Oestrogens and lower urinary tract function

There is increasing evidence from animal and human studies that sex steroids have an important effect on the female lower urinary tract during adult life. Oestrogen receptors have been identified throughout the brain, pontine micturition centre and in the bladder, urethra and pelvic floor. Fluctuations in the circulating level of oestrogens and progesterone occurring during the menstrual cycle and in pregnancy influence the prevalence of urinary symptoms and the results of urodynamic investigation. In addition, the menopause and subsequent oestrogen deficiency have been implicated in the aetiology of a number of urogenital complaints including incontinence, urgency and recurrent urinary tract infection (UTI). However, the use of hormone replacement therapy for these conditions has given conflicting and largely disappointing results. The aim of this paper is to discuss the role of oestrogen in the pathogenesis and treatment of lower urinary tract dysfunction.     

Ⅲ型子宫切除术对患者下尿路功能的影响及其机制研究*

 目的： 通过对Ⅲ型子宫切除手术前后患者尿流动力学指标数据的分析对比,评估术后患者下尿路功能改变情况,探寻其发生机制、主要影响因素和变化趋势。方法: 选取Ⅲ型子宫切除手术患者,于术前后12～14 d和术后3个月分别对患者行尿流动力学检查,分析患者手术前后的尿动力学参数。结果: Ⅲ型子宫切除术后12～14 d残余尿量、尿流时间、排尿感容量和最大膀胱压较术前明显增加（P<0.05）;最大尿流率、平均尿流率、排尿量、膀胱容量、顺应性、逼尿肌压力、最大尿道压和最大尿道闭合压较术前明显下降（P<0.05）。术后3个月残余尿量、尿流时间、排尿感容量和最大膀胱压较术前增加（P<0.05）;而最大尿流率、逼尿肌压力、顺应性、最大尿道压和最大尿道闭合压则下降（P<0.05）。术后3个月与12～14 d相比最大尿流率、平均尿流率、排尿量、膀胱容量、顺应性和逼尿肌压力明显增加（P<0.05）,残余尿量和最大膀胱压明显减小（P<0.05）。结论: Ⅲ型子宫切除术后12～14 d多数患者出现明显的下尿路功能障碍：膀胱顺应性急剧减小所致储尿功能异常、逼尿肌无收缩力导致排尿功能障碍和尿道闭合压降低引起控尿功能下降。膀胱储尿、排尿功能术后3个月有所恢复,但没有恢复到术前状态。     

Relationship between urinary endogenous steroid metabolites and lower urinary tract function in postmenopausal women

To investigate the relationship between the endogenous steroid hormones and the lower urinary tract function in postmenopausal women. Thirty postmenopausal volunteer women who did not have lower urinary tract symptoms or hormone replacement therapy were enrolled in this study. Urodynamic studies included uroflowmetry, multi-channel cystometry, and urethral pressure profilometry were conducted. Gas Chromatography- Mass Spectroscopy(GC-MS) was used to measure the urinary endogenous steroid hormone metabolites. The relationship between the urinary profile of the endogenous steroids and the urodynamic parameters of these patients were investigated. The mean ages of the patients were 60.6 +/- 5.5 years, and the Body Mass Index (BMI) averaged 24.56 +/- 2.23 (kg/m2). Of the progesterone metabolites, pregnandiol was significantly related to the residual volume in the uroflowmetry and the functional urethral length parameters (R=0.98, p=0.000; R= -0.65, p=0.04). Pregnantriol was significantly related to the maximum flow rate, the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=-0.64, p=0.04; R=0.82, p=0.01; R=0.04, p=0.04; R=- 0.79, p=0.01). In the androgen metabolites, androstenedione, 5-AT, 11- keto Et, 11-betahydroxy Et, THS, and THE were significantly related to the residual volume in uroflowmetry (R=0.92, p=0.001; R=0.84, p=0.008; R=0.99, p=0.000; R=0.72, p=0.03; R=0.97, p=0.000; R=0.85, p=0.00). beta-THF/alpha-THF was significantly related to the maximum flow rate, the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=-0.76, p=0.02; R=0.67, p=0.04; R=0.74, p=0.02; R=-0.92, p=0.000). alpha-cortol was significantly related to the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=0.81, p=0.01; R=0.71, p=0.03; R=-0.87, p=0.000). Of the estrogen metabolites, estrone (E1) was significantly related to the normal desire to void (R=0.68, p=0.04) and 17beta-estradiol/estrone was also significantly related to the normal and strong desire to void (R=-0.70, p=0.03 and R=-0.74, p=0.02, respectively). The urinary progesterone and androgen metabolite concentrations were positively related to the residual volume in uroflowmetry and positively or negatively related to MUCP and FUL. However, the urinary estrone concentration was positively related to the normal desire to void and 17beta-estradiol/estrone was significantly related to the normal and strong desire to void.     

