[Show abstract][Hide abstract] ABSTRACT: The "Multidisciplinary Approach to the Study of Chronic Pelvic Pain" (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network's central study and common data elements are described.
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of interstitial cystitis/painful bladder syndrome (IC/PBS) remains incompletely understood, but is thought to involve a central disturbance in the processing of pain and viscerosensory signals. We aimed to identify differences in brain activity and connectivity between female IC/PBS patients and healthy controls in order to advance clinical phenotyping and treatment efforts for IC/PBS.
We examined oscillation dynamics of intrinsic brain activity in a large sample of well-phenotyped female IC/PBS patients and female healthy controls collected during a 10-minute resting fMRI scan as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network* project. The BOLD signal was transformed to the frequency domain and relative power was computed for multiple frequency bands.
The results demonstrated altered frequency distributions in viscerosensory (post insula), somatosensory (postcentral gyrus) and motor regions (anterior paracentral lobule, medial and ventral supplementary motor area (SMA)) in IC/PBS patients. Additionally, anterior paracentral lobule, medial SMA and ventral SMA all demonstrated increased functional connectivity to the midbrain (red nucleus) and cerebellum. This increased functional connectivity was greatest in patients reporting pain during bladder filling.
These findings suggest that women with IC/PBS have a sensorimotor component to their pathology involving an alteration in the intrinsic oscillations and connectivity within a cortico-cerebellar network previously associated with urinary bladder function.
The Journal of urology 03/2014; · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
We reviewed the significance and achievements of female urologists and urological researchers who have impacted the field of urology.
We reviewed the past and current status of female urologists and researchers in urological investigation.
Since 1962, the year that the first woman was board certified as a urologist, the number of women working in urological practice and urological research has steadily increased. As of January 2014 there are 350 female board certified urologists and in tandem a progressive increase in female researchers engaged in urological investigation. Indeed, slightly more than a quarter of urology residents today are women and the match rate is equivalent for men and women seeking a residency slot. Women are beginning to assume leadership positions in academic urology and research environments, working in all areas of the field.
As the number of women urologists and female scientists in urological investigation increased in the last 50 years, their contributions significantly advanced the practice of urology and our understanding of the previously unrecognized causes of urological disease.
[Show abstract][Hide abstract] ABSTRACT: This article reviews the basic principles and therapeutic options in the management of the neurogenic bladder due to multiple sclerosis (MS), written primarily for the non-urology provider. An algorithm for the initial management of the MS patient with lower urinary tract symptoms is provided.
Physical Medicine and Rehabilitation Clinics of North America 11/2013; 24(4):673-86. · 1.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: The female genital sensory pathways that initiate sexual arousal reflexes begin with cutaneous corpuscular receptors in the glabrous genital skin, including those of the glans clitoris. AIM: The aim of this study is to characterize the corpuscular receptors of the glans clitoris. In addition, we compared basic features with the receptors of the glans penis. MAIN OUTCOME MEASURE: Number of stained receptors. METHODS: Five cadaveric vulvectomy specimens and four cadaveric penile specimens were used. They were serially sectioned and stained with hematoxylin and eosin. Selected blocks were stained with Masson's trichrome, and immunohistochemical staining was done with neuronal markers S-100 and neurofilament. RESULTS: Using the three stains, we identified an abundance of corpuscular receptors within the glans clitoris, as compared with the surrounding prepuce. These receptors were of varied arrangements, situated in the subepithelial tissues of the glans clitoris. They were indistinguishable from the receptors of the glans penis. The number of receptors per 100× high-powered field ranged from 1 to 14, whereas the receptor density in the glans penis ranged from 1 to 3. A second type of receptor, the Pacinian corpuscle, was identified within the suspensory ligament along the trunks of the dorsal nerve but not within the glans itself. CONCLUSIONS: The glans clitoris is densely innervated with cutaneous corpuscular receptors, and these receptors are morphologically similar to the corpuscular receptors of the glans penis. The glans clitoris has greater variability in receptor density compared with the glans penis.
