STRESS INCONTINENCE OF URINE—A Consideration of Etiologic Factors in Women

Urinary continence in women is intimately associated with adequate support of the neck of the bladder. Any increase in tone of the bladder musculature, or in the intravesicular pressure, substantially increases the liability to incontinence. Obstetrical trauma may cause stress incontinence by disrupting supports of the neck of the bladder and by stretching the fascial structures of the posterior portion of the neck of the bladder. Minor injury not grossly demonstrable may occur in this way and upset the very delicate balance existing between the forces of the detrusor muscle and the resistance of the urethrovesical junction.In correcting the defects associated with stress incontinence, there are specific indications for various methods—active exercise, plastic reconstruction of the bladder and urethral supports, and the various operations for suspension of the neck of the bladder.     

A biomechanical model to assess the contribution of pelvic musculature weakness to the development of stress urinary incontinence

A biomechanical model of the female pelvic support system was developed to explore the contribution of pelvic floor muscle defect to the development of stress urinary incontinence (SUI). From a pool of 135 patients, clinical data of 26 patients with pelvic muscular defect were used in modelling. The model was employed to estimate the parameters that describe the stiffness properties of the vaginal wall and ligament tissues for individual patients. The parameters were then implemented into the model to evaluate for each patient the impact of pelvic muscular defect on the vaginal apex support and the bladder neck support, a factor that relates to the onset of SUI. For the modelling analysis, the compromise of pelvic muscular support was demonstrated to contribute to vaginal apex prolapse and bladder neck prolapse, a condition commonly seen in SUI patients, while simulated conditions of restored muscular support were shown to help re-establish both vaginal apex and bladder neck supports. The findings illustrate the significance of pelvic muscle strength to vaginal support and urinary continence; therefore, the clinical recommendation of pelvic muscle strengthening, such as Kegel exercises, has been shown to be an effective treatment for patients with SUI symptoms.     

三维超声技术对于评估压力性尿失禁女性患者盆底肌肉收缩及膀胱颈活动度的价值研究

摘要 目的：探讨三维超声技术对于评估压力性尿失禁（SUI）女性患者盆底肌肉收缩及膀胱颈活动度的价值。方法：选取2020年1月至2021年8月本院的收治的因产后SUI的女性患者60例作为观察组,另选择同期产后正常的女性受试者60例作为对照组,所有受试者均行经会阴三维超声检查。比较两组之间盆底肌肉收缩及膀胱颈活动度等相关指标的差异。结果：在静息状态和最大Valsalva状态下,观察组中盆膈裂孔前后径、左右径、肛提肌裂孔面积以及膀胱颈后角均显著大于对照组（P<0.05）,观察组尿道长度显著低于对照组（P<0.05）;而仅在最大Valsalva状态下,观察组的膀胱颈位置显著低于对照组（P<0.05）;此外观察组膀胱漏斗化所占比例显著高于对照组（P<0.05）。结论：三维超声技术可以清晰直观地显示女性盆底组织结构和功能,对于评估SUI女性患者盆底肌肉收缩及膀胱颈活动度具有一定的诊断价值,并为临床提供真实客观的影像学证据。     

Induction of oxidative stress causes functional alterations in mouse urothelium via a TRPM8‐mediated mechanism: implications for aging

The incidence of bladder conditions such as overactive bladder syndrome and its associated urinary incontinence is highly prevalent in the elderly. However, the mechanisms underlying these disorders are unclear. Studies suggest that the urothelium forms a ‘sensory network’ with the underlying innervation, alterations in which, could compromise bladder function. As the accumulation of reactive oxygen species can cause functional alterations with age, the aim of this study was to investigate whether oxidative stress alters urothelial sensory signalling and whether the mechanism underlying the effect of oxidative stress on the urothelium plays a role in aging. Five‐month‐old(young) and 24‐month‐old (aged) mice were used. H₂O₂, used to induce oxidative stress, resulted in an increase in bladder afferent nerve activity and urothelial intracellular calcium in preparations from young mice. These functional changes were concurrent with upregulation of TRPM8 in the urothelium. Moreover, application of a TRPM8 antagonist significantly attenuated the H₂O₂‐induced calcium responses. Interestingly, an upregulation of TRPM8 was also found in the urothelium from aged mice, where high oxidative stress levels were observed, together with a greater calcium response to the TRPM8 agonist WS12. Furthermore, these calcium responses were attenuated by pretreatment with the antioxidant N‐acetyl‐cysteine. This study shows that oxidative stress affects urothelial function involving a TRPM8‐mediated mechanism and these effects may have important implications for aging. These data provide an insight into the possible mechanisms by which oxidative stress causes physiological alterations in the bladder, which may also occur in other organs susceptible to aging.     

