Errol L. Bush

Chronic Aspiration of Gastric Fluid Induces the Development of Obliterative Bronchiolitis in Rat Lung Transplants

Long‐term survival of a pulmonary allograft is currently hampered by obliterative bronchiolitis (OB), a form of chronic rejection that is unique to lung transplantation. While tracheobronchial aspiration from gastroesophageal reflux disease (GERD) has clinically been associated with OB, no experimental model exists to investigate this problem. Using a WKY‐to‐F344 rat orthotopic left lung transplant model, the effects of chronic aspiration on pulmonary allograft were evaluated. Recipients received cyclosporine with or without 8 weekly aspirations of gastric fluid into the allograft. Six (66.7%) of 9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy, consistent with the development of OB. In contrast, none of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002). Of the grafts examined grossly, 83% of the allografts with chronic aspiration but only 20% without aspiration appeared consolidated (p = 0.013). Aspiration was associated with increased levels of IL‐1α, IL‐1β, IL‐6, IL‐10, TNF‐α and TGF‐β in BAL and of IL‐1α, IL‐4 and GM‐CSF in serum. This study provides experimental evidence linking chronic aspiration to the development of OB and suggests that strategies aimed at preventing aspiration‐related injuries might improve outcomes in clinical lung transplantation.

Biofilms in the normal human large bowel: fact rather than fiction

1 Van der Bij AK, Spaargaren J, Morre SA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case–control study. Clin Infect Dis 2006;42:186–94. 2 Spaargaren J, Fennema JS, Morre SA, et al. New lymphogranuloma venereum Chlamydia trachomatis variant, Amsterdam. Emerg Infect Dis 2005;11:1090–2. 3 Ward H, Martin I, Macdonald N, et al. Lymphogranuloma venereum in the United Kingdom. Clin Infect Dis 2007;44:26–32. 4 Loomis WP, Starnbach MN. T cell responses to Chlamydia trachomatis. Curr Opin Microbiol 2002;5:87–91. 5 James SP, Graeff AS, Zeitz M, et al. Cytotoxic and immunoregulatory function of intestinal lymphocytes in Chlamydia trachomatis proctitis of nonhuman primates. Infect Immun 1987;55:1137–43. 6 Zeitz M, Quinn TC, Graeff AS, et al. Mucosal T cells provide helper function but do not proliferate when stimulated by specific antigen in lymphogranuloma venereum proctitis in nonhuman primates. Gastroenterology 1988;94:353–66. 7 Morre SA, Spaargaren J, Fennema JS, et al. Realtime polymerase chain reaction to diagnose lymphogranuloma venereum. Emerg Infect Dis 2005;11:1311–12. 8 Morre SA, Ossewaarde JM, Lan J, et al. Serotyping and genotyping of genital Chlamydia trachomatis isolates reveal variants of serovars Ba, G, and J as confirmed by omp1 nucleotide sequence analysis. J Clin Microbiol 1998;36:345–51. 9 Brenchley JM, Price DA, Douek DC. HIV disease: fallout from a mucosal catastrophe? Nat Immunol 2006;7:235–9.

Coagulopathy in α‐galactosyl transferase knockout pulmonary xenotransplants

Bush EL, Barbas AS, Holzknecht ZE, Byrne GW, McGregor CG, Parker W, Duane Davis R, Lin SS. Coagulopathy in α‐galactosyl transferase knockout pulmonary xenotransplants. Xenotransplantation 2011; 18: 6–13.

Stabilization of Patients Presenting with Upper Gastrointestinal Bleeding

Paleopathological evidence and descriptions of upper gastrointestinal bleeds (UGIB), i.e., proximal to the ligament of Treitz, are limited and sometimes inconclusive. The earliest potential reference to UGIB can be traced to the Ebers Papyrus (circa 1550 BC) describing a “blood-nest” in a patient who acutely turned pale and later expired (Brothwell DR, Sandison AT. Diseases in antiquity: a survey of the diseases, injuries, and surgery of early populations. Springfield, Ill.: Thomas; 1967. xix, 766 p.). A more conclusive familiarity of peptic ulcer pathology was noted by Roman scientists during the first century and thus we know that UGIB have been known for at least 2000 years (Majno G. The healing hand: man and wound in the ancient world. Cambridge, MA: Harvard University Press; 1975. xxiii, 571 p., 6 leaves of plates p.). Risk factors for UGIB were most likely omnipresent and, as such, suffering from UGIB has more than likely always plagued humans.

Xenotransplantation of thoracic organs

Purpose of reviewWhile clinical allotransplantation is the preferred method of providing replacement organs for people with end-stage heart and lung disease, this procedure, under current donation rates, cannot supply the required demands. Thoracic organ xenotransplantation has been considered a reasonable solution to the donor crisis, but it is still a field incapable of producing grafts that are capable of surviving and functioning long enough to be clinically meaningful. To some, the barriers may seem to be insurmountable. Given the advances made over the past few years, however, successful thoracic organ xenotransplantation could become a reality in the near future. Here we review many of the important advances that have been reported recently. Recent findingsThe roles and the interactions of the immune, coagulation, and complement systems have been investigated. The development of transgenic and knockout pigs has only begun to help further elucidate these roles and interactions, instead of providing a quick solution as some may have previously hoped. SummarySignificant barriers to successful xenotransplantation still exist, but if we continue to pool academic, governmental, and industrial resources, we can overcome these barriers and help make clinical xenotransplantation a reality in the near future.