The effect of pelvic organ prolapse on lower urinary tract function

Pelvic organ prolapse (POP) is a process in which the pelvic contents, including the reproductive organ, bladder, rectum, and/or small intestines become herniated through defects in the vaginal wall. The pelvic organs are closely related to the urinary tract and thus various urinary functions can be affected. The purpose of this study was to evaluate the relationship between pelvic organ prolapse and lower urinary tract function by urodynamic studies. From March 1999 to May 2000, 40 patients with pelvic organ prolapse who underwent urodynamic studies (uroflowmetry, filling cystometry, urethral pressure profile) without barrier reduction of prolapse were analyzed. The majority of the cases of low grade POP involvedpatients with anterior wall prolapse, whereas the higher POP stages were more frequent in women with cervical cuff prolapse. Symptoms of stress urinary incontinence and hesitancy were more frequent in the patients with anterior wall prolapse. The urodynamic study showed a statistically significant increase in MUCP in patients with POP stage IV and the leading point of POP was cervical cuff. The subjective urinary symptoms of patients with POP appear to be less reliable as a diagnostic tool. POP had no adverse effect on the bladder storage function. However, POP affected the voiding function through an increase in MUCP, especially in patients with stage IV prolapse and when the leading point of POP was cervical cuff. Following the surgical correction of POP, an evaluation of the preoperative changes in the urodynamic study parameters should be performed.     

Cranberries and lower urinary tract infection prevention

Lower urinary tract infections are very common diseases. Recurrent urinary tract infections remain challenging to treat because the main treatment option is long-term antibiotic prophylaxis; however, this poses a risk for the emergence of bacterial resistance. Some options to avoid this risk are available, including the use of cranberry products. This article reviews the key methods in using cranberries as a preventive measure for lower urinary tract infections, including in vitro studies and clinical trials.     

Purinergic signalling in the lower urinary tract

The aim of this review is to describe the conceptual steps contributing to our current knowledge of purinergic signalling and to consider its involvement in the physiology and pathophysiology of the lower urinary tract. The voiding reflex involves ATP released as a cotransmitter with acetylcholine from parasympathetic nerves supplying the bladder and ATP released from urothelial cells during bladder distension to initiate the voiding reflex via P2X3 receptors on suburothelial low threshold sensory nerve fibres. This mechanosensory transduction pathway also participates, via high threshold sensory nerve fibres, in the initiation of pain in bladder and ureter. Treatment of prostate and bladder cancer with ATP is effective against the primary tumours in animal models and human cell lines, via P2X5 and P2X7 receptors, and also improves the systemic symptoms associated with advanced malignancy. Acupuncture is widely used for the treatment of urinary disorders, and a purinergic hypothesis is discussed for the underlying mechanism.     

Effect of terazosin on lower urinary tract function in the male decerebrate dog]

The effect of terazosin on the lower urinary tract function was studied by combined recording of bladder and urethral pressures and external sphincter electromyogram in 8 male decerebrate dogs. Reflex micturitions were induced by bladder filling before and after terazosin. The statistical analysis was carried out on the urodynamic parameters. During the collecting phase, terazosin at doses of 10, 30 and 100 micrograms/kg produced a significant decrease in maximum urethral pressure in the dose dependent manner. Threshold pressure was significantly shown to decrease at doses of 30 and 100 micrograms/kg. In the urodynamic parameters of the emptying phase there was a significant decrease in maximum contraction pressure at 10 and 30 micrograms/kg, and in voided volume at 100 micrograms/kg. Terazosin seems to facilitate an initiation of the bladder contraction with a decrease in threshold pressure. In concludes that alpha 1 adrenergic activity seems to take an important role for the maintenance of the urethral pressure and to control the initiation of bladder contraction in modulation with threshold pressure.     

