Medical Biology - Research Publications

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Start date: 2000 × End date: 2009 × Author: Ng, Ashley ×

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    Thrombotic thrombocytopenic purpura is associated with a high relapse rate after plasma exchange: a single-centre experience
    Frawley, Natasha ; NG, ASHLEY ; NICHOLLS, KATHLEEN ; Hogan, Chris ; COHNEY, SOLOMON ; GRIGG, ANDREW (Blackwell Snergy, 2008)
    Background: Thrombotic thrombocytopenic purpura (TTP) is a rare condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, renal and/or neurological dysfunction secondary to microvascular or macrovascular thrombosis. Despite advances in treatment, TTP remains a serious condition with significant morbidity and mortality. Methods: We undertook an audit of patients with TTP over 14 years to assess remission, relapse, survival and factors predictive of outcome using current therapy based on plasma exchange with fresh-frozen plasma. Results: Forty patients were identified between January 1992 and December 2005. Thirty-one (82%) achieved complete response (CR) to therapy using plasma exchange with fresh-frozen plasma (median 11 exchanges) and steroids. Twelve (37%) relapsed a median of 14 days following cessation of therapy, with multiple relapses occurring in two patients. TTP-related death occurred in four patients during their initial presentation and in two during subsequent relapse. Four patients were only partially responsive to first-line therapy. The absence of neurological features at presentation was the only factor predicting a sustained CR to first-line therapy (P = 0.027, log–rank analysis). The mean duration of inpatient treatment was 18 days (range 4–38 days) with 30% of patients requiring intensive care admission. Thirty-four per cent of patients acquired central venous line infection, with a median of two episodes of line sepsis per patient. Conclusion: Our results indicate the need for better treatments to reduce the high early relapse rate and significant mortality associated with current therapy.
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    Cytomegalovirus DNAemia and disease: natural history and management in settings other than allogeneic stem cell transplantation
    Ng, Ashley P. ; WORTH, LEON ; Chen, Luke ; Seymour, John F. ; Prince, H. Miles ; SLAVIN, MONICA ; Thursky, Karin (Ferrata Storti Foundation, 2005-12)
    Background and Objectives. Despite increasing intensity and profound immunosuppressionassociated with newer therapies for hematologic malignancies, little information exists regarding cytomegalovirus (CMV) reactivation in settings other than allogeneic stem cell transplantation (SCT).Design and Methods. We reviewed the epidemiology of CMV disease in patients who were CMV polymerase chain reaction (PCR) positive during treatment for hematologic malignancies without allogeneic SCT from June 1999 to June 2004.Results. Thirty-six patients with CMV reactivation were identified. Of these, 92% were undergoing investigation for fever. Fifteen patients with CMV DNAemia were treatedwith ganciclovir without CMV disease developing. Notably, 20 patients with untreated CMV DNAemia did not develop CMV disease during a median follow-up of 3.5 (1-19)months. The highest rates of reactivation were observed with HyperCVAD (7.8%) and alemtuzumab (50%).Interpretation and Conclusions. We recommend that screening for CMV DNAemia be instituted and pre-emptive therapy contemplated for asymptomatic CMV reactivationonly in patients receiving alemtuzumab therapy, but not routinely for other patients outside the allogeneic SCT setting. Indeed for such patients, detection of isolated CMV DNAemia does not imply the need for immediate therapy and future studies are needed to validate PCR detection of CMV DNA and CMV DNA titers as predictors for CMV disease.
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    Murine hematopoietic blast colony-forming cells and their progeny have distinctive membrane marker profiles
    Metcalf, D ; Ng, AP ; Loughran, SJL ; Phipson, B ; Smyth, GK ; Di Rago, L ; Mifsud, S (NATL ACAD SCIENCES, 2009-11-10)
    Two distinct bone marrow-derived blast colony-forming cells can generate colonies of lineage-restricted progenitor cells in agar cultures of murine bone marrow. Both cell types selectively had a Kit(+) ScaI(+) phenotype distinguishing them from most lineage-restricted progenitor cells. Multicentric blast colony-forming cells stimulated by stem cell factor plus interleukin-6 (IL-6) (BL-CFC-S) were separable from most dispersed blast colony-forming cells stimulated by Flt3 ligand and IL-6 (BL-CFC-F) using CD34 and Flt3R probes. Multicentric BL-CFC-S cofractionated with colony-forming units, spleen (CFU-S) supporting the possibility that the 2 cells may be identical. The colony populations generated by BL-CFC-S were similar in their phenotype and proliferative capacity to progenitor cells in whole bone marrow but the progeny of BL-CFC-F were skewed with an abnormally high proportion of Kit(-) Flt3R(+) cells whose clonogenic cells tended to generate only macrophage progeny. Both blast colony populations had a high percentage of GR1(+) and Mac1(+) cells but BL-CFC-F colonies also contained a significant population of B220(+) and IL-7R(+) cells relevant to the superior ability of BL-CFC-F colony cells to generate B lymphocytes and the known dependency of this process on Flt3 ligand and IL-7. The commitment events and phenotypic changes during the generation of differing progenitor cells in blast colonies can now be clonally analyzed in a convenient in vitro culture system.