Stress Urinary Incontinence in Women

The glycogenolysis markers (glycogen content, active and total glycogen phosphorylase [EC 2.4.1.1.] activities, and active and total acid exo-alpha-1,4-glucosidase [EC 3.2.1.3.] activities) in the urinary bladder muscle from two patients with stress urinary incontinence and concomitant detrusor instability were studied. Glycogen depletion and activation of glycogen phosphorylase were found.     

Intravesical adipose tissue: a quantitative study of its presence and location with implications for therapy and prognosis

Accurate pathologic staging of carcinomas of the urinary bladder involves assessment of invasion by the tumor into the bladder wall and beyond into perivesical soft tissue. The presence of tumor within perivesical soft tissue implies pathologic stage pT3 (AJCC/UICC system, 1997). In traditional textbooks of histology, anatomy, pathology, and in the literature, other than a single case report and a brief reference in another paper, there is no information on the presence of adipose tissue in the lamina propria or muscularis propria of the urinary bladder. Nine hundred forty-three sections from 139 cystectomy specimens were evaluated for the presence, location, and quantity of adipose tissue within the lamina propria and muscularis propria. The histology of the perivesical soft tissues and the nature of its delineation from muscularis propria were also analyzed. Adipose tissue was seen within the lamina propria in 53% (74 of 139) of cystectomies and in 17.6% (166 of 943) of the examined sections. It was located predominantly in the deep lamina propria (at or below the muscularis mucosae) in 81.1% (60 of 74) of the cystectomies and in 91% (151 of 166) of the sections. Within the lamina propria it was predominantly seen as small localized aggregates in 92% (153 of 166) of sections. All cases showed adipose tissue within the muscularis propria. Adipose tissue was identified within the superficial (inner) muscularis propria in 54% (512 of 943) of sections and was predominantly in small aggregates in 80.5% (412 of 512) of sections. It was in moderate to abundant quantities within the deep (outer) muscularis propria in 60.7% (572 of 943) of sections. The perivesical soft tissue was almost exclusively composed of adipose tissue with variable vascularity. Delineation of the perivesical adipose tissue from the deep (outer) muscularis propria was typically indistinct because muscle bundles of the latter haphazardly merged with the perivesical adipose tissue. Based on these findings, we conclude that adipose tissue is frequently present in the lamina propria and muscularis propria of the urinary bladder wall, and is usually scant in the former location and frequently abundant in the latter. Awareness of the high frequency of adipose tissue within the urinary bladder wall has prognostic and therapeutic implications. In transurethral resection of bladder tumor (TURBT) specimens, misinterpretation of tumor infiltrating adipose tissue within lamina propria (pT1) as perivesical soft tissue involvement (pT3) may potentially result in unwarranted aggressive management. Substaging of muscle invasive tumors should be performed in cystectomy specimens only, because the junction of muscularis propria and the perivesical adipose tissue is typically ill-defined. Muscularis propria adipose tissue in TURBT specimens may be erroneously assumed to be perivesical adipose tissue, potentially leading to overstaging of the primary tumor.     

Comparative morphometric study of bladder detrusor between patients with benign prostatic hyperplasia and controls

PURPOSE: We determined the change in the amount of connective tissue of the detrusor in patients with benign prostatic hyperplasia (BPH) in relation to the degree of bladder hypertrophy by ultrasound estimated bladder weight. The ratio of connective tissue-to-smooth muscle between controls and BPH cases was compared. MATERIALS AND METHODS: For normal controls we used cadaver bladders excised at autopsy from 13 men with no urinary tract diseases. Bladder wall samples were also obtained at subcapsular prostatectomy for BPH in 26 patients. On thin sections stained with Masson trichrome, the ratio of connective tissue-to-smooth muscle was measured using a computer assisted color image analysis. This ratio was compared in BPH cases with estimated bladder weight, which was measured preoperatively using transabdominal ultrasonography. RESULTS: A connective tissue-to-smooth muscle ratio ranged from 19.8 to 28.2% (mean plus or minus standard deviation 24.7+/-2.4) and from 12.9 to 53.3% (27.3+/-9.9) in control and BPH cases, respectively. In BPH cases a significant correlation was noted between estimated bladder weight and connective tissue-to-smooth muscle ratio (r=0.788, p <0.0001). Interestingly, in BPH cases with an estimated bladder weight of less than 60 gm. the ratio ranged from 12.9 to 30.4% (22.8+/-4.9), which was not significantly different compared to control cases. In contrast, in all BPH cases with an estimated bladder weight of 60 gm. or more connective tissue-to-smooth muscle ratio increased significantly to more than 30% (range 33.4 to 53.3%, mean 42.2+/-13.6%). CONCLUSIONS: These results suggest that abnormal increase of connective tissue in addition to smooth muscle hypertrophy and/or hyperplasia could contribute to advanced bladder hypertrophy caused by infravesical obstruction.     

