Publications

We determined whether inhaled corticosteroid therapy modulates the expression of the transcription factor, nuclear factor kappa B (NF- κ B), in patients with asthma. Fifteen stable patients with mild asthma underwent bronchoalveolar lavage (BAL) with bronchial biopsies in a double-blind, placebo-controlled and crossover study after placebo or after inhaled fluticasone propionate (500 μ g twice daily). Fluticasone reduced the number of eosinophils in BAL fluid (BALF) and in airway biopsies, together with an improvement of bronchial responsiveness to methacholine. However, NF- κ B DNA-binding in alveolar macrophages and in bronchial biopsies was not affected by fluticasone treatment. NF- κ B expression was also measured by immunohistochemical staining with an antibody to the p65 component of NF- κ B. Fluticasone caused an increase in the number of positive nuclear staining cells in the airway epithelium from 34.1 ± 5.0 to 64.1 ± 8.0 per mm2 (p = 0.002). In vitro studies of A549 epithelial cells stimulated by interleukin-1 β (IL-1 β ) showed that dexamethasone increased p65 protein expression analyzed by Western blot. Despite an anti-inflammatory effect of fluticasone, there was no decrease in NF- κ B–DNA binding and activation, indicating that this may not be a mechanism by which corticosteroids act in asthma. The significance of corticosteroid-induced increase in p65 protein expression is not known. Hart L, Lim S, Adcock I, Barnes PJ, Chung KF. Effects of inhaled corticosteroid therapy on expression and DNA-binding activity of nuclear factor κ B in asthma.

No abstract is provided for this article.

No abstract is provided for this article.

<h3>BACKGROUND</h3> The pathogenesis of non-asthmatic chronic dry cough remains unclear. <h3>METHODS</h3> A study was undertaken to determine whether airway inflammation could be a contributing factor by analysing inflammatory cells and cytokines in induced sputum from 19 patients with chronic dry cough of varying aetiology, excluding asthma and bronchiectasis, and from 10 normal controls. The associated causes for the chronic cough were post-nasal drip (n = 5), gastro-oesophageal reflux (n = 4), and idiopathic (n = 10). All patients had an enhanced cough reflex to capsaicin. <h3>RESULTS</h3> Sputum neutrophilia (median (interquartile range)) was found in the patients with chronic cough (59.4 (27.1)%) compared with the normal controls (28.4 (22.0)%; p&lt;0.01, 95% CI 11.3 to 42.2). Sputum levels of interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) were also significantly increased compared with normal controls (0.57 (1.08) and 0.25 (0.72) ng/ml; p&lt;0.05 (95% CI 0.05 to 1.75) for IL-8; 48.3 (34.4) and 12.6 (33.6) pg/ml, p&lt;0.01 (95% CI 8.8 to 69.8) for TNF-α). <h3>CONCLUSION</h3> Neutrophils and cytokines associated with neutrophil chemotaxis and activation may contribute to the pathogenesis of non-asthmatic chronic dry cough.

PTCA was performed in 166 patients older than 70. The primary angiographic and clinical success rates were 85% and 86%, respectively. A total of 15 major complications occurred in 10 patients (6%): 4 patients died (2%), 6 patients underwent urgent bypass surgery (4%), the incidence of acute myocardial infarction was 3% (5 patients). The 4-year survival rate was 84 +/- 8%. During the follow-up period 8 patients (5%) sustained a nonfatal myocardial infarction, 21 patients (13%) underwent a second and (or) third balloon dilatation and 17 patients (10%) underwent bypass surgery. At the end of the observation period 68% of the survivors had a sustained improvement of the functional class. This was associated with a significant reduction of the antianginal therapy. These data demonstrate that PTCA can be performed safely and effectively in patients over 70.

Objectives The purpose of this study was to investigate the medium-term (two year) outcome of the unrestricted utilization of sirolimus-eluting stents (SES) in an all-comer population. Background Despite the implantation of SES in over a million patients to date, limited data exist on long-term outcomes. Methods Sirolimus-eluting stents were used as the default strategy as part of the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry. A total of 508 consecutive patients with de novo lesions exclusively treated with SES were compared with 450 patients who received bare stents in the immediately preceding period (pre-SES group). Results Patients in the SES group more frequently had multivessel disease, more type C lesions, received more stents, and had more bifurcation stenting. At two years, the cumulative rate of major adverse cardiac events (death, myocardial infarction, or target vessel revascularization) was 15.4% in the SES group and 22.0% in the pre-SES group (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.50 to 0.91; p = 0.01). The two-year risk of target vessel revascularization in the SES group and in the pre-SES group was 8.2% and 14.8%, respectively (HR 0.53, 95% CI 0.36 to 0.79; p = 0.002). Conclusions In an unrestricted population, the beneficial effects of sirolimus-eluting stent implantation extend out to two years compared with bare-metal stents, driven by a reduction in re-intervention rates. These findings should be confirmed by the results of the large randomized trials.

No abstract is provided for this article.