Journal of Sexual Medicine 05/2013; · 3.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: This review explores the treatment of male chronic pelvic pain syndrome (CPPS) (i.e., chronic prostatitis) through the use of neuromodulation, which is the electrical stimulation of the nervous system. Neuromodulation has been used for the treatment of chronic pain for decades, and this review will examine the theory and use of neuromodulation and the various techniques available for the treatment of CPPS. METHODS: Existing literature on the use of neuromodulation of the pelvic nerves for the treatment of chronic urogenital pelvic pain was reviewed. Because of limited published research, much of the data are not explicitly for male CPPS. RESULTS: Neuromodulation techniques used for chronic pelvic pain conditions include SNS, PTNS and pudendal nerve stimulation. Only SNS and PTNS are currently approved by the US Food and Drug Administration for the treatment of urinary symptoms, and none of these methods are acknowledged as standard therapies for treating chronic pelvic pain syndromes. The improvement of urinary symptoms is more clearly defined than improvements in pain, but at least a subset of patients in most of the published studies and case series derive some benefit in the short term and limited evidence suggests that long-term improvement of symptoms is possible. However, explantation rates are high in all long-term series of patients receiving implantable neuromodulation devices. CONCLUSIONS: Neuromodulation appears to provide benefits for patients with CPPS. However, because of the paucity of data and the limitations of small studies, the conclusions of the existing literature must be carefully considered. Because we are still becoming familiar with the pathophysiology of the pain syndromes and the mechanism of neuromodulation on urinary and pain symptoms, we cannot yet predict a particular individual's response to neuromodulation. To determine the long-term efficacy of this therapy, more clinical study is needed to explore the use of neuromodulation in the treatment of male CPPS.
World Journal of Urology 04/2013; · 2.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction. The pars intermedia is an area of the vulva that has been inconsistently described in the literature. Aim. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Methods. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Main Outcome Measures. Histologic ultrastructural description of the pars intermedia. Results. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. Conclusions. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. Shih C, Cold CJ, and Yang CC. The pars intermedia: An anatomic basis for a coordinated vascular response to female genital arousal. J Sex Med **;**:**-**.
Journal of Sexual Medicine 11/2012; · 3.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction. We previously described dynamic, noncontrast magnetic resonance imaging (MRI) of the female genitalia as a reproducible, nonintrusive, objective means of quantifying sexual arousal response in women without sexual difficulties. These studies showed an increase in clitoral engorgement ranging from 50 to 300% in healthy women during sexual arousal. Aim. This study sought to evaluate the genital arousal response in women with female sexual arousal disorder (FSAD) after administration of sildenafil and placebo. We performed a multicenter, double-blind, placebo-controlled, cross-over study to assess the clitoral engorgement response using dynamic MRI in women with FSAD after administering sildenafil and placebo followed by audiovisual sexual stimulation (AVSS). Methods. Nineteen premenopausal women with FSAD underwent two MRI sessions. Subjects were randomized to receive either (i) sildenafil 100 mg during the first session followed by placebo during the second session, or (ii) placebo followed by sildenafil. During each session, baseline MR images were obtained while subjects viewed a neutral video. Subjects then ingested sildenafil or placebo. After 30 minutes, a series of MRIs were obtained at 3-minute intervals for 10 time points while subjects viewed AVSS. Main Outcome Measures. A positive sexual arousal response was achieved if clitoral volume increased ≥50% from baseline. Results. Thirteen of 19 (68%) subjects achieved a ≥50% increase in clitoral engorgement from baseline when administered sildenafil or placebo 30 minutes after dose administration. At 60 minutes after administration, 17/19 (89%) subjects receiving sildenafil and 16/19 (84%) subjects receiving placebo had responded (P value 0.3173). Conclusions. Sildenafil did not augment the genital response in women with FSAD. Secondarily, a majority of women in this study did not have impaired clitoral engorgement as measured by MRI, suggesting that FSAD is not predominantly a disorder of genital engorgement. Leddy LS, Yang CC, Stuckey BG, Sudworth M, Haughie S, Sultana S, and Maravilla KR. Influence of sildenafil on genital engorgement in women with female sexual arousal disorder. J Sex Med **;**:**-**.