Urodynamic evaluation of lower urinary tract function in relation to total abdominal hysterectomy.

This study was performed to evaluate lower urinary tract functions in asymptomatic patients by urodynamic measurements after total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty asymptomatic patients who had undergone hysterectomy for benign diseases were included in the study and urodynamic measurements were performed before and 6 weeks after total abdominal hysterectomy and bilateral salpingo-oophorectomy. There was no postoperative difference in first urge, normal urge, urgency and maximum bladder capacity but average urethral length, functional urethral length and maximum urethral closing pressure were decreased and also bladder discharging time was increased. Voided volume and residual urine volume were unchanged. It was concluded that total abdominal hysterectomy and bilateral salpingo-oophorectomy did not change the postoperative bladder loading functions in asymptomatic patients but that significant changes occurred in urethral functions.     

Prognostic factors influencing survival after nephroureterectomy for transitional cell carcinoma of the upper urinary tract

We analyzed the prognostic factors influencing survival after surgeries for upper urinary tract urothelial carcinoma (UUT-UC) with longer follow-up periods than in previous studies. Between January 2000 and December 2004, 386 patients underwent nephroureterectomy for UUT-UC. The data for the 221 patients with UUT-UC were retrospectively reviewed. Nine variables were evaluated for association with the survival outcomes of disease-specific survival. The prognostic significance was tested univariately with the log-rank test. The simultaneous effects of multiple prognostic factors were estimated by multiple regression analysis using the Cox proportional hazards model. The median follow-up was 38.4 months. The 5-year over all survival was 62.3%. Significant prognostic factors for disease-specific survival rate on univariate analysis were pathological stage (p＜0.0001), tumor grade (p＝0.0324), and venous invasion (p＜0.0001). Multivariate analysis revealed that only venous invasion was significant for disease-specific survival rate (p＝0.0205). Venous invasion was the only independent prognostic factor in pathologically localized UUT-UC.     

Pressure-flow nomogram for women with lower urinary tract symptoms

Introduction

Results of urodynamic studies performed in female patients are often difficult to interpret. The objective of the study was to develop a nomogram that would help in diagnosing functional bladder outlet obstruction (BOO) in neurologically intact women with any kind of lower urinary tract symptoms.

Material and methods

From the urodynamic database adult women were chosen with maximal flow rate (Q_max) ≤ 12 ml/s in a pressure-flow study. Four criteria were used to identify a group of patients suspected of BOO: thickened bladder wall, presence of bladder diverticula, subjective improvement on α-blockers and improvement of voiding symptoms on any form of treatment. The line separating high and low pressure zones on the pressure-flow chart was established according to the position of patients who met at least one of them.

Results

Sixty-seven patientswere investigated. Twenty-one women met at least one of the specified criteria. They had significantly higher voiding pressures (p _det(Qmax) 35 cm H₂O vs. 16.5 cm H₂O; p = 0.002). A new nomogram with one separating line (p _det(Qmax) = 1.5 × Q _max+ 10) was proposed. The difference in the distribution of women fulfilling the criteria between high pressure zone and low pressure zone was highly significant (19/35 vs. 2/32; p < 0.0001). Sensitivity, specificity, positive and negative predictive values of our nomogram in identifying patients suspected of BOO was 90.5%, 65.2%, 54.3% and 94% respectively.

Conclusions

The new nomogram can be considered a screening test which efficiently excludes obstruction among women with low Q _max in a pressure-flow study.     

Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function

Smooth muscles from the urethra and bladder display characteristic patterns of spontaneous contractile activity in the filling phase of the micturition cycle. Tonic contractions are seen in the urethral smooth muscles, and phasic contractions occur in the detrusor. Overactivity in the detrusor is a common clinical problem. The ion channels in the smooth muscle membranes play an important role in determining the functional properties, and are obvious targets for treatment of the overactive bladder. Recent evidence suggests that interstitial cells may also play a role in determining the pattern of spontaneous activity, although their precise role is less well established in the urinary tract than in the gut. The ion channels involved in these cells are also of interest. This review discusses what is known of ion channels in these tissues, and their implications for function.     

神经调控技术在下尿路功能障碍中的应用进展

对于那些传统治疗如行为疗法、药物治疗等效果不佳的顽固性下尿路功能障碍患者,神经调控术逐渐成为可供选择的治疗方案。目前,各类神经调控技术已经被越来越多的学者应用于动物实验及临床研究中,并且研究者们在继续寻找更有效的治疗下尿路功能障碍的神经调控方法以及对神经调控的作用机制进行探索。本文综述了目前常用的神经调控技术的作用原理及优势,并对近年来一些新的神经调控技术在排尿功能障碍治疗领域的应用进行分析,展示其未来的发展方向及应用前景。     

Autologous primary muscle-derived cells transfer into the lower urinary tract

The goal of these experiments was to establish the basic methodology for future clinical applications of muscle-derived cells (MDC) tissue engineering and gene transfer for the treatment of urological dysfunction. Primary MDC isolated via preplating techniques from adult female SD rats were transduced with retrovirus encoding the expression of beta-galactosidase reporter gene. The MDC were injected into the right and left lateral walls of the bladder and proximal urethra of the autologous animals (n = 6) with a 10 microl Hamilton micro syringe. The amount of injected MDC ranged from 1 to 2 x 10(6) cells. The injected tissue was harvested after 7, 14, and 28 days, sectioned and examined histologically for beta-galactosidase and immunohistochemically for fast myosin heavy chain specific to skeletal muscle. The tissues were also stained for anti-CD4 and anti-CD8 antibodies to assess for cellular immune reaction. We have detected a large number of autologous MDC expressing beta-galactosidase and positively stained for fast myosin heavy chain in the bladder and urethral wall. Many injected myoblasts and myotubes were also seen in the bladder and urethral wall at each time point. Staining of lymphocytes with anti-CD4 and anti-CD8 antibodies was negative after MDC injection at each time point. We have demonstrated the long-term survival of autologous MDC and MDC mediated gene transfer into the bladder and urethral wall. Autologous MDC and MDC mediated gene transfer may be a promising treatment to augment bladder and urethral sphincter function.     

Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat

The role of spinal metabotropic glutamate receptors (mGluRs) in control of lower urinary tract functions was evaluated in rats using an mGluR antagonist administered via the intrathecal route. Cystometrograms in combination with external urethral sphincter (EUS) EMG recordings were performed on 13 decerebrate unanesthetized Sprague–Dawley female rats (n = 6 for spinal cord intact rats; n = 7 for spinal cord transected rats). In spinal cord intact rats, a group I/II mGluR antagonist, (±)-alpha-methyl-4-carboxyphenylglycine (MCPG), at doses of 3–30 μg, changed neither bladder nor EUS EMG activity, whereas a larger dose (100 μg) produced a significant facilitation of EUS EMG activity (41% increase in the peak activity) with little effect on bladder contractions. In chronically spinal cord transected rats, MCPG (3–100 μg) had no effect on bladder and EUS EMG activity. The results suggest that group I/II mGluRs are likely to be involved in inhibition of the excitatory pathway to the EUS but not involved in the control of the bladder. The lack of effect of MCPG on the EUS EMG activity in chronic spinal cord transected rats indicates that mGluR-mediated inhibitory control of the EUS was eliminated after spinal cord injury.     

Role of spinal metabotropic glutamate receptors in regulation of lower urinary tract function in the decerebrate unanesthetized rat

Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau(181)) and the 42 amino acid isoform of beta-amyloid (Abeta42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (+/-S.D.) 76.1+/-7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4-6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 (p<0.0001), for all three markers. We conclude that T-tau, P-tau and Abeta42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, Abeta immunotherapy and tau phosphorylation inhibitors.