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Purpose: We studied the effect of oxybutynin on bladder and upper urinary tract outcomes in infants following posterior urethral valve ablation., Materials and Methods: Patients younger than 12 months old who had undergone primary endoscopic valve ablation for posterior urethral valves were screened for eligibility. Patients who had undergone urinary diversion or had other conditions that could affect lower urinary tract function were excluded. Study patients were randomized to either oxybutynin (0.2 mg/kg 3 times daily) until toilet training or active observation. The study end points were serum creatinine, estimated glomerular filtration rate, hydronephrosis improvement, vesicoureteral reflux resolution, febrile urinary tract infection and toilet training., Results: A total of 49 infants (24 receiving oxybutynin and 25 undergoing observation) were enrolled between December 2013 and September 2015 and completed at least 1 year of followup. Oxybutynin was discontinued before toilet training in 5 patients due to facial flushing in 2, bladder and upper tract dilatation in 2, and cognitive changes in 1. After a median followup of 44.2 months (range 12 to 57.6) median serum creatinine and estimated glomerular filtration rate were not significantly different between the groups (p=0.823 and p=0.722, respectively). Renal units in the oxybutynin group had a greater likelihood of hydronephrosis improvement (61.9% vs 34.8%, p=0.011) and resolution of vesicoureteral reflux (62.5% vs 25%, p=0.023). Febrile urinary tract infection (29.2% vs 40%, p=0.404), completion of toilet training (70.8% vs 76%, p=0.748) and age at toilet training (p=0.247) did not differ significantly between the oxybutynin and observation groups., Conclusions: Oxybutynin enhances hydronephrosis improvement and vesicoureteral reflux resolution following primary endoscopic valve ablation in infants but periodic monitoring is warranted.