Association of overactive bladder and stress urinary incontinence in rats with pudendal nerve ligation injury

Approximately one-third of patients with stress urinary incontinence (SUI) also suffer from urgency incontinence, which is one of the major symptoms of overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a possible cause for both SUI and OAB. Therefore, we investigated the effects of pudendal nerve ligation (PNL) on bladder function and urinary continence in female Sprague-Dawley rats. Conscious cystometry with or without capsaicin pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses of bladder muscle strips to carbachol or phenylephrine, and levels of nerve growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL rats 4 wk after the injury. Urinary frequency detected by a reduction in intercontraction intervals and voided volume was observed in PNL rats compared with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly decreased compared with sham rats. The contractile responses of detrusor muscle strips to phenylephrine, but not to carbachol, were significantly increased in PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were significantly increased compared with sham rats. These results suggest that pudendal nerve neuropathy induced by PNL may be one of the potential risk factors for OAB, as well as SUI. Somato-visceral cross sensitization between somatic (pudendal) and visceral (bladder) sensory pathways that increases NGF expression and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved in this pathophysiological mechanism.     

Stem cell applications for pathologies of the urinary bladder

New stem cell based therapies are undergoing intense research and are widely investigated in clinical fields including the urinary system. The urinary bladder performs critical complex functions that rely on its highly coordinated anatomical composition and multiplex of regulatory mechanisms. Bladder pathologies resulting in severe dysfunction are common clinical encounter and often cause significant impairment of patient’s quality of life. Current surgical and medical interventions to correct urinary dysfunction or to replace an absent or defective bladder are sub-optimal and are associated with notable complications. As a result, stem cell based therapies for the urinary bladder are hoped to offer new venues that could make up for limitations of existing therapies. In this article, we review research efforts that describe the use of different types of stem cells in bladder reconstruction, urinary incontinence and retention disorders. In particular, stress urinary incontinence has been a popular target for stem cell based therapies in reported clinical trials. Furthermore, we discuss the relevance of the cancer stem cell hypothesis to the development of bladder cancer. A key subject that should not be overlooked is the safety and quality of stem cell based therapies introduced to human subjects either in a research or a clinical context.     

Micturition and the mind: psychological factors in the aetiology and treatment of urinary symptoms in women.

The mental state of 211 women attending a urodynamic clinic was assessed using questionnaires. Patients with genuine stress incontinence had scores comparable with other patients with longstanding physical complaints. Patients with sensory urgency were more anxious than those with genuine stress incontinence. Patients with detrusor instability were as anxious as patients with sensory urgency and in addition had higher scores on the hysteria scale. A subset of patients (roughly a quarter of the total) was identified, comprising members of all three diagnostic groups, for whom urinary symptoms rendered life intolerable. These patients were as anxious, depressed, and phobic as psychiatric inpatients, emphasising the serious psychological morbidity experienced by patients with urinary symptoms. Fifty patients with detrusor instability or sensory urgency entered a randomised trial comparing psychotherapy, bladder drill, and propantheline. The psychotherapy group significantly improved on measures of urgency, incontinence, and nocturia, though not on frequency. Bladder training was an effective treatment for frequency and patients became less anxious and depressed. There was a modest improvement in frequency of micturition in patients given propantheline. Frequency may be a learnt disorder which responds to the direct symptom oriented approach of bladder training. Patients with urgency and nocturia predominating might derive more benefit from psychotherapy.     

