In the Human Urothelium and Suburothelium,Intradetrusor Botulinum Neurotoxin Type A Does Not Induce Apoptosis: Preliminary Results

Background

Intradetrusor injections of botulinum neurotoxin type A (BoNTA) are emerging as the preferred second-line treatment for neurogenic and idiopathic overactive bladder (OAB). In animal experiments, intradetrusor BoNTA injections have been shown to cause apoptosis in the bladder urothelium and suburothelium but not the detrusor.

Objective

To investigate BoNTA-induced apoptosis in patients with refractory neurogenic OAB.

Design, setting, and participants

Twelve refractory OAB patients with neurogenic detrusor overactivity resulting from multiple sclerosis (MS) and seven controls were included prospectively.

Measurements

The number of apoptotic cells before and 4 wk after first intradetrusor BoNTA (300 U of BOTOX [Allergan, Irvine, CA, USA]) injections were estimated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) staining.

Results and limitations

Comparison of TUNEL-positive cells (yes vs no) in the bladder urothelium and suburothelium revealed no significant differences in OAB patients before (4 of 12, 33%) versus after (3 of 12, 25%) BoNTA treatment (p = 0.99). In addition, no significant differences (p = 0.99) were found in OAB patients versus controls. Because our findings are based on first intradetrusor BoNTA injections only, it is unclear whether the results could be extrapolated to repeat injections.

Conclusions

In contrast to preliminary animal experiments, first intradetrusor BoNTA injections for treating refractory neurogenic OAB—a highly effective treatment—did not induce apoptosis in the bladder urothelium and suburothelium.     

Complete Periprostatic Anatomy Preservation During Robot-Assisted Laparoscopic Radical Prostatectomy (RALP): The New Pubovesical Complex-Sparing Technique

Background

Puboprostatic ligament preservation has been proposed as a method to accelerate continence recovery after radical prostatectomy (RP). However, these ligaments present anatomic continuity with the bladder, and there must be interruption at some point to expose the prostatourethral junction.

Objectives

To describe the surgical steps of pubovesical complex (PVC)–sparing robot-assisted laparoscopic RP (RALP) and present the preliminary results of our technique.

Design, setting, and participants

Thirty PVC-sparing RALP procedures were performed in patients <60 yr with clinically localised prostate cancer between 2007 and 2009 by the same surgeon.

Surgical procedure

The principles of bladder neck preservation, tension and energy-free dissection of the bundles as well as seminal vesicle sparing are applied. Ventrally, a plane of dissection is developed between the detrusor apron and the prostate. The soft connective tissue between Santorini's plexus and the prostate is blandly dissected, leaving the plexus intact and in place.

Measurements

The rates and location of positive surgical margins (PSM) as well as functional outcomes are presented.

Results and limitations

Three of 30 patients (10%) had a PSM (two apical margins and one on the left posterolateral side). At catheter removal, 24 of 30 patients (80%) were dry (0 pads), and 6 of 30 patients (20%) needed one security pad. After 3 mo, 22 of 30 patients (73%) presented an International Index of Erectile Function score >17 (with or without phosphodiesterase type 5 inhibitors). Thirteen of 22 potent patients had an Erection Hardness Score of 3, and 9 of 22 patients had a score of 4. Small sample size, low mean age of enrolled patients (52 yr), and the absence of diseases that could impair the continence and potency recovery are some of the limitations of the study. Moreover, it is difficult to quantify the effect of each applied continence-sparing technique.

Conclusions

The holistic preservation of the PVC during RALP is technically feasible. It leads towards an absolute preservation of the periprostatic anatomy that may enhance early functional outcomes. Further studies are needed to confirm our results.     