Purpose: An obstructive urinary flow pattern is frequently seen after tubularized incised plate urethroplasty for hypospadias. However, the significance of this finding has not been determined and long-term results are few. We describe postoperative long-term uroflowmetry results after puberty in males who underwent tubularized incised plate urethroplasty in childhood., Materials and Methods: A total of 126 boys underwent tubularized incised plate urethroplasty for distal penile to mid shaft hypospadias at Queen Silvia Children's Hospital in Gothenburg between 1999 and 2003. Of the patients 48 were toilet trained at surgery. We report on 40 patients who had data available at 2 and 12 months postoperatively, 7 years postoperatively and at puberty (median age 15.0 years, range 13.7 to 17.1). Of the patients 31 had distal and 9 had mid penile hypospadias. Clinical examination, urinary medical history, uroflowmetry and ultrasound measuring residual urine were performed. Maximum urinary flow was correlated to age and voided volume, using Miskolc nomograms for comparison of percentiles., Results: At 1 year postoperatively 15 boys (37.5%) had normal urinary flow (above 25th percentile), compared to 16 (40%) at 7 years and 38 (95%) at puberty (p <0.0001). Improvement was significant in patients with distal (p <0.0001) and mid penile hypospadias (p = 0.008), as well as in patients who did (p = 0.0078) and did not undergo intervention (p <0.0001). During followup 5 patients underwent meatotomy due to obstructive symptoms and 4 underwent dilation. Three of these 9 patients had lichen sclerosus., Conclusions: There is great potential for normalization of urinary flow at puberty for boys with hypospadias treated with tubularized incised plate urethroplasty. Unless symptoms occur, a conservative approach seems preferable., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The existence of an inhibitory rectovesical reflex elicited by noxious colorectal afferent input was previously documented in an isovolumetric cystometry model with a ligated urethra. We compared the effect of noxious colorectal distension on bladder cystometry with an open and a ligated urethra., Materials and Methods: We used female Sprague Dawley® rats anesthetized with urethane. The effect of noxious (60 mm Hg) colorectal distension on intermittent and continuous cystometry with an open urethra was studied and then compared to inhibiting isovolumetric bladder contractions in the same rat after ligating the urethra. We evaluated volume, the pressure micturition threshold, the intercontraction interval, bladder contraction frequency and amplitude of micturition contractions., Results: Noxious colorectal distension at 60 mm Hg did not significantly influence volume or the pressure micturition threshold during intermittent cystometry. It also did not influence the pressure micturition threshold, the intercontraction interval or bladder contraction frequency during continuous cystometry. After urethral ligation 60 mm Hg colorectal distension inhibited isovolumetric bladder contraction frequency in the same rat (mean ± SEM 0.363 ± 0.207 vs 0.886 ± 0.106 contractions per minute, p <0.05). This inhibition persisted a mean of 289.08 ± 91.24 seconds after deflating the rectal balloon., Conclusions: The inhibitory rectovesical reflex elicited by noxious colorectal distension clearly occurred in an isovolumetric bladder model with a ligated urethra but only to a negligible extent in filling related voiding contractions. Our results suggest that the inhibitory rectovesical reflex, most likely at the level of the lumbosacral spinal cord, is the result of an additive noxious urethral and colonic afferent stimulus., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the role of N-methyl-D-aspartate (NMDA) glutamatergic receptors in the development of functional bladder changes after partial urethral obstruction we investigated the effects of repeat injection of MK-801, a noncompetitive NMDA receptor antagonist, on the micturition reflex in conscious obstructed rats., Materials and Methods: In 9 female Wistar rats 1.0 mg/kg MK-801 was injected intramuscularly once weekly just prior to the creation of partial urethral obstruction until 5 weeks after obstruction. Five to 7 days after the last injection of MK-801 conscious filling cystometry was performed and compared with that in 9 obstructed rats treated with vehicle (saline). Conscious filling cystometry was also compared in 9 and 7 sham operated rats treated with repeat injection of MK-801 and vehicle, respectively., Results: Partial urethral obstruction caused a significant increase in bladder weight. However, chronic MK-801 treatment did not affect bladder weight in obstructed or sham operated rats. In the obstructed/MK-801 vs the obstructed/vehicle group chronic treatment with MK-801 significantly increased bladder capacity (2.29 +/- 0.12 vs 1.73 +/- 0.16 ml, p <0.01) and voided volume (2.00 +/- 0.10 vs 1.56 +/- 0.17 ml, p <0.05) without changes in voiding efficiency (87.5% +/- 1.6% vs 87.8% +/- 1.7%) or micturition pressure (55.8 +/- 2.3 vs 56.4 +/- 3.0 cm water). Interestingly neither the frequency nor amplitude of premicturition contractions during filling was different in the groups. In sham operated rats chronic MK-801 treatment did not change bladder capacity, voided volume, voiding efficiency or micturition pressure significantly., Conclusions: The results in the current study suggest that bladder outlet obstruction causes NMDA receptor mediated alterations in bladder afferent pathways in the rat.

Purpose: Neuroplasticity in afferent pathways, including C-fiber bladder afferents, is believed to be one of the major causes of changes in bladder function after partial urethral obstruction. We determined if capsaicin sensitive C-fiber bladder afferents are involved in the development of pre-micturition contractions after partial urethral obstruction in the rat., Materials and Methods: Female Wistar rats were preemptively treated with capsaicin (100 mg/kg subcutaneously) or resiniferatoxin (0.3 mg/kg subcutaneously) prior to the creation of obstruction. Before and 6 weeks after obstruction micturition profiles were compared among the 3 groups, including obstructed rats preemptively treated with capsaicin (BO/CAP) or resiniferatoxin (BO/RTX) and untreated obstructed rats (BO/-). In addition, conscious filling cystometry was performed after obstruction., Results: Instillation of capsaicin solutions into the eye or bladder induced significant irritative reactions in BO/- but not in BO/CAP or BO/RTX, indicating that the effect of pretreatment with capsaicin or resiniferatoxin lasted 6 weeks. Voided volume per micturition on micturition profiles was decreased after partial urethral obstruction in all 3 groups. On conscious filling cystometry a significant increase in bladder capacity, voided volume and micturition threshold pressure was noted in BO/CAP but not in BO/RTX compared with BO/-. In contrast, there was no significant change in residual volume, voiding efficiency or micturition pressure among the 3 groups. The prevalence of pre-micturition contractions was 100% in BO/CAP and BO/RTX, and 83% in BO/-., Conclusions: Capsaicin sensitive C-fiber afferents are not essential to induce pre-micturition contractions but they are involved in functional alterations in bladder afferent pathways after partial urethral obstruction in rats.

