The hypoxic tissue microenvironment as a driver of mucosal inflammatory resolution

On the backdrop of all acute inflammatory processes lies the activation of the resolution response. Recent years have witnessed an emerging interest in defining molecular factors that influence the resolution of inflammation. A keystone feature of the mucosal inflammatory microenvironment is hypoxia. The gastrointestinal tract, particularly the colon, exists in a state of physiological hypoxia and during active inflammation, this hypoxic state is enhanced as a result of infiltrating leukocyte oxygen consumption and the activation of oxygen consuming enzymes. Most evidence suggests that mucosal hypoxia promotes the active resolution of inflammation through a variety of mechanisms, including extracellular acidification, purine biosynthesis/salvage, the generation of specialized pro-resolving lipid mediators (ie. resolvins) and altered chemokine/cytokine expression. It is now appreciated that infiltrating innate immune cells (neutrophils, eosinophils, macrophages) have an important role in molding the tissue microenvironment to program an active resolution response. Structural or functional dysregulation of this inflammatory microenvironment can result in the loss of tissue homeostasis and ultimately progression toward chronicity. In this review, we will discuss how inflammatory hypoxia drives mucosal inflammatory resolution and its impact on other microenvironmental factors that influence resolution

Spitzer observations of extragalactic H II regions - III. NGC 6822 and the hot star, H II region connection

Using the short-high module of the Infrared Spectrograph on the Spitzer Space Telescope, we have measured the [S IV] 10.51, [Ne II] 12.81, [Ne III] 15.56, and [S III] 18.71-micron emission lines in nine H II regions in the dwarf irregular galaxy NGC 6822. These lines arise from the dominant ionization states of the elements neon (Ne$^{++}$, Ne$^+$) and sulphur (S$^{3+}$, S$^{++}$), thereby allowing an analysis of the neon to sulphur abundance ratio as well as the ionic abundance ratios Ne$^+$/Ne$^{++}$ and S$^{3+}$/S$^{++}$. By extending our studies of H II regions in M83 and M33 to the lower metallicity NGC 6822, we increase the reliability of the estimated Ne/S ratio. We find that the Ne/S ratio appears to be fairly universal, with not much variation about the ratio found for NGC 6822: the median (average) Ne/S ratio equals 11.6 (12.2$\pm$0.8). This value is in contrast to Asplund et al.'s currently best estimated value for the Sun: Ne/S = 6.5. In addition, we continue to test the predicted ionizing spectral energy distributions (SEDs) from various stellar atmosphere models by comparing model nebulae computed with these SEDs as inputs to our observational data, changing just the stellar atmosphere model abundances. Here we employ a new grid of SEDs computed with different metallicities: Solar, 0.4 Solar, and 0.1 Solar. As expected, these changes to the SED show similar trends to those seen upon changing just the nebular gas metallicities in our plasma simulations: lower metallicity results in higher ionization. This trend agrees with the observations.Comment: 22 pages, 13 figures. To be published in MNRAS. reference added and typos fixed. arXiv admin note: text overlap with arXiv:0804.0828, which is paper II by Rubin et al. (2008

Duplex ultrasound in aneurysm surveillance following endovascular aneurysm repair: a comparison with computed tomography aortography

ObjectivesCumulative radiation dose, cost, and increased demand for computed tomography aortography (CTA) suggest that duplex ultrasonography (DU) may be an alternative to CTA-based surveillance. We compared CTA with DU during endovascular aneurysm repair (EVAR) follow-up.MethodsPatients undergoing EVAR had clinical and radiological follow-up data entered in a prospectively maintained database. For the purpose of this study, the gold standard test for endoleak detection was CTA, and an endoleak detected on DU alone was assumed to be a false positive result. DU interpretation was performed independently of CTA and vice versa.ResultsOne hundred thirty-two patients underwent EVAR, of whom 117 attended for follow-up ranging from six months to nine years (mean, 32 months). Adequate aneurysm sac visualisation on DU was not possible in 1.7% of patients, predominantly due to obesity. Twenty-eight endoleaks were detected in 28 patients during follow-up. Of these, 24 were initially identified on DU (four false negative DU examinations), and eight had at least one negative CTA with a positive DU prior to diagnosis. Twenty-three endoleaks were type II in nature and three of these patients had increased sac size. There was one type I and four type III endoleaks. Two of these (both type III) had an increased sac size. Of 12 patients with increased aneurysm size of 5 mm or more at follow-up, five had an endoleak visible on DU, yet negative CTA and a further five had endoleak visualisation on both DU and CTA. Of six endoleaks which underwent re-intervention, all were initially picked up on DU. One of these endoleaks was never demonstrated on CTA and a further two had at least one negative CTA prior to endoleak confirmation. Positive predictive value for DU was 45% and negative predictive value 94%. Specificity of DU for endoleak detection was 67% when compared with CTA, because of the large number of false positive DU results. Sensitivity for DU was 86%, with all clinically significant endoleaks demonstrated on CTA also detected on DU.ConclusionDespite its low positive predictive value, we found DU to be a sensitive test for the detection of clinically significant endoleaks. Given concerns about cumulative radiation exposure and cost, and the surprisingly low sensitivity of CTA for endoleak detection in this series, selective CTA based on DU surveillance may be a more appropriate long-term strategy