In Vitro Evaluation of Spider Silk Meshes as a Potential Biomaterial for Bladder Reconstruction

Reconstruction of the bladder by means of both natural and synthetic materials remains a challenge due to severe adverse effects such as mechanical failure. Here we investigate the application of spider major ampullate gland-derived dragline silk from the Nephila edulis spider, a natural biomaterial with outstanding mechanical properties and a slow degradation rate, as a potential scaffold for bladder reconstruction by studying the cellular response of primary bladder cells to this biomaterial. We demonstrate that spider silk without any additional biological coating supports adhesion and growth of primary human urothelial cells (HUCs), which are multipotent bladder cells able to differentiate into the various epithelial layers of the bladder. HUCs cultured on spider silk did not show significant changes in the expression of various epithelial-to-mesenchymal transition and fibrosis associated genes, and demonstrated only slight reduction in the expression of adhesion and cellular differentiation genes. Furthermore, flow cytometric analysis showed that most of the silk-exposed HUCs maintain an undifferentiated immunophenotype. These results demonstrate that spider silk from the Nephila edulis spider supports adhesion, survival and growth of HUCs without significantly altering their cellular properties making this type of material a suitable candidate for being tested in pre-clinical models for bladder reconstruction.     

Potential application of stem cells in urogynecology

Recent advances in stem cells therapy and tissue engineering techniques hold great promise for recovery of external urethral sphincter proper functioning and urinary incontinent patients treatment. Adult stem cells (ASCs) may be derived from striated muscles, fat tissue or as mesenchymal cells from bone marrow. These cells can differentiate in functionally normal smooth or striated muscle cells. ASCs injected to external urethral sphincter or bladder neck cause the increase in urethral closure pressure. Favourable findings of trials in animal models and in vitro encouraged to first trials in humans and hold a promising future for the treatment of urinary incontinence.     

Stress incontinence in women; treatment by retropubic urethrovesical suspension

Twenty-four retropubic urethrovesical suspension operations were performed in a five-year period. Twenty-one of the patients were satisfied with the results, although the objective success of the operation did not always correlate with subjective relief of symptoms. The commonest apparent cause for failure was the coincidence of urgency with stress incontinence, and the few true failures, due to secondary relaxation of the paraurethral supports, were often mitigated by compensatory learning on the part of the patients, many of whom remain blissfully unaware of the underlying weakness. The retropubic urethrovesical suspension operation is simple, effective, and free of complications. It is indicated as a primary procedure whenever a vaginal operation has failed to cure (or, worse, has caused) stress incontinence. It is advised as a complementary procedure for women with a secondary complaint of stress incontinence who must undergo laparotomy for other cause.     

实时三维盆底超声对产后压力性尿失禁患者疗效评估作用及与尿动力学的相关性分析

摘要 目的：探讨实时三维盆底超声对产后压力性尿失禁（SUI）患者疗效评估作用及与尿动力学的相关性。方法：选择2020年4月至2022年12月石家庄市人民医院收治的139例产后SUI患者,均接受盆底生物反馈电刺激联合盆底肌锻炼治疗。治疗前后分别进行实时三维盆底超声检查和尿动力学检查。比较治疗前后实时三维盆底超声参数、尿动力学指标差异。Pearson法分析实时三维盆底超声参数与尿动力学指标的相关性。结果：实时三维盆底超声图像特征显示：治疗前盆膈裂孔内的结构疏松,回声变弱,盆腔器官结缔组织疏松,间隙增宽,盆膈裂孔面积、尿道旋转角、膀胱尿道后角以及膀胱颈移动度较大;治疗后盆膈裂孔两侧耻骨直肠肌对称,耻骨内脏肌呈带状高回声,盆膈裂孔面积、尿道旋转角、膀胱尿道后角以及膀胱颈移动度较治疗前降低。产后SUI患者治疗后静息状态和Valsalva状态下盆膈裂孔面积、尿道旋转角、膀胱尿道后角、膀胱颈移动度均较治疗前降低（P＜0.05）,腹压漏尿点压、最大逼尿肌压力均较治疗前增加（P＜0.05）。产后SUI患者静息状态和Valsalva状态下盆膈裂孔面积、尿道旋转角、膀胱尿道后角、膀胱颈移动度与最大逼尿肌压力、腹压漏尿点压呈负相关（P＜0.05）,与最大膀胱容量和残余尿量无关（P＞0.05）。结论：产后SUI患者经盆底生物反馈电刺激联合盆底肌锻炼治疗后实时三维盆底超声参数较治疗前降低,与尿动力学改善有关。临床可通过实时三维盆底超声检查,对产后SUI患者进行临床疗效评价,以指导临床治疗。     

