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Biomedical subjects

S Juneja

Publications and source records attributed to S Juneja.

31 records · Page 2Linked to original sources

A randomized study of high-dose cytarabine in induction in acute myeloid leukemia.

High-dose cytarabine (ara-c) may overcome cytarabine resistance in leukemic blasts. It has been used as a successful salvage and in postremission therapy but not as initial induction treatment. Patients aged 15 to 60 years, presenting with newly diagnosed acute myeloid leukemia (AML) were randomized to receive either high-dose cytarabine, 3 g/m2 12 hourly on days 1, 3, 5, and 7 for 8 doses, daunorubicin 50 mg/m2 days 1 to 3, etoposide 75 mg/m2 days 1 to 7, (HIDAC-3-7) or standard dose cytarabine 100 mg/m2 continuous intravenous infusion for 7 days with daunorubicin and etoposide at the same dose and schedule as above (7-3-7). Patients could receive a second or third induction course if complete remission (CR) was not achieved. All patients received the same postinduction consolidation therapy (5-2-5) for 2 courses. Eligible patients had no prior chemotherapy or myelodysplastic disease. Patients have been followed for a median of 4.5 years. Of 301 patients treated, complete response (CR) was achieved in 71% with HIDAC-3-7 and 74% with 7-3-7. For patients in CR, the estimated median remission duration was 45 months with HIDAC-3-7 and 12 months with 7-3-7 (P = .0005 univariate analysis, P = .0004 multivariate analysis). The estimated percentage of patients relapse free 5 years after achieving a CR was 49% on HIDAC-3-7 and 24% on 7-3-7. Patients in CR tended to survive longer with HIDAC-3-7 but there were no overall survival differences between the two arms. HIDAC-3-7 was associated with significantly more toxicity in induction with more leukopenia, thrombocytopenia, nausea, and vomiting and eye toxicity (all P < .001) but a similar incidence of severe central nervous system and cerebellar toxicity compared to 7-3-7. The consolidation treatment was the same in both arms but caused significantly more leukopenia and thrombocytopenia in patients previously treated with HIDAC-3-7 induction (P < .0001). We conclude that a dose-effect exists for cytarabine in AML and that HIDAC-3-7 prolongs remission duration and disease-free survival and is tolerable when used as initial induction therapy in patients with de novo AML.

Acute Disease↗

Post-splenectomy lymphocytosis.

We describe post-splenectomy lymphocytosis (PSL) in 23 patients, a majority (20/23) of whom have undergone splenectomy as a staging procedure for Hodgkin's disease. The absolute lymphocyte count ranged from 4.0 to 8.7 x 10(9)/l. The lymphocytosis was noted 4-242 (median 70) months after splenectomy and persisted almost unchanged in most patients on prolonged follow up (median 50 months). Immunophenotyping of the lymphocytes revealed no monoclonal B cell population.

Adult↗

Association of abnormalities of chromosome 11 with t(14;18) in diffuse non-Hodgkin's lymphoma.

Cytogenetic studies of non-Hodgkin's lymphomas (NHL) have revealed a nonrandom translocation, t(14;18)(q32;q21), to be strongly correlated with follicular histology. In our recent study of 149 cases of NHL, 68 cases had a t(14;18). Forty-four of these were follicular and 24 diffuse. In the majority of cases (90%) there were additional chromosome abnormalities, which were analyzed to determine whether any were specifically associated with diffuse histology. Chromosome 11 abnormalities occurring together with the t(14;18) were found to be present in 17/68 cases; 14/17 (82%) were diffuse and 3/17 (18%) were follicular NHL. Thus, 14/24 (58%) of all diffuse lymphomas with t(14;18) had an abnormality of chromosome 11 compared to only 3/44 (7%) of follicular lymphomas, suggesting that the addition of an abnormality of chromosome 11 to a t(14;18) karyotype is associated with diffuse histology.

Adult↗

Secondary myelodysplastic syndrome following bone marrow transplantation: report of two cases.

We report two cases of secondary myelodysplastic syndrome (SMDS) which followed successful treatment of a primary malignancy with high-dose chemotherapy supported by reinfusion of autologous stem cells. The SMDS was diagnosed 24 months and 40 months, respectively, following autografting. Both patients lived for 7 months after the diagnosis of SMDS. Our cases support the view that there is an increased risk of SMDS/acute leukemia following autologous marrow transplantation.