Treatment results using a mixed fiber mesh in patients with grade IV cystocele

PURPOSE: We determined the efficacy of a modification of the 4-corner bladder and bladder neck suspension procedure using mixed fiber mesh to correct grade IV cystocele. MATERIALS AND METHODS: We evaluated 15 women with a mean age of 67 years who had severe anterior vaginal wall prolapse, of whom 3 had concurrent enterorectocele. Previously 5 patients had undergone repair of anterior vaginal wall prolapse and 2 had undergone procedures for stress urinary incontinence. In 10 patients type II stress urinary incontinence was diagnosed with urethral hypermobility and abdominal leak point pressure greater than 90 cm. water. No patients with intrinsic sphincter deficiency were enrolled in the study. A mixed fiber mesh was positioned using a modification of the 4-corner bladder and bladder neck suspension technique. Patients with concurrent enterorectocele underwent simultaneous formal repair of the posterior descensus. RESULTS: All patients were available for postoperative pelvic examination at 3-month intervals. Mean followup was 23.4 months (range 18 to 39). Of the 15 women 13 were continent (dry) at followup. No recurrent cystocele was evident, except in 1 patient who presented with segmental posterior bladder prolapse. In 2 patients new onset enterorectocele developed 6 months after mesh implantation. CONCLUSIONS: Our study confirms that the addition of mesh to the classic 4-corner bladder base and neck suspension procedure effectively treats incontinence and cystocele. We recommend this method for cases in which traditional techniques have previously failed and when the quality of suspending tissue is poor or defective, as in connective tissue disease. However, the risk of worsening enterorectocele or its new onset must be considered.     

Bladder wall abnormalities in myelodysplastic bladders: a computer assisted morphometric analysis

Myelodysplasia represents the most common cause of neurogenic bladder dysfunction in children. The specific histological features associated with myelodysplastic bladders have not been previously characterized. Our objective was to study the relationship between smooth muscle and connective tissue in control and myelodysplastic bladders using classical morphometric analysis with the assistance of an automated image analysis system. Gross histological analysis of the bladder specimens of normal stillborn fetuses showed organized muscle bundles embedded in a small amount of connective tissue. The bladder specimens of myelomeningocele stillborn fetuses showed a marked paucity of muscle bundles as well as a significantly diminished size of the muscle bundles. The myelomeningocele bladder specimens obtained from patients undergoing autopsy and those undergoing augmentation cystoplasty revealed significant interfascicular and pericellular infiltration of the smooth muscle by dense connective tissue. Quantitative morphometric analysis showed that the myelomeningocele stillborn fetuses have a significant increase in the volumetric content of connective tissue compared to control stillborn fetuses. The bladders of myelomeningocele patients who underwent autopsy or augmentation cystoplasty had a 3-fold increase in connective tissue when compared to normal controls. These findings reveal that structural changes in the histological components of the myelodysplastic bladder can be demonstrated not only in patients of varying ages undergoing autopsy or augmentation cystoplasty but also in the developing fetus. These findings enhance our understanding of the relationship of connective tissue proliferation to smooth muscle in the myelodysplastic bladder. We discuss the relationship of these findings to pathological detrusor morphology and detrusor dysfunction.     

Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401: inhibition and inactivation of glycogen phosphorylase by an activated metabolite

The racemic prodrug BAY R3401 suppresses hepatic glycogenolysis. BAY W1807, the active metabolite of BAY R3401, inhibits muscle glycogen phosphorylase a and b. We investigated whether BAY R3401 reduces hepatic glycogenolysis by allosteric inhibition or by phosphatase-catalyzed inactivation of phosphorylase. In gel-filtered liver extracts, racemic BAY U6751 (containing active BAY W1807) was tested for inhibition of phosphorylase in the glycogenolytic (in which only phosphorylase a is active) and glycogen-synthetic (for the evaluation of a:b ratios) directions. Phosphorylase inactivation by endogenous phosphatase was also studied. In liver extracts, BAY U6751 (0.9-36 micromol/l) inhibited glycogen synthesis by phosphorylase b (notwithstanding the inclusion of AMP), but not by phosphorylase a. Inhibition of phosphorylase-a-catalyzed glycogenolysis was partially relieved by AMP (500 micromol/l). BAY U6751 facilitated phosphorylase-a dephosphorylation. Isolated hepatocytes and perfused livers were tested for BAY R3401-induced changes in phosphorylase-a:b ratios and glycogenolytic output. Though ineffective in extracts, BAY R3401 (0.25 micromol/l-0.5 mmol/l) promoted phosphorylase-a dephosphorylation in hepatocytes. In perfused livers exposed to dibutyryl cAMP (100 micromol/l) for maximal activation of phosphorylase, BAY R3401 (125 micromol/l) inactivated phosphorylase by 63% but glucose output dropped by 83%. Inhibition of glycogenolysis suppressed glucose-6-phosphate (G6P) levels. Activation of glycogen synthase after phosphorylase inactivation depended on the maintenance of G6P levels by supplementing glucose (50 mmol/l). We conclude that the metabolites of BAY R3401 suppress hepatic glycogenolysis by allosteric inhibition and by the dephosphorylation of phosphorylase a.     

Is the histomorphological concept of the female pelvic floor and its changes due to age and vaginal delivery correct?

AIMS: To compare the histomorphology of pelvic floor specimens of 94 female cadavers, ten male cadavers, and 24 female symptomatic patients who underwent pelvic floor surgery, and to evaluate the association of age, parity, and sex to myogenic and/or neurogenic changes to the levator ani muscle (LAM). METHODS: The pelvic floor was biopsied at the pubococcygeus, the iliococcygeus and the coccygeus muscle. After staining, signs for myogenic/neurogenic changes to the muscle were evaluated (fibrosis, variation in fiber diameter, centralization of nuclei, small angulated fibers, and type grouping). To identify the intact neuromuscular junction stainings with NCAM (neuronal cell adhesion molecule) and acetylcholinesterase (ACE) were used. RESULTS: A significant influence of age and parity on the histomorphological criteria of myogenic cell-damage was shown in this study. Although these criteria were found even in young nulliparous women, there was a significant increase in older or parous women with at least one vaginal delivery. We failed to demonstrate significant changes between the nulliparous LAM, the male LAM, and the LAM from women with prolapse and incontinence. None of the specimen showed any obvious evidence of neuropathy. CONCLUSIONS: We have evaluated histological criteria adapted from the examination of limb muscles in the LAM of nulliparous young women. "Myogenic changes" seem to be a normal finding in the LAM. The increase of these changes with aging and parity points to mechanical stress to the LAM as the most plausible causative factor. We propose that further studies using histomorphological techniques of the pelvic floor muscle in nulliparous and parous women should clarify the potential role of our histological findings.     

Epidemiologie und Ätiologie der Harninkontinenz im Alter

Urinary incontinence is an important and common health problem, whose prevalence increases with age. Often quality of life is clearly affected for persons concerned. In the group of elderly individuals (≥60 years of age) 19.3% of women and 10.4% of men report urinary incontinence. Women most frequently describe urinary stress incontinence followed by incontinence with urge symptoms (urge incontinence, mixed incontinence). In men urinary incontinence without any symptoms of stress or urge incontinence is most common followed by incontinence with urge symptoms and stress incontinence. Urinary incontinence in the elderly is rarely due to a single reason but rather due to multiple factors. In urinary stress incontinence, a differentiation can be made between mechanical and functional problems of the sphincter mechanism caused by myogenic, neurogenic, hormonal, or iatrogenic factors as well as changes in connective tissue. In urinary incontinence with urge symptoms, geriatric detrusor function is mostly affected by neurogenic, myogenic, or urothelial factors whereas the detrusor muscle shows characteristic ultrastructural changes. In chronic urinary retention with consecutive urinary incontinence, especially in men infravesical obstruction is more often the reason than a geriatric bladder dysfunction.     

