Surgical prostate resection using Aquablation showed noninferior symptom relief compared to transurethral prostate resection but with a lower risk of sexual dysfunction. Larger prostates (50 to 80 ml) demonstrated a more pronounced superior safety and efficacy benefit. Longer term followup would help assess the clinical value of Aquablation.

The muscarinic receptor subtype-activated signal transduction mechanisms mediating rat urinary bladder contraction are incompletely understood. M 3 mediates normal rat bladder contractions; however, the M 2 receptor subtype has a more dominant role in contractions of the hypertrophied bladder. Normal bladder muscle strips were exposed to inhibitors of enzymes thought to be involved in signal transduction in vitro followed by a single cumulative concentration-response curve to the muscarinic receptor agonist carbachol. The outcome measures were the maximal contraction, the potency of carbachol, and the affinity of the M 3 -selective antimuscarinic agent darifenacin for inhibition of contraction. Inhibition of phosphoinositide-specific phospholipase C (PI-PLC) with 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine (ET-18-OCH 3 ) reduces carbachol potency and reduces darifenacin affinity, whereas inhibition of phosphatidyl choline-specific phospholipase C (PC-PLC) with O-tricyclo [5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt (D609) attenuates the carbachol maximal contraction. Inhibition of rho kinase with (R)-(ϩ)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride (Y-27632) reduces carbachol potency and increases darifenacin affinity. Inhibition of rho kinase, protein kinase A (PKA), and protein kinase G (PKG) with 1-(5-isoquinolinesulfonyl)-homopiperazine⅐HCl (HA-1077) reduces the carbachol maximal contraction, carbachol potency, and darifenacin affinity. Inhibition of protein kinase C (PKC) with chelerythrine increases darifenacin affinity, whereas inhibition of rho kinase, PKA, PKG, and PKC with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine⅐2HCl (H7) reduces the carbachol maximum and carbachol potency while increasing darifenacin affinity. Inhibition of rho kinase, PKA, and PKG with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide⅐2HCl (H89) reduces carbachol maximum and carbachol potency. Both the M 2 and the M 3 receptor subtype are involved in normal rat bladder contractions. The M 3 subtype seems to mediate contraction by activation of PI-PLC, PC-PLC, and PKA, whereas the M 2 signal transduction cascade may include activation of rho kinase, PKC, and an additional contractile signal transduction mechanism independent of rho kinase or PKC.Pharmacological data, based on the actions of subtypeselective antimuscarinic agents, can distinguish four subtypes of muscarinic acetylcholine receptors (M 1 -M 4 ). Molecular techniques have identified five muscarinic receptor subtypes (M 1 -M 5 ) arising from five separate genes (Caulfield, 1993). Both M 2 and M 3 muscarinic receptor subtypes are found in most smooth muscles. The M 2 receptor preferentially couples to the inhibition of adenylyl cyclase through the G i family of proteins, whereas the M 3 receptor preferentially couples to IP 3 generation and calcium mobilization through the G q family of proteins (Caulfield, 1993). Pertussis toxin, which ADP ribosylates and therefore inactivates the G i family of protei...

