An Overview of the Effect of Aging on the Female Urethra.

Urethral function declines by roughly 15% per decade and profoundly contributes to the pathogenesis of urinary incontinence. Individuals with poor urethral function are more likely to fail surgical management for stress incontinence that focus on improving urethral support. The reduced number of intramuscular nerves and the morphologic changes in muscle and connective tissue collectively impact urethral function as women age. Imaging technologies like MRI and ultrasound have advanced our understanding of these changes. However, substantial knowledge gaps remain. Addressing these gaps can be crucial for developing better prevention and treatment strategies, ultimately enhancing the quality of life for aging women.

Dysfunction of the aging female mouse urethra is associated with striated muscle loss and increased fibrosis: an initial report.

The decline of urethral function with advancing age plays a major role in urinary incontinence in women, impairing quality of life and economically burdening the health care system. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, we have compared functional, morphometric, and global gene expression of urethral tissues between young and old female mice. Bladder leak point pressure (LPP) measurement showed that the aged female mice had 26.55% lower LPP compared to younger mice. Vectorized Scale-Invariant Pattern Recognition (VIPR) analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed more down-regulated genes in aged than young mice. Immune response and muscle-related (striated and smooth) pathways were predominantly enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly downregulated in aged urethral tissues compared to those from young female mice. These results suggest that molecular pathways (i.e., ACVR1/FST signaling and CTGF/TGF-ß signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function.

The Potent Anti-Tumor Effects of Rhodiola Drinking Are Associated with the Inhibition of the mTOR Pathway and Modification of Tumor Metabolism in the UPII-Mutant Ha-Ras Model.

Background: SHR-5 has been used as an "adaptogen" for enhancing physical and mental performance and for fighting stress in the healthy population. The purpose of this study is to determine the chemopreventive efficacy of SHR-5 for superficial bladder cancer and to investigate the underlying mechanisms of action. Methods: UPII-mutant Ha-ras bladder-cancer-transgenic mice, that developed low-grade and noninvasive papillary transitional urothelial cell carcinoma, were fed with 1.25 and 6.25 mg/mL SHR-5 in drinking water for 6 months. The survival of the mice, obstructive uropathy, tumor burden and morphology, and proliferation were evaluated by pathological, molecular, metabolic, and statistical analyses. Results: Approximately 95% or more of the male UPII-mutant Ha-ras mice that drank SHR-5 daily survived over 6 months of age, while only 33.3% of those mice that drank normal water survived over 6 months of age (p < 0.0001); SHR-5 drinking exposure also reduced tumor-bearing bladder weight and urinary tract obstruction and inhibited mTOR signaling in neoplastic tissues. Global metabolic analysis revealed that SHR-5 resulted in increased phenolic metabolites and decreased CoA, a critical metabolic cofactor for lipid metabolism. Conclusions: Our findings highlight the potential of SHR-5 as an anti-aging agent for bladder cancer prevention through reshaping tumor metabolism via the inhibition of the mTOR signaling. Global metabolomics profiling provides a unique and efficient tool for studying the mechanisms of complex herb extracts' action.

Urethral function and failure: A review of current knowledge of urethral closure mechanisms, how they vary, and how they are affected by life events.

INTRODUCTION: A critical appraisal of the literature regarding female urethral function and dysfunction is needed in light of recent evidence showing the urethra's role in causing stress and urge urinary incontinence. METHODS: An evidence assessment was conducted using selected articles from the literature that contained mechanistic data on factors affecting urethral function and failure. RESULTS: Maximal urethral closure pressure (MUCP) is 40% lower in stress urinary incontinence (SUI) than normal controls. Evidence from five women shows relatively equal contributions to MUCP from striated/smooth muscle, vascular-plexus, connective tissue. MUCP varies twofold in individuals of similar age and declines 15% per decade even in nulliparous women. Age explains 57% of the variance in MUCP. This parallels with striated/smooth muscle loss and reduced nerve density. Factors influencing pressure variation minute-to-minute and decade-to-decade are poorly understood. Connective tissue changes have not been investigated. MUCP in de novo SUI persisting 9-months postpartum is 25% less than in age and parity-matched controls. Longitudinal studies do not show significant changes in urethral function after vaginal birth suggesting that changes in urethral support from birth may unmask pre-existing sphincter weakness and precipitate SUI. Mechanisms of interaction between support injury, pre-existing urethral weakness, and neuropathy are unclear. CONCLUSION: Urethral failure is the predominant cause of SUI and a contributing factor for UUI; potentially explaining why mixed symptoms predominate in epidemiological studies. Age-related striated muscle loss and differences between women of similar age are prominent features of poor urethral closure. Yet, connective tissue changes, vasculature function, and complex interactions among factors are poorly understood.