Purpose: We prospectively evaluated the American Urological Association (AUA) symptom index and maximum urine flow for predicting urethral stricture recurrence in men with a previous diagnosis of urethral stricture disease., Materials and Methods: Patients were recruited at our urethral stricture clinic, where all newly diagnosed and previously treated men with urethral stricture present and are treated. The AUA symptom index was completed and uroflowmetry was done. The stricture was calibrated using Jacques catheters. If an 18Fr catheter could not be passed, a retrograde urethrogram was performed. Patients were treated with filiform dilation or direct vision internal urethrotomy. Uroflowmetry was repeated when the catheter was removed 3 days later and the AUA symptom index was repeated 1 month later., Results: Data on 49 patients (170 consultations) between March 2000 and August 2001 were analyzed. Average patient age was 48 years. There was a significant negative correlation of urethral diameter with AUA symptom index and of AUA symptom index with maximum urine flow as well as a significant positive correlation of urethral diameter with maximum urine flow. We evaluated the usefulness of AUA symptom index and maximum urine flow at different cutoff levels for predicting urethral stricture in our study group. Using an AUA symptom index of greater than 10 or maximum urine flow of less than 15 ml. per second as cutoff values provided 93% sensitivity, 68% specificity, 78% positive predictive value, 89% negative predictive value and 82% overall accuracy. This method could have prevented further invasive studies in 34% of patients, while a clinically significant stricture would have been missed in only 4.3%., Conclusions: AUA symptom index combined with maximum urine flow is an accurate, time-saving and cost-effective tool for predicting recurrent stricture in patients with a known urethral stricture. It can be used to direct decision making on further invasive studies and treatment.

Purpose: We treat neonatally estrogenized rats and aromatase over expressing AROM+ male mice with infravesical obstruction using the specific aromatase inhibitors finrozole and letrozole, and analyzed whether developmentally induced alterations in urodynamics and rhabdosphincter are reversible in adulthood., Materials and Methods: Adult estrogenized rats and AROM+ mice were treated with aromatase inhibitors for 6 weeks. Maximal and mean bladder pressure, the urinary flow rates and electromyography activity were recorded from the proximal rhabdosphincter. In addition, proximal rhabdosphincter thickness in the AROM+ mouse was measured and correlated with seminal vesicle size and serum testosterone concentrations., Results: Finrozole and/or letrozole treatment significantly increased the mean maximal flow rate plus or minus SD in AROM+ mice (4.7 +/- 2.0 versus 13.3 +/- 4.4 ml. per minute, p = 0.0004) and in estrogenized rats (18.4 +/- 6.18 versus 31.1 +/- 10.85 ml. per minute for finrozole p = 0.005) and 32.4 +/- 14.3 for letrozole, p = 0.005), while bladder pressure slightly decreased. The reappearance of transient repolarization, indicating urethral lumen opening, coincided with an increased flow rate on electromyography in the proximal rhabdosphincter in rats. Relative thickness of the proximal rhabdosphincter (p = 0.007), seminal vesicle size (p = 0.0002) and mean serum testosterone concentration (472.5 +/- 230.35 versus 3,065.6 +/- 1,994.67 pg./ml., p = 0.0002) were restored after finrozole treatment in AROM+ mice., Conclusions: Current findings indicate that alterations in urodynamics, seminal vesicle size, and rhabdosphincter size and function in developmentally estrogenized male rodents are reversible when treated with aromatase inhibitor.

