Problem-based instruction is designed to provide students with a guided experience in solving an ill-structured problem. All learning in problem-based instruction stems from students initial questions about a problem situation. Currently used in medical school programs, problem-based curriculum has not been tested at the high school level. Science, Society and the Future (SSF) is an experimental problem-based course for gifted high school students. In the interdisciplinary course, students examine the meaning and impact of current science issues (the effect of electromagnetic fields on childhood leukemia, the health care system). In this study, SSF students and a group of comparison students were tested to determine changes in their spontaneous use of problem-solving steps as they consider an ill-structured problem. Results show some significant changes for the SSF group not observed in the comparison group.
Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34 ؉ cells influence relapse and event-free survival (EFS) after BMT.
Polyclonal anti-thymocyte globulin (ATG) administered before allogeneic blood hematopoietic progenitor cell transplantation reduces the risks of graft rejection and graft-versus-host disease, but may delay posttransplant immune reconstitution caused by delayed clearance of ATG from the blood. We studied graft-versus-host disease, infections, and the kinetics of immune reconstitution in 28 patients with very poor-risk hematologic malignancies who received lymphocyte-depleted, CD34(+) cell-enriched hematopoietic progenitor cell grafts from partially HLA-matched related donors (PMRD). The incidence of these clinical events was correlated with blood ATG levels in 19 transplant recipients who received rabbit ATG (r-ATG, thymoglobulin) during conditioning. Total r-ATG and the fraction of ATG antibodies that bind human cells (active ATG) were measured for up to 45 days posttransplantation using enzyme-linked immunosorbent assay and flow cytometry assays. Three patients received equine ATG (e-ATG; total dose of 60 mg/kg/day), 3 patients received 10 mg/kg r-ATG, and 22 patients received 6 mg/kg r-ATG during conditioning. All evaluable patients engrafted. Median numbers of blood CD4(+) and CD8(+) T cells at 100 days posttransplantation were 15 and 8 cells/microL, respectively. Acute graft-versus-host disease developed in 3 of 3 recipients of e-ATG and 1 of 25 recipients of r-ATG. Rapid T-cell reconstitution was seen only in younger patients. Overall mortality was 93% (26/28 patients) with poor immune reconstitution contributing to death in 21 of 28 patients. Recipients of 6 mg/kg r-ATG had peak levels of total and active r-ATG of 64+/-20 microg/mL and 9.2+/-5.8 microg/mL, respectively, with clearance of active r-ATG (t(1/2)6 days) to sub-therapeutic levels (<1 microg/mL) by a median of 15 days posttransplantation (range, 8-38 days). Delayed immune reconstitution is likely a consequence of ex vivo and in vivo purging of donor T cells in the graft coupled with inadequate thymic function rather than persistence of active r-ATG in the blood for months posttransplantation.
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