Cell transplantation after oxidative hepatic preconditioning with radiation and ischemia–reperfusion leads to extensive liver repopulation

The inability of transplanted cells to proliferate in the normal liver hampers cell therapy. We considered that oxidative hepatic DNA damage would impair the survival of native cells and promote proliferation in transplanted cells. Dipeptidyl peptidase-deficient F344 rats were preconditioned with whole liver radiation and warm ischemia–reperfusion followed by intrasplenic transplantation of syngeneic F344 rat hepatocytes. The preconditioning was well tolerated, although serum aminotransferase levels rose transiently and hepatic injury was observed histologically, along with decreased catalase activity and 8-hydroxy adducts of guanine, indicating oxidative DNA damage. Transplanted cells did not proliferate in the liver over 3 months in control animals and animals preconditioned with ischemia–reperfusion alone. Animals treated with radiation alone showed some transplanted cell proliferation. In contrast, the liver of animals preconditioned with radiation plus ischemia–reperfusion was replaced virtually completely over 3 months. Transplanted cells integrated in the liver parenchyma and liver architecture were preserved normally. These findings offer a paradigm for repopulating the liver with transplanted cells. Progressive loss of cells experiencing oxidative DNA damage after radiation and ischemia–reperfusion injury could be of significance for epithelial renewal in additional organs

Use of the bougie in simulated difficult intubation. 1. Comparison of the single-use bougie with the fibrescope.

We studied the success rates for tracheal intubation in 64 healthy patients during simulated grade III laryngoscopy after induction of anaesthesia, using either the single-use bougie or oral flexible intubating fibrescope, both in conjunction with conventional Macintosh laryngoscopy. Patients were randomly allocated to either simulated grade IIIa or grade IIIb laryngoscopy, and also to one of the two study devices. Success rates for tracheal intubation (primary outcome measure) and times taken to achieve intubation (secondary outcome measure) were recorded. For the simulated grade IIIa laryngoscopy group, the fibreoptic scope was more successful than the bougie (16/16 successful intubations vs. 8/16; p = 0.02). For the simulated grade IIIb laryngoscopy group, the fibreoptic scope was also more successful than the bougie (8/16 successful intubations vs. 1/16; p = 0.02), but clearly use of the fibreoptic scope was not as successful as it had been in simulated grade IIIa laryngoscopy (p = 0.04). With either device, median (range) total tracheal intubation times for successful attempts with either grade of laryngoscopy were less than 60 s (19-109) and there were no clinically important differences. We conclude that the fibrescope used in conjunction with Macintosh laryngoscopy is a more reliable method of tracheal intubation than the single-use bougie in both types of grade III laryngoscopy. This finding has implications for the management of patients in whom grade III laryngoscopy is encountered unexpectedly after induction of anaesthesia, and also for the management of patients previously known to have grade III view at laryngoscopy