Purpose: It has been suggested that hypocontractility or myogenic failure develops in older boys with a history of 9 posterior urethral valved as the hyperactive, poorly compliant bladders decompensate with age. Also a much higher prevalence of myogenic failure has been reported than we have observed. We determine the prevalence of myogenic failure in boys with a posterior urethral valve and whether myogenic failure was a consequence of earlier detrusor instability or diminished compliance., Materials and Methods: We retrospectively reviewed the urodynamic findings of 51 boys after transurethral ablation of a posterior urethral valve. Group 1 (longitudinal group) consisted of 11 boys 12 to 19 years old who had undergone at least 1 serial urodynamic study before and 1 after age 10 years. Group 2 (younger group) included 33 boys whose urodynamic testing was performed before age 10 years. Group 3 (older group) comprised 7 previously treated boys whose initial urodynamic study was done after age 12 years., Results: Overall, myogenic failure was noted in 3 (all group 1) of 51 (5.9%) patients. Each of the 3 boys initially had a hypocompliant bladder, and myogenic failure developed only after institution of anticholinergic therapy and resolved once anticholinergics were discontinued. An additional 34 boys treated with anticholinergics did not have myogenic failure. No tendency towards myogenic failure or marked increase in bladder capacity for age was noted in the older boys., Conclusions: In our experience myogenic failure is uncommon and more likely secondary to anticholinergic therapy than a preordained consequence of valve disease. We postulate that our proactive, early aggressive use of urodynamic studies and pharmacotherapy to identify and manage the secondary effects of valve disease reduces the incidence of myogenic failure.

Purpose: We monitored detrusor blood flow in pigs with bladder outflow obstruction., Materials and Methods: Partial urethral obstruction was created in 9 immature, female large white pigs with an implanted ring, and 10 normal animals were used for comparison. Urodynamic parameters and detrusor blood flow were measured using chronically implanted access catheters and laser Doppler fibers. Repeated recordings were made from each animal while it was lightly sedated., Results: The animals with implanted rings developed prolonged, high pressure voiding contractions in association with poor urinary flow, indicating bladder outflow obstruction, and had evidence of detrusor instability. In obstructed and normal animals detrusor blood flow was maintained during bladder filling. Elevated detrusor pressure during voiding significantly decreased blood flow to similar levels in each group. The duration of the ischemic period was much greater in obstructed animals., Conclusions: Bladder outflow obstruction is associated with repeated episodes of prolonged detrusor ischemia which may account for the biochemical and neuronal alterations in such bladders.

Purpose: We established the longitudinal changes in bladder contractility and compliance as a result of urethral obstruction using a guinea pig model., Materials and Methods: Obstruction was induced in guinea pigs by a silver ring around the urethra. Urodynamic studies were performed longitudinally in individual animals. Bladder contractility and compliance were calculated from the measured bladder pressure and urine flow rate., Results: Bladder contractility developed in distinct phases. It reached a maximum 200% increase after an average of 3.25 weeks concomitant with an almost 2-fold increase in urethral resistance, remained 150% to 200% increased during weeks 4 to 7 and then decreased to starting levels again, while urethral resistance remained almost 2-fold increased. Bladder compliance decreased by 80% during the first 3 weeks and continued to decrease to 5% of its original value after 10 to 11 weeks., Conclusions: Our data indicate that as a result of obstruction bladder function passes through a specific sequence of stages, including first a compensatory increase in contractility, then a stabilization phase and finally a decompensation state. In contrast bladder compliance shows a continuous decrease. The data suggest that for assessing how far a bladder has deteriorated due to obstruction a combination of functional and structural data may be warranted.

Purpose: We determine whether long-term bladder dysfunction is more frequent in children with posterior urethral valves who undergo early supravesical urinary diversion (pyeloureterostomy) than in those who undergo valve ablation., Materials and Methods: Urodynamic studies were performed in 59 boys with severe posterior urethral valves who were divided into 2 groups based on initial treatment of valve ablation (30) and bilateral pyeloureterostomy (29)., Results: Of the 59 boys 25 (42%) had a normal bladder, including 11 with an over distended bladder and 34 (58%) had bladder dysfunction, including instability in 22, poor compliance in 9 and myogenic failure in 3. Of the 30 boys initially treated with valve ablation 14 (46.6%) had a normal bladder, including 7 with an over distended bladder and 16 (53.4%) had bladder dysfunction, including instability in 10, poor compliance in 4 and myogenic failure in 2. Of the 29 boys initially treated with temporary bilateral pyeloureterostomy 11 (38%) had normal bladders, 4 with an over distended bladder and 18 (62%) had bladder dysfunction, including instability in 12, poor compliance in 5 and myogenic failure in 1. There were no statistically significant differences in the number or type of bladder dysfunction between the diversion and valve ablation groups., Conclusions: Therefore, temporary pyeloureterostomy did not affect bladder function adversely in the long term.

