Search PubMed⌕ Search

Biomedical subjects

D Joshua

Publications and source records attributed to D Joshua.

48 records · Page 3Linked to original sources
PubMed1993

Interleukin-6 receptor expression and saturation on the bone marrow cells of patients with multiple myeloma.

Expression of the interleukin-6 (IL-6) receptor on B cells and plasma cells in the bone marrow (n = 18) and peripheral blood (n = 32) of patients with multiple myeloma and the relative saturation of these receptors with endogenous IL-6 has been determined by dual-labelled flow cytometric analyses. B cells were identified using an anti-CD19 monoclonal antibody and plasma cells were identified by gating on cells with high fluorescent staining with anti-CD38. With the exception of one patient, very few bone marrow plasma cells expressed the IL-6 receptor (IL-6R) (mean = 2%). This was in contrast to cells from the U-266 plasma cell line, 90% of which had IL-6R. IL-6R expression was lower on bone marrow B cells (mean = 11%) than on peripheral blood B cells (mean = 69%). Studies using either monoclonal or polyclonal anti-human IL-6 to detect endogenous receptor-bound IL-6 found that the IL-6R on bone marrow B cells and plasma cells from patients with multiple myeloma were not saturated with endogenous IL-6 and the presence of receptor-bound IL-6 tended to be associated with stable disease. Thus dysregulated IL-6R expression was not evident on the B cells and plasma cells of patients with multiple myeloma and the increased IL-6R expression on the U-266 plasma cell line was not found on patients' cells.

B-Lymphocytes↗
PubMed1991

Etoposide in leukemia.

Etoposide (VP16-213, NSC 141540) induces a complete response (CR) in 15% to 25% of previously treated patients with acute nonlymphocytic leukemia (ANLL) when used as a single agent. Etoposide has been used successfully in combination with cytarabine, daunorubicin, and amsacrine for salvage and consolidation therapies. Previously untreated ANLL patients 15 to 70 years of age were randomly assigned to cytarabine (100 mg/m2) on days 1 to 7 plus daunorubicin (50 mg/m2) on days 1 to 3 (7-3) or to the same drugs plus etoposide (75 mg/m2) on days 1 to 7 (7-3-7). Patients achieving a CR received two consolidation courses (5-2, attenuated 7-3 or 5-2-5). Among 264 eligible patients, there was a 56% CR rate with 7-3 therapy and a 59% CR rate with 7-3-7 therapy. Remission duration was significantly improved with 7-3-7 (median, 12 months with 7-3 and 18 months with 7-3-7; P = 0.01), but survival was not. Subset analysis in patients younger than 55 years of age revealed prolonged remission (median, 12 months with 7-3 and 27 months with 7-3-7; P = 0.01) and survival (median, 9 months with 7-3 and 17 months with 7-3-7; P = 0.04) with the 7-3-7 regimen. Hematologic toxicity was similar for both regimens during induction, but significantly more severe for 7-3-7 during consolidation therapy. Etoposide is active in ANLL and prolongs remission when used in induction therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Etoposide in acute nonlymphocytic leukemia. Australian Leukemia Study Group.

Previously untreated patients with acute nonlymphocytic leukemia (ANLL) aged 15 to 70 years were randomized to either cytosine arabinoside 100 mg/m2/d continuous intravenous (IV) infusion days 1 through 7, daunorubicin 50 mg/m2/d IV days 1 through 3 (7-3), or the same drugs intensified with etoposide 75 mg/m2/d IV days 1 through 7 (7-3-7) as induction therapy. Patients achieving complete remission (CR) received two courses of consolidation therapy (5-2 or 5-2-5) followed by maintenance therapy. Of 264 eligible patients, CR occurred in 56% of 7-3 and 59% of 7-3-7 patients; 7-3-7 significantly improved remission duration (P = .01). The median remission duration was 12 months for 7-3 and 18 months for 7-3-7. Survival was similar when the two arms were compared overall. Subset analysis performed to identify patients with the most benefit showed that etoposide significantly prolonged remission duration in younger patients (less than 55 years) with a median of 12 months for 7-3 and 27 months for 7-3-7 (P = .01). Survival appeared to be prolonged with 7-3-7 in patients aged less than 55 years, with a median of 9 months for 7-3 as compared with 17 months for 7-3-7 (P = .03). In older patients (aged greater than or equal to 55 years), 7-3-7 was more toxic, with significantly more severe [World Health Organization (WHO) grade 3 or 4] stomatitis (P = .02) and no additional clinical benefit. Hematologic toxicity for induction courses was similar, with granulocytopenia less than 0.5 x 10(9)/L for a median of 16 days per course for 7-3 and 15 days for 7-3-7. Hematologic toxicity was more severe for 5-2-5 consolidation courses (P = .003). Induction and consolidation therapy intensified with etoposide resulted in significantly improved remission duration but not survival.

Adolescent↗
PubMed1988

Clinical response of hairy-cell leukaemia to interferon-alpha: results of an Australian study.

Twelve patients with documented, progressive hairy-cell leukaemia were treated with human lymphoblastoid interferon-alpha. All patients initially received a three-month course of interferon-alpha (3 x 10(6) U each day) which resulted in two complete remissions and 10 partial remissions. All eight patients who were dependent upon packed red-cell transfusions became independent of them and the three patients with the most severe, pretreatment pancytopenia also became independent of platelet transfusions. The histological appearance of the bone marrow improved in all patients; in three patients, a complete resolution of the leukaemic infiltrate was recorded. Adverse reactions occurred in 10 patients, but these were mild and did not interrupt treatment in seven patients. Moderate reactions that required a temporary reduction in the dose of interferon-alpha were seen in three patients. Ten patients subsequently received maintenance therapy with interferon-alpha (3 x 10(6) U, three times a week). A haematological improvement continued to be seen in all patients, and the results, with a minimum of one year of follow-up, are presented.

Adult↗
PubMed1979

Some properties of the colony forming cell in adult acute leukaemia.

Variations in the concentration and physical characteristics of the bone marrow derived colony forming cell(CFC) have been studied in patients with acute leukaemia. Two-hundred-and-fifteen marrow samples from 83 patients provide the basis for this analysis. CFC concentration confirmed the clinical remission/relapse status and yielded some guidelines to prognosis in individual patients while the proportions of CFC in DNA synthesis also proved to be a most reliable indicator of disease status. In remission, CFC concentrations return to normal values whilst on presentation and in the relapse phase of acute leukaemia CFC numbers are reduced. Biophysical profiles of CFC established using albumin density gradient and velocity sedimentation studies also indicated the state of the leukaemic process in individual patients. By applying physical laws to the data obtained from such profiles, the mean volume, diameter, density and mass of CFC were calculated. CFC from leukaemic patients in relapse were up to twice the volume and mass although slightly less dense than CFC from normal patients. The reasons for these changes are explained and discussed.

Acute Disease↗