探讨女性盆底功能障碍性疾病的相关因素及盆底超声测定压力性尿失禁SUI的临床意义

目的:探讨女性盆底功能障碍性疾病的相关因素及盆底超声测定压力性尿失禁SUI的临床意义。方法:选取我院2019年-2020年共收治的63例盆底功能障碍性疾病患者作为研究对象,将其分为研究组,另取同期来我院进行体检的63例健康女性作为对照组,对所有女性应用盆底超声检测,对比两组女性静息状态下和Valsalva状态下的盆底超声检查指标,对通过问卷调查方式,调查两组女性的一般临床治疗,对于女性盆底功能障碍性疾病的相关因素进行单因素分析与多因素分析,最终得出盆底肌功能障碍性疾病的相关因素。结果:在静息状态下通过盆底超声发现,研究组与对照组膀胱尿道后角、肛提肌裂孔面积、尿道倾斜度对比差异显著(P<0.05),两组女性膀胱颈位置、膀胱位置对比无明显差异(P>0.05);在Valsalva状态下通过盆底超声发现,研究组与对照组膀胱尿道后角、肛提肌裂孔面积、尿道倾斜度、膀胱颈位置、膀胱位置对比差异显著(P<0.05);两组女性年龄、BMI、孕次、产次、绝经情况以及白带清洁度是否≥Ⅲ度情况对比差异显著(P<0.05),两组女性子宫肌瘤史情况对比无显著差异(P>0.05);logistic回归分析结果显示,年龄、绝经情况、子宫肌瘤史和白带清洁度≥Ⅲ度不是盆底功能障碍性疾病的独立危险因素(P>0.05),BMI、孕次、产次为盆底功能障碍性疾病的独立危险因素(P<0.05)。结论:盆底肌超声在对盆底功能障碍性疾病患者压力性尿失禁的诊断中具有重要价值,在静息状态下和Valsalva状态下发现患者的膀胱经移动情况与尿道倾斜情况。年龄、BMI、孕次、产次、绝经情况以及白带清洁度是否≥Ⅲ度可能与盆底功能障碍性疾病具有一定关系,BMI、孕次、产次为盆底功能障碍性疾病的独立危险因素。     

The distribution of noradrenergic nerves and small,intensely fluorescent (SIF) cells in the cat urinary bladder

Summary Fluorescence and electron microscopy have been used to study the distribution of noradrenergic nerves in the smooth muscle of the cat urinary bladder. Using the former technique, relatively few fluorescent noradrenergic nerves were observed in the body and fundus, while a rich plexus occurred adjacent to muscle cells of the bladder neck. The trigone could not be distinguished neuromorphologically from detrusor muscle in this region. Electron microscopy showed that the majority of noradrenergic terminals in the body and fundus were associated with presumptive cholinergic axons, while in the bladder neck noradrenergic terminals formed typical neuroeffector relationships with individual smooth muscle cells.Numerous ganglia occurred both in the adventitia and among the smooth muscle bundles, particularly in the bladder neck. The majority of the nerve cell bodies were non-fluorescent, although many contained bright orange autofluorescent granules, believed to be lysosomes. A small minority of ganglion cells were associated with fluorescent noradrenergic nerve terminals, thereby providing structural evidence for limited intraganglionic inhibition. In addition, occasional groups of small intensely fluorescent (SIF) cells were observed in some intramural ganglia and these were subsequently identified in the electron microscope. The possibility that these cells may provide a second inhibitory influence on bladder activity was considered.     

