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Whole Bladders (whole + bladder)
Selected AbstractsInvasive bladder carcinoma: A pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2001Abderrahim Zouhair M.D. Abstract From November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49,86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m2) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was sucessfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four-year overall and disease-specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4-year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low-stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population. © 2001 Wiley-Liss, Inc. [source] Effects of imatinib mesylate (Glivec®) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladderNEUROUROLOGY AND URODYNAMICS, Issue 3 2006Yasue Kubota Abstract Aims In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. Methods Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. Results Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 ,M) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 ,M) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. Conclusions The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Lack of effectiveness of botulinum neurotoxin A on isolated detrusor strips and whole bladders from mice and guinea-pigs in vitroBJU INTERNATIONAL, Issue 10 2009Sarah Howles OBJECTIVE To differentiate between the effects of parasympathetic and sensorimotor stimulation of isolated mouse and guinea-pig bladders in vitro by measuring the pressure increases to electrical field stimulation (EFS) and then comparing the effects of botulinum neurotoxin A (BoNT-A) applied either to the lumen or to the external bathing medium. MATERIALS AND METHODS Isolated mouse and guinea-pig bladders and detrusor strips were exposed to EFS in vitro before and after the addition of BoNT-A. The rationale of this method was that BoNT-A applied to the outside of the bladder would first affect the parasympathetic nerves before diffusing inwards to affect the sensorimotor innervation. BoNT-A applied intravesically would first reach the sensorimotor nerves and only later the parasympathetic nerves. Initial experiments on strips of detrusor were conducted to establish the correct dosage and application time of BoNT-A. RESULTS Contrary to our expectations, BoNT-A application failed to produce any significant effects on either the detrusor strips or whole bladders. CONCLUSIONS Our experimental design failed to show any effect of BoNT-A on the contractility of detrusor muscle strips or whole bladders from mice and guinea-pigs. The reason for this is unclear, but may be related to tissue spending inadequate time incubated with BoNT-A under physiological conditions. [source] Phosphodiesterase-linked inhibition of nonmicturition activity in the isolated bladderBJU INTERNATIONAL, Issue 9 2004J.I. Gillespie Over the past few months Gillespie has published several papers in the BJU International investigating the overactive bladder and BOO, using novel models and theories. This next paper continues these concepts and shows that the mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder model is slowed by cAMP. These findings will have important implications in future pharmacological strategies in the overactive bladder. OBJECTIVE To explore the influence of intracellular cAMP on phasic activity in the isolated bladder (phasic rises in intravesical pressure associated with waves of contraction and local stretches that can be activated by muscarinic or nicotinic agonists), as it has been argued that this activity underlies nonmicturition contractions, and that it contributes to the generation and modulation of afferent nerve activity. MATERIALS AND METHODS Isolated whole bladders from female guinea pigs (270,300 g) were cannulated via the urethra and suspended in a chamber containing oxygenated Tyrode solution at 33,35 °C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder. RESULTS Forskolin (1,3 µmol/L), an activator of adenyl cyclase, reduced the frequency and amplitude of the phasic activity induced by the muscarinic agonist arecaidine (300 nmol/L). There were similar changes in frequency and amplitude in bladders exposed to the nonspecific phosphodiesterase (PDE) inhibitor iso-butyl-methyl-xanthene (IBMX). The actions of specific PDE inhibitors were explored to assess which isoenzymes might be responsible for regulating phasic activity. ENHA (PDE-2), zaprinast (PDE-5, -6, -8, -9 and -11) and siguazodan (PDE-3) had no effect. Zardavarine (PDE-3, -4) and Ro 20-1724 (PDE-4) reduced both the frequency and amplitude of the phasic activity. Nerve-mediated rises in intravesical pressure were also inhibited by Ro 20-1724, and the inhibition was more pronounced at 6.5 Hz than at 30 Hz stimulation. Ro 20-1724 inhibited nerve-mediated fluctuations induced by prolonged (200 s) stimulation at 6.5 Hz. CONCLUSION The mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder are slowed by cAMP. Degradation of intracellular cAMP in the cells responsible for phasic activity appears to involve primarily PDE-4. The importance of these observations in relation to the overall physiological regulation of the bladder are discussed, and the possible importance of these findings in the development of pharmacological strategies to modulated bladder activity reviewed. [source] | ||||||||||