyzed with Ringer solution containing 10 microM physostigmine, ACh levels in dialysates rapidly and dose dependently increased following administration of various doses of choline and reached a maximum within 20 min. In contrast, choline levels in dialysates increased after a lag period of 20 min following the administration. When the striatum was dialyzed with physostigmine-free Ringer solution, ACh could not be detected in dialysates both before and even after choline administration. After addition of hemicholinium-3 to the perfusion fluid, the choline-induced increase in ACh levels in dialysates was abolished. Following administration of choline, the tissue content of choline and ACh increased within 20 min. These results suggest that administered choline is rapidly taken up into the intracellular compartment of the cholinergic neurons, where it enhances both the release and the biosynthesis of ACh.

No abstract

We examined the effects of hypoxia (8% O2) on in vivo tyrosine hydroxylation, a rate-limiting step for catecholamine synthesis, in the rat adrenal gland. The hydroxylation rate was determined by measuring the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition. One hour after hypoxic exposure, DOPA accumulation decreased to 60% of control values, but within 2 h it doubled. At 2 h, the apparent Km values for tyrosine and for biopterin cofactor of tyrosine hydroxylase (TH) in the soluble fraction were unchanged, whereas the Vmax value increased by 30%. The content of total or reduced biopterin was unchanged, but the content of tyrosine increased by 80%. Tyrosine administration had little effect on DOPA accumulation under room air conditions but enhanced DOPA accumulation under hypoxia. After denervation of the adrenal gland, the hypoxia-induced increase in DOPA accumulation and in the Vmax value was abolished, whereas the hypoxia-induced increase in tyrosine content was persistent. These results suggest that in vivo tyrosine hydroxylation is enhanced under hypoxia, although availability of oxygen is reduced. The enhancement is the result of both an increase in tyrosine content coupled with increased sensitivity of TH to changes in tyrosine tissue content and of an increase in dependence of TH on tyrosine levels. The increase in the sensitivity of TH and in the Vmax value is neurally induced, whereas the increase in tyrosine content is regulated by a different mechanism.

Several investigators have reported patients with acute pure red cell aplasia (PRCA) caused by anticonvulsants, antibiotics, or antithyroid agents. Allopurinol is known to be a causative agent of aplastic anemia, but there have been few reports of acute PRCA induced by allopurinol. We describe here a 15-year-old boy who suffered from anemia 6 weeks after initiation of allopurinol therapy; his anemia immediately improved after cessation of the drug. His bone marrow showed severe erythroid hypoplasia with a myeloid/erythroid ratio of 18.6 and low expression of glycophorin A detected on cell-surface antigen analysis. No morphological abnormalities were observed in myeloid series and megakaryocytes. The prolonged plasma iron disappearance rate and the decreased plasma iron turnover rate also indicated erythroid hypoplasia. He had been free from any infections, including parvovirus B19, before manifestation of PRCA. Taken together, these results suggest a diagnosis of acute PRCA. This side effect of allopurinol should be taken into consideration.

CEP alone or combined with CS was useful for the management of pediatric chronic ITPs.