Bowel bladder dysfunction in control children in a pediatric urology office.

INTRODUCTION: Bowel bladder dysfunction (BBD) is common in children. Risk factors for BBD include age, gender, obesity, and behavioral issues such as ADHD. We investigated the modified Swedish Bowel-Bladder questionnaire as a sensitive indicator of BBD in healthy children. OBJECTIVES: We tested the usefulness of the Swedish Bowel-Bladder Questionnaire (BBQ) as an indicator of BBD in children not complaining of bowel/bladder dysfunction at the time of their visit to a pediatric urologist. Our secondary aim was to identify correlations between BBQ scores and risk factors such as gender, BMI, and ADHD. STUDY DESIGN: All families in our Pediatric Urology practice with patients >30 months old who were reportedly toilet trained were provided the Swedish BBQ. Total score as well as sub-scores for storage, emptying, and constipation were prospectively collected. Presenting diagnosis, gender, BMI, and ADHD history were collected. BBQ scores for patients with voiding dysfunction were compared to controls: a) those with genital problems (e.g. hydrocele/undescended testes), b) those with CAKUT (congenital anomalies of the kidneys and urinary tract). BBQ scores were analyzed as a continuous variable vs the potential risk factors (ADHD, obesity, age, and gender) using univariable/multivariable regression analysis. RESULTS: The median BBQ score for the 328 control patients (95 CAKUT and 233 genital) was 2.25 with an IQR: 1 to 6. In contrast, the median BBQ was higher for those with possible voiding dysfunction; n = 282; 9 with an IQR: 5 to 15). Total BBQ score exceeded 6 in 16% (52/328) of control patients. On multivariable analysis, age-adjusted total BBQ scores increased with ADHD in our controls (p = 0.03) but were unaffected by gender or BMI. On multivariable analysis of the voiding dysfunction group, total BBQ scores similarly decreased with age (p < 0.001) and increased with ADHD (p < 0.001) and were affected by gender (p = 0.024). BMI percentile had no significant effect in either cohort. DISCUSSION AND CONCLUSION: The Swedish BBQ was used in a U.S population and demonstrated trends towards increased voiding dysfunction associated with younger age, female gender, and ADHD. We learned that voiding dysfunction in children with ADHD is not associated with constipation and improves over time. Additionally, 16% of children with genital or urinary abnormalities and no voiding complaints have noticeable BBD uncovered by the BBQ. Hence, we conclude that the Swedish BBQ is a sensitive indicator of BBD even in children not complaining of those problems.

Epididymo-Orchitis Leading to Global Testicular Infarction in a Pediatric Patient - A Case Report.

Epididymo-orchitis (EO) is a common urologic condition that rarely requires surgical intervention. Global testicular infarction is an exceedingly uncommon complication of EO and is thought to occur when severe epididymal edema compresses testicular vessels. We present a rare case of global testicular infarction secondary to EO in a 17-year-old boy. Predicting which cases of EO will progress to testicular ischemia is challenging, as no clear risk factors have been identified. Early recognition of testicular compromise requires a high degree of clinical suspicion and may provide the opportunity for testis-sparing intervention.

A survey of pediatric urology fellowship applicants: past priorities to guide future possibilities.

BACKGROUND: The number of applicants to pediatric urology fellowships is often lower than the available positions (chart), giving applicants significant influence over where they ultimately match. Historically, interviews were conducted at individual hospitals, in-person, with residents bearing most costs. The objective of this study was to understand the factors associated with where applicants decide to apply, interview, and match for fellowship, as well as barriers within this process. METHODS: A 24-question survey was sent via email to all applicants who successfully matched into pediatric urology fellowship from 2013 to 2019. Questions included: demographics; factors associated with where they applied, interviewed, and ranked; and barriers within the application process. RESULTS: A total of 126 recent and current fellows were contacted, and 73 (60%) completed the full survey (51% male and 49% female). On average, respondents applied to 10 programs, interviewed at 9, and ranked 8. The most important factors in choosing where to apply/interview were: volume of surgical cases, diversity of surgical cases, and advice from mentors. The most important factors when making a rank list were: clinical autonomy, reputation of program, and structure of program. Hospital facilities were only rated "important" by 12% of respondents. 82% (60 respondents) faced at least one personal or professional barrier during the application process. The most common barrier was "cost of interviewing" (59%, 43 respondents). Personal vacation time was used by 61% of applicants during interviews, with 37% using more than 5 days. DISCUSSION: This study is the first to explore the factors that applicants consider when choosing where to apply, interview, and rank for pediatric urology fellowship. This information is important to understand due to the current supply and demand of fellowship positions. We are limited by extrapolating more general conclusions about applicants as a whole from a survey with a 60% response rate and the lack of an available validated survey in this realm. CONCLUSIONS: This study has shown that most pediatric urology fellowship applicants apply to programs primarily based on perceived surgical volume and reputational factors. These same factors are used when making a rank list. Many applicants faced personal or professional barriers during the application process, largely due to costs and time away from work and family. While recent interviews have transitioned to a virtual format by necessity, prior applicants did not rate hospital facilities as important to them. Overall, there is room to improve this process based on such feedback.

