Effect of indacaterol on exercise endurance and lung hyperinflation in COPD.

Background: Indacaterol is a novel, inhaled, once-daily ultra long-acting β(2)-agonist (ultra-LABA) for the treatment of COPD. This study investigated the effect of indacaterol on exercise endurance, and on lung hyperinflation during exercise and at rest in patients with moderate-to-severe COPD.

Methods: In this double-blind, placebo-controlled, two-period crossover study (3-week treatment, 3-week washout between treatments), patients were randomized to receive indacaterol 300 μg once-daily or matching placebo.

Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells.

The heat and capsaicin receptor, TRPV1, is required for the detection of painful heat by primary afferent pain fibers (nociceptors), but the extent to which functional TRPV1 channels are expressed in the CNS is debated. Because previous evidence is based primarily on indirect physiological responses to capsaicin, here we genetically modified the Trpv1 locus to reveal, with excellent sensitivity and specificity, the distribution of TRPV1 in all neuronal and non-neuronal tissues. In contrast to reports of widespread and robust expression in the CNS, we find that neuronal TRPV1 is primarily restricted to nociceptors in primary sensory ganglia, with minimal expression in a few discrete brain regions, most notably in a contiguous band of cells within and adjacent to the caudal hypothalamus.

Recent advances in pharmacotherapy for dyspnea in COPD.

Dyspnea is the most distressing symptom experienced by those suffering from advanced stages of chronic obstructive pulmonary disease (COPD). Activity-related dyspnea in COPD is multifactorial but is associated with increased central neural drive, impaired dynamic respiratory mechanics and abnormal respiratory muscle function. Each of these components can potentially be targeted for pharmacotherapy.

The role of pharmacotherapy in mild to moderate chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide and most of those afflicted have mild to moderate disease as measured by spirometry. There is mounting evidence that even mild airway obstruction is associated with activity-related dyspnea, exercise limitation, impaired quality of life, increased hospitalization and mortality. As our understanding of the complex, heterogeneous pathophysiology and clinical consequences of milder COPD continues to grow, there is increasing interest in the potential impact of therapeutic interventions beyond smoking cessation.

Effect of obesity on respiratory mechanics during rest and exercise in COPD.

The presence of obesity in COPD appears not to be a disadvantage with respect to dyspnea and weight-supported cycle exercise performance. We hypothesized that one explanation for this might be that the volume-reducing effects of obesity convey mechanical and respiratory muscle function advantages. Twelve obese chronic obstructive pulmonary disease (COPD) (OB) [forced expiratory volume in 1 s (FEV(1)) = 60%predicted; body mass index (BMI) = 32 ± 1 kg/m(2); mean ± SD] and 12 age-matched, normal-weight COPD (NW) (FEV(1) = 59%predicted; BMI = 23 ± 2 kg/m(2)) subjects were compared at rest and during symptom-limited constant-work-rate exercise at 75% of their maximum.

Receptor tyrosine kinases and their activation in melanoma.

Receptor tyrosine kinases (RTKs) and their downstream signalling pathways have long been hypothesized to play key roles in melanoma development. A decade ago, evidence was derived largely from animal models, RTK expression studies and detection of activated RAS isoforms in a small fraction of melanomas. Predictions that overexpression of specific RTKs implied increased kinase activity and that some RTKs would show activating mutations in melanoma were largely untested.

Neuropathic Nav1.3-mediated sensitization to P2X activation is regulated by protein kinase C.

Background: Increased neuronal excitability and spontaneous firing are hallmark characteristics of injured sensory neurons. Changes in expression of various voltage-gated Na+ channels (VGSCs) have been observed under neuropathic conditions and there is evidence for the involvement of protein kinase C (PKC) in sensory hyperexcitability. Here we demonstrate the contribution of PKC to P2X-evoked VGSC activation in dorsal root ganglion (DRG) neurons in neuropathic conditions.

Effects of BMI on static lung volumes in patients with airway obstruction.

Background: Both chronic airway obstruction and obesity are increasing in prevalence but the effect of their combination on pulmonary function parameters across the range of airway obstruction is unknown.

Methods: We studied the impact of increasing BMI on static lung volumes and airway function in a cohort of 2,265 subjects from a large pulmonary function laboratory database who were 40 to 80 years of age and met GOLD (Global Initiative for Chronic Obstructive Lung Disease) spirometric criteria for COPD (postbronchodilator FEV₁/FVC < 0.7).

Validation of rapid automated tissue synchronization imaging for the assessment of cardiac dyssynchrony in sinus and non-sinus rhythm.

Aims: Cardiac resynchronization therapy is showing benefits for an increasing number of indications but fails to predict response in up to 20-30% of subjects. Echocardiographically assessed dyssynchrony has been proposed as a potential stratifier but current methods are time-consuming and suffer poor reproducibility, thus limiting their clinical utility. This study compared the accuracy, time efficiency, and reproducibility of automated tissue synchronization imaging (Auto TSI) vs.

