In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

Background: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS. Aim: To investigate the effects of salbutamol on neutrophil function. Methods: The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days’ treatment with placebo or salbutamol (ALI/ARDS group). Alveolar–capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured. Results: In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar– capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils. Conclusion: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways

Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury

Background: Reduced bioactive vascular endothelial growth factor (VEGF) has been demonstrated in several inflammatory lung conditions including the acute respiratory distress syndrome (ARDS). sVEGFR-1, a soluble form of VEGF-1 receptor, is a potent natural inhibitor of VEGF. We hypothesised that sVEGFR-1 plays an important role in the regulation of the bioactivity of VEGF within the lung in patients with ARDS. Methods: Forty one patients with ARDS, 12 at risk of developing ARDS, and 16 normal controls were studied. Bioactive VEGF, total VEGF, and sVEGFR-1 were measured by ELISA in plasma and bronchoalveolar lavage (BAL) fluid. Reverse transcriptase polymerase chain reaction for sVEGFR-1 was performed on BAL cells. Results: sVEGFR-1 was detectable in the BAL fluid of 48% (20/41) of patients with early ARDS (1.4– 54.8 ng/ml epithelial lining fluid (ELF)) compared with 8% (1/12) at risk patients (p = 0.017) and none of the normal controls (p = 0.002). By day 4 sVEGFR-1 was detectable in only 2/18 ARDS patients (p = 0.008). Patients with detectable sVEGFR-1 had lower ELF median (IQR) levels of bioactive VEGF than those without detectable sVEGFR-1 (1415.2 (474.9–3192) pg/ml v 4761 (1349–7596.6) pg/ml, median difference 3346 pg/ml (95% CI 305.1 to 14711.9), p = 0.016), but there was no difference in total VEGF levels. BAL cells expressed mRNA for sVEGFR-1 and produced sVEGFR-1 protein which increased following incubation with tumour necrosis factor a. Conclusion: This study shows for the first time the presence of sVEGFR-1 in the BAL fluid of patients with ARDS. This may explain the presence of reduced bioactive VEGF in patients early in the course of ARDS

Outcomes following oesophagectomy in patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database

Introduction: This report describes the case mix and outcomes of patients with oesophageal cancer admitted to adult critical care units following elective oesophageal surgery in England, Wales and Northern Ireland. Methods: Admissions to critical care following elective oesophageal surgery for malignancy were identified using data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database. Information on admissions between December 1995 and September 2007 were extracted and the association between in-hospital mortality and patient characteristics on admission to critical care was assessed using multiple logistic regression analysis. The performance of three prognostic models (Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and the ICNARC physiology score) was also evaluated. Results: Between 1995 and 2007, there were 7227 admissions to 181 critical care units following oesophageal surgery for malignancy. Overall mortality in critical care was 4.4% and in-hospital mortality was 11%, although both declined steadily over time. Eight hundred and seventy-three (12.2%) patients were readmitted to critical care, most commonly for respiratory complications (49%) and surgical complications (25%). Readmitted patients had a critical care unit mortality of 24.7% and in-hospital mortality of 33.9%. Overall in-hospital mortality was associated with patient age, and various physiological measurements on admission to critical care (partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio, lowest arterial pH, mechanical ventilation, serum albumin, urea and creatinine). The three prognostic models evaluated performed poorly in measures of discrimination, calibration and goodness of fit. Conclusions: Surgery for oesophageal malignancy continues to be associated with significant morbidity and mortality. Age and organ dysfunction in the early postoperative period are associated with an increased risk of death. Postoperative serum albumin is confirmed as an additional prognostic factor. More work is required to determine how this knowledge may improve clinical management

Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Introduction: Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis. Methods: A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization. Results: 100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238). Conclusions: Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings. Trial Registration: International Standard Randomized Control Trial Registry ISRCTN64637517

Basic life support providers’ assessment of centre of the chest and inter-nipple line for hand position and their underlying anatomical structures

INTRODUCTION Effective chest compression is an integral part of good quality cardiopulmonary resuscitation. There remains uncertainty over the optimal method for identifying the correct hand position for chest compression. The aim of this study was to identify the relationship between basic life support (BLS) providers assessment of the inter-nipple line (INL) versus the centre of the chest (CoC) and to identify the anatomical structures underneath these land marks. METHOD Thirty consecutive patients having elective CT scans of the thorax were recruited and photographs of the patient fully clothed were taken in the supine position. 30 healthcare students trained in BLS were asked to mark the ‘point between the nipples’ and the ‘centre of the chest’ on each photograph in a random sequence. Corresponding points were marked on the CT images and the underlying anatomical structures were identified. RESULTS Hand positions using CoC landmark were significantly higher and were more variable than INL landmark (Measurement represented as ratio of sternal length: mean CoC 0.709, 95% CI 0.677, 0.740 vs mean INL 0.803 95% CI 0.772, 0.835; p<0.0001). Structures underneath CoC and INL hand positions were significantly different; CoC compressing predominantly the aortic arch and ascending aorta and INL compressing the left ventricle and left ventricular outflow (p<0.001). Hand positions were not significantly affected by gender of patients. CONCLUSION Both the centre of the chest landmark and inter-nipple line identify positions on the lower third of the sternum. The centre of the chest technique identifies a point that is consistently higher and more variable than the inter-nipple line. Structures compressed under both landmarks were different although the implications of this are unknown