Robotic upper tract surgery in infants 6 months or less: is there enough space?

Robot-assisted laparoscopic surgery (RALS) has recently been described in children < 1 year old. However, little data exist on robotic utilization in infants ≤ 6 months old, likely due to concerns for limited intraabdominal space and decreased distance between ports in this cohort. We hypothesized that the robotic approach can be successfully used for infants ≤ 6 months old. A prospectively collected database of patients undergoing urologic robotic surgery at our institution was reviewed. Patients ≤ 6 months and ≥ 4 kg were included. Patient demographics, intraoperative details, hospital length of stay, and complications were reviewed. Descriptive statistics were performed. Twelve patients ≤ 6 months old underwent urologic robotic surgery by three surgeons at our institution (2013-2019): pyeloplasty (6), ureteroureterostomy (4), heminephrectomy (1), and nephrectomy (1). Median age at surgery was 4.75 months (IQR 4, 6). Median weight was 7.09 kg (IQR 6.33, 7.78). Median console time was 105 min (IQR 86, 123). For all procedures, 8-mm robotic arm ports were used. No procedures were converted to open. Median post-operative hospital stay was 24 h (IQR). Febrile UTI was the only complication occurring within 30 days of surgery (n = 4, 33%; 7-20 days, Clavien grade 2). For those undergoing pyeloplasty or ureteroureterostomy (n = 10), postoperative ultrasound showed improved (n = 9) or stable hydronephrosis (n = 1). At a median follow-up of 19.73 months (IQR 4.27, 38.32), no patient required an unplanned secondary intervention. Robotic upper urinary tract surgery is feasible and safe in patients ≤ 6 months of age and can be performed successfully with the same technique as for older children.

Validation of the modified Bosniak classification system to risk stratify pediatric cystic renal masses: An international, multi-site study from the pediatric urologic oncology working group of the societies for pediatric urology.

BACKGROUND: Pediatric cystic renal lesions are challenging to manage as little is known about their natural course. A modified Bosniak (mBosniak) classification system has been proposed for risk stratification in pediatric patients that takes ultrasound (US) and/or computed tomogram (CT) characteristics into account. However, literature validating this system remains limited. OBJECTIVE: To determine if the mBosniak classification system correlates with pathologic diagnoses. The hypothesis is that mBosniak classification can stratify the risk of malignancy in children with renal cysts. STUDY DESIGN: Patients treated for cystic renal masses with available imaging and pathology between 2000 and 2019 from five institutions were identified. Clinical characteristics and pathology were obtained retrospectively. Characteristics from the most recent US, CT, and/or magnetic resonance imaging (MRI) were recorded. Reviewers assigned a mBosniak classification to each scan. mBosniak scores 1/2 were considered low-risk and 3/4 high-risk. These groups were compared with pathology (classified as benign, intermediate, malignant). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated to assess this categorization as a screening tool to guide surgical intervention. Agreement between imaging modalities was also explored. RESULTS: 99 patients were identified. High-risk imaging findings were correlated with malignant or intermediate pathology with a sensitivity of 88.3%, specificity of 84.6%, PPV of 89.8%, NPV of 82.5%, +LR of 5.7, and -LR of 0.14. The sensitivity for detecting malignant lesions only was 100%. There was substantial agreement between US/CT (n = 55; κ = 0.66) and moderate agreement between US/MRI (n = 20; κ = 0.52) and CT/MRI (n = 13; κ = 0.47). DISCUSSION: The mBos classification system is a useful tool in predicting the likelihood of benign vs. intermediate or malignant pathology. The relatively high sensitivity and specificity of the system for prediction of high-risk lesions makes this classification applicable to clinical decision making. In addition, all malignant lesions were accurately identified as mBosniak 4 on imaging. This study adds substantial data to the relatively small body of literature validating the mBosniak system for risk stratifying pediatric cystic renal lesions. CONCLUSIONS: Pediatric cystic renal lesions assigned mBosniak class 1/2 are mostly benign, whereas class 3/4 lesions are likely intermediate or malignant pathology. We observed that the mBosniak system correctly identified pathology appropriate for surgical management in 88% of cases and did not miss malignant pathologies. There is substantial agreement between CT and US scans concerning mBos classification.