We determined the effect of late-phase responses to allergen challenge of mildly allergic asthmatic patients on the expression and release of the cytokines IL-10 and MIP-1alpha from peripheral blood monocytes.Sixteen mildly allergic asthmatics were exposed to increasing concentrations of allergen aerosol. Nine demonstrated an early response alone (single responders), while seven had an early followed by a late response (dual responders). Monocytes were isolated from venous blood before and 24 h after allergen challenge, and placed in short-term culture for determination of IL-10 mRNA expression by reverse-transcription polymerase chain reaction and protein release. MIP-1alpha protein release was measured by radioimmunoassay.IL-10 mRNA expression was significantly higher in dual responders than early responders alone, for unstimulated monocytes or for monocytes exposed to lipopolysaccharide or IL-1beta. In addition, the release of IL-10 and MIP-1alpha from monocytes of dual responders was also enhanced.Circulating monocytes are primed to release more of the cytokines, IL-10 and MIP-1alpha, in dual but not in single responders, at 24 h after allergen. They may contribute to allergen-induced inflammatory responses in the airways.

Importance Among patients undergoing percutaneous coronary intervention (PCI), it remains unclear whether the treatment efficacy of P2Y 12 inhibitor monotherapy after a short course of dual antiplatelet therapy (DAPT) depends on the type of P2Y 12 inhibitor. Objective To assess the risks and benefits of ticagrelor monotherapy or clopidogrel monotherapy compared with standard DAPT after PCI. Data Sources MEDLINE, Embase, TCTMD, and the European Society of Cardiology website were searched from inception to September 10, 2023, without language restriction. Study Selection Included studies were randomized clinical trials comparing P2Y 12 inhibitor monotherapy with DAPT on adjudicated end points in patients without indication to oral anticoagulation undergoing PCI. Data Extraction and Synthesis Patient-level data provided by each trial were synthesized into a pooled dataset and analyzed using a 1-step mixed-effects model. The study is reported following the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data. Main Outcomes and Measures The primary objective was to determine noninferiority of ticagrelor or clopidogrel monotherapy vs DAPT on the composite of death, myocardial infarction (MI), or stroke in the per-protocol analysis with a 1.15 margin for the hazard ratio (HR). Key secondary end points were major bleeding and net adverse clinical events (NACE), including the primary end point and major bleeding. Results Analyses included 6 randomized trials including 25 960 patients undergoing PCI, of whom 24 394 patients (12 403 patients receiving DAPT; 8292 patients receiving ticagrelor monotherapy; 3654 patients receiving clopidogrel monotherapy; 45 patients receiving prasugrel monotherapy) were retained in the per-protocol analysis. Trials of ticagrelor monotherapy were conducted in Asia, Europe, and North America; trials of clopidogrel monotherapy were all conducted in Asia. Ticagrelor was noninferior to DAPT for the primary end point (HR, 0.89; 95% CI, 0.74-1.06; P for noninferiority = .004), but clopidogrel was not noninferior (HR, 1.37; 95% CI, 1.01-1.87; P for noninferiority &amp;amp;gt; .99), with this finding driven by noncardiovascular death. The risk of major bleeding was lower with both ticagrelor (HR, 0.47; 95% CI, 0.36-0.62; P &amp;amp;lt; .001) and clopidogrel monotherapy (HR, 0.49; 95% CI, 0.30-0.81; P = .006; P for interaction = 0.88). NACE were lower with ticagrelor (HR, 0.74; 95% CI, 0.64-0.86, P &amp;amp;lt; .001) but not with clopidogrel monotherapy (HR, 1.00; 95% CI, 0.78-1.28; P = .99; P for interaction = .04). Conclusions and Relevance This systematic review and meta-analysis found that ticagrelor monotherapy was noninferior to DAPT for all-cause death, MI, or stroke and superior for major bleeding and NACE. Clopidogrel monotherapy was similarly associated with reduced bleeding but was not noninferior to DAPT for all-cause death, MI, or stroke, largely because of risk observed in 1 trial that exclusively included East Asian patients and a hazard that was driven by an excess of noncardiovascular death.

ABSTRACT We use the 13CO (2–1) emission from the SEDIGISM (Structure, Excitation, and Dynamics of the Inner Galactic InterStellar Medium) high-resolution spectral-line survey of the inner Galaxy, to extract the molecular cloud population with a large dynamic range in spatial scales, using the Spectral Clustering for Interstellar Molecular Emission Segmentation (scimes) algorithm. This work compiles a cloud catalogue with a total of 10 663 molecular clouds, 10 300 of which we were able to assign distances and compute physical properties. We study some of the global properties of clouds using a science sample, consisting of 6664 well-resolved sources and for which the distance estimates are reliable. In particular, we compare the scaling relations retrieved from SEDIGISM to those of other surveys, and we explore the properties of clouds with and without high-mass star formation. Our results suggest that there is no single global property of a cloud that determines its ability to form massive stars, although we find combined trends of increasing mass, size, surface density, and velocity dispersion for the sub-sample of clouds with ongoing high-mass star formation. We then isolate the most extreme clouds in the SEDIGISM sample (i.e. clouds in the tails of the distributions) to look at their overall Galactic distribution, in search for hints of environmental effects. We find that, for most properties, the Galactic distribution of the most extreme clouds is only marginally different to that of the global cloud population. The Galactic distribution of the largest clouds, the turbulent clouds and the high-mass star-forming clouds are those that deviate most significantly from the global cloud population. We also find that the least dynamically active clouds (with low velocity dispersion or low virial parameter) are situated further afield, mostly in the least populated areas. However, we suspect that part of these trends may be affected by some observational biases (such as completeness and survey limitations), and thus require further follow up work in order to be confirmed.