Star Formation in Extreme Environments: The Effects of Cosmic Rays and Mechanical Heating

Context: Molecular data of extreme environments, such as Arp 220, but also NGC 253, show evidence for extremely high cosmic ray (CR) rates (10^3-10^4 * Milky Way) and mechanical heating from supernova driven turbulence. Aims: The consequences of high CR rates and mechanical heating on the chemistry in clouds are explored. Methods: PDR model predictions are made for low, n=10^3, and high, n=10^5.5 cm^-3, density clouds using well-tested chemistry and radiation transfer codes. Column densities of relevant species are discussed, and special attention is given to water related species. Fluxes are shown for fine-structure lines of O, C+, C, and N+, and molecular lines of CO, HCN, HNC, and HCO+. A comparison is made to an X-ray dominated region model. Results: Fine-structure lines of [CII], [CI], and [OI] are remarkably similar for different mechanical heating and CR rates, when already exposed to large amounts of UV. HCN and H2O abundances are boosted for very high mechanical heating rates, while ionized species are relatively unaffected. OH+ and H2O+ are enhanced for very high CR rates zeta > 5 * 10^-14 s^-1. A combination of OH+, OH, H2O+, H2O, and H3O+ trace the CR rates, and are able to distinguish between enhanced cosmic rays and X-rays.Comment: 13 pages, 8 figures, A&A accepte

Turbulent molecular gas and star formation in the shocked intergalactic medium of Stephan's Quintet

We report on single-dish radio CO observations towards the inter-galactic medium (IGM) of the Stephan's Quintet (SQ) group of galaxies. Extremely bright mid-IR H2 rotational line emission from warm molecular gas has been detected by Spitzer in the kpc-scale shock created by a galaxy collision. We detect in the IGM CO(1-0), (2-1) and (3-2) line emission with complex profiles, spanning a velocity range of 1000 km/s. The spectra exhibit the pre-shock recession velocities of the two colliding gas systems (5700 and 6700 km/s), but also intermediate velocities. This shows that much of the molecular gas has formed out of diffuse gas accelerated by the galaxy-tidal arm collision. A total H2 mass of 5x10^9 Msun is detected in the shock. The molecular gas carries a large fraction of the gas kinetic energy involved in the collision, meaning that this energy has not been thermalized yet. The turbulent kinetic energy of the H2 gas is at least a factor of 5 greater than the thermal energy of the hot plasma heated by the collision. The ratio between the warm H2 mass derived from Spitzer IRS spectroscopy and the H2 mass derived from CO fluxes is ~0.3 in the IGM of SQ, which is 10-100 times higher than in star-forming galaxies. In the shocked region, the ratio of the PAH-to-CO surface luminosities, commonly used to measure the star formation efficiency of the H2 gas, is lower (up to a factor 75) than the observed values in star-forming galaxies. We suggest that turbulence fed by the galaxy-tidal arm collision maintains a high heating rate within the H2 gas. This interpretation implies that the velocity dispersion on the scale of giant molecular clouds in SQ is one order of magnitude larger than the Galactic value. The high amplitude of turbulence may explain why this gas is not forming stars efficiently. [abridged version]Comment: Revised abstract and small editing to match published version. 15 pages, 5 figures. Accepted for publication in Ap

Skeletal trade-offs in coralline algae in response to ocean acidification

Ocean acidification is changing the marine environment, with potentially serious consequences for many organisms. Much of our understanding of ocean acidification effects comes from laboratory experiments, which demonstrate physiological responses over relatively short timescales. Observational studies and, more recently, experimental studies in natural systems suggest that ocean acidification will alter the structure of seaweed communities. Here, we provide a mechanistic understanding of altered competitive dynamics among a group of seaweeds, the crustose coralline algae (CCA). We compare CCA from historical experiments (1981-1997) with specimens from recent, identical experiments (2012) to describe morphological changes over this time period, which coincides with acidification of seawater in the Northeastern Pacific. Traditionally thick species decreased in thickness by a factor of 2.0-2.3, but did not experience a change in internal skeletal metrics. In contrast, traditionally thin species remained approximately the same thickness but reduced their total carbonate tissue by making thinner inter-filament cell walls. These changes represent alternative mechanisms for the reduction of calcium carbonate production in CCA and suggest energetic trade-offs related to the cost of building and maintaining a calcium carbonate skeleton as pH declines. Our classification of stress response by morphological type may be generalizable to CCA at other sites, as well as to other calcifying organisms with species-specific differences in morphological types