Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

Non‐pharmacological treatments for COPD

Chronic obstructive pulmonary disease (COPD) affects roughly 10% of the global population and is growing in prevalence annually. COPD is characterized by progressive non‐reversible narrowing of airways mainly due to cigarette smoking. Therapeutic interventions aimed at altering this progressive disease course can largely be grouped into pharmacological or non‐pharmacological therapies. The focus of this paper is on the non‐pharmacological aspects of COPD management, reviewing the current literature to provide an evidence‐based management approach. Non‐pharmacological therapies reviewed in this article include the implementation of comprehensive care models utilizing a coordinated multidisciplinary team, tele‐monitoring and patient‐centred approach to optimize COPD care and improve compliance. Preventing progression of COPD via smoking cessation remains of paramount importance, and newer therapeutic options including electronic cigarettes show promise in small studies as cessation aids. COPD has systemic manifestations that can be ameliorated with the enrollment in pulmonary rehabilitation programmes, which focus on exercise endurance to improve dyspnoea and quality of life. Advanced therapeutics for COPD includes lung volume reduction surgery for a pre‐specified cohort and minimally invasive bronchoscopic valves that in recent reviews show promise. Lastly, patients on maximal COPD therapy with progressive disease can be referred for lung transplantation; however, this often requires a highly selected and motivated patient and care team. Survival rates for lung transplantation are improving; thus, this procedure remains a viable option as more expertise and experience are gained.     

A mutation of the common receptor subunit for interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and IL-5 that leads to ligand independence and tumorigenicity

The cytokines interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor bind with high affinity to a receptor complex that contains a ligand-specific alpha-chain and a common beta-chain, h beta c. We report here the isolation of a mutant form of h beta c, from growth factor-independent cells, that arose spontaneously after infection of a murine factor-dependent hematopoietic cell line (FDC-P1) with a retroviral h beta c expression construct. Analysis of this h beta c mutation shows that a small (37 amino acid) duplication of extracellular sequence that includes two conserved sequence motifs is sufficient to confer ligand-independent growth on these cells and lead to tumourigenicity. Because this is a conserved region in the cytokine receptor superfamily, our results suggest that the large family of cytokine receptors has the capacity to become oncogenically active.     

Sleep and long-term ventilation

The development of sleep-disordered breathing is common in patients with chronic respiratory insufficiency due to neuromuscular and restrictive disorders, as well as in those with COPD. Nocturnal hypoventilation and obstructive and central apneas result in daytime symptoms of hypersomnolence and fatigue, and contribute to abnormalities in awake gas exchange. Long-term mechanical ventilation, delivered invasively by tracheostomy or more recently by NPPV, has been shown to eliminate sleep-disordered breathing and correct abnormalities in nocturnal gas exchange, resulting in an improvement in sleep quality. Improved daytime symptoms and gas exchange, with the suggestion of a decrease in morbidity and mortality, support the use of long-term mechanical ventilation during sleep in selected patients with these disorders.     

Induced sputum for the diagnosis of pulmonary tuberculosis: Is it useful in clinical practice?

BACKGROUND:

Diagnosing pulmonary tuberculosis (PTB) is challenging in patients who are unable to spontaneously expectorate. Published evidence suggests that induced sputum (IS) is the least invasive and most cost-effective method of diagnosis, and should be used before fibre-optic bronchoscopy (FOB).

METHODS:

The medical records of 337 adults treated for PTB in northern Alberta between 1997 and 2007 were reviewed to determine whether local practice patterns reflect the evidence. Microbiological data were collected from the Provincial Laboratory for Public Health. Demographic information was collected from the patients’ charts.

RESULTS:

A total of 8.5% (26 of 307) of PTB patients had IS collected, whereas 35.8% (110 of 307) underwent FOB. Among FOB patients, 56.4% (62 of 110) had no sputum sent before the procedure and 29% (18 of 62) of these patients were smear positive. Only five patients referred for FOB had IS sent previously. There were no demographic factors predictive of IS use, whereas being an inpatient at a teaching facility or having a nodule or mass on chest x-ray was predictive of FOB referral. Because so few IS samples were available, not all patients had spontaneously expectorated sputum, IS and FOB tests performed; thus, the calculated yields were not comparable with one another.

CONCLUSIONS:

Despite published evidence recommending IS collection before FOB referral in suspected PTB patients, clinicians in our health region appeared to prefer early FOB over IS by a large margin. This practice pattern is less cost effective and exposes patients and health care workers to greater risk. Further research is needed to identify the reasons for the underuse of sputum induction.     

日本血吸虫重组22kD表膜蛋白免疫水牛的效果观察

目的 用重组日本血吸虫22kD表膜蛋白（rSj22)免疫水牛,检测特异性IgG抗体的应答水平,并观察抗血吸虫的保护效果。方法 用抗原（rSj22)加佐剂（Quil-A)肌肉注射免疫水牛,以1000条日本血吸虫尾蚴攻击感染,感染后55d剖杀,计算减虫和减卵率,用免疫印斑和ELISA方法测定抗体反应。结果 免疫组每头牛血清均能特异地识别Quil-A对照组相比,减虫率仅8.5%肝卵EPG减少12.3%,粪卵EPG减少26.8%,但均无统计学意义,结论 用rSj22kD抗原免疫水牛诱导的特异性IgG抗体不能发挥免疫保护作用。     

Alternatives to lung transplantation: lung volume reduction for COPD

Emphysema is disabling and progressive and hallmarked by decreased exercise tolerance and impaired quality of life. Surgical interventions that reduce lung volume have been the focus of multiple interventions for decades; however, until recently, limited evidence has documented their effectiveness. Lung volume reduction surgery (LVRS) underwent rigorous study in the National Emphysema Treatment Trial (NETT), which demonstrated its short-term and long-term effectiveness, associated morbidity and mortality, and the essential factors that predict LVRS success or failure. This article summarizes the major results of the NETT and briefly reviews newer bronchoscopic lung volume reduction techniques that show promise as alternative treatments for select patients with COPD undergoing consideration for lung transplantation.     