Normal rat bladder contractions are mediated by the M 3 muscarinic receptor subtype. The M 2 receptor subtype mediates contractions of the denervated, hypertrophied bladder. This study determined signal transduction mechanisms mediating contraction of the denervated rat bladder. Denervated bladder muscle strips were exposed to inhibitors of enzymes thought to be involved in signal transduction in vitro followed by a cumulative carbachol concentration-response curve. Outcome measures were the maximal contraction, the potency of carbachol, and the affinity of darifenacin for inhibition of contraction. Inhibition of phosphoinositide-specific phospholipase C (PI-PLC) with 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine (ET-18-OCH 3 ) has no effect on denervated bladder contractions, whereas inhibition of phosphatidyl choline-specific phospholipase C (PC-PLC) with O-tricyclo[5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt (D609) attenuates the carbachol maximum and potency. Inhibition of rho kinase with (R)-(ϩ)- trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamidedihydrochloride (Y-27632) reduces carbachol maximum, carbachol potency, and increases darifenacin affinity. Inhibition of rho kinase, protein kinase A (PKA), and protein kinase G (PKG) with 1-(5-isoquinolinesulfonyl)-homopiperazine⅐HCl (HA-1077) reduces the carbachol maximum and potency. Inhibition of PKC with chelerythrine increases darifenacin affinity, whereas inhibition of rho kinase, PKA, PKG, and protein kinase C (PKC) with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine⅐2HCl (H7) reduces the carbachol potency while increasing darifenacin affinity. Inhibition of rho kinase, PKA, and PKG with N-[2-(pbromocinnamylamino)ethyl]-5-isoquinolinesulfonamide⅐2HCl (H89) increases darifenacin affinity. This study demonstrates that different signal transduction mechanisms mediate the contractile response in the denervated rat bladder than in normal rat bladder. In normal rat bladder, PI-PLC and PC-PLC mediate the contraction, but in denervated bladder only PC-PLC is involved. In the denervated bladder, the rho kinase pathway is more dominant than in normal bladders. PKA seems to mediate a contractile response in normal bladders, whereas it seems to inhibit contraction in denervated bladders.The affinity of subtype-selective muscarinic receptor antagonist drugs indicates that contraction is mediated by the M 3 receptor in most smooth muscles under normal conditions (Caulfield, 1993;Caulfield and Birdsall, 1998). However, direct M 2 -mediated contractile response to muscarinic agonist has been shown for cat esophageal smooth muscle cells . In contrast, cells isolated from the cat lower esophageal sphincter (LES) circular smooth muscle, like urinary bladder smooth muscle, are inhibited from contracting by subtype-selective antimuscarinic drugs with affinities typical of M 3 receptors. Induction of esophagitis by perfusing the esophagus with HCl switches the signal transduction mechanism in LES cells toward the pathway observed in esophageal cel...

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Penetrating trauma to the scrotum often requires operative intervention, with testicular salvage only possible when enough testicular tissue can be re‐approximated in the traumatic setting. The present report represents the largest series of gunshot wound trauma to the scrotum in the literature. Further, it validates recommendations of the European Association of Urology guidelines on urological trauma that advocate operative intervention due to minimal rates of patient morbidity and the inherent limitations of scrotal ultrasonography in discerning testicular compromise. OBJECTIVE To report our 20‐year experience of gunshot wounds (GSWs) to the scrotum and outline the management of this traumatic injury. PATIENTS AND METHODS We queried our institutional database for patients presenting with GSWs to the scrotum between 1985 and 2006. All patients underwent the standard trauma evaluation upon presentation, including physical examination of the external genitalia. Management was dictated by the presence or absence of a penetrating injury to the scrotum and associated traumatic injuries. Nonoperative and operative management of traumatic injury to the scrotum were used. Testicular salvage was performed when anatomically feasible. If testicular salvage was not feasible, an orchiectomy was performed. RESULTS Scrotal exploration was performed in 91 (94%) patients while six (6%) patients were treated nonoperatively. Testicular injury was found in 44 (48%) patients undergoing exploration, six (7%) of whom had bilateral testicular injuries, which gave a total of 50 injured testicles. Of the injured testicles, 24 (48%) could not be salvaged and required orchiectomy, while 26 (52%) were debrided and repaired. The most common associated genitourinary (GU) injuries were to the corpora cavernosum (n= 20 [21%]) and urethra (n= 10 [10%]). Soft tissue injury of the extremities occurred in 54 patients (56%), representing the most common non‐GU‐associated injury. Postoperative complications occurred infrequently: one patient (1%) returned for abscess drainage and one (1%) for haematoma evacuation. CONCLUSIONS The present report confirms that any patient with a penetrating injury to the scrotum should undergo immediate scrotal exploration. A low clinical suspicion for performing additional studies to rule out associated urethral and/or penile injury is clinically warranted. Testicular loss occurs in ≈50% of injured testicles.

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