Adult↗

Effects of 5-fluorouracil or total-body irradiation on murine bone marrow microvasculature.

This study was designed to investigate the changes in the murine bone marrow microvasculature following treatment with 5-fluorouracil (5-FU) or total-body irradiation (TBI). Seventy 8- to 12-week-old C3H male mice received either 5-FU at a dose of 150 mg/kg intravenously (i.v.) or TBI at a dose of 8 Gy in two fractions 4 hours apart. Femurs from the treated mice were studied by vascular casting, using mercox, and by routine histology at days 5, 21, and 90. On day 5, the sinusoids were markedly swollen, and many were fused with one another. This was accompanied by significant reduction in the bone marrow cellularity. The central sinus was grossly dilated in both TBI- and 5-FU-treated groups. The pronounced sinusoidal dilatation on day 5 appears to be a mechanical effect due to hematopoietic cell loss resulting in relative negative pressure outside the sinusoids. On day 21, the sinusoidal swelling had subsided, and the overall vascular volume appeared to be restored to normal. However, there was a large variation in the shape and size of the sinusoids, and those present were not uniformly distributed. This may be due to the result of mechanical pressure from the reconstituted hematopoietic cells. Whether these changes in the shape and distribution of sinusoids have functional significance--for instance, release of the hematopoietic cells into the circulation--remains to be established.

Animals↗

Adult T cell leukaemia lymphoma in a non-aboriginal Australian woman with no apparent risk factors.

OBJECTIVE: To present a case of adult T cell leukaemia lymphoma (ATLL) in a non-Aboriginal Australian woman with no apparent risk factor. CLINICAL FEATURES: A 43-year-old Australian woman of European descent presented with a febrile illness associated with generalised lymphadenopathy and splenomegaly. INVESTIGATIONS: There was lymphocytosis in the peripheral blood with a T helper cell phenotype. There were also lytic bone lesions with associated hypercalcaemia. HTLV-1 antibody was detected by agglutination assay and confirmed by western blot test. TREATMENT AND OUTCOME: After initial response to CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), she relapsed and died with central nervous system involvement eight months after the initial diagnosis. CONCLUSION: To our knowledge this is only the third case of ATLL in a non-Aboriginal person in Australia.

Adult↗

Role of a germ cell-specific sulfolipid-immobilizing protein (SLIP1) in mouse in vivo fertilization.

Sulfolipid-immobilizing protein 1 (SLIP1) is a germ cell plasma membrane protein that binds specifically to sulfogalactosylglycerolipid, a sulfoglycolipid found preferentially in mammalian male germ cells (Lingwood, Can. J. Biochem. Cell. Biol. 63:1077-1085, 1985b). SLIP1 in mouse and rat sperm exists on the periacrosomal membrane, where sperm initially bind to eggs. Using the in vitro mouse sperm-egg binding assay with in vitro-capacitated sperm, we obtained results previously suggesting that sperm SLIP1 is involved in mouse sperm-zona pellucida interaction. In this study, using the in vitro sperm-egg binding assay, we showed that SLIP1 in uterine sperm was similarly engaged in this process. Involvement of mouse sperm SLIP1 was also shown to be important in the in vivo fertilization process. Superovulated females inseminated with caudal epidididymal and vas deferens sperm preexposed to anti-SLIP1 IgG yielded only 20% fertilized zygotes, while 80% fertilization was observed in females inseminated with sperm preincubated with preimmune serum IgG. The lower fertilization rate was not due to changes in the sperm capacitation rate as assessed by chlortetracycline staining.

Animals↗

Clumping of lymphoma cells in peripheral blood induced by EDTA.

A peripheral blood smear from a patient with probable splenic lymphoma with villous lymphocytes (SLVL) showed clumping of lymphoma cells. The clumping was not seen in films made from unanticoagulated blood, and has not been previously described in lymphomas. The patient also had metastatic prostatic adenocarcinoma for 30 months before lymphoma was diagnosed and the clumped cells posed diagnostic problems.

Adenocarcinoma↗

Sequential karyotypes in non-Hodgkin lymphoma: their nature and significance.

