Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to ...postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery.
We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications.
A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio 95% CI: 0.93 0.85, 1.01 per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio 95% CI: 0.94 0.90, 0.98 per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate 95% CI: 0.29 0.11, 0.48 ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004).
Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.
Hydrogen activation using a novel tribenzyltin Lewis acid Cooper, Robert T.; Sapsford, Joshua S.; Turnell-Ritson, Roland C. ...
Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences,
08/2017, Letnik:
375, Številka:
2101
Journal Article
Recenzirano
Over the last decade there has been an explosion in the reactivity and applications of frustrated Lewis pair (FLP) chemistry. Despite this, the Lewis acids (LAs) in these transformations are often ...boranes, with heavier p-block elements receiving surprisingly little attention. The novel LA Bn₃SnOTf (1) has been synthesized from simple, inexpensive starting materials and has been spectroscopically and structurally characterized. Subtle modulation of the electronics at the tin centre has led to an increase in its Lewis acidity in comparison with previously reported R₃SnOTf LAs, and has facilitated low temperature hydrogen activation and imine hydrogenation. Deactivation pathways of the R₃Sn⁺ LA core have also been investigated. This article is part of the themed issue 'Frustrated Lewis pair chemistry'.
Pulmonary hypertension (PHT) is an emerging common complication of hereditary hemolytic anemias. It has been mechanistically and epidemiologically linked to intravascular hemolysis and decreased ...nitric oxide (NO) bioavailability. While this complication has been described in approximately 30% of adult patients with sickle cell disease and thalassemia, the prevalence of PHT in patients with paroxysmal nocturnal hemoglobinuria (PNH), an acquired disease with the highest levels of intravascular hemolysis observed, has never been determined. PNH patients frequently have symptoms consistent with both hemolysis and PHT including severe fatigue and dyspnea on exertion. Therefore, we examined for the presence of PHT in PNH and explored potential mechanisms associated with its development by measuring the ability of plasma to instantaneously consume NO using ozone-based chemiluminescence. Doppler echocardiography was performed in 24 hemolytic PNH patients to estimate pulmonary artery systolic pressures. Systolic PHT was defined by a tricuspid regurgitant jet velocity (TRV) ≥ 2.5m/s at rest. Eleven (46%) patients had elevated pulmonary artery systolic pressures (mean TRV 2.7m/s ± 0.08) and one (4%) had severely elevated pressures (TRV 3.5m/s). Plasma from PNH patients (n=28) consumed 32.26 ± 8.74μM NO while normal subjects (n=9) consumed 2.42 ± 0.77μM NO (p=0.03). LDH levels correlated with NO consumption (p<0.001). Of the 24 patients evaluated for pulmonary pressure, there was no significant correlation between PHT and severity of NO consumption. In a separate analysis, 4 patients treated with eculizumab in the initial pilot study demonstrated a lower NO consumption at 7.34 ± 5.68μM NO at a median of 3.1 (2.3 – 3.1) years after starting eculizumab. Interestingly, 8 of 12 patients not on primary warfarin prophylaxis had PHT whereas only 3 of 12 patients on warfarin had PHT (p=0.04). In addition, warfarin therapy correlated inversely with TRV (R=−0.54; P=0.007). In summary, 1) PHT appears to be extremely common in patients with PNH, adding an additional hemolytic anemia to the growing list of human hemolytic diseases associated with PHT, 2) patients with PNH demonstrate high levels of NO consumption that are highly correlated to intravascular hemolysis (LDH) in these patients, 3) warfarin therapy is associated with lower rates of pulmonary hypertension supporting a strong rationale for primary prophylaxis with warfarin, and 4) eculizumab therapy is associated with reduced levels of NO consumption. Since NO consumption is associated with increased risk of thrombosis, it is possible that NO consumption contributes to thrombosis in PNH patients with PHT. Thus, inhibition of intravascular hemolysis and subsequent NO consumption may be a reasonable approach to reducing thrombotic risk and potentially the incidence of PHT in PNH. Additional studies are required to determine the contributions of chronic pulmonary thromboembolic disease, intravascular hemolysis and reduced NO bioavailability to the pathogenesis of pulmonary hypertension in PNH.
