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101.
102.
The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy 总被引:12,自引:4,他引:8 下载免费PDF全文
Rosenberg PS Alter BP Bolyard AA Bonilla MA Boxer LA Cham B Fier C Freedman M Kannourakis G Kinsey S Schwinzer B Zeidler C Welte K Dale DC;Severe Chronic Neutropenia International Registry 《Blood》2006,107(12):4628-4635
In patients with severe congenital neutropenia (SCN), sepsis mortality is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman-Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN, sepsis mortality was stable at 0.9% per year. The hazard of MDS/AML increased significantly over time, from 2.9% per year after 6 years to 8.0% per year after 12 years on G-CSF. After 10 years, the cumulative incidence was 8% for sepsis mortality and 21% for MDS/AML. A subgroup of SCN patients (29%) received more than the median dose of G-CSF (> or = 8 microg/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC < 2.188 x 10(9)/L [2188/microL] at 6-18 months). In these less-responsive patients, the cumulative incidence of adverse events was highest: after 10 years, 40% developed MDS/AML and 14% died of sepsis, compared with 11% and 4%, respectively, of more responsive patients whose ANC was above the median on doses of G-CSF below the median. Risk of MDS/AML may be similar in SDS and SCN. In less-responsive SCN patients, early hematopoietic stem cell transplantation may be a rational option. 相似文献
103.
Belfor N Amici S Boxer AL Kramer JH Gorno-Tempini ML Rosen HJ Miller BL 《Mechanisms of ageing and development》2006,127(2):203-207
In this paper, we review the history, clinical, cognitive, imaging and neuropathological features of corticobasal degeneration (CBD). Additionally, we report new findings on the neuropsychological profile of 14 patients with CBD compared to 14 with Alzheimer's disease. Increasing awareness of this disorder has led to the realization that specific cognitive and imaging changes are common with CBD degeneration and that these changes help with clinical diagnosis. 相似文献
104.
The neurocognitive features of juvenile-onset Huntington disease (HD) are not well understood. We present three patients with onset of HD symptoms before age 10 years in whom speech delay was the first symptom. Speech delay predated motor symptoms by at least 2 years, and language function was consistently impaired on formal testing. Screening for speech delay is particularly important in children with a family history of HD. 相似文献
105.
Siddiqui GK Maclean AB Elmasry K Wong te Fong A Morris RW Rashid M Begent RH Boxer GM 《Angiogenesis》2011,14(2):155-161
Purpose
For patients with epithelial ovarian cancer (EOC) cytoreduction, with a combination of taxane and platinum, is the standard of care. Despite this, approximately 50% of patients with advanced disease will relapse and moreover 15–20% of cases of EOC are resistant to platinum based chemotherapy. Vascular Endothelial Growth Factor (VEGF), an angiogenic factor, is associated with poor prognosis. This study was undertaken to examine whether there is an association between VEGF-A expression in the tumour of EOC patients and their response to platinum based chemotherapy. 相似文献106.
James B. Bussel Donald M. Arnold Michael A. Boxer Nichola Cooper Jiri Mayer Hany Zayed Sandra Tong Anne-Marie Duliege 《American journal of hematology》2019,94(5):546-553
Two randomized, double-blind, placebo-controlled studies demonstrated responses (≥50 000/μL) to fostamatinib in adults with long-standing immune thrombocytopenia (ITP). The long-term safety and efficacy of fostamatinib were evaluated in a follow-on, open-label extension (OLE) study. Patients received double-blind fostamatinib in the randomized trials, and responders continued the same dose, 100 to 150 mg BID, in the OLE study. Nonresponders received 100 mg BID for 4 weeks and could escalate to 150 mg BID at week 4. Endpoints included stable response, platelet count ≥50 000/μL at 4/6 biweekly (randomized trials) or 2/3 monthly visits (OLE), and overall response, ≥1 platelet count ≥50 000/μL during weeks 1 to 12. A total of 146 patients received fostamatinib including 123 in the OLE study. Median treatment duration was 6.7 months. Baseline median ITP duration was 8 years and median platelet count was 16 000/μL; prior treatments included thrombopoietic (TPO) agents (47%), splenectomy (35%), and rituximab (32%). Twenty-seven (18%) patients achieved a stable response with median duration of >28 months and a median platelet count of 89 000/μL. Sixty-four (44%) patients achieved an overall response (including stable responders) with a median platelet count of 63 000/μL and a median response duration of >28 months. Twenty-four of 71 (34%) patients who had failed TPO agents achieved overall responses to fostamatinib. The most common adverse events (AEs) were diarrhea, hypertension, nausea, epistaxis, and abnormal liver function tests. Most AEs were mild/moderate and resolved or were managed with dose reduction, dose interruption, and/or secondary medication. Almost half of the patients achieved an overall response, and most of these maintained their responses for >2 years. No new or increased frequency of AEs was seen at up to 31 months of treatment. 相似文献
107.