Transcriptomic Analysis of Human Mesenchymal Stem Cell Therapy in Incontinent Rat Injured Urethra.

Periurethral human mesenchymal stem cell (hMSC) injections are associated with functional improvement in animal models of postpartum stress urinary incontinence (SUI). However, limited data exist on the role of hMSCs in modulating gene expression in tissue repair after urethral injury. To this end, we quantified temporal gene expression modulation in hMSCs, and in injured rat urethral tissue, using RNA-seq in an animal model of SUI, over a 3-day period following urethral injury, and local hMSC injection. We injected PKH fluorescent-labeled hMSC into the periurethral space of rats following a 4 h vaginal distention (VD) (three rats per time point). Control rats underwent VD injury only, and all animals were euthanized at 12, 24, 36, 72 h postinjury. Rat urethral and vaginal tissues were frozen and sectioned. Fluorescent labeled hMSCs were distinguished from adjacent, unlabeled rat urethral tissue. RNA was prepared from hMSCs and urethral tissue obtained by laser dissection of frozen tissue sections and sequenced on an Illumina HiSeq 2500. Differentially expressed genes (DEGs) over 72 h were evaluated using a two-group t-test (p < 0.05). Our transcriptional analyses identified candidate genes involved in tissue injury that were broadly sorted by injury and exposure to hMSC throughout the first 72 h of acute phase of injury. DEGs in treated urethra, compared with untreated urethra, were functionally associated with tissue repair, angiogenesis, neurogenesis, and oxidative stress suppression. DEGs included a variety of cytokines, extracellular matrix stabilization and regeneration genes, cytokine signaling modification, cell cycle regulation, muscle differentiation, and stabilization. Moreover, our results revealed DEG changes in hMSCs (PKH-labeled) harvested from injured urethra. The expressions are related to DNA damage repair, transcription activation, stem cell regulation, cell survival, apoptosis, self-renewal, cell proliferation, migration, and injury response. Impact statement Stress urinary incontinence (SUI) affects nearly half of women over 40, resulting in reduced quality of life and increased health care cost. Development of SUI is multifactorial and strongly associated with vaginal delivery. While stem cell therapy in animal models of SUI and limited preliminary clinical trials demonstrate functional improvement of SUI, the role of stem cell therapy in modulating tissue repair is unclear impeding advanced clinical trials. Our work provides a new understanding of the transcriptional mechanisms with which human mesenchymal stem cells improve acute injury repair thus guiding the development of cell-based therapies for women with nonacute established SUI.

Is trigonitis a neglected, imprecise, misunderstood, or forgotten diagnosis?

To consolidate our understanding of "trigonitis" and its relevance in current urologic practice, we reviewed the literature on this entity. The MEDLINE, EMBASE, and Cochrane databases (1905 to present) were systematically reviewed for any English language articles addressing the following terms: trigonitis, cystitis trigoni, cystitis cystica, squamous metaplasia, pseudomembranous trigonitis, vaginal metaplasia, infection or inflammation of the trigone, and trigonitis in recurrent urinary tract infections (rUTI). Abstracts or articles not focused on trigonitis, or those only repeating findings from other original articles on trigonitis, and studies in children or men were excluded. Reported histologic findings on trigonitis, theories regarding its pathophysiology, and therapeutic strategies were reviewed. From 57 relevant articles, only 27 focused on trigonitis. Cystoscopic evaluation of the trigone described inflammatory lesions of cystitis cystica, occasionally small stones or pus-filled lesions, an appearance that should be differentiated from white patches of squamous metaplasia. Embryologic formation of the trigone, history of rUTIs, and effects of hormones on the trigone have been proposed as underlying pathophysiologic mechanisms. Numerous therapeutic strategies have been reported to treat symptomatic trigonitis, including antibiotic therapy, intravesical instillation of different agents, electrofulguration, and laser coagulation. However, no treatment indication criteria have been well established so far, and long-term data are lacking. Despite several reports describing histologic and endoscopic findings of trigonitis, its prevalence, pathophysiology, and treatment have remained poorly defined. Its relevance in the management of rUTIs should be further evaluated.

Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis.

