Exercise presents a considerable stress to the pulmonary system and ventilation-perfusion (Va/Q) heterogeneity increases with exercise, affecting the efficiency of gas exchange. In particular, prolonged heavy exercise and maximal exercise are known to increase Va/Q heterogeneity and these changes persist into recovery. We hypothesized that the spatial heterogeneity of pulmonary perfusion would be similarly elevated after prolonged exercise. To test this, athletic subjects (n = 6, Vo(2max) = 61 ml. kg(-1).min(-1)) with exercising Va/Q heterogeneity previously characterized by the multiple inert gas elimination technique (MIGET), performed 45 min of cycle exercise at approximately 70% Vo(2max). MRI arterial spin labeling measures of pulmonary perfusion were acquired pre- and postexercise (at 20, 40, 60 min post) to quantify the spatial distribution in isogravitational (coronal) and gravitationally dependent (sagittal) planes. Regional proton density measurements allowed perfusion to be normalized for density and quantified in milliliters per minute per gram. Mean lung density did not change significantly in either plane after exercise (P = 0.19). Density-normalized perfusion increased in the sagittal plane postexercise (P =or <0.01) but heterogeneity did not (all P >or= 0.18), likely because of perfusion redistribution and vascular recruitment. Density-normalized perfusion was unchanged in the coronal plane postexercise (P = 0.66), however, perfusion heterogeneity was significantly increased as measured by the relative dispersion [RD, pre 0.62(0.07), post 0.82(0.21), P < 0.0001] and geometric standard deviation [GSD, pre 1.74(0.14), post 2.30(0.56), P < 0.005]. These changes in heterogeneity were related to the exercise-induced changes of the log standard deviation of the ventilation distribution, an MIGET index of Va/Q heterogeneity (RD R(2) = 0.68, P < 0.05, GSD, R(2) = 0.55, P = 0.09). These data are consistent with but not proof of interstitial pulmonary edema as the mechanism underlying exercise-induced increases in both spatial perfusion heterogeneity and Va/Q heterogeneity.

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Objective: The most appropriate medication regimen to mitigate the consequences hepatic encephalopathy remains inconclusive. This review seeks to serve as a reference for clinicians to help guide therapy decisions with regard to hepatic encephalopathy. Methods: A comprehensive literature review between August 2018 and April 2019 was accomplished with the assistance of a medical librarian. Sources of literature review include PubMed, MEDLINE, SCOPUS, ProQuest Central, CINAHL, and ProQuest Dissertations. The authors selected randomized clinical and double-blind cross-over trials evaluating probiotics, zinc, polyethylene glycol, rifaximin, and flumazenil. Sixteen clinical trials are discussed in this review. Pertinent safety, efficacy, and statistical and clinical outcomes are summarized by the authors. Conclusions: The most appropriate regimen to mitigate the consequences of hepatic encephalopathy remains elusive; however, the agents discussed within this review offer alternative options for patients unresponsive to or intolerant of traditional lactulose therapy. This review seeks to serve as a repository for relevant clinical trials, and as a reference for clinicians to help guide therapy decisions.

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Objective: To review and consider the immunomodulatory ramifications of glycopeptide and lipopeptide antibiotics in a patient with severe asthma, hyper-immunoglobulin E (IgE) syndrome, and osteonecrosis of the jaw. Case Summary: A 36-year-old male patient with a pertinent past medical history of hyper-IgE syndrome, severe asthma, and osteonecrosis of the jaw attributed to steroid use initially presented to the emergency department, where imaging of the jaw suggested an infectious process. Following months of vancomycin therapy as an outpatient, the patient was switched to daptomycin to facilitate once-daily infusions. Following this change, the patient experienced significantly less asthma exacerbations and fewer admissions to the hospital for asthma-related issues. Discussion: Though daptomycin is associated with eosinophilia, and this patient’s eosinophil counts did increase while on the drug, an inverse relationship developed concerning the number of hospital admissions for asthma exacerbations. A review of the literature indicates that select glycopeptides, such as vancomycin, have pro-inflammatory effects, while other related drugs, such as the lipopeptide daptomycin, may not result in clinical manifestations of an inflammatory process. Tumor necrosis factor-α, interleukin-1β, and interleukin-6 have been implicated in this process. This patient may have been particularly susceptible to the effects of the glycopeptides due to his diagnosis of hyper-IgE syndrome, which has been independently associated with reactive airway diseases. Conclusion: Cytokine migration and activation by select glycopeptide and lipopeptide antibiotics warrant consideration from clinicians when determining the most appropriate treatment regimens. Further research is required to elucidate whether the pro-inflammatory properties of vancomycin warrant a change in first-line therapy to daptomycin in select cases.