The authors could detect regional neutrophil activation in VILI even when end-expiratory derecruitment was prevented and impairment of gas exchange was not evident. Concomitant end-expiratory derecruitment converted this activation into profound inflammation with decreased aeration and regional shunting.

No abstract

Rationale: Bronchoconstriction in asthma leads to heterogeneous ventilation and the formation of large and contiguous ventilation defects in the lungs. However, the regional adaptations of pulmonary perfusion (Q ) to such ventilation defects have not been well studied. Methods: We used positron emission tomography to assess the intrapulmonary kinetics of intravenously infused tracer nitrogen-13 ( 13 NN), and measured the regional distributions of ventilation and perfusion in 11 patients with mild asthma. For each subject, the regional washout kinetics of 13 NN before and during methacholineinduced bronchoconstriction were analyzed. Two regions of interest (ROIs) were defined: one over a spatially contiguous area of high tracer retention (TR) during bronchoconstriction and a second one covering an area of similar size, showing minimal tracer retention (NR). Results: Both ROIs demonstrated heterogeneous washout kinetics, which could be described by a two-compartment model with fast and slow washout rates. We found a systematic reduction in regional Q to the TR ROI during bronchoconstriction and a variable and nonsignificant change in relative Q for NR regions. The reduction in regional Q was associated with an increase in regional gas content of the TR ROI, but its magnitude was greater than that anticipated solely by the change in regional lung inflation. Conclusion: During methacholine-induced bronchoconstriction, perfusion to ventilation defects are systematically reduced by a relative increase in regional pulmonary vascular resistance.Keywords: emission computed tomography; pulmonary gas exchange; vascular resistance; vasoconstriction; ventilation-perfusion ratio It is well established that severe heterogeneity of regional ventilation contributes significantly to gas exchange impairment in asthma. However, the extent to which regional pulmonary perfusion adapts to match changes in ventilation during an asthma attack is unknown. Evidence for severe heterogeneity of regional ventilation in patients with asthma has come from measurements with external scintillation counters (1, 2), single-photon emission computed tomography (CT) of Technegas (3), nuclear magnetic resonance imaging after a single-breath inhalation of hyperpolarized helium (4), and high-resolution CT (5-10). Most of these studies, however, did not quantify regional ventilation during normal breathing and did not evaluate the effect of bronchoconstriction on regional pulmonary perfusion.Changes in regional perfusion during bronchoconstriction (BC) have been measured using technetium ( 99m Tc)-labeled macroaggregated albumin (11,12). In one study, perfusion defects of segmental or smaller size were reported mainly at the periphery of middle or lower lung zones in children with asthma, despite normal chest X-rays, blood gases, and peak expiratory flows (13). That study, however, did not assess whether these perfusion defects corresponded to defects in ventilation. Another study assessed ventilation with krypton ( 81m Kr) gas and perfusion with 99m Tc ...

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) has been proposed to be an epithelial cell receptor for Pseudomonas aeruginosa involved in bacterial internalization and clearance from the lung. We evaluated the role of CFTR in clearing P. aeruginosa from the respiratory tract using transgenic CF mice that carried either the ΔF508 Cftr allele or an allele with a Cftr stop codon (S489X). Intranasal application achieved P. aeruginosa lung infection in inbred C57BL/6 ΔF508 Cftr mice, whereas ΔF508 Cftr and S489X Cftr outbred mice required tracheal application of the inoculum to establish lung infection. CF mice showed significantly less ingestion of LPS-smooth P. aeruginosa by lung cells and significantly greater bacterial lung burdens 4.5 h postinfection than C57BL/6 wild-type mice. Microscopy of infected mouse and rhesus monkey tracheas clearly demonstrated ingestion of P. aeruginosa by epithelial cells in wild-type animals, mostly around injured areas of the epithelium. Desquamating cells loaded with P. aeruginosa could also be seen in these tissues. No difference was found between CF and wild-type mice challenged with an LPS-rough mucoid isolate of P. aeruginosa lacking the CFTR ligand. Thus, transgenic CF mice exhibit decreased clearance of P. aeruginosa and increased bacterial burdens in the lung, substantiating a key role for CFTR-mediated bacterial ingestion in lung clearance of P. aeruginosa.