Cardiac disease in chronic obstructive pulmonary disease

The cardiac manifestations of chronic obstructive pulmonary disease (COPD) are numerous. Impairments of right ventricular dysfunction and pulmonary vascular disease are well known to complicate the clinical course of COPD and correlate inversely with survival. The pathogenesis of pulmonary vascular disease in COPD is likely multifactorial and related to alterations in gas exchange and vascular biology, as well as structural changes of the pulmonary vasculature and mechanical factors. Several modalities currently exist for the assessment of pulmonary vascular disease in COPD, but right heart catheterization remains the gold standard. Although no specific therapy other than oxygen has been generally accepted for the treatment of pulmonary hypertension in this population, there has been renewed interest in specific pulmonary vasodilators. The coexistence of COPD and coronary artery disease occurs frequently. This association is likely related to shared risk factors as well as similar pathogenic mechanisms, such as systemic inflammation. Management strategies for the care of patients with COPD and coronary artery disease are similar to those without COPD, but care must be given to address their respiratory limitations. Arrhythmias occur frequently in patients with COPD, but are rarely fatal and can generally be treated medically. Use of beta-blockers in the management of cardiac disease, while a theoretical concern in patients with increased airway resistance, is generally safe with the use of cardioselective agents.     

African Americans and men with severe COPD have a high prevalence of osteoporosis

Osteoporosis is a non-pulmonary manifestation whose true prevalence is uncertain in severe chronic obstructive pulmonary disease (COPD). We describe the prevalence and risk factors for osteoporosis in a large, well characterized COPD cohort. Dual energy x-ray absorptiometry of the lumbar spine and hip, full pulmonary function testing, cardiopulmonary exercise test, 6 minute walk distance and demographics were performed in 179 non-selected COPD patients. Patients were 59 +/- 7 years old, smoked 53 +/- 32 pack years, FEV(1) 26% +/- 9.8, and 45% were currently taking prednisone. Bone mineral density measurements were abnormal in 97%; 66% had dual energy X-ray absorptiometry defined osteoporosis, while 31% had osteopenia. The prevalence of osteoporosis in males versus females was 70% versus 62% (p = 0.33); both groups had similar fracture rates. The prevalence of osteoporosis in African Americans versus Caucasians was 69% versus 65% (p = 0.78). Caucasians had a significantly lower Ward's Triangle T score than African Americans (-2.52 +/- -0.96 vs. -2.16 +/- -0.91, p = 0.04). Those with bone fractures took higher doses of prednisone than those without fractures. Univariate analysis identified BMI and FVC% as predictors for osteoporosis (p = 0.03 OR 0.934 p = 0.006 OR 0.974). Multivariate analysis revealed only FVC% as a significant predictor (p = 0.006, OR 0.974). Osteoporosis is highly prevalent in severe COPD, and affects males and African Americans to a similar degree as females and Whites. Osteoporosis should be considered in severe COPD regardless of race or gender.     

Effects of lung volume reduction surgery on sleep quality and nocturnal gas exchange in patients with severe emphysema

STUDY OBJECTIVES: We hypothesized that associated with improvements in respiratory mechanics, lung volume reduction surgery (LVRS) would result in an improvement in both sleep quality and nocturnal oxygenation in patients with severe emphysema. DESIGN: Prospective randomized controlled trial. SETTING: University hospital. PATIENTS: Sixteen patients (10 men, 63 +/- 6 years [+/- SD]) with severe airflow limitation (FEV(1), 28 +/- 10% predicted) and hyperinflation (total lung capacity, 123 +/- 14% predicted) who were part of the National Emphysema Treatment Trial.Interventions and measurements: Patients completed 6 to 10 weeks of outpatient pulmonary rehabilitation. Spirometry, measurement of lung volumes, arterial blood gas analysis, and polysomnography were performed prior to randomization and again 6 months after therapy. Ten patients underwent LVRS and optimal medical therapy, while 6 patients received optimal medical therapy only. RESULTS: Total sleep time and sleep efficiency improved following LVRS (from 184 +/- 111 to 272 +/- 126 min [p = 0.007], and from 45 +/- 26 to 61 +/- 26% [p = 0.01], respectively), while there was no change with medical therapy alone (236 +/- 75 to 211 +/- 125 min [p = 0.8], and from 60 +/- 18 to 52 +/- 17% [p = 0.5], respectively). The mean and lowest oxygen saturation during the night improved with LVRS (from 90 +/- 7 to 93 +/- 4% [p = 0.05], and from 83 +/- 10 to 86 +/- 10% [p = 0.03], respectively), while no change was noted in the medical therapy group (from 91 +/- 5 to 91 +/- 5 [p = 1.0], and from 84 +/- 5 to 82 +/- 6% [p = 0.3], respectively). There was a correlation between the change in FEV(1) and change in the lowest oxygen saturation during the night (r = 0.6, p = 0.02). In addition, there was an inverse correlation between the change in the lowest oxygen saturation during the night and the change in residual volume (- r = 0.5, p = 0.04) and functional residual capacity (- r = 0.6, p = 0.03). CONCLUSION: In patients with severe emphysema, LVRS, but not continued optimal medical therapy, results in improved sleep quality and nocturnal oxygenation. Improvements in nocturnal oxygenation correlate with improved airflow and a decrease in hyperinflation and air trapping.