Does twinkle artifact truly represent a kidney stone on renal ultrasound?

INTRODUCTION: Nephrolithiasis is detected on ultrasound by the presence of an echogenic focus, posterior acoustic shadowing and/or twinkle artifact (TA). TA has been shown to be highly predictive of nephrolithiasis in adults with renal colic and ureteral stones. We sought to evaluate if TA is reliable for diagnosing nephrolithiasis in the pediatric population. METHODS: We reviewed renal ultrasound reports indicating presence or absence of TA associated with a single echogenic focus in the kidney or ureter. Exclusion criteria were age >18, multiple echogenic foci or medullary calcinosis, no follow-up, or TA located outside the kidney or ureter. Stone was confirmed either by CT within 3 months of color Doppler ultrasound, visualization on ureteroscopy, or patient report of passing the stone. RESULTS: Five hundred and ninety-nine ultrasound reports were reviewed and 293 met inclusion criteria. Sixty-nine had diffuse twinkle without echogenic focus and 224 showed TA with single echogenic focus. 135 patients had confirmatory information available (Summary Table). Nephrolithiasis was diagnosed using TA and confirmed on confirmatory studies for 49 ultrasounds. The majority of confirmed stones were in the kidney (n = 40; 82%) and mean size of confirmed stones on ultrasound was 5 mm (range 1.5-10). Sensitivity, specificity, positive predictive value and negative predictive value of TA for detecting nephrolithiasis were 83%, 78%, 74% and 86% respectively. CONCLUSIONS: Compared to the adult literature, TA in children has lower sensitivity, specificity and positive predictive value, but similar negative predictive value for diagnosing nephrolithiasis. This may be related to renal location and smaller stone size. The presence of TA should be weighed in the setting of other clinical and radiographic evidence of nephrolithiasis.

Baseline Renal Volumes in Children Born With Cloacal Anomalies.

OBJECTIVE: To better understand why children born with cloacal anomalies are at a high risk of renal insufficiency, this study aims to determine baseline renal volume in children with cloacal anomalies compared to controls. We hypothesized children with cloacal anomalies would be born with less renal volume. METHODS: An IRB approved database of children with cloacal anomalies was reviewed. Controls were female patients with 2-vessel umbilical cord or preauricular tags who underwent screening renal ultrasound. Children were included if they had a renal ultrasound in the first 3 months of life. Cloacal exstrophy, horseshoe and cross-fused ectopic kidneys were excluded. Total and individual kidney volumes were compared between the 2 groups. RESULTS: The study cohort consisted of 109 patients, 46 (42.2%) cloaca patients and 63 (57.8%) controls. In unadjusted analyses, average total renal volume for cloaca and control patients was 22.4 cm3 vs 25.5 cm3 respectively (P = .1006), and there was no significant difference when adjusting for age (P = .3915). The estimated difference in renal unit volume between cloaca patients without solitary kidneys and controls was -1.6 cm3 (95%C.I.: -3.6, 0.4; P = .1201), and there was no significant difference when adjusting for age (P = .4725). The age-adjusted difference in renal unit volume between cloaca patients with solitary kidney and controls was 1.8 cm3 (95%CI: -1.1, 4.8; P = .2148). CONCLUSIONS: Children with cloacal anomalies have similar baseline renal volumes as children without cloacal anomalies. Therefore, the increased risk of renal insufficiency in this patient population appears to be due to renal injury postnatally.

