Pancreatic islet transplantation has the potential to be an effective treatment for type 1 diabetes mellitus. While recent improvements have improved 1-year outcomes, follow-up studies show a persistent loss of graft function/survival over 5 years. One possible cause of islet transplant failure is the immunosuppressant regimen required to prevent alloimmune graft rejection. Although there is evidence from separate studies, mostly in rodents and cell lines, that FK506 (tacrolimus), rapamycin (sirolimus), and mycophenolate mofetil (MMF; CellCept) can damage pancreatic beta-cells, there have been few side-by-side, multiparameter comparisons of the effects of these drugs on human islets. In the present study, we show that 24-h exposure to FK506 or MMF impairs glucose-stimulated insulin secretion in human islets. FK506 had acute and direct effects on insulin exocytosis, whereas MMF did not. FK506, but not MMF, impaired human islet graft function in diabetic NOD*scid mice. All of the immunosuppressants tested in vitro increased caspase-3 cleavage and caspase-3 activity, whereas MMF induced ER-stress to the greatest degree. Treating human islets with the GLP-1 agonist exenatide ameliorated the immunosuppressant-induced defects in glucose-stimulated insulin release. Together, our results demonstrate that immunosuppressants impair human beta-cell function and survival, and that these defects can be circumvented to a certain extent with exenatide treatment.
J-tubes are associated with higher complication rates requiring tube replacement compared with PEG tubes. The main causes of J-tube replacement are dislodgement and obstruction.
In a recent quality assurance project we learned that nearly half of the handovers we examined were characterized as unsatisfactory by our residents, who provided examples in which their anxiety had been piqued and patient care had been affected. These reports substantiated a growing body of literature on the relationship between the quality of handover and the quality of patient care, so we sought to improve the quality and consistency of the in-hosptial handovers undertaken by our internal medicine residents. Senior residents attended morning report for three consecutive month long blocks and evaluated the quality of the handovers using an observational protocol comprised of 16 aspects of effective handover.During the first block, the resident observed a median of eight of the 16 practices occurring across the 46 handovers, and a large amount of variability. At the beginning of the subsequent block we presented a concise introduction to a structured handover procedure (SBARR). The median quality of the subsequent 33 handovers rose to 11, and the variability decreased considerably. In the next block we refined the SBARR orientation to focus on the errors observed in the previous blocks, and the improvement in the quality and variability was sustained. The minor change, which requires few resources to sustain, had a favourable impact on the quality of our residents' in-hospital handovers.
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