Epidemiology and etiology of urinary incontinence in the elderly

Urinary incontinence is an important and common health problem, whose prevalence increases with age. Often quality of life is clearly affected for persons concerned. In the group of elderly individuals (> or =60 years of age) 19.3% of women and 10.4% of men report urinary incontinence. Women most frequently describe urinary stress incontinence followed by incontinence with urge symptoms (urge incontinence, mixed incontinence). In men urinary incontinence without any symptoms of stress or urge incontinence is most common followed by incontinence with urge symptoms and stress incontinence. Urinary incontinence in the elderly is rarely due to a single reason but rather due to multiple factors. In urinary stress incontinence, a differentiation can be made between mechanical and functional problems of the sphincter mechanism caused by myogenic, neurogenic, hormonal, or iatrogenic factors as well as changes in connective tissue. In urinary incontinence with urge symptoms, geriatric detrusor function is mostly affected by neurogenic, myogenic, or urothelial factors whereas the detrusor muscle shows characteristic ultrastructural changes. In chronic urinary retention with consecutive urinary incontinence, especially in men infravesical obstruction is more often the reason than a geriatric bladder dysfunction.     

Immunohistochemical detection of steroid receptors in a case of pulmonary lymphangioleiomyomatosis

Abnormal proliferation of smooth muscle cells in pulmonary lymphangioleiomyomatosis (LAM) is thought to be influenced by estrogen and progesterone. However, the results of previous studies using cytosolic methods to measure estrogen and progesterone receptor content in lung tissue from these patients have been inconsistent. We used immunohistochemical methods to study the tissue distribution of estrogen and progesterone receptors in LAM as well as in smooth muscle of several other organs, including histologically normal lung, colon, bladder, prostate, uterus, and uterine leiomyomas. Progesterone receptor was expressed strongly and estrogen receptor more weakly by the abnormal myoid cells of LAM. Hormone receptors were absent from all other constituents of lung tissue in our patient. These findings were similar to those in histologically normal myometrium and uterine leiomyomas. Although we found focal labeling of prostatic stromal cells with anti-progesterone receptor, no other smooth muscle tissue expressed either estrogen or progesterone receptor. We conclude that LAM is an abnormal proliferation of smooth muscle cells that express both estrogen and progesterone receptors.     

Interstitial cystitis followed by total cystectomy

A case of interstitial cystitis which was ultimately treated by total cystectomy is presented. Examination of the rare bladder specimen revealed thickening and contraction of the bladder, submucosal ulcerations and involvement of the bladder wall, with bands of collagenous connective tissue extending into the perivesical adipose tissue. Increased numbers of mast cells and a chronic lymphocytic infiltrate were present in the submucosa. The immunologic aspects of the disease are discussed and the literature reviewed.     

Morphologic changes in detrusor muscles of patients with chronic obstruction of lower urinary tract. Electronmicroscopic and immunohistochemical findings

The anterior bladder wall and actin- and myosin-like immunoreactivities within the detrusor muscles in patients with chronic obstruction of the lower urinary tract were examined by means of a MOP Videoplan image-processing system, electronmicroscopy, and light microscopic immunohistochemistry. The image-processing system demonstrated an excess of connective tissue elements between smooth muscle bundles in the anterior wall of the bladder similar to the results of previous studies dealing with the trabeculated posterior wall. Under electronmicroscopy, myofilaments were shown to be multidirectionally arranged in the smooth muscle cells in contrast to the regular arrangement in controls. Dense areas in the cytoplasm of the detrusor muscle also appeared to be abnormally distorted and/or elongated in the electronmicrographs. In support of these findings, actin- and myosin-like immunoreactivities in the muscle layer of the bladder were significantly less intense than in the controls. These results suggest that chronic obstruction of the lower urinary tract causes histopathologic alterations in both the intervening connective tissue and the detrusor muscle. This study raises the possibility that the aforementioned morphologic abnormalities are involved in the occurrence of uninhibited detrusor contraction and abnormal detrusor reflex in patients with lower urinary tract obstruction.     