Lung hyperinflation and its reversibility in patients with airway obstruction of varying severity.

The natural history of lung hyperinflation in patients with airway obstruction is unknown. In particular, little information exists about the extent of air trapping and its reversibility to bronchodilator therapy in those with mild airway obstruction. We completed a retrospective analysis of data from individuals with airway obstruction who attended our pulmonary function laboratory and had plethysmographic lung volume measurements pre- and post-bronchodilator (salbutamol).

The role of inflammation in the pathogenesis of non-small cell lung cancer.

The link between chronic immune activation and tumorigenesis is well established. Compelling evidence has accumulated that histologic assessment of infiltration patterns of different host immune response components in non-small cell lung cancer specimens helps identify different prognostic patient subgroups. This review provides an overview of recent insights gained in the understanding of the role played by chronic inflammation in lung carcinogenesis.

Comparison of arterial stiffness and microcirculatory changes following abdominal aortic aneurysm grafting.

Background: Abdominal aortic aneurysm (AAA) surgery provides a unique opportunity to study the impact of arterial stiffness on central haemodynamics, reflected in augmentation index (AI). The aneurysmal aorta is significantly stiffer than undilated age-matched aorta.

Aim: We investigated whether replacement of an aneurysmal aorta with a compliant graft would result in a decrease in AI, which would thus decrease myocardial workload parameters.

Respiratory function and the obesity paradox.

Purpose Of Review: Obese individuals have impaired respiratory function relative to their normal-weight counterparts. Despite these negative effects, obesity is paradoxically associated with better survival in individuals with chronic obstructive pulmonary disease (COPD). The purpose of this review is to describe this 'obesity paradox', to discuss the effects of obesity on respiratory function, and to speculate as to whether obesity-related alterations in respiratory mechanics can influence the natural history of COPD.

Aortic plaque rupture in the setting of acute lower limb ischemia.

Acute aortic plaque rupture is an uncommon cause of acute lower limb ischemia. The authors report sequence computed tomographic imaging of a distal aortic plaque rupture in a young man with bilateral lower limb complications. Clinical awareness, prompt recognition and imaging, and appropriate treatment of this uncommon condition are necessary to improve patient outcomes.

The impact of human pregnancy on perceptual responses to chemoreflex vs. exercise stimulation of ventilation: a retrospective analysis.

We examined the impact of human pregnancy on breathlessness intensity at matched levels of ventilation (V˙E) during isoxic hyperoxic CO₂ rebreathing and incremental cycle exercise tests in 21 healthy women in the third trimester (TM₃) and again ∼5 months post-partum (PP). Pregnancy had no significant (P > 0.05) effect on the slope or threshold of the breathlessness intensity-V˙E relationship during both exercise and rebreathing.

Dexamethasone added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus blockade.

Background And Objectives: Corticosteroids have been used successfully to prolong the duration of local anesthetic action after peripheral nerve and epidural blockade. We hypothesized that the addition of dexamethasone to mepivacaine would prolong the duration of analgesia after ultrasound-guided supraclavicular brachial plexus block for patients undergoing upper-limb surgery.

Methods: After Federal Health Department and institutional review board approval, 45 adult patients undergoing elective hand or forearm surgery under supraclavicular brachial plexus blockade were randomized to receive either 30 mL mepivacaine 1.

Optimizing pulmonary rehabilitation in chronic obstructive pulmonary disease--practical issues: a Canadian Thoracic Society Clinical Practice Guideline.

Pulmonary rehabilitation (PR) participation is the standard of care for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite bronchodilator therapies. However, there are questions about specific aspects of PR programming including optimal site of rehabilitation delivery, components of rehabilitation programming, duration of rehabilitation, target populations and timing of rehabilitation. The present document was compiled to specifically address these important clinical issues, using an evidence-based, systematic review process led by a representative interprofessional panel of experts.

The Physicians' Practice Assessment Questionnaire on asthma and COPD.

We describe a new tool, the Physicians' Practice Assessment Questionnaire (PPAQ), designed for the global self-assessment of implementation of asthma and COPD guidelines, as determined by the percentage of patients in whom physicians estimate that they implement guidelines key recommendations. Some of its properties were assessed by a group of 47 general practitioners (GPs), and test-retest data were obtained in repeating the questionnaire at a 5-week interval without intervention in a sub-group of 28 practitioners. Answers to the various questions were globally reproducible.

Evolution of mycotic aortic aneurysm treatment by endovascular repair.

Introduction: Endovascular intervention for mycotic aortic aneurysms is now an alternative treatment option.

Case Report: An 83-year-old male presented with confusion and pyrexia of unknown origin. Acute deterioration and subsequent computed tomography scan of the abdomen revealed a contained rupture of a mycotic aortic aneurysm for which the patient had a successful endovascular repair.