A multicenter, prospective, randomized clinical trial comparing tension-free vaginal tape surgery and no treatment for the management of stress urinary incontinence in elderly women.

AIMS: The aim of our study was to test the hypothesis that elderly women undergoing tension-free vaginal tape surgery (TVT) will have a better quality of life (QOL) and satisfaction compared to non-treated women despite age- and technique-related potential morbidity. METHODS: This multicenter, prospective, randomized, controlled trial enrolled a total of 69 women aged over 70 years who initially consented to be randomized to either undergo immediate TVT surgery or to wait for 6 months before submitting to the same surgery (control group). The main outcomes measured at every visit (pre-randomization, 8-12 weeks and 6 months) consisted of the Incontinence-Quality of Life (I-QOL) Questionnaire, the Patient Satisfaction Questionnaire and the Urinary Problems Self-assessment Questionnaire, among others. RESULTS: The analysis included 31 patients in the immediate surgery group and 27 subjects in the control group. Peri-operative complications in the immediate surgery group were bladder perforation (22.6%), urinary retention (12.9%), urinary tract infection (3.2%) and de novo urgency (3.2%). At 6 months, the mean I-QOL scores for the TVT and control groups were respectively 96.5 +/- 15.5 and 61.6 +/- 19.8 (P < 0.0001); mean Patient Satisfaction scores were respectively 8.0 +/- 2.7 and 2.0 +/- 2.4 (P < 0.0001); and mean Urinary Problems scores were respectively 4.5 +/- 4.3 and 11.6 +/- 3.5 (P < 0.0001). CONCLUSION: At 6 months post-randomization, the group of elderly women who underwent immediate TVT surgery showed a significant improvement in QOL, patient satisfaction and less urinary problems compared to the group of women waiting for the same surgery.

Multi-centre study of intraurethral valve-pump catheter in women with a hypocontractile or acontractile bladder.

OBJECTIVES: To compare the safety, effectiveness and patient satisfaction of an intraurethral valve-pump catheter (In-Flow) versus the current standard of care, clean intermittent catheterization (CIC), for females with hypocontractile or acontractile bladder. MATERIALS AND METHODS: The study was a multi-centre, prospective, single-arm crossover study. Eligible patients underwent a 1-week In-Flow tolerability trial. Successful patients then continued through an 8-week baseline phase using CIC, followed by a 16-week In-Flow treatment phase, and a final 4-week treatment withdrawal phase. Outcome measures included post-void residual (PVR), Wagner incontinence-specific quality of life (I-QOL), rate of urinary tract infection and adverse events. At study completion, open enrollment was offered. RESULTS: A total of 273 women with a mean age of 48.9 years using CIC entered the study in 18 centres under either the original (n=88) or revised protocols (n=185). The revised protocol included the addition of a 1-week tolerability trial. The reasons for the large early withdrawal of subjects (169/273) were mainly related to initial discomfort and leakage. A total of 77 patients completed the In-Flow treatment phase. PVR was comparable during baseline CIC phase and In-Flow treatment phase (20.3 ml vs. 16.1 ml), with significantly improved quality of life (QOL; mean improvement of I-QOL score +25.9; p<0.001). CONCLUSION: The In-Flow catheter appears to be a viable alternative to CIC. A subgroup of patients, mainly those unsatisfied with the currently available treatments, was more likely to tolerate In-Flow catheters, and they may achieve enhanced independence and QOL.

Return of spontaneous erection during long-term intracavernosal alprostadil (Caverject) treatment.