Purpose: In rats, urethral obstruction was previously shown to lead to detrusor instability, but bladder instability in conscious animals has not been well characterized. The present study was designed to describe the consequences of bladder outlet obstruction on urodynamic parameters in the conscious rat. A categorization of different types of bladder instability in conscious rats is described., Materials and Methods: Cystometry was performed on conscious animals with chronically implanted lines. Recordings of the micturition pattern and the bladder pressure during the micturition cycle were made from normal female rats and those with instability caused by infravesical outflow obstruction., Results: In control rats, the peak micturition pressure was low (45.6+/-2.5 cm. H2O) and only small pressure fluctuations occurred before or after micturition. Rats with outlet obstruction exhibited bladder hypertrophy, high micturition pressure (95.5+/-6.8 cm. H2O) as well as marked spontaneous activity throughout the micturition cycle. According to the spontaneous activity profile we identified four main patterns of abnormal micturition cycles., Conclusion: Urethral obstruction in rats leads to a significant increase in bladder weight and to altered micturition patterns which reveal clear similarities with features of the cystometric profiles performed in men with infravesical outflow obstruction. These modifications are not consistently correlated with an increase in bladder weight.

Purpose: We evaluated the clinical use of the renal resistive index in identifying patients with acute urinary tract obstruction., Materials and Methods: Of 54 patients with suspected acute urinary tract obstruction who underwent measurements of renal resistive index 19 had unilateral obstruction documented with excretory urography and comprise our study sample. The contralateral nonobstructed kidneys served as controls. Criteria for obstruction were a resistive index of 0.70 or greater or a side to side difference of 0.10 or greater. We calculated sensitivity, specificity, and positive and negative predictive values., Results: Sensitivity for obstruction was 42% with 11 false-positive cases, specificity was 79%, and positive and negative predictive values were 67 and 57%, respectively., Conclusions: Renal resistive index measurements are not valuable in detecting acute urinary tract obstruction.

Purpose: We assess the long-term effects of finasteride on bladder outlet obstruction and symptoms in the treatment of patients with benign prostatic hyperplasia., Materials and Methods: Of the original 36 patients assigned to treatment with 5 mg. finasteride daily (group 1) or placebo (group 2) for 6 months 27 completed an open extension study of 5 mg. finasteride for 4 more years. The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline, 6 months and 4.5 years., Results: The treatment resulted in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period, whereas improvement in maximum flow rate did not achieve statistical significance. Concomitantly, there was a significant improvement in obstructive and irritative symptoms., Conclusions: Finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely. However, the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly. The beneficial effect is long-lasting.

Purpose: We document changes in pressure-flow study parameters in patients treated by transurethral microwave thermotherapy., Materials and Methods: Pressure-flow study tracings before and after therapy from 75 patients with benign prostatic hyperplasia were analyzed. Patients were stratified according to the predominant type of obstruction at screening (constrictive or obstructive)., Results: An improvement in Madsen score and flow rates was noted at 6 months in both groups. In contrast to compressive obstruction patients, however, those with constrictive obstruction also showed significant changes in pressure-flow study parameters, including detrusor pressure at maximum flow, maximum flow rate and urethral resistance factor., Conclusions: Patients with predominantly constrictive obstruction are the best candidates for microwave thermotherapy.

Purpose: The urodynamic effects of intravesical resiniferatoxin and capsaicin were investigated in rats., Materials and Methods: Continuous cystometry was performed in conscious, female Sprague-Dawley rats with and without outflow obstruction., Results: Intravesical instillation of resiniferatoxin facilitated micturition. The potency of the drug was approximately 1,000 times higher than that of capsaicin. Repeated instillations of resiniferatoxin for 6 consecutive days caused desensitization to resiniferatoxin. This was not found with repeated instillations of capsaicin. Capsaicin was also effective in rats with bladder hypertrophy, while resiniferatoxin was not., Conclusions: The findings suggest that resiniferatoxin can induce desensitization of vanilloid receptor-mediated release of tachykinins in the rat urinary bladder and that intravesical resiniferatoxin would be an interesting alternative to intravesical capsaicin in the treatment of selected cases of bladder hypersensitivity/hyperactivity.

