A total of 145 consecutive patients receiving a colorectal anastomosis were randomized to 'test' or 'no test' once the anastomosis had been completed. Anastomotic testing was performed with the pelvis filled with saline and the rectum distended by sigmoidoscopic insufflation of air. Any leaks demonstrated were oversewn. A water-soluble contrast enema was performed on the tenth postoperative day. Seventy-four patients were randomized to 'test' and 71 to 'no test' but one patient was withdrawn from each group leaving a total of 143 for analysis. The two groups were well matched for age, sex, diagnosis and operative details. Eighteen (25 per cent) air leaks were detected and repaired in the 'test' group. After operation there were three (4 per cent) clinical leaks in the 'test' group and ten (14 per cent) in the 'no test' group (Fisher's exact test, P = 0.043). There were eight (11 per cent) radiological leaks in the 'test' group and 20 (29 per cent) in the 'no test' group (P = 0.006). Intraoperative air testing and repair of colorectal anastomoses significantly reduces the risk of postoperative clinical and radiological leaks.
Multiple organ failure is a common mode of death following abdominal aortic aneurysm repair, particularly after rupture. Cytokines are the principal mediators of the inflammatory response to injury and high levels of circulating cytokines have been associated with poor outcome in major trauma and sepsis. Abdominal aortic aneurysm repair results in an ischaemia-reperfusion injury to the tissues distal to the site of aortic clamping. The inflammatory response in these tissues causes the release of cytokines, principally Interleukins 1-beta, 6, and 8, and Tumour Necrosis Factor alpha. If released in large enough concentrations, these cytokines may enter the circulation and gain access to organs distant to the site of initial injury. Circulating cytokines cause dysfunction of the renal, cardiovascular, respiratory, nervous and musculo-skeletal systems. The combination of these individual changes in organ function is the multiple-organ dysfunction syndrome, which may progress to multiple organ failure.
Background: The optimal surgical management of patients in end stage chronic renal failure with secondary hyperparathyroidism is controversial. One approach advocated is four gland parathyroidectomy without reimplantation. The aim of this study was to review the medium term results of this procedure. Methods: Fifty four consecutive patients with end stage chronic renal failure and secondary hyperparathyroidism who had a four gland parathyroidectomy without reimplantation were studied. The procedure was performed by a single surgeon with a median (range) follow up of 29 (0-70) months. Results: Most patients (76%) developed postoperative hypocalcaemia but this was easily treated and doses of long term drugs necessary to prevent this were low. Pre-operative bone symptoms, hypercalcaemia, hyperphosphataemia, and an increased alkaline phosphatase were improved or resolved in most patients. Thirteen (24%) patients had an undetectable postoperative parathyroid hormone (PTH), (6 of 12 (50%) with a functioning renal transplant and 7 of 42 (17%) who required dialysis, p = 0.02). Median (range) postoperative PTH values in these groups were 0.1 (0.1-31) compared with 1.0 (0.1-24) pmol/l (p = 0.085) respectively. The remaining 41 of 54 (76%) patients had residual PTH secretion and postoperative hyperparathyroidism was identified in eight (15%) patients with only two requiring neck reexploration. Conclusion: Four gland parathyroidectomy without reimplantation produced good medium term biochemical and clinical results. Most patients had minor residual PTH secretion that may contribute to this and mitigate concerns regarding adynamic bone disease. Endogenous PTH secretion is only completely lost in a few patients but occurs more often in those with a functioning renal transplant. Bone densitometry is required to investigate the long term impact of this procedure.
Aims/hypothesisRapamycin (sirolimus) is one of the primary immunosuppressants for islet transplantation. Yet there is evidence that the long-term treatment of islet-transplant patients with rapamycin may be responsible for subsequent loss of islet graft function and viability. Therefore, the primary objective of this study was to elucidate the molecular mechanism of rapamycin toxicity in beta cells.MethodsExperiments were performed on isolated rat and human islets of Langerhans and MIN6 cells. The effects of rapamycin and the roles of mammalian target of rapamycin complex 2 (mTORC2)/protein kinase B (PKB) on beta cell signalling, function and viability were investigated using cell viability assays, insulin ELISA assays, kinase assays, western blotting, pharmacological inhibitors, small interfering (si)RNA and through the overproduction of a constitutively active mutant of PKB.ResultsRapamycin treatment of MIN6 cells and islets of Langerhans resulted in a loss of cell function and viability. Although rapamycin acutely inhibited mTOR complex 1 (mTORC1), the toxic effects of rapamycin were more closely correlated to the dissociation and inactivation of mTORC2 and the inhibition of PKB. Indeed, the overproduction of constitutively active PKB protected islets from rapamycin toxicity whereas the inhibition of PKB led to a loss of cell viability. Moreover, the selective inactivation of mTORC2 using siRNA directed towards rapamycin-insensitive companion of target of rapamycin (RICTOR), mimicked the toxic effects of chronic rapamycin treatment.Conclusions/interpretationThis report provides evidence that rapamycin toxicity is mediated by the inactivation of mTORC2 and the inhibition of PKB and thus reveals the molecular basis of rapamycin toxicity and the essential role of mTORC2 in maintaining beta cell function and survival.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-012-2475-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
In high-risk patients the autologous transposed brachiobasilic fistula has equivalent patency and lower complication rates than those reported for polytetrafluoroethylene interposition grafts.
: Hydrogen sulphide ameliorated the renal dysfunction associated with ischaemic damage, and has potential as a therapy against IR injury in NHB donor kidney transplantation.
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