Pyelonephritis is a bacterial infection of the kidney and is most commonly caused by Escherichia coli. Recurrent infections can cause significant renal inflammation and fibrosis ultimately resulting in declining kidney function. Before improved clinical management and prevention of pyelonephritis can be instituted, a reliable animal model must be established in order to study the mechanisms of progression, recurrence, and therapeutic efficacy. The transurethral infection model closely mimics human pyelonephritis but exhibits considerable variation due to its reliance on urethral reflux to transport the bacteria to the kidney. Herein, a detailed surgical protocol for performing bacterial injections into the rat renal pelvis is provided and confirmed by non-invasive Magnetic Resonance Imaging (MRI). Using this protocol, animals receive direct exposure to a desired concentration of E. coli bacteria and can fully recover from the surgical procedure with adequate post-operative care. This facilitates subsequent longitudinal MRI assessments of the experimental animal models for comparison with saline (sham) controls. Using this direct delivery approach, the severity of infection is controllable and applicable for mechanistic studies of progression as well as development of novel treatment strategies.

Local release from affinity-based polymers increases urethral concentration of the stem cell chemokine CCL7 in rats.

The protein chemokine (C-C motif) ligand 7 (CCL7) is significantly over-expressed in urethral and vaginal tissues immediately following vaginal distention in a rat model of stress urinary incontinence. Further evidence, in this scenario and other clinical scenarios, indicates CCL7 stimulates stem cell homing for regenerative repair. This CCL7 gradient is likely absent or compromised in the natural repair process of women who continue to suffer from SUI into advanced age. We evaluated the feasibility of locally providing this missing CCL7 gradient by means of an affinity-based implantable polymer. To engineer these polymers we screened the affinity of different proteoglycans, to use them as CCL7-binding hosts. We found heparin to be the strongest binding host for CCL7 with a 0.323 nM dissociation constant. Our experimental approach indicates conjugation of heparin to a polymer backbone (using either bovine serum albumin or poly (ethylene glycol) as the base polymer) can be used as a delivery system capable of providing sustained concentrations of CCL7 in a therapeutically useful range up to a month in vitro. With this approach we are able to detect, after polymer implantation, significant increase in CCL7 in the urethral tissue directly surrounding the polymer implants with only trace amounts of human CCL7 present in the blood of the animals. Whole animal serial sectioning shows evidence of retention of locally injected human mesenchymal stem cells (hMSCs) only in animals with sustained CCL7 delivery, 2 weeks after affinity-polymers were implanted.

Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment.

Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in the in vivo murine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness using Pseudomonas aeruginosa (gram negative bacteria) and Staphylococcus aureus (gram positive bacteria). Our studies show that hMSCs secrete bioactive molecules which are antimicrobial in vitro against Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL-37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived), the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human, Cftr: mouse) activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.

Mesenchymal stem cell therapy in a rat model of birth-trauma injury: functional improvements and biodistribution.

INTRODUCTION AND HYPOTHESIS: We evaluated the potential role of human mesenchymal stem cells (hMSCs) in improvement of urinary continence following birth-trauma injury. METHODS: Human MSCs were injected periurethrally or systemically into rats immediately after vaginal distention (VD) (n = 90). Control groups were non-VD (uninjured/untreated, n = 15), local or systemic saline (injection/control, n = 90), and dermofibroblast (cell therapy/control, n = 90). Leak-point pressure (LPP) was measured 4, 10, and 14 days later. Urethras were morphometrically evaluated. In another sets of VD and non-VD rats, the fate of periurethrally injected hMSC, biodistribution, and in vivo viability was studied using human Alu genomic repeat staining, PKH26 labeling, and luciferase-expression labeling, respectively. RESULTS: Saline- and dermofibroblast-treated control rats demonstrated lower LPP than non-VD controls at days 4 and 14 (P < 0.01). LPP after systemic hMSC and periurethral hMSC treatment were comparable with non-VD controls at 4, 10, and 14 days (P > 0.05). Local saline controls demonstrated extensive urethral tissue bleeding. The connective tissue area/urethral section area proportion and vascular density were higher in the local hMSC- versus the saline-treated group at 4 and 14 days, respectively. No positive Alu-stained nuclei were observed in urethras at 4, 10, and 14 days. PKH26-labelled cells were found in all urethras at 2 and 24 h. Bioluminescence study showed increased luciferase expression from day 0 to 1 following hMSC injection. CONCLUSIONS: Human MSCs restored the continence mechanism with an immediate and sustained effect in the VD model, while saline and dermofibroblast therapy did not. Human MSCs remained at the site of periurethral injection for <7 days. We hypothesize that periurethral hMSC treatment improves vascular, connective tissue, and hemorrhage status of urethral tissues after acute VD injury.

