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Biomedical subjects

P MacCallum

Publications and source records attributed to P MacCallum.

6 recordsLinked to original sources

Reversible posterior leukoencephalopathy syndrome following CHOP chemotherapy for diffuse large B-cell lymphoma.

A 63-year-old female with stage IE diffuse large B-cell lymphoma developed reversible posterior leukoencephalopathy syndrome (RPLS) following CHOP chemotherapy, with typical clinical and radiological findings. RPLS is a rare neurological syndrome characterised by visual disturbances, seizures, headaches and altered conscious level which has been associated with malignant hypertension, pre-eclampsia and some drugs, including ciclosporin. It has not been previously reported following CHOP chemotherapy. Alternative treatment should be considered for patients who develop this rare complication.

Antineoplastic Combined Chemotherapy Protocols↗

Optimising testing for phospholipid antibodies.

AIM: To compare anticardiolipin (ACL) and anti-beta2 glycoprotein 1 (beta2gp1) enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid syndrome (APS) and to incorporate these results into a meta-analysis of published data. METHOD: Three representative commercial ACL ELISAs and an in house beta2gp1 assay were optimised and then assessed on 124 sera from normal donors, patients with infection, or patients with APS. A Medline search was screened for papers meeting defined criteria to conduct a meta-analysis. The performance of the assays used in this study was included. RESULTS: A non-quantitative ACL assay performed at least as well as the anti-beta2gp1 assay in the diagnosis of APS. Meta-analysis confirmed that neither assay is perfect, although the anti-beta2gp1 assay had a higher specificity and lower sensitivity than the ACL assay. CONCLUSIONS: The pooled data suggest that the ACL assay is used to investigate thrombosis without overt underlying pathology and that the improved specificity of the anti-beta2gp1 assay is exploited where infection, connective tissue disease, or atheroma are present.

Antibodies, Anticardiolipin↗

Definition of the transcription factors which bind the differentiation responsive element of the Epstein-Barr virus BZLF1 Z promoter in human epithelial cells.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus and an important human pathogen. Initiation of the EBV lytic cycle is dependent upon transcription of the EBV BZLF1 gene. Our previous studies of transcriptional regulation of the BZLF1 Z promoter (Zp) in human SCC12F epithelial cells identified a region within Zp that is responsive to epithelial cell differentiation. In the present study, we localize this differentiation responsive element to the CREB/AP-1-like binding site (TGACATCA) between -67 to -60 bp within Zp, previously designated ZII, and furthermore show that homodimers and heterodimers of CREB and ATF-1 specifically bind ZII. Consistent with a regulatory role for CREB and ATF-1 in differentiation dependent BZLF1 expression, ZII was able to bind approximately 3-fold more CREB and ATF-1 when incubated with nuclear extract obtained from populations of SCC12F cells enriched for the differentiated phenotype than when incubated with extract obtained from populations enriched for the undifferentiated phenotype. In addition, CREB and ATF-1 were found to increase in abundance during SCC12F differentiation. These results indicate a regulatory role for CREB and ATF-1 in differentiation-dependent expression of BZLF1 in human epithelial cells.

Activating Transcription Factor 1↗

Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.

Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.

Adolescent↗

Near haploid acute lymphoblastic leukemia: seven new cases and a review of the literature.

Seven new cases are described of near haploid acute lymphoblastic leukemia (ALL) and the findings reviewed together with updated complete remission duration and survival data for the 21 cases already published. The patients were four males and three females, with an age range 2-19 years; all had an immunophenotype consistent with common ALL. The poor prognostic outlook for patients with near haploid ALL is confirmed by the median remission duration of 14 months for these patients, which is comparable to that for the previously published cases. The pattern of chromosome loss was marked particularly by the presence of two copies of chromosomes 10, 14, 18, 21 and both sex chromosomes. Populations of hyperdiploid cells with double the near haploid number were observed in six of the patients, one of whom demonstrated further clonal evolution, and it is proposed that some cases classified as hyperdiploid ALL with greater than 50 chromosomes may also have arisen from a near haploid stem line.

Adolescent↗