Enrichment by counterpart centrifugal elutriation of human lymphocytes cytotoxic to human tumour cells. 下载免费PDF全文
The enriched fractions of cytotoxic cells responsible for natural killer (NK) activity against both human sarcoma and neuroblastoma (LA-N2) cell lines were readily obtained by countercurrent centrifugal elutriation (CCE). The NK cells were obtained in the larger lymphocyte fractions (fraction 6 +/- 1), having a mean cell volume of 180 u3. The cytotoxic-enriched fraction contained 51% large lymphocytes having cytoplasmic granules. On the other hand, monocytes were purified to greater than 90% and isolated in another fraction (final fraction) and these cells had the lowest NK activity against both human tumour cell lines. However, compared with the lymphocyte fractions, small and large monocytes displayed greater antibody-dependent cellular cytotoxicity (ADCC) activity against human B erythrocytes. These results indicate that NK found to have activity against both tumour cells lines were larger lymphocytes, not small monocytes. Thus, countercurrent centrifugal elutriation (CCE) can provide a sensitive method to obtain enriched fractions of large lymphocytes contained tumoricidal activity against human sarcoma and neuroblastoma cell lines. 相似文献
108.
Synergistic effect of heparin and chemotactic factor on polymorphonuclear leukocyte aggregation and degranulation. 总被引:1,自引:0,他引:1 下载免费PDF全文
M. S. Cairo J. Allen C. Higgins R. L. Baehner L. A. Boxer 《The American journal of pathology》1983,113(1):67-74
The in vitro effects of therapeutic amounts of polyanionic heparin on human polymorphonuclear leukocytes (PMN) aggregation and on the release of cationic lactoferrin from PMN-specific granules were investigated. Incubation of 1 X 10(7) human PMNs with 0.3 unit/ml of heparin followed by stimulation with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 2 X 10(-7) M significantly increased PMN aggregation, compared with controls. Cytochalasin B potentiated aggregation, which was further increased by incubation of the PMNs with heparin. Similarly, heparin also increased PMN degranulation and lactoferrin release following stimulation with FMLP with or without cytochalasin B, compared with controls. In addition, human lactoferrin complexed with heparin on a sucrose density gradient and caused a significant shift in the migration of 3H-heparin. Finally, rabbits pretreated with intravenous heparin resulting in prolongation of their activated partial thromboplastin time (APTT) to 1.5 to 2.5 times baseline had more profound reduction in PMN counts following a challenge with the secretagogue phorbol myristate acetate (PMA). These studies demonstrate that heparin can interact synergistically with chemotactic stimuli known to evoke lactoferrin release, which in turn leads to enhancement of PMN aggregation. Our data further suggest that heparin may be contraindicated in the treatment of syndromes with increased PMN aggregation such as endotoxin-induced Schwartzman-type reactions. 相似文献
109.
Chester KA Bhatia J Boxer G Cooke SP Flynn AA Huhalov A Mayer A Pedley RB Robson L Sharma SK Spencer DI Begent RH 《Disease markers》2000,16(1-2):53-62
Single chain Fv antibodies (sFvs) have been produced from filamentous bacteriophage libraries obtained from immunised mice. MFE-23, the most characterised of these sFvs, is reactive with carcinoembryonic antigen (CEA), a glycoprotein that is highly expressed in colorectal adenocarcinomas. MFE-23 has been expressed in bacteria and purified in our laboratory for two clinical trials; a gamma camera imaging trial using 123I-MFE-23 and a radioimmunoguided surgery trial using 125I-MFE-23, where tumour deposits are detected by a hand-held probe during surgery. Both these trials show MFE-23 is safe and effective in localising tumour deposits in patients with cancer. We are now developing fusion proteins which use MFE-23 to deliver a therapeutic moiety; MFE-23::CPG2 targets the enzyme carboxypeptidase G2 (CPG2) for use in the ADEPT (antibody directed enzyme prodrug therapy) system and MFE::TNF alpha aims to reduce sequestration and increase tumor concentrations of systemically administered TNF alpha. 相似文献
110.
Characteristics Associated with Home Health Care Referrals at Hospital Discharge: Results from the 2012 National Inpatient Sample 下载免费PDF全文