In vitro studies of glucose metabolism of the rabbit urinary bladder

The urinary bladder, as do all smooth muscle organs, depends on the delivery of oxygen and metabolic substrates for proper functioning. Although glucose metabolism has been studied and evaluated for a variety of smooth muscle systems, little is known about carbohydrate metabolism of the urinary bladder. In the present investigation glucose metabolism and glycogen formation of the urinary bladder of the rabbit was studied in vitro. Isolated urinary bladder strips were prepared from bladder base and body and the following metabolic determinations were made: glucose utilization, glycogen formation, CO2, and lactic acid formation. In addition, the effect of insulin on glucose metabolism was investigated. Glucose utilization was similar in bladder base and body (6.57 +/- 0.67 mumols/gm./2 hours in combined tissues). Eighty-one percent of the glucose utilized was metabolized to lactate whereas 11% was oxidized to CO2 and 4.7% was incorporated into glycogen. Insulin caused a small but significant increase in glucose utilization by bladder strips.     

Structure of trabeculated detrusor smooth muscle in cases of prostatic hypertrophy

The light and electron microscopic structure of biopsy samples of trabeculated urinary bladder from patients with proven outlfow obstruction due to prostic hypertrophy has been compared with the morphology of control bladder specimens. In the latter the detrusor muscle bundles were composed of smooth muscle cells closely packed together with very little intervening connective tissue. In contrast, irrespective of age, detrusor muscle from trabeculated bladders contained many muscle bundles in which the constituent cells were of relatively small diameter and were widely separated from each other by dense masses of connective tissue. No morphological evidence for smooth muscle hypertrophy or hyperplasia was obtained in the present study. In the electron microscope the connective tissue between the smooth muscle cells of trabeculated bladders was seen to contain, in addition to collagen fibrils, an extensive meshwork of electron-dense microfibrils apparently in continuity with the basal laminae of the smooth muscle cells. Regions of close approach between smooth muscle cells were seemingly unaffected by trabeculation as was the distrubution and fine structure of autonomic nerve terminals. These observations are intended to form a baseline for comparision with the results of future morphological studies of trabeculation arising in response to different aetiological factors.     

The effect of urinary incontinence and overactive bladder symptoms on quality of life in young women

OBJECTIVE: To assess the consequences that the symptoms of urinary incontinence and an overactive bladder have on the quality of life in young, community-dwelling women. SUBJECTS AND METHODS: A population-based, cross-sectional cohort study was conducted in women aged 20-45 years. Urogenital symptoms and quality of life were assessed using standardized questionnaires, e.g. the Urogenital Distress Inventory and Incontinence Impact Questionnaire. RESULTS: The prevalence of symptoms of stress incontinence (39%), urge incontinence (15%) and an overactive bladder (12%) was high in this young population. Compared with urge incontinence, the symptoms of an overactive bladder similarly reduced the quality of life, but stress incontinence did not significantly affect the quality of life. Women with symptoms of an overactive bladder were especially limited in their mobility, whereas urge incontinence was especially associated with feelings of embarrassment. Although many women reported to be bothered by their symptoms, only a minority consulted their physician for them. CONCLUSIONS: The symptoms of urinary incontinence and overactive bladder are common among young adult women and have the same detrimental effect on quality of life as urge incontinence. The reduction in mobility associated with overactive bladder symptoms may be especially distressing for these young and active women.     

