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ABSTRACT: Intracerebral hemorrhage (ICH) contributes significantly to the morbidity and mortality of patients suffering from acute leukemia. While ICH is often identified in autopsy studies of leukemic patients, it is rare for ICH to be the presenting sign that ultimately leads to the diagnosis of leukemia. We report a patient with previously undiagnosed acute precursor B-cell lymphoblastic leukemia (ALL) who presented with diffuse encephalopathy due to ICH in the setting of an acute blast crisis. The diagnosis of ALL was initially suspected, because of the hyperleukocytosis observed on presentation, then confirmed with a bone marrow biopsy and flow cytometry study of the peripheral blood. Furthermore, detection of the BCR/ABL Philadelphia translocation t(9:22)(q34:q11) in this leukemic patient by fluorescent in situ hybridization permitted targeted therapy of the blast crisis with imatinib (Gleevec). Understanding the underlying etiology of ICH is pivotal in its management. This case demonstrates that the presence of hyperleukocytosis in a patient with intracerebral hemorrhage should raise clinical suspicion for acute leukemia as the cause of the ICH.
Clinical neurology and neurosurgery 09/2010; 112(7):575-7. · 1.30 Impact Factor
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ABSTRACT: Histone deacetylase inhibitors (HDACI), can improve survival after lethal hemorrhagic shock, and modulate the inflammatory response after hemorrhage/lipopolysaccharide (LPS). The current experiments were designed to study the effects of HDACI after hemorrhage and severe hypoxia.
Splenic leukocytes from trauma and non-trauma patients (n=4-5/group) were exposed to severe hypoxia with/without suberoylanilide hydroxamic acid (SAHA, 400 nM) for 8h. Cytokines were measured by ELISA and RT-PCR, and hypoxia inducible factor (HIF)-1a and heme oxygenase (HO)-1 by Western blot.
After hemorrhage and hypoxia, SAHA increased IL-1b gene (4.7+/-1.2-fold) and protein expression (2.1+/-0.6-fold) in trauma splenic leukocytes. It also reduced IL-10 gene expression (0.6+/-0.2-fold), but did not alter TNFa or IL-6 levels. This unexpected pro-inflammatory response may be due to a decrease in HIF-1a and HO-1 protein levels.
In this model of severe hypoxia, treatment with SAHA increased the inflammatory response in trauma leukocytes, possibly through inhibition of the HIF-1/HO-1 pathway. Splenic leukocytes from non-trauma patients were variably affected by SAHA. Taken in context with the known anti-inflammatory properties of HDACI after hemorrhage/LPS, these findings suggest that the immune-modulating functions of HDACI are dependent on the type and severity of both the priming injury and subsequent insult.
Cytokine 03/2010; 49(3):303-11. · 3.02 Impact Factor
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British Journal of Haematology 03/2009; 145(2):262-4. · 4.94 Impact Factor
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British Journal of Haematology 12/2008; 144(5):800-2. · 4.94 Impact Factor
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ABSTRACT: The present study analysed the clinicopathological features of nine myelodysplastic syndrome (MDS) patients in which del(20q) was the sole cytogenetic abnormality and a control group of 17 adult patients with idiopathic thrombocytopenic purpura (ITP). Seven of nine del(20q) patients were thrombocytopenic and six of nine were mildly anaemic at presentation. There was no significant morphological dysplasia identified in the del(20q) group as compared with the ITP group. These results indicate that MDS with del(20q) commonly presents with thrombocytopenia and has minimal morphological dysplasia. Cytogenetic analysis on adult patients undergoing bone marrow sampling for thrombocytopenia may help avoid misdiagnosis of MDS with del(20q) as ITP.
British Journal of Haematology 11/2007; 139(2):265-8. · 4.94 Impact Factor
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ABSTRACT: We performed a multi-institutional retrospective analysis of the morphologic features, immunophenotype, cytogenetics, and BCR-ABL transcript characterization of cases of Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML). We compared these cases with cases of documented chronic myelogenous leukemia in myeloid blast crisis (CML-MBC). Patients with Ph+ AML were less likely to have splenomegaly or peripheral basophilia and had lower bone marrow cellularity and myeloid/erythroid ratios than patients with CML-MBC. Additional specific cytogenetic abnormalities that typically occur in CML-MBC were less common in Ph+ AML. Of 7 patients with Ph+ AML treated with imatinib mesylate, 6 showed at least a partial hematologic response, but the responses were of a short duration (median, 2.5 months). The median survival of patients with Ph+ AML was 9 months, similar to that of patients with CML-MBC (7 months). Ph+ AML is a rare aggressive acute leukemia with some features distinct from CML-MBC.
American Journal of Clinical Pathology 05/2007; 127(4):642-50. · 2.60 Impact Factor