OBJECTIVES: To investigate the effect of long-term intracavernosal self-injection of alprostadil (Caverject) on the penile circulation and return of spontaneous erection in men with arteriogenic erectile dysfunction. METHODS: Seventy men with a stable heterosexual partner entered the titration phase of this open-label, flexible-dose study. The effective alprostadil dose (ie, the dose producing penile rigidity adequate for intercourse and lasting up to 60 minutes) was determined before entry into the 12-month self-treatment home phase. Duplex ultrasonography was used to measure the peak systolic velocity and diameter of the cavernosal arteries at the end of the titration phase and after 4, 8, and 12 months of the home phase. The efficacy, tolerability, and return of spontaneous erections were assessed from the patients' diaries and by interview at each clinic visit. Sixty-three men entered the home phase; 49 of them filled out the diaries and 42 completed the study. RESULTS: An effective dose was established for 67 (96%) of the 70 men (median dose 15 microg). During the home phase, 94% of men responded to alprostadil, and the median dose remained unchanged. Complete duplex ultrasound data were obtained in 38 men and showed significant increases in postinjection peak systolic velocity in both cavernosal arteries (P <0.001 at 12 months) and between the preinjection and postinjection cavernosal arterial diameters (P = 0.0001) compared with baseline. Reports of a return of spontaneous erections increased throughout the study compared with baseline (37%, 26 of 70) and were confirmed by interview for 46 (85%) of 54 men with available data overall. Treatment was generally well accepted, with low incidences of penile pain (23%), prolonged erection, which resolved spontaneously (6%), and fibrosis (1%). CONCLUSIONS: Intracavernosal alprostadil was effective, acceptable, and generally well tolerated in men with arteriogenic erectile dysfunction. Long-term treatment improved the penile circulation, and most men reported an increase in return of spontaneous erections.

Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates in intensive care unit patients: a multicenter study.

OBJECTIVES: Indwelling urinary catheters are the leading source of nosocomial urinary tract infections (NUTIs). The Bardex I.C. catheter is a hydrogel latex Foley catheter with a monolayer of silver metal applied to the inner and outer surfaces of the catheter. We investigated the Bardex I.C. catheter for its ability to decrease the NUTI rate in critical care units. METHODS: Five hospitals participated in a blind prospective study, exchanging the standard latex Foley catheter for the Bardex I.C. Foley catheter. The device use rate and NUTI rate were monitored. Data were collected and analyzed using Wilcoxon rank sum test and four-way analysis of variance. A cost analysis was also performed. RESULTS: The baseline period, intervention period, and number of device days was similar for both periods. The unadjusted catheter-associated infection rate during the baseline and intervention periods was 7.1 and 4.5 infections per 1000 catheter days, respectively (P <0.01). The adjusted catheter-associated infection rate during the baseline and intervention periods was 8.1 and 4.9 infections per 1000 catheter days, respectively. This was not statistically significant (P = 0. 13). CONCLUSIONS: A trend toward a reduction in NUTIs with the use of the hydrogel/silver-coated catheter was noted in all intensive care units at each institution as shown by the unadjusted and adjusted catheter-associated infection rates. One hospital demonstrated a statistically significant reduction in NUTIs. However, statistical significance was not met when the results were adjusted. The cost analysis at one institution demonstrated cost savings with the use of the silver-coated catheter. Future analysis may require a double-blind, prospective-controlled study of longer duration to reach statistical significance.

Antiproliferative activity is present in bladder but not renal pelvic urine from interstitial cystitis patients.

PURPOSE: To determine whether an antiproliferative urine factor that we previously discovered to be specific for urine from interstitial cystitis (IC) patients originated in the lower urinary tract or a more proximal site. MATERIALS AND METHODS: Sequential catheterized urine specimens were collected under sterile conditions from the bladder and renal pelvis of 20 IC patients and one control patient (with stress incontinence). Antiproliferative activity was determined by 3H-thymidine incorporation of primary normal adult bladder epithelial cells cultured with pH- and osmolality-corrected bladder or ureteral urine specimens; significant inhibition was defined as a change in 3H-thymidine incorporation greater than 2 standard deviations from the mean of control cells. RESULTS: Bladder urine specimens from 19 of 20 IC patients significantly inhibited 3H-thymidine incorporation as compared to cell medium alone (mean change for bladder specimens = -68.7+/-7.5%), while a renal pelvic specimen from only 1 of 20 IC patients inhibited proliferation significantly (mean change for renal pelvic specimens = 3.2+/-3.4%) (p<.001 by Fisher's exact test). The one inhibitory IC renal pelvic specimen inhibited by 31% while a bladder specimen obtained during the same procedure inhibited by 94%. In comparison, neither bladder nor renal pelvic urine from the control patient had inhibitory activity. CONCLUSIONS: The antiproliferative factor previously found in the urine of IC patients appears to be made and/or activated in the distal ureter or urinary bladder.

Diagnosing bladder outlet obstruction in women.