Transvaginal urethrolysis was performed in 48 patients with urethral obstruction following 1 or more urethral suspension procedures. A needle suspension procedure had been performed in 19 patients (40%), retropubic urethropexy in 17 (35%) and pubovaginal sling in 10 (21%). A good response as indicated by normal voiding with minimal or no irritative symptoms was achieved in 33 patients (65%). The most common presenting complaints were irritative voiding symptoms (71%) and urinary retention (60%). Fluoroscopic urodynamic evaluation frequently demonstrated urethral hypersuspension, a cystocele and/or elevated voiding pressures. No patient had stress urinary incontinence as a result of the procedure. Urethral obstruction should be recognized as a potential complication following surgical correction of female stress urinary incontinence. Transvaginal urethrolysis is a safe and effective method to manage this problem.

A nonrandomized pilot study was done of 139 patients with symptomatic benign prostatic hyperplasia treated with 3 prostatic heating devices. Of the patients 19 underwent transrectal hyperthermia with the Biodan Prostathermer and in 15 the Primus Prostate Machine was used. At 2 1/2 years 7 of 19 patients (37%) patients in the Prostathermer group and 6 of 15 (40%) in the Primus group had adequate sustained improvement and had not undergone further treatment. At 1 year 55 of 100 patients (55%) treated with the Thermex-II section transurethral thermotherapy unit had a satisfactory result, with 40 (40%) having undergone transurethral resection of the prostate. The number of patients who failed therapy increased with each followup. Analysis of pretreatment parameters, including patient age, prostate size, peak urinary flow rate, post-void residual urine volume and symptom score, did not predict a successful outcome. Although these devices have minimal effect on peak urinary flow rate, a subset of patients enjoy symptomatic improvement.

The passive electrical properties of guinea pig detrusor muscle were studied in order to determine how bladder outflow obstruction and reversal might modify the electrical activity of the bladder and, thus, contractility. Experimental bladder outflow obstruction was produced in guinea pigs and resulted in an increase in bladder weight with a decrease in spontaneous electrical activity, membrane time constant and space constant. In addition, the membrane Na-K pump activity increased with obstruction. Following reversal of obstruction, bladder weight gain associated with obstruction was only partially reversible. The decrease in the membrane time constant induced by obstruction was almost fully reversible following release of obstruction. In contrast, the membrane space constant which reflects spread of current, in addition to spontaneous electrical activity, were only partially reversible. The membrane Na-K pump activity of the detrusor muscle decreased to control levels following reversal of bladder outflow obstruction. There was no significant change in the resting membrane potential of detrusor smooth muscle with either obstruction or following reversal of obstruction. These results suggest, that, the changes in the bladder smooth muscle membrane electrical properties induced by experimental bladder outflow obstruction are only partially reversible following release of obstruction. Furthermore, the results suggest that, the dysfunctional cystometric patterns associated with bladder outflow obstruction might not only be due to changes in detrusor innervation but, fundamental reorganization of the detrusor's electrical syncytium with irreversible suppression of cell-to-cell transfer of electrical activity.

Analysis of preoperative and postoperative detrusor pressure-flow measurements with the aid of the IBM compatible software package CLIM in 29 patients who underwent transurethral prostatic resection indicated that CLIM supplies reliable obstruction parameters that are recommended for preoperative assessment and postoperative followup, and that approximately a third of the patients who present with prostatism are nonobstructed, suggesting that the indication for transurethral resection of the prostate is over assessed.

