Ingraft chimerism in lung transplantation - a study in a porcine model of obliterative bronchiolitis

<p>Abstract</p> <p>Background</p> <p>Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB). Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs.</p> <p>Methods</p> <p>A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E) was assessed and the fluorescence in situ hybridization (FISH) method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors.</p> <p>Results</p> <p>Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (<it>R </it>= 0.610 - 0.671 and <it>p </it>< 0.05) and of obliteration of the bronchial lumen (<it>R </it>= 0.698 and <it>p </it>< 0.01). All allografts with preserved epithelium showed epithelial chimerism throughout the follow-up. Antirejection medication did not prevent, but delayed the appearance of Y chromosome positive cells in the epithelium (<it>p </it>< 0.05), or bronchial wall (<it>p </it>< 0.05).</p> <p>Conclusions</p> <p>In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.</p

Phase II study of gemcitabine and vindesine in patients with previously untreated non-resectable non-small-cell lung cancer

Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m−2 was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m−2 was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3–4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3–4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9–36%). Median response duration was 31 weeks (range 11–83 weeks) and median survival time 31 weeks (range 2–171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity. © 1999 Cancer Research Campaig

Lattice Thermal Boundary Resistance

Control and modelling of thermal transport at the nanoscale has emerged either as a key issue in modern nanoscience or as a compelling demand for the ever- increasing miniaturization process in information technologies: here the thermal budget of nanodevices is basically ruled over by heat exchanges across interfaces, and the relevant physics is cast in terms of a thermal boundary resistance. In this chapter, we present a unified discussion about the fundamental knowledge developed in this framework. Starting from the most general thermodynamical description of an interface, where the driving force for heat transport is identified together with the actual location and thickness of the interface itself, we define what the thermal boundary resistance is in fact. We then delve into the most successful modelling approaches, based either on the phonon picture or on the atomistic picture. Adopting different assumptions and employing different implementation strategies, they offer a complementary description of the physi- cal mechanisms underlying thermal boundary resistance, and they provide useful computational protocols to predict its value in realistic systems