6,963 publications from this institution
Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](−)quinuclidinyl benzilate ([3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25° C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 µM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1 - and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional Studies.
The president has gone out on a very precarious limb to find the consensus necessary to effect change.He has promised Americans that they can have more security and peace ofmind about their health care coverage, including improved benefits and a higher quality of care, simply by wringing savings out of the fat of the current system.This has led to charges from some quarters that the president is trying to get something for nothing.That assessment is too harsh.But it is true that the president is trying to convince the American people to sit still for fairly nasty surgery by promising that it will not hurt very much.How much pain the "haves" in the current system believe reform will bring will determine the fate of Clinton's plan.Small businesses are already yelling loudly that a mandate to cover workers will cost jobs and lots of them.Although the tobacco industry is not what it once was, it is still a force to be reckoned with in American politics, and big increases in vice taxes will not sit well with them or their concerned and ready to lobby cousins in the alcohol, gambling, and food industries.Advocates for elderly people and the very poor will vigorously protest if their current entitlement programmes are targeted for more than minimal cuts.And, as eager as many Americans are for lower costs, many will wince over the notion of capping of the rate at which insurance premiums for the basic or baseline package of health care services can rise-a strategy that some fear will deny them access to the next generation of medical technology and breakthroughs.Once the euphoria over the fact that the nation has finally managed to talk seriously about doing something about its
New-generation coronary stents that release zotarolimus or everolimus have been shown to reduce the risk of restenosis. However, it is unclear whether there are differences in efficacy and safety between the two types of stents on the basis of prospectively adjudicated end points endorsed by the Food and Drug Administration.In this multicenter, noninferiority trial with minimal exclusion criteria, we randomly assigned 2292 patients to undergo treatment with coronary stents releasing either zotarolimus or everolimus. Twenty percent of patients were randomly selected for repeat angiography at 13 months. The primary end point was target-lesion failure, defined as a composite of death from cardiac causes, any myocardial infarction (not clearly attributable to a nontarget vessel), or clinically indicated target-lesion revascularization within 12 months. The secondary angiographic end point was the extent of in-stent stenosis at 13 months.At least one off-label criterion for stent placement was present in 66% of patients. The zotarolimus-eluting stent was noninferior to the everolimus-eluting stent with respect to the primary end point, which occurred in 8.2% and 8.3% of patients, respectively (P<0.001 for noninferiority). There were no significant between-group differences in the rate of death from cardiac causes, any myocardial infarction, or revascularization. The rate of stent thrombosis was 2.3% in the zotarolimus-stent group and 1.5% in the everolimus-stent group (P=0.17). The zotarolimus-eluting stent was also noninferior regarding the degree (+/-SD) of in-stent stenosis (21.65+/-14.42% for zotarolimus vs. 19.76+/-14.64% for everolimus, P=0.04 for noninferiority). In-stent late lumen loss was 0.27+/-0.43 mm in the zotarolimus-stent group versus 0.19+/-0.40 mm in the everolimus-stent group (P=0.08). There were no significant between-group differences in the rate of adverse events.At 13 months, the new-generation zotarolimus-eluting stent was found to be noninferior to the everolimus-eluting stent in a population of patients who had minimal exclusion criteria. (ClinicalTrials.gov number, NCT00617084.)
No abstract is provided for this article.
Background The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. Objectives The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD). Methods In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models. Results Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; pinteraction = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; pinteraction = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: −0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients. Conclusions Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050) (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)
Asthma may affect 5 to 10 per cent of the population, yet remains underdiagnosed and undertreated. It is probably the only common treatable condition whose prevalence and severity is increasing [1,2] and there is evidence from several countries that mortality has risen, despite advances in therapy [3,4]. In New Zealand the problem has reached epidemic proportions and asthma is now one of the commonest causes of death in young people [5]. Even in the United States, which was unaffected by the epidemic of asthma deaths in the 1960s, there are now indications that the mortality from asthma may be rising [6]. These alarming statistics should encourage greater effort to be put into elucidating the pathogenesis of asthma. Several advances have recently been made in elucidating the mechanisms of asthma and this should eventually lead to more effective treatment. Bronchial hyperresponsiveness, an exaggerated bronchoconstrictor response to many different stimuli, is a key feature of asthma, and relates more closely to the severity of asthma and the frequency of symptoms than does resting lung function [7]. To determine the cause of asthma it is necessary to understand the mechanisms of bronchial hyperresponsiveness, and effective control of asthma symptoms implies a reduction in bronchial responsiveness. Increased bronchial responsiveness follows exposure to allergens, upper respiratory tract infection, and certain industrial chemicals. There is now considerable experimental evidence that induced hyperresponsiveness in animals is associated with inflammation of the airways [8]. Histopathological studies from asthmatic patients who have died during asthma attacks show marked inflammation in the airways, with infiltration of inflammatory cells, particularly eosinophils, disruption of airway epithelium and plugging of the airway lumen by viscous mucus [9]. Similar, but less severe, pathological changes have also been described in bronchial biopsies from asthmatics with relatively mild disease [10] and this supports the experimental evidence that airway inflammation may underly bronchial hyperresponsiveness. Bronchial microvascular leakage is also a typical feature, leading to oedema of the submucosa and extravasation of plasma which may be linked to bronchial hyperresponsiveness [11]. The previously held view that asthma could be explained by release of mast cell mediators which cause bronchospasm must now be modified. It now seems likely that several different cells are involved in the pathogenesis of asthma, and that these cells produce a variety of mediators which interact in a complex way to produce a number of pathological effects which, together, contribute to bronchial hypeiTesponsiveness and the clinical features of asthma. Recent advances have been made by recognition of the different cells and inflammatory mediators participating in asthma, and of the neural mechanisms which may contribute to or modify these inflammatory events.