Biofeedback in treatment of urinary incontinence in stroke patients

Urinary incontinence can occur poststroke owing to weakness or incoordination of sphincter muscles, impaired bladder sensation, or hyperreflexic, neurogenic bladder. Four male subjects who had urinary incontinence associated with a stroke that had occurred 8 months to 10 years earlier, and who averaged 1.6 to 7.5 accidental voidings per week, participated in an outpatient study with a 4-week scheduled-voiding baseline, 2 to 5 sessions of biofeedback-assisted bladder retraining, and 6- to 12-month follow-up. Training sessions included stepwise filling of the bladder and manometric feedback display of bladder pressure, abdominal pressure, and external anal sphincter pressure. Training procedures were designed to teach subjects to attend to bladder sensations, inhibit bladder contractions, and improve voluntary sphincter muscle control. All four subjects achieved and maintained continence regardless of substantial differences in subject characteristics, including laterality of stroke, degree of sensory impairment, and independence in daily activities.     

STRESS INCONTINENCE IN WOMEN—Treatment by Retropubic Urethrovesical Suspension

Twenty-four retropubic urethrovesical suspension operations were performed in a five-year period. Twenty-one of the patients were satisfied with the results, although the objective success of the operation did not always correlate with subjective relief of symptoms. The commonest apparent cause for failure was the coincidence of urgency with stress incontinence, and the few true failures, due to secondary relaxation of the paraurethral supports, were often mitigated by compensatory learning on the part of the patients, many of whom remain blissfully unaware of the underlying weakness.The retropubic urethrovesical suspension operation is simple, effective, and free of complications. It is indicated as a primary procedure whenever a vaginal operation has failed to cure (or, worse, has caused) stress incontinence. It is advised as a complementary procedure for women with a secondary complaint of stress incontinence who must undergo laparotomy for other cause.     

盆底超声参数预测剖宫产术后压力性尿失禁的效能及其与盆底组织E-cadherin和Vimentin表达的关系研究

摘要 目的：研究盆底超声参数预测剖宫产术后压力性尿失禁（SUI）的效能及其与盆底组织钙粘附蛋白E（E-cadherin）和波形蛋白（Vimentin）表达的关系。方法：选取2020年1月～2021年1月湖南省妇幼保健院收治的124例剖宫产患者。将其按照是否发生SUI分为SUI组18例以及无SUI组106例。对所有患者均进行盆底超声检查,比较两组静息期（R）、张力期Valsalva动作（V）的膀胱尿道后角（PUA）以及膀胱颈到耻骨联合下缘水平垂直距离（BNS）,膀胱颈移动度（BND）、尿道旋转角度（UR）。通过受试者工作特征（ROC）曲线分析盆底超声参数预测剖宫产术后SUI的效能。另外,对比两组盆底组织E-cadherin和Vimentin mRNA水平,采用Pearson相关性分析各项盆底超声参数和盆底组织E-cadherin、Vimentin mRNA表达的相关性。结果：SUI组R-PUA、V-PUA、BND以及UR均高于无SUI组,而R-BNS以及V-BNS均低于无SUI组（均P＜0.05）。ROC曲线分析结果：各项盆底超声参数联合预测剖宫产术后SUI的效能均优于各项参数单独预测。SUI组盆底组织E-cadherin mRNA水平低于无SUI组,而Vimentin mRNA水平高于无SUI组（均P＜0.05）。经Pearson相关性分析发现,R-PUA、V-PUA、BND、UR均和盆底组织E-cadherin mRNA水平呈负相关关系,与Vimentin mRNA水平呈正相关关系;而R-BNS、V-BNS均和盆底组织E-cadherin mRNA水平呈正相关关系,与Vimentin mRNA水平呈负相关关系（均P＜0.05）。结论：盆底超声参数预测剖宫产术后SUI的效能较高,且和盆底组织E-cadherin、Vimentin表达有关。     

Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female rat.