Drainage-related ultrasonography (DRUS): a novel technique for discriminating obstructive and nonobstructive hydroureters in children.

BACKGROUND: Despite advances in urologic imaging, the paucity of an optimal technique that accurately clarifies obstructive and nonobstructive hydroureter exists. OBJECTIVE: This study was conducted to introduce a novel and modified ultrasonographic technique, known as drainage-related ultrasonography (DRUS), discriminating obstructive and nonobstructive, nonrefluxing hydroureter. MATERIALS AND METHODS: A total of 358 children (mean age, 3.7 years) with 418 nonrefluxing hydroureter were included. These children were composed of two groups of obstructive nonrefluxing (141 children with 157 dilated ureters) and nonobstructive, nonrefluxing (217 children with 261 hydroureter). The definite diagnosis regarding the subtype of hydroureter was derived from appropriate investigation. The maximum diameter of the dilated ureter, which was observed on ultrasonography, was recorded before and after 3 h of catheterization, as D1 and D2, respectively. To assess the D ratio, a formula was developed, that is, [(|D1 - D2|)/D1] × 100. Values were recorded and cutoff points were set to discriminate between subtypes. RESULTS: Obstructive versus nonobstructive subtypes of nonrefluxing hydroureter were clarified with 78.5 % sensitivity and 83.4 % specificity, by setting a cutoff point of 22 % for the D ratio. Regardless of the cutoff point assigned to the reduction in D (D2 compared with D1), DRUS revealed 93.9 % sensitivity, 80.6 % specificity, 63.2 % positive predictive value, and 97.4 % negative predictive value in discriminating upper from lower obstruction. CONCLUSION: DRUS affords favorable results in terms of differentiating between obstructive and nonobstructive, nonrefluxing hydroureter, as well as between upper and lower obstruction in obstructive cases. It has the potential to become an efficient imaging modality in the diagnostic algorithm of hydroureter.

Mutation screen of LOXL1 in patients with female pelvic organ prolapse.

OBJECTIVES: The LOXL1 (lysyl oxidase-like 1) gene encodes a copper-dependent monoamine oxidase that catalyzes the deamination of a lysine residue in the cross-linking of tropoelastin monomers to form elastin. LOXL1-KO mice do not deposit normal elastic fibers in their genitourinary tract resulting in postpartum pelvic organ prolapse and lower urinary tract dysfunction with decreased bladder capacity and lower voiding pressure. We sought to identify which single nucleotide polymorphisms in the LOXL1 coding sequence play a role in female pelvic organ prolapse. METHODS: A total of 66 patients were screened, 48 in the case group and 18 in the control group. The 7 exons of LOXL1 were evaluated for any polymorphisms. RESULTS: Three missense sequence changes (Arg141Leu, Gly153Asp, and Ser159Ala) and 3 silent mutations (Asp292Asp, Ala320Ala, and Ile521Ile) were identified. None of these polymorphisms were found to differ significantly in frequency in the case group compared with the control group. CONCLUSIONS: Our findings do not support an association of any LOXL1 exonal single nucleotide polymorphisms with the diagnosis of female pelvic organ prolapse.

The role of CXCL12 and CCL7 chemokines in immune regulation, embryonic development, and tissue regeneration.

Chemotactic factors direct the migration of immune cells, multipotent stem cells, and progenitor cells under physiologic and pathologic conditions. Chemokine ligand 12 and chemokine ligand 7 have been identified and investigated in multiple studies for their role in cellular trafficking in the setting of tissue regeneration. Recent early phase clinical trials have suggested that these molecules may lead to clinical benefit in patients with chronic disease. Importantly, these two proteins may play additional significant roles in directing the migration of multipotent cells, such as mesenchymal stem cells and hematopoietic progenitor cells. This article reviews the functions of these two chemokines, focusing on recruitment to sites of injury, immune function modulation, and contributions to embryonic development. Additional research would provide valuable insight into the potential clinical application of these two proteins in stem cell therapy.

Stem cell homing factor, CCL7, expression in mouse models of stress urinary incontinence.