Gender-related neuronal and smooth muscle damage of guinea pig isolated urinary bladder from anoxia-glucopenia and reperfusion injury and its relationship to glycogen content

AIMS: To investigate the effects of anoxia and glucopenia (A-G) on both male and female guinea pig urinary bladder. METHODS: In whole bladders superfused with oxygenated Krebs' solution, intrinsic nerves underwent electrical field stimulation (EFS) and smooth muscle stimulated with carbachol, ATP, and high potassium. The effect of 1, 2, or 3 hr A-G on the contractile response and the ensuing recovery in Krebs' solution, was monitored. Glycogen content in male and female urinary bladders was also measured. RESULTS: Under different stimuli male urinary bladder proved to contract more efficiently than female organ. After 1 hr A-G the EFS response of male urinary bladder was virtually abolished and returned to 60% of control response in the recovery phase; in female bladder the EFS responses fully recovered during the reperfusion phase. Full recovery of the response to carbachol, ATP, and high potassium stimulations was observed in both genders. A-G had to be extended to 2 hr to cause smooth muscle impairment (higher in male than in female) and a neuronal impairment in female urinary bladders. When 2-deoxyglucose (2-DG), an inhibitor of glycolysis, was added during 1 hr A-G, both neuronal and smooth muscle damages were significantly enhanced in male, as well as, though to a lesser extent, in female bladder. A significantly higher glycogen content was observed in female as compared to male bladders, which was inversely related with the duration of exposure to A-G. CONCLUSIONS: The higher resistance of female urinary bladder to A-G/reperfusion, can be partly ascribed to the higher glycogen content.     

Use of injectable fat to obstruct the urethra in rabbits

Bulking agents have been injected to correct urinary incontinence for at least 15 years. The injection seeks to increase bladder outlet resistance by partially obstructing the urethra and thereby reduce urinary leakage in patients with stress urinary incontinence. Although the implant is effective and requires a shorter in-hospital stay than more traditional procedures, no ideal implant substance has been discovered. To assess the effectiveness of injected fat as a bulking agent, we injected small volumes of perivesical fat into the bladder neck in New Zealand White (NZW) rabbits and tested the effect on the bladder. In eight rabbits, we harvested perivesical fat and partially closed the urethral lumen with an initial injection. A second injection 1 month later completely closed the urethral lumen. We injected six other rabbits with similar volumes of saline as controls. Two weeks after the second injection, we measured micturition frequency, bladder weight, response to electrical field stimulation, and response to bethanecol in each group. Fat implants were present at the injection site in each case 4 weeks after the first injection. Rabbits receiving fat implants had increased micturition frequency, increased bladder weight, and increased response to bethanecol and field stimulation. Previous studies have demonstrated that these changes are characteristic of mild outlet obstruction in rabbits. Injected fat can be made to close the urethra and create bladder outlet obstruction in rabbits. The short-term success of fat as a bulking agent in this experiment is encouraging and suggests the need for longer term studies. © 1995 Wiley-Liss, Inc.     

Bladder dysfunction in patients with cauda equina lesions

AIMS: Data on lower urinary tract (LUT) function obtained in larger, systematically studied populations of patients with cauda equina lesions are limited. We report urinary function in 65 patients with chronic lesions. METHODS: A urinary function questionnaire was used, and neurological examination, quantitative electromyography (EMG) of the external anal sphincter (EAS) muscles, EMG assessment of the sacral reflex, and conventional urodynamic measurements were performed. RESULTS: Severe LUT dysfunction was found in 14%/15%, moderate in 27%/46%, and mild in 46%/39% men/women. Urinary symptoms interfered with daily life in 88%/92% and sexual life in 72%/67% of sexually active men/women. Symptoms of disturbed bladder emptying were the most common (95%/92% men/women), followed by urinary incontinence (56%/71%) and symptoms of overactive bladder (40%/56%). Perianal sensation was abnormal in 96%, EMG of the EAS muscle in 88%, and sacral reflex in 84% of patients. In 40%/17% men/women, a postvoid residual (>100 ml) was found. On filling cystometry overactive bladder was found in 21%/0%, reduced detrusor capacity in 9%/15%, and during voiding phase an acontractile detrusor or detrusor underactivity were found in 59%/85% men/women. Using multiple linear regression analysis, perianal sensory loss (P=0.0001) and female gender (P<0.02) had a significant positive effect on urinary incontinence score. CONCLUSIONS: Our study demonstrated significant LUT dysfunction, which disturbed the life of the majority of patients with chronic lesions of the cauda equina. Due to poor correlation between patients' symptoms and urodynamic findings cystometric surveillance is proposed in all patients with significant cauda equina lesions.