tdic(9;12): a nonrandom chromosome abnormality in childhood B-cell precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study

In a review of 432 children with newly diagnosed acute lymphoblastic leukemia (ALL), we identified a new nonrandom translocation, tdic(9;12)(p1?1;p1?2), in the leukemic marrow cells of eight patients. Seven had hypodiploid karyotypes that lacked chromosomes 9 and 12 and contained a der(12), tdic(9;12); the eighth had a pseudodiploid karyotype with two normal 9 chromosomes, one normal 12 and the der(12), tdic(9;12). Abnormalities involving chromosomes other than 9 and 12 were noted in four of the eight patients. All cells with the tdic(9;12) expressed both the common ALL antigen and HLA-DR. Cytoplasmic immunoglobulin, a marker of pre-B ALL, was detected in one case with the tdic(9;12) but was absent in the other seven. Our results suggest that the tdic(9;12)(p1?1;p1?2) rearrangement is specifically associated with leukemic B cell precursors.     

Do we need ‘new’ omega-3 polyunsaturated fatty acids formulations?

The therapeutic value of omega-3 polyunsaturated fatty acids (PUFAs), mainly (but not only) found in fish oils, eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively), has been extensively studied in a wide variety of disease conditions, predominantly in cardiovascular disease. However, the significant difference in efficacy observed in various conditions with different dosages seems to be at least partly related to the large discrepancy in quality of the product and to the bioavailability of the omega-3 PUFA. The research of new sources (e.g., from arctic Krill oil) and pharmaceutical forms of omega-3 PUFA (e.g., omega-3 carboxylic acids) is needed in order to detect the one with the best bioavailability and efficacy, and with a parallel reduction in the production costs. There is also the need to understand if long-term PUFA supplementation could increase the efficacy of the already-available evidence–based therapies for cardiovascular disease prevention and for the management of the diseases where the use of PUFA could have a possible improving effect.     

Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin

A case of transcobalamin II (TCII) deficiency in which a total absence of TCII was demonstrated both functionally and immunologically is reported. Unlike previously described patients, this child has been maintained on oral hydroxocobalamin, 2 mg daily, without any parenteral supplementation for the last five years. At the age of six years her development is normal and her health is good. Plasma cobalamin levels are in the range of 3,000 ng/L and most of this appears to be bound to a molecule, which on gel filtration, elutes with albumin. In an extended family study, a clear separation of heterozygotes from both the propositus and from normal subjects suggests that the underlying defect in this condition is confined to a single gene.     

Associations of dialysis modality and infectious mortality in incident dialysis patients in Australia and New Zealand

BACKGROUND: The aim of the present investigation is to compare rates, types, causes, and timing of infectious death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients in Australia and New Zealand. STUDY DESIGN: Observational cohort study using the Australian and New Zealand Dialysis and Transplant Registry data. SETTING & PARTICIPANTS: The study included all patients starting dialysis therapy between April 1, 1995, and December 31, 2005. PREDICTOR: Dialysis modality. OUTCOMES & MEASUREMENTS: Rates of and time to infectious death were compared by using Poisson regression, Kaplan-Meier, and competing risks multivariate Cox proportional hazards model analyses. RESULTS: 21,935 patients started dialysis therapy (first treatment PD, n = 6,020; HD, n = 15,915) during the study period, and 1,163 patients (5.1%) died of infectious causes (PD, 529 patients; 7.6% versus HD, 634 patients; 4.2%). Incidence rates of infectious mortality in PD and HD patients were 2.8 and 1.7/100 patient-years, respectively (incidence rate ratio PD versus HD, 1.66; 95% confidence interval [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses allowing for an interaction between time on study and modality because of identified nonproportionality of hazards, PD consistently was associated with increased hazard of death from infection compared with HD after 6 months of treatment (<6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2 years HR, 1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95% CI, 1.26 to 1.80; >6 years HR, 2.76; 95% CI, 1.76 to 4.33). This increased risk of infectious death in PD patients was largely accounted for by an increased risk of death caused by bacterial or fungal peritonitis. LIMITATIONS: Patients were not randomly assigned to their initial dialysis modality. Residual confounding and coding bias could not be excluded. CONCLUSIONS: Dialysis modality selection significantly influences risks, types, causes, and timing of fatal infections experienced by patients with end-stage kidney disease in Australia and New Zealand.     

DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.