This paper describes the development of a laser induced fluorescence (LIF) technique to quantify the thickness and spatial distribution of transient liquid fuel films formed as a result of spray–wall ...interaction. The LIF technique relies on the principle that upon excitation by laser radiation the intensity of the fluorescent signal from a tracer like 3-pentanone is proportional to the film thickness. A binary solution of 10% (v/v) of 3-pentanone in iso-octane is used as a test fuel with a Nd:YAG laser as the excitation light source (utilising the fourth harmonic at wavelength 266 nm) and an intensified CCD camera is used to record the results as fluorescent images. The propagation of the excitation laser beam through the optical piston is carefully controlled by total internal reflection so that only the fuel film is excited and not the airborne droplets above the film, which had been previously shown to induce significant error. Other known sources of error are also carefully minimised. Calibrated temporally resolved benchmark results of a transient spray from a gasoline direct injector impinging on a flat quartz crown under atmospheric conditions are presented, with observations and discussion of the transient development of the fuel film. The calibrated measurements are consistent with previous studies of this event and demonstrate the applicability of the technique particularly for appraisal of CFD predictions. The potential utilisation of the technique under typical elevated ambient conditions is commented upon.
Although there is increasing evidence of a pathogenic role for eosinophils in the airway epithelium, there is little direct evidence which demonstrates that eosinophils influence epithelial cell ...activity in humans. We have cultured human nasal epithelial cells in vitro and studied the effect of isolated human eosinophils on the ciliary beat frequency (CBF) and cell membrane integrity of these cells after incubation in the absence or presence of 0.1 microM phorbol 12-myristate 13-acetate (PMA) or 0.1 mg/ml opsonized latex beads and the absence or presence of 10(-5) M nedocromil sodium. CBF was monitored by an analogue contrast-enhancement technique, and cell damage was assessed by release of 51Cr from the cells. Cell cultures were also assessed for the percentage of eosinophil cationic protein (ECP) released into the medium at the end of incubation. Neither 0.1 microM PMA, 0.1 mg/ml opsonized latex beads, 10(-5) M nedocromil sodium, nor eosinophils alone altered the CBF of the epithelial cells. PMA-stimulated eosinophils, however, attenuated the CBF significantly, from 10.2 +/- 0.3 to 8.8 +/- 0.4 Hz (P less than 0.05) after 15 h of incubation. Similarly, opsonized latex bead-stimulated eosinophils led to a significant attenuation of CBF from 9.2 +/- 0.3 to 8.4 +/- 0.3 Hz (P less than 0.05), 6.9 +/- 0.5 Hz (P less than 0.001), and 7.5 +/- 0.3 Hz (P less than 0.001) after 2, 15, and 24 h of incubation, respectively.
Although cigarette smoking is of paramount importance in the development of chronic obstructive pulmonary disease (COPD), only a small proportion of smokers develop the disease. We tested the ...hypothesis that the response of the bronchial epithelium to cigarette smoke (CS) differs in patients with COPD. Such a difference might explain in part why only some cigarette smokers develop the disease. We established primary explant cultures of human bronchial epithelial cells (HBEC) from biopsy material obtained from never-smokers who had normal pulmonary function, smokers with normal pulmonary function, and smokers with COPD, and exposed these for 20 min to CS or air. Measurements were subsequently made over a period of 24 h of transepithelial permeability and release of interleukin (IL)-1beta and soluble intercellular adhesion molecule-1 (sICAM-1). In addition, intracellular reduced glutathione (GSH) levels were measured after 24 h incubation. Exposure to CS increased the permeability of these cultures in all study groups, but the most marked effect was observed in cultures from patients with COPD (mean increase, 85.5%). The smallest CS-induced increase in the permeability was observed in HBEC cultured from smokers with normal pulmonary function (mean, 25.0%), and this was significantly lower than that of HBEC from never-smokers (mean, 53.4%) (P<0.001). Compared with exposure to air, exposure to CS led to a significantly increased release of these mediators from cultures of the never-smoker group (mean 250.0% increase in IL-1beta and mean 175.3% increase in sICAM-1 24 h after exposure) and COPD group (mean 383.3% increase in IL-1beta and mean 97.4% increase in sICAM-1 24 h after exposure). In contrast, CS exposure did not influence significantly the release of either mediator from the cells of smokers with normal pulmonary function. Levels of intracellular GSH were significantly higher in cultures of HBEC derived from smokers, both those with normal pulmonary function and those with COPD, compared with cultures from healthy never-smokers. Exposure to CS significantly decreased the concentration of intracellular GSH in all cultures. However, the fall in intracellular GSH was significantly greater in cells from patients with COPD (mean 72.9% decrease) than in cells from never-smokers (mean 61.4% decrease; P = 0.048) or smokers with normal pulmonary function (mean 43.9% decrease; P = 0.02). These results suggest that whereas smokers with or without COPD demonstrate increased levels of GSH within bronchial epithelial cell cultures, those with COPD have a greater susceptibility to the effects of CS in reducing GSH levels and causing increased permeability and release of proinflammatory mediators such as IL-1beta and sICAM-1.
