Phosphorylation of murine double minute-2 on Ser166 is downstream of VEGF-A in exercised skeletal muscle and regulates primary endothelial cell migration and FoxO gene expression.

We demonstrated in a previous study that murine double minute (Mdm)-2 is essential for exercise-induced skeletal muscle angiogenesis. In the current study, we investigated the mechanisms that regulate Mdm2 activity in response to acute exercise and identified VEGF-A as a key stimulator of Mdm2 phosphorylation on Ser(166) (p-Ser166-Mdm2). VEGF-A and p-Ser166-Mdm2 protein levels were measured in human and rodent muscle biopsy specimens after 1 bout of exercise. VEGF-A-dependent Mdm2 phosphorylation was demonstrated in vivo in mice harboring myofiber-specific deletion of VEGF-A (mVEGF(-/-)) and in vitro in primary human and rodent endothelial cells (ECs). Exercise increased VEGF-A and p-Ser166-Mdm2 protein levels respectively by 157 and 68% in human muscle vs. pre-exercise levels. Similar results were observed in exercised rodent muscles compared to sedentary controls; however, exercise-induced Mdm2 phosphorylation was significantly attenuated in mVEGF(-/-) mice. Recombinant VEGF-A elevated p-Ser166-Mdm2 by 50-125% and stimulated migration by 33% in ECs when compared to untreated cells, whereas the Mdm2 antagonist Nutlin-3a abrogated VEGF-driven EC migration. Finally, overexpression of a Ser166-Mdm2 phosphorylation mimetic increased EC migration, increased Mdm2 to FoxO1 binding (+55%), and decreased FoxO1-dependent gene expression compared with ECs overexpressing WT-Mdm2. Our results suggest that VEGF-mediated Mdm2 phosphorylation on Ser(166) is a novel proangiogenic pathway within the skeletal muscle.

Impact of previous abdominal surgery on robot-assisted radical cystectomy.

OBJECTIVE: We analyzed the effect of previous abdominal surgery (PAS) on consecutive patients who underwent robot-assisted radical cystectomy (RARC). MATERIALS AND METHODS: From 2005 to 2008, 73 patients at a single institution underwent RARC with bilateral extended pelvic lymph node dissection and urinary diversion. Lysis of adhesions was performed robotically and laparoscopically. Records were reviewed to assess the impact of PAS on operative outcomes and complications up to 3 months after surgery. RESULTS: Of the 73 patients, 37 (51%) had undergone PAS. Of these 37, 6 (16%) had PAS above the umbilicus, and 31 (84%) had surgery either above and below or strictly below the umbilicus. Patients with PAS were significantly older than those without (P<0.01). No statistically significant difference was seen with respect to blood loss, transfusion requirement, operative time, lysis of adhesion time, length of ICU stay, overall hospital stay, or the need for reoperation between patients with PAS and those without PAS. The overall postoperative complication rate was higher in the group with PAS (P=0.04). Lymph node yield was higher in patients without PAS (P<0.01). Patients with PAS below the umbilicus had a significantly longer hospital stay than patients with surgery strictly above the umbilicus had (P=0.01). Whether individuals had previously undergone single or multiple surgeries had no significance. CONCLUSION: Robot-assisted radical cystectomy in patients with a history of previous surgery may carry a higher risk for postoperative complications. However, previous operations do not appear to affect the likelihood of a safely completed robotic operation. Patients should be counseled about their risk of obstacles after surgery.

Sacral Neuromodulation for Bladder Atony - A Case Report.

In most cases, sacral neuromodulation is used as a treatment for urge incontinence and symptoms of urgency and frequency. It is most used in those who are refractory to traditional management. It is much less common to be used for bladder atony. In this report, we present a case of a 24-year-old woman with a history of urinary retention and bladder atony who failed medical management and subsequently had an InterStim sacral neuromodulator implanted. After implantation, she was able to discontinue intermittent catheterization and had a decrease in her postvoid residual from 848 to 72 mL.

Case Report: Successful Staged Ureteroscopic Treatment of a 5 cm Staghorn Renal Calculus.

It is widely accepted that percutaneous nephrostolithotorny (PCNL) is the standard of choice for the removal of large staghorn renal calculi. Although data exists supporting a stagad ureteroscopic as an alternate treatment for stones up to 3 cm in select patients, little data exists to support a ureteroscopic approach for stones as large as 5 cm. We present a case of a 68 year old female with a 5 cm staghorn renal calculus managed successfully with a staged ureteroscopic approach. A staged ureteroscopic approach can be effective in treating stones as large as 5 cm.