In order to compare the performance of "all-in-one" magnetic resonance imaging (MRI) and "all-in-one" multidetector computed tomography (MDCT) in the preharvest evaluation 25 potential living donors underwent both MRI and MDCT. MRI was performed on a high-performance 1.5-T scanner, computed tomography (CT) on a 4-row multidetector-scanner. Both scan protocols included angiography of the arterial and venous hepatic systems. CT additionally included infusion of a biliary contrast agent. Data analysis was performed by 4 reviewers, based on source images, multiplanar reformats, and three-dimensional ( L iving donor liver transplantation has evolved into a widely accepted therapeutic option to alleviate the persistent shortage of cadaveric liver transplants. [1][2][3] This innovative procedure allows healthy adults to donate a portion of their liver to compatible recipients suffering from end-stage liver disease. [4][5][6][7] Besides of augmenting the transplant organ pool, living donor liver transplantation involves the advantage of performing an elective operation, access to a graft in best condition, and lowering the likelihood of recipient death while waiting for a suitable organ. 8 In combination with improved surgical technique and highly developed immunosuppression, 9 this results in recipient survival rates as good as those obtained after conventional liver transplantation with full-sized deceased donor organs. 10 The critical issue of this procedure is the risk to the donors, who were healthy until the transplantation; this risk is now estimated to be 0.5% mortality and 21% postoperative morbidity. 1,11,12 To reduce such risk to a minimum, and also to avoid donor-recipient mismatch, the potential donors have to undergo an extensive stepwise evaluation process before being admitted to donation. Special attention is hereby paid to the determination of the liver volumes 13-17 and the recognition of vascular anomalies. [18][19][20] In fact, a majority of the candidates is eliminated mostly due to unfavorable hepatic parenchymal, biliary, or vascular morphology.In the recent past, this preharvest assessment

Immune cells are activated during cellular responses to antigen by two described mechanisms: (i) direct uptake of antigen and (ii) extraction and internalization of membrane components from antigen-presenting cells. Although endocytosis of microbial antigens by pattern recognition molecules (PRM) also activates innate immunity, it is not known whether this involves extraction and internalization of microbial surface components. Epithelial cells on mucosal surfaces use a variety of receptors that are distinct from the classical endocytic PRM to bind and internalize intact microorganisms. Nonclassical receptor molecules theoretically could act as a type of endocytic PRM if these molecules could recognize, bind, extract, and internalize a pathogen-associated molecule and initiate cell signaling. We report here that the interaction between the cystic fibrosis transmembrane conductance regulator (CFTR) and the outer core oligosaccharide of the lipopolysaccharide (LPS) in the outer membrane of Pseudomonas aeruginosa satisfies all of these conditions. P. aeruginosa LPS was specifically recognized and bound by CFTR, extracted from the organism's surface, and endocytosed by epithelial cells, leading to a rapid (5-to 15-min) and dynamic translocation of nuclear transcription factor NF-B. Inhibition of epithelial cell internalization of P. aeruginosa LPS prevented NF-B activation. Cellular activation depended on expression of wild-type CFTR, because both cultured ⌬F508 CFTR human airway epithelial cells and lung epithelial cells of transgenic-CF mice failed to endocytose LPS and translocate NF-B. CFTR serves as a critical endocytic PRM in the lung epithelium, coordinating the effective innate immune response to P. aeruginosa infection.

An MRI examination that consists of a HASTE sequence allows one to detect, exclude, or monitor pulmonary lesions that are 5 mm and bigger. Suspicious lesions smaller than 5 mm still need to be validated using CT.

No abstract