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111.
Hospital care following emergency admission: a critical incident case study of the experiences of patients with advanced lung cancer and Chronic Obstructive Pulmonary Disease 下载免费PDF全文
112.
Vincristine efficacy and safety in treating immune thrombocytopenia: a retrospective study of 35 patients 下载免费PDF全文
Jérôme Stirnemann Najett Kaddouri Medhi Khellaf Anne‐Sophie Morin Virginie Prendki Marc Michel Arsène Mekinian Philippe Bierling Pierre Fenaux Bertrand Godeau Olivier Fain 《European journal of haematology》2016,96(3):269-275
Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 109 platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6–13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan–Meier curve). Predictive factors (univariate analysis) of an initial and long‐term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost. 相似文献
113.
Anna Sophie Klaeschen 《Expert review of clinical pharmacology》2016,9(4):567-578
Novel insights into molecular mechanisms have altered our understanding of the pathogenesis of autoimmune skin disorders. Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease characterized by auto-aggressive skin inflammation which histologically presents with interface dermatitis. This inflammation is driven by interferon (IFN)-regulated proinflammatory cytokines that orchestrate the B- and T-cell mediated lesional inflammation. During the last years, therapeutic strategies have focused on these players: biologicals targeting type I IFNs and their receptors as well as anti-B-cell drugs have been investigated in clinical trials with variable success. Very recently, CLE gene expression analyses revealed lesional activation of several pathways of the immune system, thus providing potential new therapeutic targets. In this article, we review the current knowledge concerning pathways and key mediators involved in the pathogenesis of cutaneous lupus erythematosus (including TLR-dependent and TLR–independent immune activation, NfkB, TBK1, PI3K, MAPK, JAK/STAT-pathway) and their inhibitors (e.g. chloroquine, bufalin, duvelisib, rapamycin, R788, KN-93, amlexanox, tofacitinib, ruxolitinib, baricitinib), and discuss emerging strategies for the treatment of CLE and related diseases. 相似文献
114.
Inhibition of Virus Attachment to CD4+ Target Cells Is a Major Mechanism of T Cell Line–adapted HIV-1 Neutralization 下载免费PDF全文
Sophie Ugolini Isabelle Mondor Paul W.H.I. Parren Dennis R. Burton Shermaine A. Tilley Per Johan Klasse Quentin J. Sattentau 《The Journal of experimental medicine》1997,186(8):1287-1298
Antibody-mediated neutralization of human immunodeficiency virus type–1 (HIV-1) is thought to function by at least two distinct mechanisms: inhibition of virus–receptor binding, and interference with events after binding, such as virus–cell membrane fusion. Here we show, by the use of a novel virus–cell binding assay, that soluble CD4 and monoclonal antibodies to all confirmed glycoprotein (gp)120 neutralizing epitopes, including the CD4 binding site and the V2 and V3 loops, inhibit the adsorption of two T cell line–adapted HIV-1 viruses to CD4+ cells. A correlation between the inhibition of virus binding and virus neutralization was observed for soluble CD4 and all anti-gp120 antibodies, indicating that this is a major mechanism of HIV neutralization. By contrast, antibodies specific for regions of gp120 other than the CD4 binding site showed little or no inhibition of either soluble gp120 binding to CD4+ cells or soluble CD4 binding to HIV-infected cells, implying that this effect is specific to the virion–cell interaction. However, inhibition of HIV-1 attachment to cells is not a universal mechanism of neutralization, since an anti-gp41 antibody did not inhibit virus–cell binding at neutralizing concentrations, implying activity after virus–cell binding. 相似文献
115.
Jung C Meinzer U Montcuquet N Thachil E Château D Thiébaut R Roy M Alnabhani Z Berrebi D Dussaillant M Pedruzzi E Thenet S Cerf-Bensussan N Hugot JP Barreau F 《The Journal of clinical investigation》2012,122(6):2239-2251
Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer's patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood. In mice infected with Yersinia pseudotuberculosis, we found that PP barrier dysfunction is dependent on the Yersinia virulence plasmid and the expression of TLR-2 by hematopoietic cells, but not by intestinal epithelial cells. Upon TLR-2 stimulation, Y. pseudotuberculosis-infected monocytes activated caspase-1 and produced IL-1β. In turn, IL-1β increased NF-κB and myosin light chain kinase activation in intestinal epithelial cells, thus disrupting the intestinal barrier by opening the tight junctions. Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection. 相似文献
116.
117.
Giorgos L. Chouliaras Antonis Kattamis Vasilis Berdoukas Efstathios D. Gotsis Sophie Mavrogeni Vassilis Ladis 《British journal of haematology》2010,151(4):397-401
Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR‐derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P < 0·001). The prevalence of CD was 32·9% in patients with T2* ≤ 8 ms, 12·5% in patients with T2* > 8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14–20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible. 相似文献
118.
Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans 下载免费PDF全文
119.
Risk factors associated with intracranial hemorrhage in adults with immune thrombocytopenia: A study of 27 cases 下载免费PDF全文
Sara Melboucy‐Belkhir Mehdi Khellaf Alexandre Augier Marouane Boubaya Vincent Levy Guillaume Le Guenno Louis Terriou Bertrand Lioger Mikaël Ebbo Anne‐Sophie Morin Marie‐Paule Chauveheid Marc Michel Farid Belkhir Frédégonde About Christian Rose Guillaume Moulis Arsene Mekinian Jérôme Stirnemann Thomas Papo Stéphane Cheze Eric Rosenthal Jean‐François Viallard Nicolas Schleinitz Lionel Galicier Daniel Adoue Olivier Lambotte Mohamed Hamidou Bertrand Godeau Olivier Fain 《American journal of hematology》2016,91(12):E499-E501
120.