Significant rate of lower urinary tract dysfunction in patients with sacrococcygeal teratomas.

BACKGROUND: Sacrococcygeal teratoma (SCT) is the most commonly occurring presacral tumor and can affect the lower urinary tract by direct mass effect, or as a sequela from surgical resection. Despite the potential impact on urologic function, there is no current standard for urological involvement or follow-up for these patients. The purpose of this study was to evaluate the need for urologic involvement for lower urinary tract dysfunction (LUTD) in patients with SCTs at our institution. METHODS: We performed a retrospective chart review of patients diagnosed with SCT and managed at our institution between 1990 and 2019. Data collected included: patient demographics, surgical and pathology reports, presence of tethered cord or anorectal malformation, and need for urologic involvement for LUTD. LUTD included acute urinary retention, need for chronic intermittent catheterization, and/or urinary incontinence. Acute urinary retention was defined as requiring catheterization to empty the bladder for a limited time (outside the standard post-operative indwelling catheter time period) and the eventual return to spontaneous voiding. Chronic intermittent catheterization was defined as those with urinary retention that has persisted and required continued catheterization at the time of chart review. Urinary incontinence was defined as urine leakage in children older than 3 years of age. Patients with unavailable records were excluded. Comparison between groups was performed with Mann Whitney and chi-squared tests. RESULTS: Forty-five patients with SCTs were identified. LUTD was identified in 23 patients (51%). The most common reason for LUTD was urinary retention (n = 16, 70%): 9 patients had acute retention and 7 had chronic retention (Fig. 1). Nine patients (39%) had urinary incontinence: 2 of these patients (4% of all SCT patients) had urinary fistulas (vesicovaginal (n = 1) and urethrovaginal (n = 1)). Only 5 patients (22%) had LUTD recognized preoperatively. Nine patients had concomitant tethered cord, and 7 of these (78%) had LUTD. Of patients with LUTD, Altman type IV was the most common location (n = 10, 43%). There was no significant difference in tumor type between those with and without LUTD. Patients without LUTD had significantly shorter follow-up. CONCLUSIONS: Greater than 50% of patients with SCTs have known LUTD. Two of these patients were found to have urinary fistulas requiring urinary diversion. A multidisciplinary team including urology should be involved upfront in the management of patients with SCTs, and LUTD should be routinely assessed at follow-up visits. Evaluation for a urinary fistula should occur in the presence of urinary incontinence.

Utilization of Augmentation Cystoplasty for Myelomeningocele Patients Remained Stable Over the Past Decade.

OBJECTIVE: To understand the utilization of augmentation cystoplasty (AC) for the management of neurogenic bladder in children with myelomeningocele (MMC). AC carries considerable risk. To mitigate this, recent studies have emphasized alternatives to AC, but it is unknown if these interventions have resulted in fewer ACs being performed. Our goal was to evaluate the use of AC in MMC patients over the past decade. We hypothesized that the use of AC had decreased and that the age at AC increased. METHODS: Using the Pediatric Health Information System, we studied patients with MMC who had an AC between January 2009 and December 2018. International Classification of Disease procedure codes were used to identify AC procedures. We quantified trends in AC utilization by estimating the annual proportion of MMC admissions with an AC. We also assessed trends in patient age at the time of AC. RESULTS: Proportion of AC per MMC admissions across the study period was 4.8%. There was no significant annual trend in the overall number of ACs performed each quarter over the past decade nor was there any change in the estimated annual incidence rate ratio of AC (1.01, 95% confidence interval 0.96, 1.05; P =.75). The estimated annual change in patient age at procedure remained relatively constant over the study period (-0.03 years, 95% confidence interval -0.13, 0.07; P = .51). CONCLUSION: Practice patterns for the utilization of AC in MMC did not change significantly over the past decade despite prominent voices in the literature emphasizing alternative interventions in this patient population.

Phenazopyridine: A Preoperative Way to Identify Ureteral Orifices.

