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.
Mean BP is lower with 1-piece cuffs vs. 2-piece cuffs. Differences are greater with oscillometry. When performing validation studies and measurements for clinical purposes, cuff type should be taken into account.
Background: Effi cient islet isolation is dependent on specifi c digestion with collagenase of the extra-cellular matrix (ECM) within the islet-exocrine interface of the human pancreas. Islets yields from young donors (<30 years) are usually insuffi cient for transplantation, although these islets would potentially provide better physiological function than those from older donors. The reason for the poor yields is unknown. In this study, we used a novel assay to compare collagenase digestion of two principle components of the ECM of the isletexocrine interface in young and old donors. Methods: With appropriate consent and ethical approval, human pancreata were retrieved from 5 young donors (aged 19-28 years) and 6 old donors (aged 45-60 years). Cold ischaemia time was <10 hours. Tissue blocks (~0.5 cm3) were snap-frozen in liquid N2. Specimens were cryo-sectioned onto slides at 10-15-ƒÝM thickness and stored at -25oC. Specimens were thawed and incubated ¡ÓLiberase at 1.4mg/mL in HBSS for 5 min. at 37oC. Digestion of the ECM within the islet-exocrine interface was analysed by double immunolabelling for insulin and Collagen V or VI and semi-quantifi ed by morphometry using image analysis (Zeiss KS-400). A mean number of 13¡Ó1 and 15¡Ó1 islets were assessed in control or Liberase-treated sections respectively. Data were expressed as area of collagen sub-type/ islet area. Statistical analysis was by Mann-Whitney U-test. Results: After 5 minutes incubation, Liberase had begun to digest the exocrine tissue although islets within the specimen were unaffected. The mean islet area was unchanged in specimens from young (14572¡Ó2400 vs 12698¡Ó1604 ƒÝm2 in untreated) and old (11881¡Ó1095 vs 12541¡Ó806 ƒÝm2 in untreated) donors. In contrast ECM components were undergoing digestion. Peri-islet Collagen V content in young and old donors was signifi cantly reduced by 34% (from 0.210¡Ó0.022 to0.138¡Ó0.014 /islet area) and by 35% (from 0.235¡Ó0.024 to 0.153¡Ó0.007/islet area) respectively by Liberase treatment. Similarly peri-islet Collagen VI content in young and old donors was signifi cantly reduced by 29% (from 0.298¡Ó0.017 to 0.213¡Ó0.022/islet area) and by 34% (from 0.322¡Ó0.015 to 0.212¡Ó0.011/islet area) respectively. Collagen VI remained signifi cantly higher (p<0.05) than Collagen V in specimens from both young and old donors. Conclusions: Collagenase digestion of peri-insular Collagen V and VI within the pancreas of young donors is not impaired. These data suggest that inadequate digestion of these components of the peri-insular ECM is not the reason for poor islet yields from young donors. We are currently investigating the digestion of other components of the ECM in young donors.
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