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Defective macrophage phagocytosis has been demonstrated in both alveolar and monocyte-derived macrophages (MDMs) from COPD patients, contributing to the persistence of airway bacteria. We hypothesised that MDM phagocytic capacity may relate to exacerbation susceptibility and would remain stable over time. MDMs were cultured from whole blood collected from 70 stable COPD patients, and subsequently repeated in 30 patients. Phagocytosis of three prey; fluorescently-labelled inert beads, or heat-killed Haemophilus influenzae (HI) & Streptococcus pneumoniae (SP) was measured. The mean age was 72.1 years (SD9.2), FEV 1 predicted 55.4% (17.9) and 33% current smokers. Phagocytosis of HI, but not SP or beads, was significantly less with increasing exacerbation frequency (p 1 %predicted, smoking history or ICS use (all p>0.05). In the 30 patients with repeated MDMs after a median time of 9 (6-13) months, there was no significant change in phagocytic capacity of any prey (p>0.05, Figure 1B). Defective phagocytosis of HI, but not SP or beads, is associated with higher exacerbation frequency in stable COPD, although the phagocytic capacity of any prey remained stable over time. Further work is needed to determine whether improvement in phagocytic capacity can reduce future risk of exacerbations.
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No abstract is provided for this article.
Drug-eluting coronary stents are being used with increasing frequency in patients undergoing percutaneous coronary intervention. Although these stents have shown remarkably low rates of restenosis compared with their predecessors, there have been increasing concerns lately regarding their safety. Extensive data have been published that demonstrate a higher risk of very late stent thrombosis with drug-eluting stents; however, this has not had any impact on long-term mortality or the risk of myocardial infarction when compared with bare-metal stents. Their overall net clinical benefit therefore still favors their use. Recent research has led to a greater understanding of the multifactorial cause of stent thrombosis, which has enabled measures to be taken to reduce an individual patient's risk. In the future, new stent designs and new antiplatelet agents may help to reduce this risk further.
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Resistance to the anti-inflammatory effects of glucocorticoids in asthma and other inflammatory and immune diseases is uncommon, but presents a management problem. Understanding the mechanisms of steroid resistance provides new insights into the mechanism of steroid action as well as the underlying chronic disease process. In patients with primary steroid-resistant (SR) asthma there is no abnormality in the pharmacokinetics of the exogenous steroid and no significant defect in steroid binding to the glucocorticoid receptor (GR). Recent studies have demonstrated a marked reduction in the binding of GR to DNA; this appears to be due to increased binding of GR to the transcription factor activator protein-1 (AP-1). Secondary steroid resistance in asthma may arise in response to the release of cytokines that activate AP-1 and other transcription factors that bind directly to GR. A similar effect may also be seen with high concentrations of beta 2-agonists that activate another GR binding transcription factor, CREB. Several existing and novel treatment strategies are possible in the management of SR asthma.