We developed a new model of partial urethral obstruction using the guinea pig. We placed jeweler's jump rings loosely around the proximal urethra of immature guinea pigs and allowed the obstruction to develop gradually as the animal grew. After four or eight weeks of obstruction, we studied the filling and emptying characteristics of the bladder during continuous repetitive cycling under urethane anesthesia. Following this examination, bladders were removed and weighed. Wet weight was compared to urodynamic findings. We identified four abnormal urodynamic patterns: high pressure voiding, instability, poor compliance and decompensation. All obstructed bladders showed weight gain associated with muscle hypertrophy, but the degree of weight gain was different for each of the various urodynamic categories. High pressure voiding was associated with the least weight gain, whereas instability and decompensation showed the most weight gain. The results are consistent with a thesis that partial urethral outlet obstruction in the guinea pig gives rise to several distinct forms of abnormal voiding characterized by high pressure in the early stages, and progressing to more advanced forms of dysfunction characterized by instability and decompensation in the later stages.

Rats were subjected to infravesical outflow obstruction for six weeks. The bladder function was followed by cytometrical and in vitro investigations and by recordings of micturition pattern before and after removal of the obstruction. Cytometrical investigations showed that outflow obstruction for six weeks induced a bladder instability. Further, in the presence of obstruction the micturition pressure was large as was the bladder capacity and the rats had residual urine. After removal of the obstruction the bladder function rapidly normalized. The bladder instability disappeared within one week, bladder capacity decreased as did the micturition pressure. Moreover, only a minor amount of residual urine was present post-obstruction. In vitro investigation showed that the response to carbachol and to electrical stimulation was similar in normal and obstructed bladders. However, after removal of the obstruction a supersensitivity to carbachol as well as to electrical stimulation had developed. Obstructed bladders showed a markedly decreased response to substance P. The sensitivity to substance P was rapidly enhanced post-obstruction and after four days the response was restored to the control level. The present study shows that the bladder function in rats with infravesical outflow obstruction rapidly normalized after removal of the obstruction. The disappearance of the bladder instability despite the developed supersensitivity to muscarinic receptor stimulation supports the opinion that the bladder instability is not of muscarinic origin.

The histories of 22 infants presenting during the first year of life with obstructive uropathy due to posterior urethral valves were analyzed to determine outcome and prognostic features. Mean patient age at the time of the initial surgical intervention was 39 days, and the mean duration of followup inclusive of renal function data was 5.8 years. One patient died (5 per cent) and one had end stage renal disease. The mean preoperative and postoperative serum creatinine concentrations during the initial hospitalization were 3.1 and 1.4 mg. per dl., respectively. Neither value was significantly predictive of the creatinine concentration at final followup. In contrast, the nadir creatinine value during the first year of life correlated significantly with final renal function. Children with nadir creatinine values less than or equal to 0.8 mg. per dl. by 12 months of age maintained creatinine levels less than or equal to 1.1 mg. per dl. at the time of final evaluation, whereas children with higher values during the first year of life were likely to have progressive renal failure. Of 19 final creatinine determinations 6 were normal and 5 exceeded 1.5 mg. per dl. Proteinuria, hypertension, renal biopsy findings, urinary infection, unilateral nephrectomy and type of surgery did not correlate significantly with functional outcome. Followup studies of longer duration are needed to determine the ultimate outcome of these patients, more than half of whom had some degree of renal insufficiency at final evaluation.

Beta-adrenergic activity of the proximal urethra was studied in 11 patients. Maximum urethral pressure was recorded before, and 20 and 60 minutes after the intravenous administration of 0.5 mg. orciprenaline sulfate. There was a 40 per cent or more decrease in the maximum urethral pressure in 6 of the 11 patients. Beta-adrenoreceptor agonists could prove useful in facilitating vesical emptying by reducing urethral resistance in patients with neurogenic bladder dysfunction.

Using a tri-lumen graduated 10F catheter we attempted to record static (lateral) pressures at successive points in the urethra, synchronous with intravesical pressure recorded during voiding. Based on our understanding of the essential physical principles described by many earlier investigators we attempted numerous studies in a predominantly male population, which included normal male and female subjects, and male subjects with bladder outlet obstruction of varied etiology. We also attempted to evaluate the effects of the Valsalva maneuver, augmenting the detrusor contraction and artificial distal obstruction (penile compression) on the micturitional static urethral pressure profiles. Studies also were performed to compare the static urethral pressure profiles obtained with the anterograde (catheter withdrawal) and with the retrograde (catheter insertion during voiding) techniques. All of these studies have helped in understanding the various factors, such as double obstructions, artifactual catheter obstructions and incompetent distal sphincter mechanisms, in the interpretation of the micturitional static urethral pressure profile.

