The proinflammatory stimulus of chorioamnionitis is commonly associated with preterm delivery. Women at risk of preterm delivery receive antenatal glucocorticoids to functionally mature the fetal lung. However, the effects of the combined exposures of chorioamnionitis and antenatal glucocorticoids on the fetus are poorly understood. Time-mated ewes with singleton fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) either preceding or following maternal intramuscular betamethasone 7 or 14 days before delivery, and the fetuses were delivered at 120 days gestational age (GA) (term = 150 days GA). Gestation matched controls received intra-amniotic and maternal intramuscular saline. Compared with saline controls, intra-amniotic LPS increased inflammatory cells in the bronchoalveolar lavage and myeloperoxidase, Toll-like receptor 2 and 4 mRNA, PU.1, CD3, and Foxp3-positive cells in the fetal lung. LPS-induced lung maturation measured as increased airway surfactant and improved lung gas volumes. Intra-amniotic LPS-induced inflammation persisted until 14 days after exposure. Betamethasone treatment alone induced modest lung maturation but, when administered before intra-amniotic LPS, suppressed lung inflammation. Interestingly, betamethasone treatment after LPS did not counteract inflammation but enhanced lung maturation. We conclude that the order of exposures of intra-amniotic LPS or maternal betamethasone had large effects on fetal lung inflammation and maturation.
Our study showed that corticosteroids did not influence inflammation in early phase ARDS and that hyperoxia aggravated lung injury which could not be modulated by dexamethasone in early phase ARDS.
Hyperpronation is a common foot problem in dancers. The aim of this study was to investigate the usage and effectiveness of orthotics in the management of symptomatic hyperpronation among dancers. A prospective cohort study of all dancer-patients in the investigators' practice who were prescribed orthotics for new symptoms related to hyperpronation between July 2008 and January 2009 was conducted. In this group, the longitudinal medial arch angle of the foot was measured by the foot build registration system (FBRS), both barefoot and while wearing the orthotics. In addition, patients filled out questionnaires addressing perceived effectiveness of the orthotics for pain reduction and dance ability, among other items. A second retrospective study was conducted in order to obtain longitudinal data regarding dancers' compliance with, and subjective evaluation of, wearing orthotics over the preceding 6 years. Among participating dancers who met criteria for the prospective (N = 24) or retrospective (N = 81) aspects of the study (total N = 105), 67% wore orthotics at the time of follow-up. The average compliance in usage was 6.0 (± 1.5 ) days per week and 7.5 (± 3) hours per day. The average rate of satisfaction was 67.9 (± 26.5), average degree of relief in symptoms was 58.3 (± 28.3), and self-reported degree of improvement in dance ability was 45.7 (± 27.9) on a 100 mm Visual Analogue Scale (VAS). There was a significant decrease in pain from the day of orthotics prescription to follow-up (25.9%, or 18.9 mm decrease on the VAS, CI 6.6-30.9, p = 0.005) in the prospective group (N = 24). Orthotics were found to decrease the medial longitudinal arch angle significantly during static stance with the orthotic in place (CI 0.08-1.65, p = 0.03). It is concluded that the dancers in this study demonstrated a high rate of compliance in obtaining and wearing their orthotics and experienced a significant decrease in pain.
Background: Acute respiratory distress syndrome (ARDS) can have various causes. The study objective was to investigate whether different pathophysiologic models of ARDS would show different respiratory, cardiovascular and inflammatory outcomes. Methods: We performed a prospective, randomized study in 27 ventilated ewes inducing ARDS using three different techniques to mimic the pulmonary causes of ARDS (ARDSp): warm saline lavage (n = 6), intratracheal hydrochloric acid (HCl; n = 6), intratracheal albumin (n = 10), and one technique to mimic an extrapulmonary cause of ARDS (ARDSexp): intravenous lipopolysaccharide (LPS iv; n = 5). ARDS was defined when PaO 2 was < 15 kPa (112 mmHg) when ventilated with PEEP 10 cm H 2 O and FiO 2 = 1.0. The effects on gas exchange were investigated by calculating the oxygenation index (OI) and the ventilation efficacy index (VEI) every 30 min for a period of 4 h. Post mortem lung lavage was performed to obtain broncho-alveolar lavage fluid (BALF) to assess lung injury and inflammation. Lung injury and inflammation were assessed by measuring the total number and differentiation of leukocytes, the concentration of protein and disaturated phospholipids, and interleukine-6 and-8 in the BALF. Histology of the lung was evaluated by measuring the mean alveolar size, alveolar wall thickness and the lung injury score system by Matute-Bello et al., as markers of lung injury. The concentration of interleukin-6 was determined in plasma, as a marker of systematic inflammation. Results: The OI and VEI were most affected in the LPS iv group and thereafter the HCl group, after meeting the ARDS criteria. Diastolic blood pressure was lowest in the LPS iv group. There were no significant differences found in the total number and differentiation of leukocytes, the concentration of protein and disaturated phospholipids, or interleukin-8 in the BALF, histology of the lung and the lung injury score. IL-6 in BALF and plasma was highest in the LPS iv group, but no significant differences were found between the other groups. It took a significantly longer period of time to meet the ARDS criteria in the LPS iv group.
Recruitment manoeuvres improved oxygenation, but SMRM was superior, with respect to hemodynamics and pulmonary inflammation, in ventilated sheep suffering from ARDS induced by lung lavage.
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