PURPOSE: There are no universally accepted urodynamic criteria for diagnosing female bladder outlet obstruction. When accepted criteria for men are applied to women, the diagnosis of obstruction may often be missed, which is most likely due to differences in voiding dynamics. We propose video urodynamic criteria for diagnosing obstruction in women, and describe the urodynamic findings in those with and without obstruction. MATERIALS AND METHODS: We reviewed the charts of 331 women who underwent multichannel video urodynamics for nonneurogenic voiding dysfunction. Of these women 261 (mean age 55.8 years) had evaluable voiding pressure flow studies with simultaneous video fluoroscopy of the bladder outlet during voiding. At video urodynamics cases were classified as obstructed if there was radiographic evidence of obstruction between the bladder neck and distal urethra in the presence of a sustained detrusor contraction. Strict pressure flow criteria were not used. Maximum flow rate, detrusor pressure at maximum flow rate, post-void residual, bladder capacity and the incidence of detrusor instability were compared between obstructed and unobstructed cases. RESULTS: A total of 76 women met the criteria for obstruction (mean age 57.5 years), while 184 (mean age 55) did not. Causes of obstruction were dysfunctional voiding in 25 cases, cystocele in 21, primary bladder neck obstruction in 12, iatrogenic from incontinence surgery in 11, urethral stricture in 3, uterine prolapse in 2, urethral diverticulum in 1 and rectocele in 1. Obstructed cases had lower mean maximum flow rate (9 versus 20.2 ml. per second, p <0.0001), higher mean detrusor pressure at maximum flow rate (42.8 versus 22.1 cm. water, p <0.0001) and higher mean post-void residual (157 versus 33 ml., p <0.0001). There was no difference in bladder capacity (381 versus 347 ml.) or incidence of detrusor instability (45 versus 41%). CONCLUSIONS: Using the proposed video urodynamic criteria obstructed cases had significantly higher voiding pressures, lower flow rates and higher post-void residual than unobstructed cases, as expected. However, absolute values, especially for voiding pressure, are not as dramatic in women as in men. Pressure flow studies alone may fail to diagnose obstruction but simultaneous imaging of the bladder outlet during voiding greatly facilitates diagnosis.

Evaluation of the role of neurolinins and urecholine hypersensitivity in an animal model of infravesical outflow obstruction.

OBJECTIVES: To determine whether detrusor muscle strips from a male rat with infravesical outflow obstruction model demonstrate supersensitivity to parasympathomimetic and neurokinin NK-1 and NK-2 selective agonists. METHODS: Bladder instability developed after 6 weeks of partial urethral obstruction. The micturition frequency and voided volume were determined in unanesthetized animals. Detrusor hypertrophy was confirmed by evaluation of bladder weight. In vitro organ bath was used to compare the affinity and maximal activity of bethanechol and neurokinin NK-1 and NK-2 selective agonists on strips from the detrusor muscle of sham and obstructed rats. Bethanechol, N-Ac[Arg6, Sar9, Met(O2)]-SP(6-11), and [beta-Ala8]-NKA(4-10) were used to characterize cholinergic muscarinic, neurokinin NK-1 and NK-2 receptors. Results. No significant differences in affinities and maximal responses were found using 10-mg detrusor muscle strips with each of the three agonists. CONCLUSIONS: Bladder instability produced by outlet obstruction does not involve changes in the affinity or maximal activity of cholinergic muscarinic, neurokinin NK-1 and NK-2 receptors. Furthermore, detrusor supersensitivity to neurokinins or bethanechol was not seen. This suggests that bladder instability is not due to an increased affinity or maximal response to neurokinins or parasympathomimetics.

Hyperreflexia of the urinary bladder: possible role of the efferent function of the capsaicin sensitive primary afferents.