OBJECTIVE: To identify difficult to see ureteral orifices (UOs), urologists need a method to stain the urine. Phenazopyridine, a urinary analgesic which discolors the urine orange, can be administered orally preoperatively. We evaluated the usefulness of phenazopyridine in identifying the UOs and optimal timing of administration. METHODS: Adult patients undergoing endoscopic procedures at the Stratton VA were prospectively enrolled. Preoperative metabolic panels were reviewed. Exclusion criteria were renal insufficiency (creatinine clearance <50 mL/min), severe hepatitis or severe liver disease, glucose-6-phosphate dehydrogenase deficiency, previous hypersensitivity to phenazopyridine, or pregnancy. In phase 1, patients undergoing office flexible cystoscopy were administered 200 mg phenazopyridine the morning of the procedure. Because of the robust orange color of the urine, phase 2 was implemented. In phase 2, patients undergoing rigid cystoscopy in the operating room took 200 mg phenazopyridine at 7 PM the night before surgery. Upon entry into the bladder, UOs were identified and urine color was graded (0 = no dye, 1 = weak, 2 = moderate, and 3 = strong). Patients were assessed postoperatively for side effects. RESULTS: Five patients were included in phase 1. The mean time from medication to cystoscopy was 153 minutes (range 17-304 minutes). One-third of patients had excretion of grade 3 orange urine that obscured inspection of the bladder mucosa. The study design was adjusted and we transitioned to phase 2. Twenty-three patients were enrolled in phase 2. The mean time from phenazopyridine dose to cystoscopy was 14 hours (range 13-17 hours). Seventy-three percent of patients had grade 2 efflux from the UOs. CONCLUSION: Phenazopyridine can successfully identify UOs and can be administered as early as the evening before the procedure.

Physical, Complementary, and Alternative Medicine in the Treatment of Pelvic Floor Disorders.

PURPOSE OF REVIEW: The purpose of the study was to catalog the most recent available literature regarding the use of conservative measures in treatment of pelvic floor disorders. RECENT FINDINGS: Pelvic floor disorders encompass abnormalities of urination, defecation, sexual function, pelvic organ prolapse, and chronic pain, and can have significant quality of life implications for patients. Current guidelines recommend behavioral modifications and conservative treatments as first-line therapy for pelvic floor disorders. We have reviewed the literature for articles published on physical, complementary, and alternative treatments for pelvic floor disorders over the past 5 years. Review of pelvic floor muscle physiotherapy (PFMT) and biofeedback (BF) shows a benefit for patients suffering from bladder dysfunction (incontinence, overactive bladder), bowel dysfunction (constipation, fecal incontinence), pelvic organ prolapse, and sexual dysfunction (pelvic pain). Combination of PFMT and BF has shown improved results compared to PFMT alone, and some studies find that electrical stimulation can augment the benefit of BF and PFMT. Additionally, acupuncture and cognitive behavioral therapy has shown to be an effective treatment for pelvic floor disorders, particularly with respect to pelvic pain. This update highlights beneficial conservative treatments available for pelvic floor dysfunction, and supplements the current literature on treatment options for patients suffering from these disorders.

Use of Nonprostate Ultrasound in Urology Practice.

INTRODUCTION: Ultrasound imaging is necessary for the care of urology patients, and urology residents are encouraged to learn ultrasound technique and interpretation. However, there is limited mandated education in this field. Currently the only ultrasound procedure considered an index case is transrectal ultrasound for prostate biopsy. We investigated the current use of nonprostate ultrasound in urological practice. METHODS: We reviewed ABU (American Board of Urology) certification and recertification logs of practicing urologists from 2012 to 2014. We obtained data for the codes 76700-76776 (kidney), 76870 (scrotal), 76999 (unlisted) and 93975-93981 (Doppler including penile). Codes 51798 (post-void residual) and 76950 (ultrasound for interstitial radiotherapy) were excluded from the study. We analyzed the results based on self-identified demographic information provided by the urologists. RESULTS: The practices of 2,427 urologists were reviewed and of these, 43% billed for at least 1 renal, scrotal or penile ultrasound. General and subspecialist urologists perform similar percentages of ultrasound studies, except for pediatrics (0% penile) and andrology (40% penile). Of those who reported on practice type (2,067) 82% self-identify as in private practice and performed more ultrasound studies than academic urologists, including renal 42% vs 23%, scrotal 33% vs 15% and penile 8% vs 6%, respectively. Men performed more nonprostate ultrasounds than women (44% vs 36%, p <0.001). CONCLUSIONS: In addition to prostate ultrasound, renal and scrotal ultrasound is relevant to all urologists regardless of practice model or subspecialty. Graduating residents can expect to perform ultrasound examinations in their practices and, therefore, in addition to prostate ultrasound we should train residents in renal and scrotal ultrasound.

Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

Protein phosphatase magnesium-dependent-1A (PPM1A) dephosphorylates SMAD2/3, which suppresses TGF-ß signaling in keratinocytes and during Xenopus development; however, potential involvement of PPM1A in chronic kidney disease is unknown. PPM1A expression was dramatically decreased in the tubulointerstitium in obstructive and aristolochic acid nephropathy, which correlates with progression of fibrotic disease. Stable silencing of PPM1A in human kidney-2 human renal epithelial cells increased SMAD3 phosphorylation, stimulated expression of fibrotic genes, induced dedifferentiation, and orchestrated epithelial cell-cycle arrest via SMAD3-mediated connective tissue growth factor and plasminogen activator inhibitor-1 up-regulation. PPM1A stable suppression in normal rat kidney-49 renal fibroblasts, in contrast, promoted a SMAD3-dependent connective tissue growth factor and plasminogen activator inhibitor-1-induced proliferative response. Paracrine factors secreted by PPM1A-depleted epithelial cells augmented fibroblast proliferation (>50%) compared with controls. PPM1A suppression in renal cells further enhanced TGF-ß1-induced SMAD3 phosphorylation and fibrotic gene expression, whereas PPM1A overexpression inhibited both responses. Moreover, phosphate tensin homolog on chromosome 10 depletion in human kidney-2 cells resulted in loss of expression and decreased nuclear levels of PPM1A, which enhanced SMAD3-mediated fibrotic gene induction and growth arrest that were reversed by ectopic PPM1A expression. Thus, phosphate tensin homolog on chromosome 10 is an upstream regulator of renal PPM1A deregulation. These findings establish PPM1A as a novel repressor of the SMAD3 pathway in renal fibrosis and as a new therapeutic target in patients with chronic kidney disease.-Samarakoon, R., Rehfuss, A., Khakoo, N. S., Falke, L. L., Dobberfuhl, A. D., Helo, S., Overstreet, J. M., Goldschmeding, R., Higgins, P. J. Loss of expression of protein phosphatase magnesium-dependent 1A during kidney injury promotes fibrotic maladaptive repair.

Stone volume is best predictor of operative time required in retrograde intrarenal surgery for renal calculi: implications for surgical planning and quality improvement.

Retrograde intrarenal surgery (RIRS) is highly successful at eliminating renal stones of various sizes and compositions. As urologists are taking on more complex procedures using RIRS, this has led to an increase in operative (OR) times. Our objective was to determine the best predictor of OR time in patients undergoing RIRS. We retrospectively reviewed the records of patients undergoing unilateral RIRS for solitary stones over a 10 year time span. Stones were fragmented and actively extracted using a basket. Variables potentially affecting OR time such as patient age, sex, BMI, lower pole stone location, volume, Hounsfield units (HU), composition, ureteral access sheath (UAS) use, and pre-operative stenting were collected. Multivariable linear and stepwise regression was used to evaluate the predictors of OR time. There were 118 patients that met inclusion criteria. The median stone volume was 282.6 mm3 (IQR 150.7-644.7) and the mean OR time was 50 min (±25.9 SD). On univariate linear regression, stone volume had a moderate correlation with OR time (y = 0.022x + 38.2, r 2 = 0.363, p < 0.01). On multivariable stepwise regression, stone volume had the strongest impact on OR time, increasing time by 2.0 min for each 100 mm3 increase in stone volume (p < 0.001). UAS added 13.5 (SE 3.9, p = 0.001) minutes and renal lower pole location added 9 min (SE 4.3, p = 0.03) in each case they were used. Pre-operative stenting, HU, calcium oxalate stone composition, sex, and age had no significant effect on OR time. Amongst the main stone factors in RIRS, stone volume has the strongest impact on operative time. This can be used to predict the length of the procedure by roughly adding 2 min per 100 mm3 increase in stone volume.

