Growing Up With Neurogenic Bladder: Navigating the Challenges and Controversies in Pediatric to Adult Transition and Lifelong Care: A Report From the Neurogenic Bladder Research Group (NBRG).

OBJECTIVE: Young adults with spina bifida (and other congenital neurologic diseases) have their own aspirations that may include education, employment, relationships and having children. As they move from pediatric to adult care, they must eventually transition to an adult healthcare team. The objective of this paper is to review the challenges and controversies in the transitional and adult care of people with congenital neurourological diseases. METHODS: The Research Group convened a meeting of its members and invited guests to better understand the healthcare challenges faced by these patients as they become adults. The group examined potential research opportunities focused on people with these diagnoses and themes related to their healthcare. RESULTS: Trust and clear communication are essential for effective patient transition. Ideally parents are involved in the transition to help reinforce independent self-care and responsibility. Adolescents require education about sexual health and independence, which may not be part of the core skillset of a urologist. The healthcare team must promote self-management and autonomy as early as practical. One of the major limitations is that adult care lacks the coordination of pediatric care, and patients may not have a "medical home." Multidisciplinary clinics are ideal but face logistical barriers in adult medicine. Additional barriers include limited physicians with the required specialized training. In the adult system, financial constraints are a key challenge for patients and providers. CONCLUSION: Collaboration, supported by institutions and new research, is vital for improving the neurourological care of young adults with complex diseases. TRIAL REGISTRATION: This study reports on the proceedings of a meeting, and therefore clinical trial registration was not necessary.

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.

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.

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.

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.

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.

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.

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.

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.

Transurethral autologous myoblast injection for treatment of urinary incontinence in children with classic bladder exstrophy.

PURPOSE: The application of autologous myoblasts is an area of active research that may represent an improved alternative for the treatment of urinary incontinence. In this study we investigated the effectiveness of autologous myoblast injection for the treatment of urinary incontinence in children with classic bladder exstrophy. MATERIALS AND METHODS: Seven boys and 1 girl with persistent urinary incontinence were entered in the study. All children had undergone staged bladder repair and bladder neck reconstruction, and 5 patients had received 1 to 3 transurethral injections of bulking agent. Autologous myoblasts were isolated from abdominal muscle biopsy and cultured before endourethral injection. After the procedure patients underwent pelvic floor electrical stimulation and continued pelvic floor exercises that had been started at least 1 year before injection. The clinical outcomes (based on a 24-hour voiding diary), and cystometric and urodynamic studies were evaluated. Followup ranged from 12 to 18 months (average 15.3). RESULTS: There was a significant, time dependent improvement in urinary continence. At final followup all 7 boys (88% of patients) were socially dry (daytime dryness more than 3 hours), including 3 (38%) who were completely dry. Urodynamic studies revealed an increase in mean bladder capacity (p <0.001), detrusor leak point pressure (p <0.001) and average maximum urinary flow (p <0.01). All 7 boys (vs only 2 patients preoperatively) achieved normal voiding with demonstrable voiding detrusor contraction in the presence of a compliant stable bladder (p <0.05). CONCLUSIONS: Our results suggest that transurethral autologous myoblast injection is a valid option for the treatment of structural urinary incontinence in children with classic bladder exstrophy. However, favorable preoperative urodynamic profiles and postoperative pelvic floor electrical stimulation may have contributed to the outcome in this series.

Comparison of different techniques for hemostasis in a rabbit model of hypospadias repair.

PURPOSE: We compared the cellular and ultrastructural changes in the urethral wall following application of different hemostasis techniques in a rabbit model of hypospadias surgery. MATERIALS AND METHODS: Rabbits were allocated into 5 groups. In group 1 animals underwent surgery without application of any hemostasis technique; in group 2 continuous penile tourniquet was applied for 30 minutes; in group 3, 3 intermittent periods of 10-minute penile tourniquet were applied with 3-minute intervals of reperfusion; in group 4 epinephrine was injected to maintain a 30-minute period of hemostasis; and in group 5 epinephrine vehicle (normal saline) was injected during the procedure. Early urothelium ultrastructural damage was studied 1 hour postoperatively with electron microscopy. Apoptotic damage and histopathological changes were determined 48 hours following the procedure. Late onset complications were assessed with retrograde urethrography and evaluation of tissue fibrosis at 8 weeks postoperatively. RESULTS: Electron microscope studies demonstrated urothelium ultrastructural damage in all hemostasis groups compared to controls. However, the changes were most prominent in group 4. The apoptosis index of urethral wall myocytes in groups 1 and 5 was significantly lower compared to other groups. Moreover, the number of apoptotic myocytes in epinephrine injected animals was significantly higher than in the continuous or intermittent tourniquet group as well as the normal saline injected group. At 8 weeks postoperatively collagen deposition in the urethral wall of rabbits in group 4 was higher than that in group 1. Although urethrocutaneous fistula was found in only 1 rabbit in group 4, the difference was not significant. CONCLUSIONS: Hemostasis techniques applied for maintaining a bloodless surgical field during hypospadias repair may lead to ischemia/reperfusion tissue damage in the urethral wall. Our findings suggest that epinephrine injection may result in more prominent cellular changes compared to tourniquet techniques. However, further experimental and human studies are required to draw a firm conclusion.

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.

Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice.

Aerial parts of Swertia longifolia Boiss. (Gentianaceae), which grows in the north of Iran, were screened for hepatoprotective activity against paracetamol (acetaminophen)-induced hepatotoxicity in Swiss mice. Pretreatment with total plant extract and swerchirin, the major component of the plant, significantly reduced the elevation of biochemical parameters, AST (aspartate aminotransferase), ALT (alanine aminotransferase) and ALP (alkaline phosphatase), the enzymes that are increased by liver damage (P < 0.001). Our results indicated that total plant extract and swerchirin were hepatoprotective in the range of 6-50 mg kg(-1) orally.

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.

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.