前列腺增生症术前尿动力学检查的意义

目的:探讨前列腺增生症(BPH)患者术前尿动力学检查的意义.方法:对306例患者术前进行尿动力学检查,并对术后症状改善情况进行分析.结果:术前膀胱出口梗阻(BOO)合并膀胱逼尿肌功能损害较轻,或基本正常的患者术后疗效理想,合并逼尿肌收缩功能障碍(IDC)的大部分患者术后1个月内恢复,排尿通畅、尿频等症状减轻或消失.术后半年仍疗效不佳的60例患者中,术前逼尿肌不稳定(DI)13例,逼尿肌低顺应性17例,逼尿肌活动低下(DUA)25例,膀胱出口仍有梗阻5例.结论:造成BPH术后疗效不佳的主要原因与逼尿肌的功能受损有关.尿动力学检查能正确判断患者是否有BOO,还可评估膀胱逼尿肌功能,从而对BPH的治疗方案、治疗时机的选择,特别是对术后疗效的预测、评估及查明疗效不佳的原因有着重要的指导作用.     

亚急性衰老大鼠逼尿肌舒缩功能变化的实验研究

目的观察D—gal致亚急性衰老大鼠膀胱逼尿肌舒缩功能的变化。方法在初筛合格的sD大鼠颈背部皮下注射浓度为5％的D—gaI生理盐水溶液125mg·kg^-1·d^-1连续8周。用离体逼尿肌条实验观察动物逼尿肌舒缩功能,并进行组织病理形态学观察。结果与正常对照组比较,模型组动物逼尿肌自发性收缩频率加快（P〈0．01）．顺应性、弹力下降（P〈0．05～0．01）,但收缩性没有明显改变（P〉0．05）;ATP对亚急性衰老逼尿肌中的收缩作用增强,ISO在亚急性衰老动物逼尿肌中的抑制收缩作用减弱（P〈0．05～0．01）;病理形态学观察显示,模型动物膀胱形态改变明显,逼尿肌中胶原纤维组织所占比例增加（P〈0．01）。结论亚急性衰老大鼠逼尿肌舒缩功能及神经受体敏感性发生显著改变。     

良性前列腺增生患者术前行尿动力学检查的意义

目的探讨良性前列腺增生症（BPH）患者术前行尿动力学检查的临床意义。方法对150例BPH患者术前进行压力一容积和压力一流率测定。结果150例BPH患者中膀胱出口梗阻（Boo）102例,无BOO15例,膀胱出口可疑梗阻33例。BOO患者前列腺体积大于无BOO患者,最大尿流率小于无BOO患者。BOO患者中有逼尿肌不稳定收缩（DI）32例,无BOO患者中DI6例。结论尿动力学检查有助于判断有无BOO的存在,了解BPH患者逼尿肌的功能且预测术后疗效,更好地指导临床治疗和把握手术指征。     

舍尼亭联合α受体阻滞剂对逼尿肌过度活动患者尿动力学的影响

目的探讨舍尼亭联合α受体阻滞剂治疗良性前列腺增生伴逼尿肌过度活动尿动力学的影响及疗效。方法 108例良性前列腺增生伴逼尿肌过度活动患者随机分为观察组和对照组,各54例,分别给予舍尼亭联合可多华和可多华单用治疗。结果治疗前两组Qmax、Pdet、VV、PVR、24 h排尿次数之间差异无统计学意义(P>0.05),治疗后两组Pdet、PVR、24 h排尿次数均较治疗前显著降低,VV则显著升高(P均<0.05),Qmax与治疗前差异无统计学意义(P>0.05),两组各指标之间差异有统计学意义(P<0.05)。治疗后均显著下降,观察组均显著低于对照组(P<0.05),观察组6例(11.11%)、对照组5例(9.26%)出现轻度不良反应,两组差异无统计学意义。结论舍尼亭联合α受体阻滞剂能有效改善尿动力学,缓解良性前列腺增生患者的逼尿肌过度活动,安全有效。     

针灸治疗BPH致膀胱逼尿肌收缩无力TURP术后的临床观察

目的观察针灸治疗良性前列腺增生致膀胱逼尿肌无力患者经尿道前列腺电切术后效果。方法选择因良性前列腺增生、膀胱过度充盈致逼尿肌损伤,引起膀胱逼尿肌收缩无力并行经尿道前列腺电切术38例患者,术后采用电针刺激关元、中极、肾俞、次髎、三阴交、足三里穴,观察疗效。结果治疗4个疗程后,35例TURP术后留置膀胱造瘘管（1～8）周后全部拔除,排尿通畅。3例膀胱逼尿肌收缩功能几乎无任何改善。长期留置膀胱造瘘治疗。结论针灸治疗良性前列腺增生致膀胱逼尿肌无力经尿道前列腺电切术后疗效明确,可以减少膀胱造瘘率,提高患者的生活质量。     

