Despite an initial decrease in complications soon after continent catheterizable channel creation, late problems appeared on long-term evaluation. In our experience no specific factor predicted the likelihood of complications. Nevertheless, despite the need for surgical revision, good functional outcomes were evidenced in this series.
Maladaptive bladder muscle overgrowth and de-differentiation in human bladder obstructive conditions is instigated by coordinate responses to three stimuli: mechanical strain , tissue hypoxia , and extracellular matrix remodeling.1 ,2 Pathway analysis of genes induced by obstructive models of injury in bladder smooth muscle cells (BSMCs) identified a mammalian target of rapamycin (mTOR)-specific inhibitor as a potential pharmacological inhibitor. Strain-induced mTOR-specific S6K activation segregated differently from ERK1/2 activation in intact bladder ex vivo. Though rapamycin's antiproliferative effects in vascular smooth muscle cells are well known , its effects on BSMCs were previously unknown. Rapamycin significantly inhibited proliferation of BSMCs in response to mechanical strain , hypoxia , and denatured collagen. Rapamycin inhibited S6K at mTOR-sensitive phosphorylation sites in response to strain and hypoxia. Rapamycin also supported smooth muscle actin expression in response to strain or hypoxia-induced de-differentiation. Importantly , strain plus hypoxia synergistically augmented mTOR-dependent S6K activation , Mmp7 expression and proliferation. Forced expression of wild-type and constitutively active S6K resulted in loss of smooth muscle actin expression. Decreased smooth muscle actin , increased Mmp7 levels and mTOR pathway activation during in vivo partial bladder obstruction paralleled our in vitro studies. These results point to a coordinate role for mTOR in BSMCs responses to the three stimuli and a potential new therapeutic target for myopathic bladder disease.
These data describe the level of decisional conflict in couples agreeing to proceed with hypospadias repair, with no evidence of significant discrepancy between them. The novel description of factors related to decreased decisional conflict might help focus efforts aimed at minimizing difficulties encountered during the decision making process.
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