Publications

We have postulated that bacteria able to dehydrogenate the bile-acid nucleus are important in the aetiology of cancer of the colon. In this paper we report on screening for the ability to carry out two such reactions. The relevant enzymes are produced by a high proportion of strains of Clostridium paraputrificum, C. tertium and C. indolis, and by small numbers of strains in other clostridial species, but not by organisms of the other genera tested. Strains able to dehydrogenate the bile-acid nucleus represent a high proportion of the lecithinase-negative clostridia isolated from faeces of people living in Britain but a low proportion of those from people living in Uganda or Hong Kong.

Objectives. We hypothesized that atherectomy would be superior to balloon angioplasty for ostial and nonostial left anterior descending coronary artery lesions. Background. Balloon angioplasty of ostial coronary artery lesions has been associated with a lower procedural success rate and a higher rate of complications and of restenosis than angioplasty of nonostial stenoses. Directional coronary atherectomy has been proposed as an alternative therapy for ostial lesions. Methods. In the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-1), 1, 012 patients were randomized to undergo either procedure; 563 patients had proximal left anterior descending coronary artery lesions, of which 74 were ostial. We compared balloon angioplasty with directional atherectomy for early and 6-month results for ostial as well as nonostial proximal left anterior descending coronary artery lesions. Results. Directional atherectomy led to an initially higher gain in minimal lumen diameter for ostial lesions (1.13 vs. 0.56 mm, respectively, p < 0.001) but a higher rate of adjudicated non-Q wave myocardial infarction (24% vs. 13%, respectively, p < 0.001) than balloon angioplasty and no improvement in restenosis rates (48% vs. 46%, respectively). In the nonostial proximal left anterior descending coronary artery lesions, angiographic restenosis was reduced (51% vs. 66%, p = 0.012), but this was also associated with a higher rate of periprocedural myocardial infarction (8% vs. 2%, p = 0.008 by site and 24% vs. 8%, p < 0.001 by adjudication) and no difference in the need for subsequent coronary artery bypass surgery (7.3% vs. 8.4%, respectively) or repeat percutaneous coronary intervention (24% vs. 26%, respectively). Conclusions. For ostial left anterior descending coronary artery stenoses, both procedures yielded similar rates of initial success and restenosis, but atherectomy was associated with more non-Q wave myocardial infarction. In this trial the predominant angiographic benefit (increased early gain and less angiographic restenosis) of atherectomy for the left anterior descending coronary artery was in proximal nonostial lesions. However, the tradeoffs for this angiographic advantage were more in-hospital myocardial infarctions and no decrease in clinical restenosis.

At the time of the Absorb II study design in July 2011, commercialization of the Absorb scaffold (Abbott Vascular, Santa Clara, CA) was just starting, following approval with CE mark in December 2010. At that time, clinical evidence of the everolimus-eluting Absorb scaffold had been attained without the use of a comparator. There was a need to conduct a trial with the metallic comparator that was at that time the best-in-class drug-eluting stent. The aims of the trial were to assess the additional value of the technology in order to generate evidence-based data that would support the introduction of this novel device in clinical practice and to guide interventional cardiologists in its early use.

BackgroundRespiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.ObjectivesWe sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16–induced COPD exacerbations and its relationship to disease severity.MethodsBronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests.ResultsRV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function.ConclusionsExperimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations. Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity. We sought to determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16–induced COPD exacerbations and its relationship to disease severity. Bronchial mucosal inflammatory cell phenotypes were determined at preinfection baseline and following experimental RV infection in 17 Global Initiative for Chronic Obstructive Lung Disease stage II subjects with COPD and as controls 20 smokers and 11 nonsmokers with normal lung function. No subject had a history of asthma/allergic rhinitis: all had negative results for aeroallergen skin prick tests. RV infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T lymphocytes in patients with COPD and nonsmokers. Monocytes/macrophages, CD4+ T lymphocytes, and CD20+ B lymphocytes were increased in all subjects. At baseline, compared with nonsmokers, subjects with COPD and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T lymphocytes but fewer numbers of CD4+ T lymphocytes and CD20+ B lymphocytes. The virus-induced inflammatory cells in patients with COPD were positively associated with virus load, illness severity, and reductions in lung function. Experimental RV infection induces bronchial mucosal eosinophilia and neutrophilia only in patients with COPD and monocytes/macrophages and lymphocytes in both patients with COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load and illness severity. Antiviral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations.

Background EIB is particularly frequent in elite athletes and represents a distinct phenotype of clinical asthma (Parsons JP et al. 2013) . Baseline spirometry and clinical symptoms have been shown to be poorly predictive of EIB (Bonini M et al. 2007) . Small airways (SA) represent a relevant topic in Respiratory Medicine and their involvement in chronic inflammatory pulmonary diseases has been extensively studied. However, the role of SA in EIB still needs to be clarified. Aim To assess if SA function and inflammation may be considered reliable predictive markers of EIB in elite athletes. Methods Study procedures of this ongoing study are summarized in Fig.1. Results Out of the 40 athletes representing the powered study population, 10 Caucasian males (mean age: 31.9±9 yrs) were studied. Baseline spirometry was normal in all subjects (FEV1 107.4±12.1%; FVC 110.3±15.2%; FEV1/FVC 81.6±5.9%). Seven athletes were atopic and 3 referred respiratory symptoms. Two athletes showed a positive response (FEV1 fall >10%) to the EVH challenge. Exhaled nitric oxide alveolar concentration was significantly higher in the two athletes with EIB. No differences were detected in spirometric values, clinical symptoms, airways resistance and reactance between subjects with- or without EIB. Conclusions Preliminary data seem to suggest a role of SA inflammation in predicting EIB. This research hypothesis should be supported by the completion of the study.

