Objective. The aims of this prospective study were to determine the bowel function and the anal sphincter function in women with urinary stress incontinence by means of anorectal manometry and to ...look for manometric variables which could predict the development of surgery demanding genital prolapse after Burch colposuspension.
Subjects. During 1991-1992 twenty-one women with urodynamicaiiy proven genuine stress urinary incontinence were consecutively operated upon with the Burch colposuspension. No concomitant prolapse repair surgery was performed. Forty-four healthy subjects without anorectal disorders were used as controls.
Methods. All subjects were investigated with anorectal manometry using a microtransducer catheter. A standardized questionnaire concerning bowel function was answered at interview. The manometry and interview were performed preoperatively and one year after the Burch colposuspension.
Results. According to the preoperative questionnaire, fecal incontinence was found in 62%, constipation in 38% and straining at defecation in 71%. There were no significant differences in any of the manometric parameters between the preoperative and the one-year postoperative assessment. The patients with prolapse operations after the colposuspension (n = 6) had a significanth lower anal squeeze pressure area (p = 0.029) preoperatively compared to the control subjects. The patients without prolapse surgery (n = 15) did not differ in manometric parameters from the control subjects.
Conclusion. Bowel dysfunction is common in women with stress urinary incontinence. The women with low anal squeeze pressure area preoperatively are at risk for the development of genital prolapse after Burch colposuspension.
Over the past decade efforts have been made to develop less invasive surgical treatment for female stress urinary incontinence (SUI). Abdominal urethrocystopexy with fibrin sealant combined with a ...couple of absorbable sutures has previously been reported as a promising method. This prospective observational study was aimed at evaluating the efficacy and safety of abdominal urethrocystopexy through a minilaparotomy using solely fibrin sealant (Tisseel) as the fixation glue. Forty-three women with objectively proven SUI were operated upon with this method. The subjective cure rates at 1 and 3 years' follow-up were 72% and 55%, respectively. The corresponding objective cure rates were 64% and 60%. No serious major operative complications occurred. One patient had transient urinary retention for 3 months. Otherwise, micturition was established within a median 1 day (range 1-3 days) after the operation. The result of this pilot study indicates a cure rate lower than that obtained with the conventional abdominal Burch colposuspension. Thus the method cannot be recommended as a standard procedure for treatment of SUI.
The insulin receptor substrate-1 (IRS1) is phosphorylated on serine 307 (human sequence, corresponding to murine serine 302) in response to insulin as part of a feedback loop that controls IRS1 ...phosphorylation on tyrosine residues by the insulin receptor. This in turn directly affects downstream signaling and is in human adipocytes implicated in the pathogenesis of insulin resistance and type 2 diabetes. The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). The mTORC1-downstream p70 ribosomal protein S6 kinase (S6K1), which is activated by insulin, can phosphorylate IRS1 at serine 307 in vitro and is considered the physiological protein kinase. Because the IRS1 serine 307-kinase catalyzes a critical step in the control of insulin signaling and constitutes a potential target for treatment of insulin resistance, it is important to know whether S6K1 is the physiological serine 307-kinase or not. We report that, by several criteria, S6K1 does not phosphorylate IRS1 at serine 307 in response to insulin in intact human primary adipocytes: (i) The time-courses for phosphorylation of S6K1 and its phosphorylation of S6 are not compatible with the phosphorylation of IRS1 at serine 307; (ii) A dominant-negative construct of S6K1 inhibits the phosphorylation of S6, without effect on the phosphorylation of IRS1 at serine 307; (iii) The specific inhibitor of S6K1 PF-4708671 inhibits the phosphorylation of S6, without effect on phosphorylation of IRS1 at serine 307. mTOR-immunoprecipitates from insulin-stimulated adipocytes contains an unidentified protein kinase specific for phosphorylation of IRS1 at serine 307, but it is not mTOR or S6K1.
Funding Agencies|Swedish Diabetes Fund||Novo Nordic Foundation||University of Linkoping||Swedish Research Council||