Proximal urethral obstruction, a common cause of prostatism in young and middle-aged men, often is misdiagnosed as prostatitis, neurogenic bladder or a psychogenic voiding disorder. Simple urodynamic studies (uroflowmetry and cystometry) do not distinguish a poor flow owing to bladder neck obstruction from that caused by poor detrusor contractility in these patients. Only the simultaneous measurement of detrusor pressure and uroflowmetry can make this distinction. A total of 23 patients with unsuspected proximal urethral obstruction underwent synchronous video-pressure-flow electromyography studies, and were treated and followed for a minimum of 1 year. Treatment by transurethral prostatic resection or bladder neck incision almost always was curative but alpha-adrenoceptor blocking agents have not been effective. All patients who underwent transurethral prostatic resection or bladder neck incision at the 5 and 7 o'clock positions have had retrograde ejaculation but both patients who underwent unilateral bladder neck incision reported antegrade ejaculation.

The concentrations of substance P and vasoactive intestinal polypeptide (VIP) were determined in the upper, middle, and lower part of the bladder of rats with and without infravesical outflow obstruction. In the obstructed animals there was a significant increase in bladder weight and the total amounts of substance P and VIP were increased. However, the concentrations of substance P were significantly lower than in the control bladders. The concentrations of VIP, on the other hand, were significantly higher in the middle and lower parts of obstructed bladders than in the controls. In isolated strips of the normal and obstructed bladders VIP had neither contractile nor relaxant effects. The peptide had no effect on electrically induced contractions. Substance P produced concentration-dependent contractions in both normal and obstructed bladders. However, obstructed bladders were significantly less sensitive than controls. It is concluded that the bladder instability seen in rats with infravesical outflow obstruction cannot be explained only in terms of changes in the bladder content of substance P or VIP.

A physical phenomenon known as elastic jump occurs downstream of an elastic constriction applied to a collapsible tube. This flow anomaly is analogous to the hydraulic jump that occurs in surface flows. Some investigators have predicted that an elastic jump could occur in the male urethra (during voiding) in the cavernous segment between constrictions at the membranous and meatal regions. To identify and understand this flow anomaly, and to obtain clinical correlations in human male subjects we have attempted several radiological and urodynamic studies in normal and abnormal subjects. The studies were retrograde urethrography, voiding cystourethrography, static pressure recordings during voiding and uroflowmetry. Retrograde urethrography was believed to delineate accurately the anatomy of the bulbous urethra. Voiding cystourethrography showed the geometry of the functional bulb. Our observations in 43 male subjects suggest that the site and degree of elastic jump depend on the severity of bladder neck or prostatic obstruction, magnitude of detrusor pressure (energy) during voiding, degree of distal constriction and position in which the subject voids. The animal studies (23 dogs) confirmed our clinical urodynamic impression.

Multiple peak and average urinary flow rates were measured in 34 normal men. In addition, this population was compared to 114 patients with prostatic obstruction. No matter which flow rate measurement is used some overlap is present between the 2 populations. The sensitivity of the flow rate test was defined for the 90 or 95 per cent limit of each normal and abnormal population. The specificity of both tests also was statistically determined. The ability to separate abnormal from normal voiding is enhanced significantly if peak flow rate is the measurement made. The loss of specificity for average flow rate is owing to a greater percentage of both populations, normal or abnormal, within the overlap region between the 2.

We treated 25 patients with posterior urethral valves by a perineal urethrotomy approach that required no sophisticated radiological or endoscopic equipment. The over-all results were considered good in 17 patients (68 per cent) who had restoration of normal micturition and renal function. Of the remaining patients 4 (16 per cent) had some residual stricture that responded to urethral dilation, 2 (8 per cent) had fairly normal micturition with occasional dribbling, 1 had persistent chronic renal insufficiency despite adequate relief of obstruction and 1 died of renal failure. The results of this approach are comparable to other methods described in the literature. The method is particularly appropriate in developing countries or in centers with limited urological facilities.