The examination of sequential karyotypes in hematologic disorders has demonstrated that karyotypic changes are often associated with concurrent changes in clinical behavior. Acquired abnormalities that recur among different patients may also suggest genomic areas important to tumor progression. We therefore examined sequential karyotypes in 21 patients with non-Hodgkin lymphoma (NHL). Sixteen of the 21 karyotypes demonstrated changes, including the majority of 6 small lymphocytic, 11 follicular, and 4 intermediate and high-grade diffuse lymphomas. The t(14;18)(q32;q21) occurred in ten initial karyotypes was retained in all cases. The band most frequently affected by newly acquired abnormalities was 14q32 (n = 5); chromosomes 1 and 2 (n = 5, each), and the 17p arm (n = 4) were also commonly affected. The acquired deletion of all or part of 17p appeared to be associated with a poor prognosis. Histologic transformation and karyotypic change did not correlate. This study of sequential karyotypes in NHL 1) confirms the primary importance of the t(14;18), 2) suggests that the 14q32 band is involved frequently in both primary and secondary cytogenetic events, and 3) suggests other genomic regions of potential significance to progression.

Adult↗

Cytogenetic analysis of 147 cases of non-Hodgkin's lymphoma: non-random chromosomal abnormalities and histological correlations.

A prospective cytogenetic study of patients with non-Hodgkin's lymphoma (NHL) presenting to one institution was commenced in 1983 as part of a larger study including histology, immunophenotyping, cytokinetics and survival. 175 patients were studied over 5 years and G-banded karyotypes were successfully obtained in 147. Chromosome abnormalities were detected in 135 cases (92%) with the commonest abnormality being t(14;18)(q32;q21) in 69 cases. Other non-random translocations were much less frequent, i.e. t(11;14) in seven cases and t(8;14) in four cases. Other specific structural changes included partial deletions of 6q (breakpoints ranging within q13-q23), 3q (breakpoints ranging within q21-q27), 1q and 10q22. Chromosome regions highlighted as being frequently involved in structural abnormalities were 11q13-q25, 1p22-p36, 3q21-q27 and 6q13-q23. Several specific recurring breakpoints were identified and these included 14q32, 18q21, 1p36 and 6q21. Frequently occurring numerical abnormalities were gains of chromosomes 3, 7, X and 12. Correlation with histological type showed, as expected, that t(14;18) was present in 89% of follicular lymphoma but also occurred in 30% of diffuse lymphoma. Abnormalities of 11q were correlated with the diffuse histologies as a group, whereas both numerical and structural abnormalities of chromosome 3 correlated with the diffuse large cell lymphoma (DLCL) subtype, and t(11;14) with diffuse small cleaved cell lymphoma (DSCCL). Although not statistically significant, abnormalities of 6q occurred twice as frequently in DLCL than in any other variety. However, several other commonly occurring abnormalities, such as extra copies of chromosomes 7, X, 12 and most of the structural abnormalities of 1p, did not correlate with any histological type. Therefore this large cytogenetic study has confirmed some previously reported correlations between specific chromosome abnormalities and histological subtypes of non-Hodgkin's lymphoma and has also identified some new correlations which may prove useful in the investigation of the biological basis of the disease.

Chromosome Aberrations↗

Trisomy 4 in acute nonlymphocytic leukemia. An Australian case.

We report a case of acute nonlymphocytic leukemia, type M4 according to the FAB classification, whose cytogenetics showed trisomy 4 and multiple double minute chromosomes. The patient gave no history of exposure to toxic or carcinogenic substances.

Acute Disease↗

Correlation of immunological surface antigens with survival in diffuse large cell lymphoma.

The prognostic value of immunophenotyping lymphomas with a panel of monoclonal antibodies (Mab) to various lymphoid antigens was assessed by studying 47 cases of diffuse large cell lymphoma. Cell suspensions were analysed by flow cytometry after labelling by indirect immunofluorescence. Thirty-eight cases were demonstrated to be of B cell and nine of T cell phenotype. Univariate analysis demonstrated that survival was significantly longer in patients expressing higher levels of HLA-DR (p = 0.01) and normal levels of CD8 (p = 0.04) but was not significantly associated with any of the other antigens. Our results support the possible value of HLA-DR in determining the prognosis of patients with diffuse large cell lymphoma.

Adult↗