OBJECTIVES: Animal models of vaginal distention (VD) have demonstrated increased expression of chemokine (C-C motif) ligand 7 (CCL7) In this study, we investigated the expression of CCL7 in mice models of simulated birth trauma-induced urinary incontinence using VD and pudendal nerve transection (PNT). METHODS: Forty-nine mice were divided into 6 groups: VD, sham VD, PNT, sham PNT, anesthesia, and age-matched controls. The urethra, vagina, and rectum were harvested for the expression of CCL7 immediately or 24 hours after assigned procedure. Venous sampling for quantification of serum CCL7 was also performed. An analysis of variance model was used to compare the relative expression of CCL7 in each group. RESULTS: Urethral CCL7 expression in the VD group was significantly higher than control group after 24 hours (P < 0.01). There was no difference in the urethral CCL7 expression in PNT, sham PNT, sham VD, or anesthesia groups compared with the controls. No statistically significant difference was noted in the vaginal and rectal expression of CCL7 between any of the groups except for sham PNT. Statistically significant differences were noted in the serum CCL7 expression in the VD, PNT, and sham PNT (P < 0.01 in all) groups after 24 hours compared with the control group. CONCLUSIONS: This study demonstrates overexpression of urethral CCL7 after VD but not PNT. This suggests that nerve injury does not contribute to the CCL7 overexpression. The overexpression of CCL7 in the serum of mice after VD suggests a translational potential where CCL7 measurement could be used as a surrogate for injury after delivery.

¹9F MRI tracer preserves in vitro and in vivo properties of hematopoietic stem cells.

Hematopoietic stem cells (HSCs) have numerous therapeutic applications including immune reconstitution, enzyme replacement, regenerative medicine, and immunomodulation. The trafficking and persistence of these cells after administration is a fundamental question for future therapeutic applications of HSCs. Here, we describe the safe and efficacious labeling of human CD34(+) HSCs with a novel, self-delivering perfluorocarbon ¹9F magnetic resonance imaging (MRI) tracer, which has recently been authorized for use in a clinical trial to track therapeutic cells. While various imaging contrast agents have been used to track cellular therapeutics, the impact of this MRI tracer on HSC function has not previously been studied. Both human CD34(+) and murine bone marrow (BM) HSCs were effectively labeled with the MRI tracer, with only a slight reduction in viability, relative to mock-labeled cells. In a pilot study, ¹9F MRI enabled the rapid evaluation of HSC delivery/retention following administration into a rat thigh muscle, revealing the dispersal of HSCs after injection, but not after surgical implantation. To investigate effects on cell functionality, labeled and unlabeled human HSCs were tested in in vitro colony forming unit (CFU) assays, which resulted in equal numbers of total CFU as well as individual CFU types, indicating that labeling did not alter multipotency. Cobblestone assay forming cell precursor frequency was also unaffected, providing additional evidence that stem cell function was preserved after labeling. In vivo tests of multipotency and reconstitution studies in mice with murine BM containing labeled HSCs resulted in normal development of CFU in the spleen, compared to unlabeled cells, and reconstitution of both lymphoid and myeloid compartments. The lack of interference in these complex biological processes provides strong evidence that the function and therapeutic potential of the HSCs are likely maintained after labeling. These data support the safety and efficacy of the MRI tracer for clinical tracking of human stem cells.

Application of different scaffolds for bladder wall regeneration: the bladder as a natural bioreactor.

OBJECTIVES: We investigated the potential of different scaffolds for in vivo construction of bladder muscular and urothelial wall. Bladder wall was used as a bioreactor to create a model of the natural environment for cellular interactions, growth, and differentiation. METHODS: Forty rabbits were divided into 10 groups. Different scaffolds were implanted between bladder mucosa and seromuscular layer. Scaffolds used in each group were one layer or a three-layered combination of tissue-engineered pericardium (TEP), biofilm, and polyglycolic acid (PGA). In all groups, a biopsy of full thickness of bladder was dissected. Muscular and urothelial layers were separated and minced into small fragments. Fragments were seeded above the urothelial layer and urothelial fragments were placed on the scaffold under the seromuscular layer. One group served as control and no scaffold was inserted between the separated bladder layers. After 2 and 6 weeks, biopsies were performed for histologic examinations (trichrome, smooth muscle α-actin, and pancytokeratin AE1/AE3, CD34, CD31). RESULTS: Histopathological examinations showed granulomatous reaction and severe inflammation in biofilm-containing groups. Samples with TEP alone and with PGA-coated TEP as scaffolds revealed more organized bladder wall in two different layers with mature urothelial and smooth muscle cells. The number of CD34+ cells and CD31+ microvessels increased continuously during 6 weeks. CONCLUSIONS: Our results demonstrated the effective role of PGA-coated TEP as a potential scaffold for muscular and urothelial fragment seeding in bladder wall acting as a natural bioreactor. Biodegradable scaffolds could be helpful in association with acellular matrices to optimize the cell attachment and in vivo bladder wall construction.