Journal of Sexual Medicine 05/2012; 9(10):2693-7. · 3.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Many bladder pain syndrome/interstitial cystitis (BPS/IC) patients report multiple pain locations outside the pelvis. No research has examined pain using a whole-body diagram, pain-associated adjustment factors, or the impact of pain in multiple body areas on patients' quality of life (QoL). OBJECTIVE: Compare and contrast pain in BPS/IC patients and controls using a whole-body diagram (visible body areas). Examine the association between patient adjustment factors and greater number of body pain areas (pain phenotypes). DESIGN, SETTING, AND PARTICIPANTS: Validated questionnaires were collected from diagnosed, tertiary-care, outpatient, female BPS/IC patients (n=193) and age-matched controls (n=115). Scales included a body pain area diagram, demographics/history, pain severity, BPS/IC symptoms, pain, depression, catastrophizing, and QoL. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cross-tabulation and analysis of variance models addressed the patient and control differences. RESULTS AND LIMITATIONS: Patients reported more pain than controls in all reported body areas. Four pain phenotypes were created based on increasing counts of body locations (BPS/IC only, BPS/IC+plus 1-3 additional locations, BPS/IC plus 4-9, BPS/IC ≥10). Patients reported more body pain locations, pain, urinary symptoms, depression, catastrophizing, and diminished QoL than controls. The increased-pain phenotype was associated with poorer psychosocial adjustment and diminished physical QoL, but catastrophizing and low scores for mental QoL remained stable across all patient groups. This study was cross-sectional, relying on correlation-based analyses, thus causality cannot be established. CONCLUSIONS: Patients reported numerous systemic pain symptoms outside the areas associated with the bladder/pelvic region, and increased numbers of body pain sites were associated with poorer patient outcomes (ie, pain severity, depression). This study illustrates the significant negative impact of pain on patient adjustment in BPS/IC. These findings suggest that clinicians carefully consider pain location distributions and the potential impact of body pain phenotypes during patient evaluation and treatment planning.
[Show abstract][Hide abstract] ABSTRACT: Objective. The goal of this study is to describe comorbid characteristics in patients who have priapism, and their treatment outcomes. Methods. Chart review was undertaken on men who had a diagnosis of priapism from a tertiary medical center, from 2000-2010. Men with priapism due exclusively to the use of prescription erectile aids and medications were not included in the review. Results. We identified 79 patients with the priapism. The most common type of priapism was the low flow variant. High flow priapism was identified in 2 patients. The most common general comorbid condition associated with priapism was mental illness (including substance abuse), which was present in 56% of the patients. Neurogenic priapism accounted for 19% of the total priapism events. Psychopharmaceutical agents and recreational drugs were commonly associated with ischemic priapism. Acute complications of priapism treatment were not common, but long-term complications, especially erectile dysfunction, were frequent. Conclusions. We describe the characteristics and outcomes of a large group of patients with priapism. Our experience at a tertiary care center indicates that mental illness, including substance abuse disorders, is a highly prevalent comorbid condition in men who experience priapism. Consistent with previous reports, erectile dysfunction is the most common complication from priapism and its treatment, occurring in the majority of men.
[Show abstract][Hide abstract] ABSTRACT: We performed this study to identify the source of complexes recorded during corpus cavernosum electromyography.
A total of 10 healthy male volunteers 19 to 54 years old (mean age 36) with normal erectile function, participated in the study. A Porti electrodiagnostic system (TMS International, Enschede, The Netherlands) connected to a notebook computer recorded low frequency corpus cavernosum electromyography complexes via penile surface electrodes in 3 phases. In phase 1 baseline corpus cavernosum electromyography was recorded for 30 minutes. In phase 2 penile skin block was performed followed by 30 minutes of corpus cavernosum electromyography recording. Phase 3 consisted of intracavernous block followed by corpus cavernosum electromyography recording for 30 minutes. During all 3 phases startling auditory stimuli and median nerve stimulation were used at random intervals to evoke a sympathetic nervous system response. A suprapubic electrode was used as a control to record sympathetic electrodermal activity.
In phase 1 all subjects had spontaneous and evoked corpus cavernosum complexes. The penile skin block used in phase 2 did not affect the presence of these complexes, which remained present in all subjects. During phase 3 no spontaneous or evoked corpus cavernosum complexes were recorded in any subjects, indicating that the intracavernous block eliminated the corporally generated signal. All subjects in all 3 phases demonstrated a sympathetic electrodermal response in the suprapubic electrode in response to evoking stimuli.
This study confirms the penile cavernous tissue, and not the penile skin or surrounding tissue, as the origin of the corpus cavernosum electromyography complex. Further refinement of this technique may render it useful in the evaluation of neurogenic and myogenic erectile dysfunction.
