Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology

<p>Abstract</p> <p>Background</p> <p>Pulsus paradoxus estimated by dynamic change in area under the oximeter plethysmograph waveform (PEP) might provide a measure of acute asthma severity. Our primary objective was to determine how well PEP correlates with forced expiratory volume in 1-second (%FEV₁) (criterion validity) and change of %FEV₁(responsiveness) during treatment in pediatric patients with acute asthma exacerbations.</p> <p>Methods</p> <p>We prospectively studied subjects 5 to 17 years of age with asthma exacerbations. PEP, %FEV₁, airway resistance and accessory muscle use were recorded at baseline and at 2 and 4 hours after initiation of corticosteroid and bronchodilator treatments. Statistical associations were tested with Pearson or Spearman rank correlations, logistic regression using generalized estimating equations, or Wilcoxon rank sum tests.</p> <p>Results</p> <p>We studied 219 subjects (median age 9 years; male 62%; African-American 56%). Correlation of PEP with %FEV₁demonstrated criterion validity (r = - 0.44, 95% confidence interval [CI], - 0.56 to - 0.30) and responsiveness at 2 hours (r = - 0.31, 95% CI, - 0.50 to - 0.09) and 4 hours (r = - 0.38, 95% CI, - 0.62 to - 0.07). PEP also correlated with airway resistance at baseline (r = 0.28 for ages 5 to 10; r = 0.45 for ages 10 to 17), but not with change over time. PEP was associated with accessory muscle use (OR 1.16, 95% CI, 1.11 to 1.21, P < 0.0001).</p> <p>Conclusions</p> <p>PEP demonstrates criterion validity and responsiveness in correlations with %FEV₁. PEP correlates with airway resistance at baseline and is associated with accessory muscle use at baseline and at 2 and 4 hours after initiation of treatment. Incorporation of this technology into contemporary pulse oximeters may provide clinicians improved parameters with which to make clinical assessments of asthma severity and response to treatment, particularly in patients who cannot perform spirometry because of young age or severity of illness. It might also allow for earlier recognition and improved management of other disorders leading to elevated pulsus paradoxus.</p

Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein.

Epithelial cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces

Feature Adaptive Sampling for Scanning Electron Microscopy

A new method for the image acquisition in scanning electron microscopy (SEM) was introduced. The method used adaptively increased pixel-dwell times to improve the signal-to-noise ratio (SNR) in areas of high detail. In areas of low detail, the electron dose was reduced on a per pixel basis, and a-posteriori image processing techniques were applied to remove the resulting noise. The technique was realized by scanning the sample twice. The first, quick scan used small pixel-dwell times to generate a first, noisy image using a low electron dose. This image was analyzed automatically, and a software algorithm generated a sparse pattern of regions of the image that require additional sampling. A second scan generated a sparse image of only these regions, but using a highly increased electron dose. By applying a selective low-pass filter and combining both datasets, a single image was generated. The resulting image exhibited a factor of ≈3 better SNR than an image acquired with uniform sampling on a Cartesian grid and the same total acquisition time. This result implies that the required electron dose (or acquisition time) for the adaptive scanning method is a factor of ten lower than for uniform scanning

Automated Separation of Visceral and Subcutaneous Adiposity in In Vivo Microcomputed Tomographies of Mice

Reflecting its high resolution and contrast capabilities, microcomputed tomography (μCT) can provide an in vivo assessment of adiposity with excellent spatial specificity in the mouse. Herein, an automated algorithm that separates the total abdominal adiposity into visceral and subcutaneous compartments is detailed. This algorithm relies on Canny edge detection and mathematical morphological operations to automate the manual contouring process that is otherwise required to spatially delineate the different adipose deposits. The algorithm was tested and verified with μCT scans from 74 C57BL/6J mice that had a broad range of body weights and adiposity. Despite the heterogeneity within this sample of mice, the algorithm demonstrated a high degree of stability and robustness that did not necessitate changing of any of the initially set input variables. Comparisons of data between the automated and manual methods were in complete agreement (R2 = 0.99). Compared to manual contouring, the increase in precision and accuracy, while decreasing processing time by at least an order of magnitude, suggests that this algorithm can be used effectively to separately assess the development of total, visceral, and subcutaneous adiposity. As an application of this method, preliminary data from adult mice suggest that a relative increase in either subcutaneous, visceral, or total fat negatively influences skeletal quantity and that fat infiltration in the liver is greatly increased by a high-fat diet