Advanced maternal age as a risk factor for stress urinary incontinence: a review of the literature.

The pathophysiology of stress urinary incontinence (SUI) is multifactorial and evidence supports a critical role of pregnancy and vaginal delivery. This review dissects epidemiologic literature to determine the weight of evidence on the role of advanced maternal age (AMA) as a risk factor for the development of subsequent or persistent SUI. We conducted a Medline search using the keywords postpartum, SUI, maternal age, pregnancy, and incontinence. The published literature was critically analyzed. Evidence supports that childbirth trauma contributes to the development and severity of SUI. Yet, there is contradicting evidence as to whether AMA increases the risk. AMA clearly represents an independent risk factor for postpartum SUI. However, long-term studies did not confirm this observation. Whether this finding is suggestive of a true biologic signal that is lost with competing risk factors over time warrants further research.

Vesicoureteral reflux and primary bladder neck dysfunction in children: urodynamic evaluation and randomized, double-blind, clinical trial on effect of α-blocker therapy.

PURPOSE: Primary bladder neck dysfunction has been under diagnosed as a treatable cause of vesicoureteral reflux. We evaluated the effect of prazosin administration on vesicoureteral reflux resolution and urodynamic parameters in children with idiopathic primary reflux and primary bladder neck dysfunction. MATERIALS AND METHODS: A total of 62 children (mean ± SD age 7.9 ± 2.4 years) with documented vesicoureteral reflux and urodynamics proved primary bladder neck dysfunction were randomized to receive either 0.025 mg/kg α-blocker (prazosin, 40 patients) or placebo (22) nightly for 1 week with a subsequent increase to 2 divided doses. Patients were followed for 12 months with clinical evaluation and uroflowmetry performed every 2 months, and each patient underwent complete urodynamic study at 6-month intervals. RESULTS: In the placebo group no uroflowmetry or urodynamic parameter changed significantly at 1-year followup. A 60% decrease in reflux grade was observed in the treatment group compared to 17% in the placebo group. Mean maximal detrusor pressure, post-void residual and opening time were significantly decreased in both followup sessions in the prazosin group (p <0.05). Average flow rate improved from 4.30 to 12.80 ml per second at 6 months and to 13.10 ml per second at 12 months (both p <0.05). CONCLUSIONS: Special attention should be given to secondary causes of vesicoureteral reflux (such as primary bladder neck dysfunction, an underdiagnosed entity in children), since conventional treatment will most likely fail if these conditions are not addressed promptly. In this study prazosin was effective therapy for children with vesicoureteral reflux and primary bladder neck dysfunction.

Biodegradable mini plate and screw: a secure method for internal fixation of symphysis pubis in animal model of pubic diastasis.

OBJECTIVES: To investigate short-term results of symphysis pubis reapproximation in a simulated animal model of pubic diastasis using biodegradable plate and screw, in comparison with animals with no fixation, in terms of inflammatory reaction, histologic changes, and three-dimensional pelvic bone CT (3D-CT) scan. METHODS: Fifteen male goats were divided in 3 groups and underwent midline pubic symphysiotomy. In GI (n = 6), the pubes were brought together with sutures through the bone and fixed by placing a biodegradable plate and screws. In GII (n = 3), symphysis was brought together by inserting sutures. Animals' pubes received no fixation in GIII (n = 6). Three-dimensional CT scan was performed, after 3 months in GII, and at the third and sixth months in GI and GIII. Furthermore, tissue-implant interface was examined for tissue reaction and implant degradation. RESULTS: Pelvic bone 3D-CT scan in the biodegradable group revealed characteristic differences in pubic diastasis, iliac wing angle, and inter-triradiate distance compared with GII and GIII. Decreases of 21.8 +/- 0.7 mm, 7.28 +/- 0.4 mm, and 7.43 +/- 1.5 degrees were observed in pubic diastasis, inter-triradiate distance, and iliac wing angle, respectively, in biodegradable group in comparison with GIII in the sixth month. Neither clinical nor histologic evidence of inflammation due to insertion of biodegradable system was reported. CONCLUSIONS: Pubic bone adaptation with biodegradable plate and screws is a safe and reliable procedure for secure anterior pubic fixation in bladder exstrophy. Easy intraoperative handling, no long-term traction, biocompatibility, and no disturbance in skeletal growth are important prerequisites for introduction of this method of pubic approximation into clinical practice.