Phospholipase C mediated Ca signals in murine urinary bladder smooth muscle

Muscarinic stimulation of urinary bladder induces contraction via an increase in intracellular Ca²⁺ concentration that results from Ca²⁺ influx through Ca²⁺ channels and/or IP₃-mediated Ca²⁺ release controlled by phospholipase C (PLC) signalling. The significance of PLC/IP₃ signalling in this cascade has recently been questioned because PLC inhibitors were without effect on carbachol-induced contractions in detrusor muscle strips. However, PLC/IP₃-mediated Ca²⁺ release was clearly observed in recordings of Ca²⁺ signals in isolated myocytes. Therefore, we investigated the presence of PLC/IP₃-dependent Ca²⁺ release by directly monitoring Ca²⁺ signals in intact detrusor muscle strips. Concomitant Ca²⁺ signals from Ca²⁺ channel activity were eliminated by the Ca²⁺ channel antagonist isradipine (3 µM) or by the use of muscles from Ca_v1.2 channel-deficient (SMACKO) mice. In absence of Ca²⁺ channel activity, carbachol elicited contractions and Ca²⁺ signals in muscles from wild type and SMACKO mice that were inhibited by the PLC inhibitor U73122 (10 µM). The results show that PLC/IP₃-dependent Ca²⁺ release is activated by stimulation with carbachol in urinary bladder smooth muscle but has a minor contribution to overall carbachol-induced Ca²⁺ signals.     

Age-related changes of P2X(1) receptor mRNA in the bladder detrusor from men with and without bladder outlet obstruction

The urinary bladder purinergic system is reported to change with age and with bladder dysfunction. Here, we examined the expression of purinergic P2X(1) receptors in detrusor and mucosa (urothelium+lamina propria) from male control bladder and investigated age-related P2X(1) receptor mRNA expression in control and obstructed detrusor. Biopsy specimens were obtained at cystoscopy from control patients (n=46, age range 30-86years) and patients diagnosed with outlet obstruction (n=29, 46-88years). Calponin expression (measured by RT-PCR) was similar in control and obstructed detrusor and did not change with age. Quantitative competitive RT-PCR was used to measure P2X(1) receptor and GAPDH mRNA in control and obstructed detrusor. P2X(1) receptor mRNA expression was 9-fold (p<0.0001) higher in the detrusor than in the mucosa. Expression of mRNA for the internal control GAPDH remained stable with age and across control and obstructed detrusor. No difference in P2X(1) receptor expression was observed between control and obstructed detrusor (p=0.35). However, an age-related decrease in P2X(1) mRNA expression was observed in control (n=27; p=0.0054; Spearman coefficient r=-0.520) but not obstructed detrusor (n=19; p=0.093; r=-0.396). Downregulation of P2X(1) mRNA expression might occur as a result of an increased component of neural ATP release in the aging bladder.     

The integrative physiology of the bladder

Normal bladder function is complex, resulting from the co-operative interaction of numerous regulatory cell types, of which the interstitial cells and the peripheral neurones are particularly interesting. Collectively, these comprise the myovesical plexus, which appears to confer structural and functional characteristics on the bladder loosely akin to those of the gut. These include functional modularity, which gives rise to the potential for localised and propagating peristalsis-like movements in the bladder wall according to the prevailing physiological conditions. Localised modular activity during filling may contribute to normal generation of sensation and exaggerated modular activity may give rise to urinary urgency. Enhanced co-ordination of modular activity occurs in various models of detrusor overactivity; it leads to surges of contraction over a large part of the bladder wall, generating phasic changes in intravesical pressure. During voiding, the myovesical plexus sustains detrusor contraction at the behest of the brainstem, monitoring state of bladder fullness as it does so, as a guide to the required duration for which it has to keep up the effort. Accordingly, the bladder wall itself may house structures which render the bladder the effector level in a hierarchy of lower urinary tract regulation. Dysfunction in these vital regulatory structures is an underestimated factor in the pathophysiology of clinical bladder problems.