Cyclical estrogen and free radical damage to the rabbit urinary bladder.

INTRODUCTION AND HYPOTHESIS: There are a number of lower urinary tract dysfunctions (LUTD) that occur primarily in women. Our hypothesis is that cyclical estrogen will produce LUTD in part by the generation of free radicals and oxidative damage to cellular and subcellular membranes. METHODS: Twenty female rabbits were divided into five groups: control, ovariectomized (Ovx), Ovx receiving continuous estrogen, Ovx receiving cyclical estrogen ending off estrogen, and Ovx receiving cyclical estrogen ending on estrogen. Statistical analyses used ANOVA followed by the Tukey analysis for individual differences. RESULTS: High estrogen increased bladder mass, contraction, compliance, and blood flow and decreased oxidative damage. Low estrogen decreased bladder mass, contraction, compliance, and blood flow and increased oxidative damage. CONCLUSIONS: The decreased blood flow associated with increased oxidative damage demonstrates that cyclical damage to cellular membranes occurs. This supports the hypothesis that cycling estrogen may play a role in the etiology of LUTD of women.

Effect of co-enzyme Q10 and alpha-lipoic acid on response of rabbit urinary bladder to repetitive stimulation and in vitro ischemia.

OBJECTIVES: To determine the efficacy of coenzyme Q10 (CoQ10) and alpha-lipoic acid (alpha-LA), either alone or in combination, to protect the contractile responses of the rabbit urinary bladder from damage caused by repetitive stimulation in the presence or absence of in vitro ischemia. METHODS: Four groups of New Zealand white rabbits (4 per group) were treated with vehicle (group 1), CoQ10 (group 2), alpha-LA (group 3), or CoQ10 plus alpha-LA (group 4) for 2 weeks. At the end of the treatment period, eight longitudinal strips from each rabbit bladder body were placed in oxygenated Tyrode's solution with glucose (normal physiologic medium). The strips were stimulated by field stimulation, carbachol, and KCl, and the responses were recorded. One half of the strips were switched for 1 hour to Tyrode's solution with no glucose equilibrated with nitrogen (ischemia medium). Simultaneously, all strips were subjected to 1 h of repetitive field stimulation followed by 1 hour of recovery in normal physiologic medium, and the responses to all stimuli were recorded again. RESULTS: CoQ10 showed no protective effect. Alpha-LA resulted in increased contractile responses of the control bladder and showed a moderate protective effect for all forms of stimulation. The combination, however, showed a significantly greater increase in the contraction of the control bladder and a greater protective effect than alpha-LA alone. CONCLUSIONS: The combination of alpha-LA and CoQ10 treatment enhanced the contractile response in normal medium and diminished the contractile dysfunction induced by repetitive field stimulation and ischemia.

Effect of letrozole on urinary bladder function in the female rabbit.

OBJECTIVE: To investigate the effect of letrozole (a potent aromatase inhibitor that effectively inhibit the synthesis of oestrogen) on bladder contraction with changes in morphology and biochemistry. MATERIALS AND METHODS: Sixteen female New Zealand white rabbits were separated into four equal groups; groups 1-3 were given oral letrozole for 1, 2 and 3 weeks, and group 4 was given saline and served as the control group. At the end of the medication period each rabbit was anaesthetized and the bladder muscle strips were used for contractile, histological and biochemical studies. RESULTS: The concentration of serum oestrogen was significantly lower and testosterone was significantly higher in letrozole-treated rabbits than in the control group. The rabbits treated for 1 week with letrozole showed significant decreases in the contractile responses to electrical field stimulation, ATP and carbachol, but not to KCl. Contractility returned to normal in the rabbits treated for 2 and 3 weeks. Letrozole resulted in an increased volume percentage of collagens and decreased bladder compliance. The volume percentage of the smooth muscle component also changed, with a significant decrease at 1 week and then a gradual increase at 2 and 3 weeks. Contractile dysfunction was absent at 2 and 3 weeks, which was consistent with no change in sarcoplasmic reticulum Ca(2+)-ATPase content or mitochondrial function. CONCLUSIONS: The bladder contractility decline in the first week and was restored at 2 and 3 weeks. The present study unexpectedly showed the possibility that testosterone might be as important as oestrogen in the contractile function of the female bladder.