Browsing by Subject "Pneumonia"
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Item A cohort-study of patients suspected for MERS-CoV in a referral hospital in Saudi Arabia(Elsevier, 2017) Al-Tawfiq, Jaffar A.; Alfaraj, Sarah H.; Altuwaijri, Talal A.; Memish, Ziad A.; Department of Medicine, IU School of MedicineItem Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures(American Physiological Society, 2015-07-15) Schweitzer, Kelly S.; Chen, Steven X.; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J.; Hubbard, Walter C.; Kim, Elena S.; Lai, Xianyin; Wang, Mu; Kranz, William D.; Carroll, Clinton J.; Ray, Bruce D.; Bittman, Robert; Goodpaster, John; Petrache, Irina; Department of Biochemistry & Molecular Biology, IU School of MedicineThe increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.Item Handheld Point-of-Care Lactate Measurement at Admission Predicts Mortality in Ugandan Children Hospitalized with Pneumonia: A Prospective Cohort Study(American Society of Tropical Medicine and Hygiene, 2019-01) Ma, Cary; Gunaratnam, Lourdes Cynthia; Ericson, Austin; Conroy, Andrea L.; Namasopo, Sophie; Opoka, Robert O.; Hawkes, Michael T.; Pediatrics, School of MedicineGlobally, pneumonia is the leading cause of death among children younger than 5 years old, with most deaths occurring in low-income countries. Rapid bedside tools to assist practitioners to accurately triage and risk-stratify these patients may improve clinical care and patient outcomes. We conducted a prospective cohort study of children with pneumonia admitted to two Ugandan hospitals to examine the predictive value of a single point-of-care lactate measurement using a commercially available handheld device, the Lactate Scout Analyzer. One hundred and fifty-five children were included, 90 (58%) male, with a median (interquartile range [IQR]) age of 11 (1.4–20) months. One hundred and twenty-five (81%) patients had chest indrawing, 133 (86%) were hypoxemic, and 75 (68%) had a chest x-ray abnormality. In-hospital mortality was 22/155 (14%). Median (IQR) admission lactate level was 2.4 (1.8–3.6) mmol/L among children who survived versus 7.2 (2.6–9.7) mmol/L among those who died (P < 0.001). Lactate was a better prognostic marker of mortality (area under receiver operator characteristic 0.76, 95% confidence interval: 0.69–0.87, P ≤ 0.001), than any single clinical sign or composite clinical risk score. Lactate level at admission of < 2.0, 2.0–4.0, and > 4.0 mmol/L accurately risk-stratified children, with 5-day mortality of 2%, 11% and 26%, respectively (P < 0.001). Slow lactate clearance also predicted subsequent mortality in children with repeated lactate measurements. Hand-held lactate measurement is a clinically informative and convenient tool in low-resource settings for triage and risk stratification of pediatric pneumonia.