Previous studies have demonstrated that a high level of shear stress can produce platelet aggregation without the addition of any agonist. We investigated whether high shear stress could cause both platelet aggregation and shedding of microparticles from the platelet plasma membrane. A coneplate viscometer was used to apply shear stress and microparticle formation was measured by flow cytometry. It was found that microparticle formation increased as the duration of shear stress increased. Both microparticles and the remnant platelets showed the exposure of procoagulant activity on their surfaces. Investigation of the mechanisms involved in shear-dependent microparticle generation showed that binding of von Willebrand factor (vWF) to platelet glycoprotein lb, influx of extracellular calcium, and activation of platelet calpain were required to generate microparticles under high shear stress conditions. Activation of protein kinase C (PKC) promoted shear-dependent microparticle formation. Epinephrine did not influence microparticle formation, although it enhanced platelet aggregation by high shear stress. These findings suggest the possibility that local generation of microparticles in atherosclerotic arteries, the site that pathologically high shear stress could occur, may contribute to arterial thrombosis by providing and expanding a catalytic surface for the coagulation cascade.
This study investigated factors associated with the development of human herpesvirus (HHV)-6 encephalitis. Among 111 enrolled subjects, 12 patients developed central nervous system (CNS) dysfunction. CNS dysfunction in four patients was found to have no association with HHV-6. The remaining eight patients displayed HHV-6 encephalitis (n ¼ 3), limbic encephalitis (HHV-6 DNA in cerebrospinal fluid was not examined; n ¼ 3) or CNS dysfunction because of an unidentified cause (n ¼ 2). Realtime PCR showed CNS dysfunction in the latter eight patients, which developed concomitant with the appearance of high plasma levels of HHV-6 DNA (X10 4 copies/ml). Overall, eight of the 24 patients with high-level HHV-6 DNA developed CNS dysfunction, whereas no patients developed CNS dysfunction potentially associated with HHV-6 infection if peak HHV-6 DNA was o10 4 copies/ ml. We next analyzed plasma concentrations of IL-6, IL-10 and tumor necrosis factor-a among patients who displayed high-level plasma HHV-6 DNA and found elevated IL-6 concentrations preceding HHV-6 infection in patients who developed CNS dysfunction. (Mean ± s.d.: 865.7 ± 1036.3 pg/ml in patients with CNS dysfunction; 56.5±192.9 pg/ml in others; P ¼ 0.01). These results suggest that high-level HHV-6 load is necessary for the development of HHV-6 encephalitis, and systemic inflammatory conditions before HHV-6 infection form the preparatory conditions for progression to encephalopathy.
Summary:A limited number of patients with adult T cell leukemia/lymphoma (ATL) who received autologous stem cell transplantation (ASCT) have been reported. We report here a case of fatal systemic Candida krusei infection in a female patient with ATL undergoing ASCT. All of the eight patients (including seven patients in the literature) with ATL who received ASCT developed relapse of ATL or death due to ASCT complication, irrespective of subtype or remission state of ATL, source or selection of SCT or conditioning regimen. At present, ASCT appears to provide little benefit for ATL in contrast to that for other types of aggressive non-Hodgkin's lymphoma. Keywords: ATL; HTLV-1; auto-BMT; auto-PBSCT Adult T cell leukemia/lymphoma (ATL) is a distinct clinicopathological entity, ie peripheral T lymphocytic malignancy caused by human T lymphotropic virus type 1 (HTLV-1). 1,2 Despite recent progress in combination chemotherapy for non-Hodgkin's lymphoma (NHL), acute and lymphoma types of ATL generally have a very poor prognosis with less than 1 year median survival because of infectious complications due to T cell immunodeficiency, multidrug resistance of ATL cells, large tumor burden with multi-organ failure and/or hypercalcemia. [3][4][5] At present, there is no standard therapy for ATL in contrast to CHOP therapy for aggressive NHL. 3,6 High-dose ablative therapy and autologous stem cell transplantation (ASCT) have been shown to be superior to non-ablative therapy in aggressive NHL as initial and salvage treatment. 7,8 High-dose therapy and ASCT has been reported in a limited number of patients with ATL, but most of those were in the form of an abstract. [9][10][11][12][13][14] We report here a case of fatal systemic Candida krusei (C. krusei) infection in a female patient with ATL undergoing ASCT, and review the reported ATL cases that received this therapy.
SummaryWe investigated the association of amyloid β-protein precursor (APP) and platelet derived microparticles in 20 normal controls and 91 patients with various diseases causing a thrombotic tendency. Compared with the controls, the mean percentage of APP-positive microparticles was significantly greater in the patients with cerebral infarction (39.1 ± 17.7%, p <0.001), diabetes (31.1 ± 12.6%, p <0.001), and uremia (30.1 ± 14.7%, p <0.01), but not in those with hypertension (8.2 ±6.3%, p = NS). Sixteen patients with cerebral infarction, 20 with diabetes, and 11 with uremia had microparticles with very high APP levels. In normal controls, 7.2 ± 3.7% of the microparticles were positive for P-selectin, while the percentage in cerebral infarction, diabetes, uremia, and hypertension was respectively 43.5 ± 15.1%, 40.0 ± 12.8%, 31.8 ±12.2%, and 11.6 ±7.3%. There was a significant correlation between P-selectin and APP positivity of microparticles. Our results suggest that microparticle APP may have a regulatory influence on coagulation abnormalities.
SummaryPegfilgrastim is a pegylated form of the granulocyte‐colony stimulating factor, filgrastim. Herein, we report the results of a multicentre, randomized, double‐blind phase III trial comparing the efficacy and safety of pegfilgrastim with filgrastim in patients with malignant lymphoma. Patients were randomized to receive either a single subcutaneous dose of pegfilgrastim or daily subcutaneous doses of filgrastim on day 4 after the completion of cyclophosphamide, cytarabine, etoposide and dexamethasone ± rituximab (CHASE(R); day 1–3) chemotherapy. The primary endpoint was the duration of severe neutropenia (DSN), defined as the number of days with neutrophil count <0·5 × 109/l in the first cycle of chemotherapy. A total of 111 lymphoma patients were randomized to either the pegfilgrastim or filgrastim group. 109 patients received either pegfilgrastim (n = 54) or filgrastim (n = 55). Efficacy data were available for 107 patients (pegfilgrastim: n = 53, filgrastim: n = 54). Both groups were well balanced in terms of gender, age, performance status and other variables. The mean DSN (±S.D.) was 4·5 (±1·2) and 4·7 (±1·3) d in the pegfilgrastim and filgrastim groups. No significant difference in safety was observed. This trial verified the non‐inferiority of a single subcutaneous dose of pegfilgrastim compared with daily subcutaneous doses of filgrastim, considering DSN as an indicator.
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