No abstract is provided for this article.

Restenosis at the site of an endoluminal procedure remains a significant problem in the practice of interventional cardiology. We present current data on intimal hyperplasia, which identify the major role of endothelial cells (ECs) in the development of restenosis. Considering endothelial denudation as one of the most important mechanisms contributing to restenosis, we focus more attention on methods of accelerating restoration of endothelial continuity. Prevention of restenosis may be achieved by promoting endothelial regeneration through the use of growth factors, EC seeding, vessel reconstruction with autologous EC/fibrin matrix, and the use of estrogen-loaded stents and stents designed to capture progenitor ECs.

Shark depredation (damage to gear and loss of bait or hooked fish by a non-target species) is a common global occurrence. Depredation events by sharks can have negative impacts for the fishers, fishery targeted species and the sharks. It is, therefore important to better understand if learning behaviour of sharks can influence rates of depredation. Recreational fishers within the World Heritage Ningaloo Reef have reported increased rates of depredation by sharks over the last 5 years. This study aimed to determine if sharks are capable of learning to associate intensive recreational fishing activities with a food reward. We also aimed to test if sharks in areas frequently fished were more habituated to recreational fishing activities than those sharks within a no-take marine sanctuary. To simulate fishing activities baited underwater video systems were deployed in the morning (A.M.), midday, and afternoon (P.M.) for six consecutive days in Fished and Unfished sites. A significant decrease in time of arrival and time to first feed of sharks was seen across days at the Fished sites. The Unfished sites had very low numbers of sharks observed (n=3) and therefore was not statistically analysed. The relative abundance of sharks did not significantly increase across days, however there was a negative correlation between lemon sharks ( Negaprion sp . ) and whalers ( Carcharhinus sp.). Our study suggests sharks are capable of being classically conditioned to recreational fishing activities and depredation rates are influenced by fisher behaviour. We have highlighted possible mitigation strategies designed to un-condition sharks to recreational fishing, including modifying fishing practices, use of deterrents based on the sensitivity of shark senses and management strategies. The best approach is likely to be enabling fishers to become more knowledgeable of how and why shark depredation events happen and take appropriate steps to avoid them.

An attempt was made to assess the mechanism of directional coronary atherectomy using different methods of analysis. Quantitative coronary angiography was used as the gold standard to assess the immediate results of atherectomy, and a comparative quantitative analysis of atherectomy and balloon angioplasty was made. To determine whether the post-atherectomy cross-sectional area is close to a circle, we compared the area measurements obtained by edge detection with those obtained by videodensitometry. Finally, the extent of a ‘Dotter’ effect was established by quantitative angiography following crossing the stenosis with the atherectomy device. For the purpose of this study, the results of the first 113 successful atherectomy procedures were reviewed. In matched lesions, directional atherectomy induced a greater increase in minimal luminal diameter than balloon angioplasty (1.6 mm vs 0.8 mm; P < 0.0001 However, this luminal improvement is due to a substantial ‘Dotter’ effect induced by the bulky atherectomy device. Following atherectomy, only a slight difference in cross-sectional area measurements between edge detection and videodensitometry (mean difference: 0.28 mm2 was found. Histologic examination of an atherectomized coronary artery showed a near-circular post atherectomy area geometry. In conclusion, directional atherectomy is a very effective device with a substantially better initial result than balloon angioplasty. However, insertion of this bulky device itself causes an important ‘Dotter’effect.

The aim of the study is the correlation between angiographic and flow velocity measurements correlated before and after PTCA. In 72 patients undergoing PTCA for a single lesion in a major coronary artery, a Doppler guidewire was used to measure distal flow velocity before and 15 minutes after angiographically successful PTCA. Both measurements were repeated after intracoronary adenosine. A computer-assisted automated edge detection (CAAS II) was used to assess the angiographic minimal luminal diameter (MLD) and percentage diameter stenosis (DS). Minimal luminal cross-sectional area (MLCSA) and percent cross-sectional area stenosis (CSA-St) were assessed with videodensitometry. Results after PTCA, MLD increased from 1.09±0.29mm to 1.83±0.33mm, DS decreased from 61±4% to 36±2% (both p&lt;0.0001), while CSA-St decreased from 79±12% to 48±16% (p&lt;0.0001). Distal coronary flow reserve (CFR) increased from 1.58±0.64 before PTCA to 2.58±0.94 after PTCA, p&lt;0.0001. Distal CFR was significantly correlated with MLD (see figure), MLCSA, DS and CSA-St before PTCA. After PTCA no correlation was observed between distal CFR and both geometric and densitometric indices of stenosis severity. In conclusion, the poor correlation after PTCA between quantitative angiographic measurements and distal coronary flow reserve may indicate acute or chronic disturbance of flow regulation and/or may reflect the limitations of angiography in the assessment of lumen geometry after PTCA.