Mahreen Hussain

Recent advances in detrusor muscle function

Contractile activation of detrusor smooth muscle is initiated by the release of transmitters from motor nerves. Acetylcholine is a ubiquitous transmitter, as also is adenosine triphosphate (ATP) in many animal bladders and in people from several patient groups with pathological bladder function. In recent years there has been progress in explaining several cellular mechanisms that link transmitter release to contraction and these will be considered. The lifetime of ATP in the neuromuscular junction is finite and broken down ultimately to adenosine, which can exert modulatory control of contractile activation. Adenosine depresses nerve-mediated contractions and two sites of action have been proposed: an action on the motor nerves via A[Formula: See Text] receptors to depress further transmitter release and a less well-defined depressant effect on the detrusor muscle. The Ca[Formula: See Text] ions that activate the contractile proteins are derived from intracellular stores, which releases their content via IP[Formula: See Text] receptor activation and Ca[Formula: See Text]-induced Ca[Formula: See Text] release. Filling of the stores in the rest interval is mediated via transmembrane flux of Ca[Formula: See Text] through Ca[Formula: See Text] channels. Activation of the channels is regulated by the level of the intracellular [Ca[Formula: See Text]], via activation and inactivation of Ca[Formula: See Text]-sensitive K[Formula: See Text] channels. Thus, Ca store filling is regulated by intracellular [Ca[Formula: See Text]] via a negative feedback process. The presence and physiological function of spontaneous contractions in detrusor remain contentious and little is known about their origin. One possibility is that they originate from random Ca[Formula: See Text] sparks, i.e. localized transient increases of [Ca[Formula: See Text]] that may eventually progress to generate a cellular Ca[Formula: See Text] transient. Observations by confocal microscopy have revealed the presence of such sparks, especially near the cell membrane, and thus provide a cellular basis for spontaneous contractions. Finally, the questions arises as to whether detrusor smooth muscle is a functional syncitium. The demonstration of small gap junctions by electron microscopy and the demonstration of the gap junction protein connexin45 indicate that the muscle mass may indeed be functionally connected. The implications regarding the spread of excitation are discussed.

How times have changed

Roy Simpson’s obituary, noting his sprinting abilities (reserve for Great Britain at the 1948 Olympics), explains an event that took place in the late 1960s.1 Roy was off on a lecture tour of South Africa. He had just …

Performing cytoreductive nephrectomy following targeted sunitinib therapy for metastatic renal cell carcinoma: a surgical perspective.

Objective: To describe for surgeons contemplating performing cytoreductive nephrectomy (CRN) on patients after neoadjuvant sunitinib compared to a benchmark of open radical nephrectomy, describing technical difficulties, safety and feasibility. Patients and Methods: We compared measurable surgical parameters and perioperative complications in 22 patients with metastatic renal cell carcinoma (mRCC) undergoing CRN after neoadjuvant sunitinib, with 28 patients who underwent open radical nephrectomy for non-metastatic disease (nmRCC). Results: Median blood loss (320 vs. 775 ml), median operative time (128 vs. 195 min) and median length of stay (5 vs. 7 days) were greater in the mRCC group. Surgery after sunitinib was technically challenging due to fibrosis, loss of the tissue planes that usually facilitate radical nephrectomy and abnormal blood vessel formation. Side effects of sunitinib resulted in predictable complications. Conclusion: CRN after treatment with sunitinib is safe and feasible in our hands, although the surgery is more time-consuming and technically demanding. A multidisciplinary approach is mandatory.