Vaginal delivery of children causes traumatic injury to tissues of the pelvic floor and is correlated with stress urinary incontinence; however, the exact mechanism of organ and tissue injury leading to incontinence development is unknown. The purpose of this project was to test the hypothesis that vaginal distension results in decreased blood flow to, and hypoxia of, the urogenital organs responsible for continence, which would suggest an ischemic and/or reperfusion mechanism of injury. Thirteen female rats underwent vaginal distension for 1 h. Thirteen age-matched rats were sham-distended controls. Blood flow to the bladder, urethra, and vagina were determined using a microsphere technique. Hypoxia of these organs was determined by immunohistochemistry. Blood flow to all three organs was significantly decreased just before release of vaginal distension. Bladder blood flow decreased further immediately after release of vaginal distension and continued to be significantly decreased 15 min after the release. Blood flow to both the urethra and vagina tripled immediately after release, inducing a rapid return to normal values. Vaginal distension resulted in extensive smooth muscle hypoxia of the bladder, as well as extensive hypoxia of the vaginal epithelium and urethral hypoxia. Bladders from sham-distended rats demonstrated urothelial hypoxia as well as focal hypoxic areas of the detrusor muscle. We have clearly demonstrated that vaginal distension results in decreased blood flow to, and hypoxia of, the bladder, urethra, and vagina, supportive of hypoxic injury as a possible mechanism of injury leading to stress urinary incontinence.     

Biofeedback in treatment of urinary incontinence in stroke patients

Urinary incontinence can occur poststroke owing to weakness or incoordination of sphincter muscles, impaired bladder sensation, or hyperreflexic, neurogenic bladder. Four male subjects who had urinary incontinence associated with a stroke that had occurred 8 months to 10 years earlier, and who averaged 1.6 to 7.5 accidental voidings per week, participated in an outpatient study with a 4-week scheduled-voiding baseline, 2 to 5 sessions of biofeedback-assisted bladder retraining, and 6- to 12-month follow-up. Training sessions included stepwise filling of the bladder and manometric feedback display of bladder pressure, abdominal pressure, and external anal sphincter pressure. Training procedures were designed to teach subjects to attend to bladder sensations, inhibit bladder contractions, and improve voluntary sphincter muscle control. All four subjects achieved and maintained continence regardless of substantial differences in subject characteristics, including laterality of stroke, degree of sensory impairment, and independence in daily activities.     

Common Urological Conditions in the Female

Stress incontinence, urge incontinence, and pyelitis of pregnancy are common urological conditions in the female. Poor therapeutic results in the treatment of stress incontinence may be traced to errors in diagnosis. Accurate diagnosis is based on an accurate history, residual urine test, the stress test, cystometric studies (to rule out neurogenic disturbances), cystourethroscopy and cystourethrography. The most important factor in the production of urge incontinence is infection. Some pathological conditions which may be associated with urge incontinence are urethritis, cystitis, urethral stricture, bladder-neck obstruction, urethral diverticula, urethral caruncle and the urgencyfrequency syndrome. Therapy is directed toward the eradication of infection and treatment of the specific lesion. In pyelitis of pregnancy it is urged that, in cases of unusual bacterial virulence and poor ureteral drainage, early cystoscopic ureteral catheter drainage should be instituted in order to prevent permanent kidney damage. The closest co-operation of urologist, gynecologist and general physician is necessary for clarification of some of the more complex problems.     

Effect of herbal extract mixture on menopausal urinary incontinence in ovariectomized rats

The decline of estrogen production after menopause is contributing factor to urinary incontinence (UI), and particularly stress urinary incontinence (SUI). We determined the preventive effects of herbal extract mixture (HEM) on UI in ovariectomized Sprague Dawley rats. Female 9-weeks old rats were ovariectomized and treated with HEM (2.2, 11, or 55 mg/kg/day) for 8 weeks. The index of urinary bladder weight to body weight in the HEM and non-ovariectomized and non-treated (SHAM) groups were slightly higher than the ovariectomized, non-treated group (OVX). The contraction index of acetylcholine to KCl on detrusor smooth muscle strips in the HEM groups showed a dose-dependent recovery. HEM treatment also significantly improved collagen levels, as shown by Masson trichrome staining, as well as hydroxyproline levels in the urinary bladder. Serum estradiol levels in the HEM groups were higher than the OVX group. In conclusion, HEM increased estradiol levels in serum and improved factors related to urinary incontinence. The improvements in estradiol levels were related to changes in urinary incontinence.