PURPOSE: Capsaicin sensitive primary afferents (CSPA) have been implicated in the pathogenesis of hyperreflexia after spinalization. In this study we investigated the role of the efferent function of these fibers in detrusor hyperreflexia and its effect on detrusor physiology and pharmacology. MATERIALS AND METHODS: Four groups of female Sprague Dawley rats were included in our study. These groups were normal controls, capsaicin treated normal rats, spinalized rats and capsaicin treated spinalized rats. Six weeks following spinalization, animals were subjected to cystometric study, and bladders were obtained for either in vitro detrusor contractility study or substance P (SP), neurokinin A (NKA) and calcitonin gene related peptide (CGRP) quantification by radioimmunoassay. RESULTS: Spinalized animals consistently developed hyperreflexia after spinalization in the form of uninhibited contractions more than 15 cm. water in amplitude. This was accompanied by increased urinary bladder total content of the neuropeptides but without any change in the detrusor contractility or neurokinin receptor pharmacology as shown by responses to KCl, electric field stimulation and neurokinin receptor selective agonists in the in vitro study. In the control group, urinary bladder total content of SP, NKA and CGRP was 0.19+/-0.03, 0.15+/-0.01 and 0.84+/-0.1 pmol/bladder respectively. In contrast, in the spinalized animals, these were 0.44+/-0.07, 0.21+/-0.03 and 2.28+/-0.34 pmol/bladder for the same peptides, respectively. Capsaicin treatment abolished hyperreflexia, which corresponded with the decrease in the neuropeptide content of the urinary bladder. The number and amplitude of the uninhibited contractions decreased dramatically. SP, NKA and CGRP reached 0.06+/-0.01, 0.07+/-0.01 and 0.44+/-0.18 pmol/bladder 2 weeks after capsaicin treatment in spinalized animals. This was associated with the occurrence of detrusor super-sensitivity to both neurokinin receptor selective agonists. CONCLUSION: This study demonstrates the importance of the efferent function of the CSPA in the pathogenesis of hyperreflexia. On the other hand, detrusor changes were shown to be a noncrucial factor in the development of hyperreflexia.

Reduction of bladder outlet resistance by selective sacral root stimulation using high-frequency blockade in dogs: an acute study.

Detrusor-sphincter dyssynergia is a main problem in supra-sacral spinal cord injured patients. The problem of high pressure voiding is also encountered in most electrically induced micturition because of the mixed somatic and autonomic fiber components of the ventral sacral root. We studied the effect of selective high-frequency blockade at the sacral nerve root in an acute spinalized canine model to prevent the deleterious consequences associated with the elevated bladder outlet resistance. A new functional electrical stimulation system which can generate one signal composed of two independent adjustable current waveforms delivered via a single bipolar electrode was used in 11 dogs. The selectivity resulted from the inhibition of the sphincteric somatic innervation by a high frequency pulse while the low frequency stimuli activated the bladder autonomic fibers. Bladder and urethral pressure as well as electromyograms of external urethral sphincter were recorded to determine whether selective high-frequency blockade occurred. Our experiments showed that we were able to achieve selective blockade of the external urethral sphincter during the simultaneous detrusor stimulation, thus obtaining a more physiologic voiding.

Evaluation of a no-needle penile injector: a preliminary study evaluating tissue penetration and its hemodynamic consequences in the rat.

OBJECTIVES: Intracavernous needle injection is an effective delivery method for pharmacotherapy of erectile dysfunction. Needle phobia, pain, and concern about local tissue injury have stimulated the search for new, less invasive means of inducing penile erection. In this preliminary communication, we evaluate a jet injector as an alternative to needle injection for intracavernous delivery of vasoactive drugs. METHODS: Jet injection was evaluated in three groups of rats receiving either India ink, saline, or papaverine into the penis. The ability of the jet injection to penetrate through the tunica albuginea and deliver liquid to the corpora cavernosa smooth muscle was assessed by the degree of staining within the corpus cavernosum (ink group), histologic change (saline group), and rise in intracavernous pressure (papaverine group). Erectile capacity following cavernous nerve electric stimulation was compared before and 1 hour after injection of saline or papaverine. RESULTS: Ink traversed the skin and tunica albuginea with extensive deposition noted within the cavernous spaces. Varying degree of subcutaneous hemorrhage were seen with saline jet injection; however, the corpus cavernous smooth muscles showed no evidence of injury. Jet injection of papaverine 3250 micrograms significantly increased cavernous pressure (39.4 +/- 4.6 cm H2O) compared with saline injection (2.8 +/- 1.3 cm H2O). CONCLUSIONS: We conclude that acute jet injection is an effective method for intracavernous delivery of drugs. Long-term effects should be evaluated prior to clinical use.