Continuous Subcutaneous Insulin Infusion (CSII) is superior to conventional insulin therapy as it improves glycemic control thus reducing the probability of diabetic complications. Notwithstanding CSII's benefits, insulin dependent diabetic patients rarely achieve optimal glucose control. Moreover, CSII is only FDA approved for 3 days and often fails prematurely for reasons that have not been fully elucidated. We hypothesize that phenolic compounds, such as m‐cresol and phenol, which are present in all commercial insulin formulations are responsible for the tissue reaction occurring at the insulin infusion site. This hypothesis was examined with in vitro cell cultures and a mouse air‐pouch model to determine cellular and tissue reactions following infusions with saline, phenolic compounds, (i.e., commercial diluent), and insulin. We demonstrated that diluent and insulin were cytotoxic to cells in culture at sub‐clinical concentrations (e.g., >1:10 of commercial insulin). Air pouch studies demonstrated that infusion of either diluted insulin or diluent itself induced three to five‐fold level of recruited leukocytes as compared to saline. At both 3‐ and 7‐days post infusion, these were predominantly neutrophils and macrophages. We conclude that phenolic compounds in commercial insulin preparations are cell and tissue toxic, which contributes to the failure of effective insulin infusion therapy.
This study showed that knot security depends on suture material, tying technique, and number of throws, but is independent of suture size. Surgeon's knot security was greater than that for square and sliding knots when using sutures commonly used in the oral cavity. Vicryl had the greatest knot security and silk had the least. For surgeon's and square knots, at least 4 throws were generally indicated to achieve knot security; for sliding knots, at least 5 throws were generally indicated. Knot security did not increase after 5 throws and 2 throws are never indicated.
Mutations in the liver glycogen phosphorylase (Pygl) gene are associated with the diagnosis of glycogen storage disease type VI (GSD‐VI). To understand the pathogenesis of GSD‐VI, we generated a mouse model with Pygl deficiency (Pygl−/−). Pygl−/− mice exhibit hepatomegaly, excessive hepatic glycogen accumulation, and low hepatic free glucose along with lower fasting blood glucose levels and elevated blood ketone bodies. Hepatic glycogen accumulation in Pygl−/− mice increases with age. Masson's trichrome and picrosirius red staining revealed minimal to mild collagen deposition in periportal, subcapsular, and/or perisinusoidal areas in the livers of old Pygl−/− mice (>40 weeks). Consistently, immunohistochemical analysis showed the number of cells positive for alpha smooth muscle actin (α‐SMA), a marker of activated hepatic stellate cells, was increased in the livers of old Pygl−/− mice compared with those of age‐matched wild‐type (WT) mice. Furthermore, old Pygl−/− mice had inflammatory infiltrates associated with hepatic vessels in their livers along with up‐regulated hepatic messenger RNA levels of C‐C chemokine ligand 5 (Ccl5/Rantes) and monocyte chemoattractant protein 1 (Mcp‐1), indicating inflammation, while age‐matched WT mice did not. Serum levels of aspartate aminotransferase and alanine aminotransferase were elevated in old Pygl−/− mice, indicating liver damage. Conclusion: Pygl deficiency results in progressive accumulation of hepatic glycogen with age and liver damage, inflammation, and collagen deposition, which can increase the risk of liver fibrosis. Collectively, the Pygl‐deficient mouse recapitulates clinical features in patients with GSD‐VI and provides a model to elucidate the mechanisms underlying hepatic complications associated with defective glycogen metabolism.
Postoperative complications did not increase significantly in the combined phacoemulsification and vitreoretinal surgery. Combined vitreoretinal surgery and phacoemulsification with foldable IOL implantation is safe and effective in treating vitreoretinal abnormalities coexisting with cataract. Based on extensive experience with the combined procedure, the authors suggest that combined surgery is recommended in select patients having simultaneous vitreoretinal pathologic changes and cataract.
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