As a weed, wheat has recently gained greater profile. Determining wheat persistence in cropping systems will facilitate the development of effective volunteer wheat management strategies. In October ...of 2000, glyphosate-resistant (GR) spring wheat seeds were scattered on plots at eight western Canada sites. From 2001 to 2003, the plots were seeded to a canola–barley–field-pea rotation or a fallow–barley–fallow rotation, with five seeding systems involving seeding dates and soil disturbance levels, and monitored for wheat plant density. Herbicides and tillage (in fallow systems) were used to ensure that no wheat plants produced seed. Seeding systems with greater levels of soil disturbance usually had greater wheat densities. Volunteer wheat densities at 2 (2002) and 3 (2003) yr after seed dispersal were close to zero but still detectable at most locations. At the end of 2003, viable wheat seeds were not detected in the soil seed bank at any location. The majority of wheat seedlings were recruited in the year following seed dispersal (2001) at the in-crop, prespray (PRES) interval. At the PRES interval in 2001, across all locations and treatments, wheat density averaged 2.6 plants m−2. At the preplanting interval (PREP), overall wheat density averaged only 0.2 plants m−2. By restricting density data to include only continuous cropping, low-disturbance direct-seeding (LDS) systems, the latter mean dropped below 0.1 plants m−2. Only at one site were preplanting GR wheat densities sufficient (4.2 plants m−2) to justify a preseeding herbicide treatment in addition to glyphosate in LDS systems. Overall volunteer wheat recruitment at all spring and summer intervals in the continuous cropping rotation in 2001 was 1.7% (3.3 plants m−2). Despite the fact that volunteer wheat has become more common in the central and northern Great Plains, there is little evidence from this study to suggest that its persistence will be a major agronomic problem. Nomenclature: Barley, Hordeum vulgare L.; canola, Brassica napus L.; field pea, Pisum sativum L.; spring wheat, Triticum aestivum L.
Background: Recent studies have suggested that airway epithelial cells of atopic and nonatopic individuals may differ in their ability to produce proinflammatory cytokines.
Methods: We have cultured ...human nasal epithelial cells (NECs) as confluent explant cultures from nasal biopsy specimens of well-characterized nonatopic normal volunteers without rhinitis (
n=8), atopic volunteers without rhinitis (
n=9), and atopic patient volunteers with rhinitis (
n=10) and measured the amounts of IL-1β, IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and RANTES released spontaneously into the culture medium by these cells in vitro. NECs from patients with allergic rhinitis were cultured from biopsy specimens obtained on two different occasions, during and after the pollen season.
Results: In general, NECs from atopic individuals released significantly greater amounts ofIL-1β, IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and RANTES than NECs from nonatopic individuals. IL-8 was released in greatest quantity and IL-1β in lowest quantity, regardless of whether the NECs were derived from atopic or nonatopic volunteers. Of the atopic individuals, NECs of atopic patients with rhinitis naturally exposed to pollen released greater quantities of all these cytokines, compared with NECs of atopic patients with rhinitis and atopic patients without rhinitis who were not exposed to allergen.
Conclusions: These results suggest that NECs of atopic individuals, who are geneticallypredisposed to upper airway disease, release increased amounts of proinflammatory cytokines and that natural exposure to allergen enhances the release of these cytokines, exacerbating the symptoms of allergic disease.