The Journal of urology 12/2011; 187(2):589-93. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The purpose of this trial was to compare usual patient education plus the Internet-based Personal Patient Profile-Prostate, vs. usual education alone, on conflict associated with decision making, plus explore time-to-treatment, and treatment choice. METHODS: A randomized, multi-center clinical trial was conducted with measures at baseline, 1-, and 6 months. Men with newly diagnosed localized prostate cancer (CaP) who sought consultation at urology, radiation oncology, or multi-disciplinary clinics in 4 geographically-distinct American cities were recruited. Intervention group participants used the Personal Patient Profile-Prostate, a decision support system comprised of customized text and video coaching regarding potential outcomes, influential factors, and communication with care providers. The primary outcome, patient-reported decisional conflict, was evaluated over time using generalized estimating equations to fit generalized linear models. Additional outcomes, time-to-treatment, treatment choice, and program acceptability/usefulness, were explored. RESULTS: A total of 494 eligible men were randomized (266 intervention; 228 control). The intervention reduced adjusted decisional conflict over time compared with the control group, for the uncertainty score (estimate -3.61; (confidence interval, -7.01, 0.22), and values clarity (estimate -3.57; confidence interval (-5.85,-1.30). Borderline effect was seen for the total decisional conflict score (estimate -1.75; confidence interval (-3.61,0.11). Time-to-treatment was comparable between groups, while undecided men in the intervention group chose brachytherapy more often than in the control group. Acceptability and usefulness were highly rated. CONCLUSION: The Personal Patient Profile-Prostate is the first intervention to significantly reduce decisional conflict in a multi-center trial of American men with newly diagnosed localized CaP. Our findings support efficacy of P3P for addressing decision uncertainty and facilitating patient selection of a CaP treatment that is consistent with the patient values and preferences.
[Show abstract][Hide abstract] ABSTRACT: The impact of early lifetime trauma on symptom severity and quality of life of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) has not been fully elucidated. We wanted to determine and compare the prevalence and impact of childhood traumatic events, with an emphasis on childhood sexual abuse, on patient symptoms, quality of life and other biopsychosocial parameters.
Subjects (female patients with IC/BPS and controls without IC/BPS) completed psychosocial phenotyping questionnaires, including a demographics/history form, and validated questionnaires focused on presenting symptoms (IC symptom indices, pain), psychosocial parameters (depression, anxiety, pain catastrophizing, sexual functioning, social support) and quality of life. Participants also completed the Childhood Traumatic Events Scale.
Questionnaires were completed by 207 IC/BPS patients and 117 controls matched for age, partner status and education. It was found that before 17 years of age, the IC/BPS cases reported higher prevalence of "raped or molested" compared to controls (24.0% vs. 14.7%; p = 0.047). Within the IC/BPS group, cases reporting previous sexual abuse endorsed greater sensory pain, depression and poorer physical quality of life at the present time compared to IC cases without a sexual abuse history. In the controls only, those reporting previous sexual abuse endorsed more depression, anxiety, stress, social maladjustment poorer mental quality of life in the present time. When the analysis was corrected for potential multiple comparison error, none of the findings remained significant in either the IC/BPS or control groups.
Childhood traumatic events, in particular sexual abuse and extreme illness, are reported as more common in IC/BPS patients than controls. Early trauma, such as the occurrence of sexual abuse, is associated with some differences in patient adjustment (e.g., pain, quality of life, depression) but this impact appears to be, at most, very modest.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 12/2011; 5(6):410-5. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: • To examine functional and molecular changes of the bladders from elastin-haploinsufficient mice (Eln(+/-) ) at baseline as well as in response to partial bladder outlet obstruction (pBOO).
• Female Eln(+/-) and wild type (Wt) mice (3-4 months old) were studied. • The bladder elastin content was quantified by measuring desmosine. • Mice were divided into two groups to undergo surgery to create pBOO or to undergo sham surgery. Three days after surgery, bladder function was evaluated by in vivo cystometry, and the contractile response of bladder strips exposed to electrical field stimulation (EFS) and carbachol was examined by ex vivo myography.
• The Eln(+/-) -sham mice had a 33.6% decrease in bladder elastin compared with Wt-sham mice. • Cystometry showed significantly decreased bladder compliance and capacity in Eln(+/-) -sham vs Wt-sham mice; pBOO increased bladder compliance and capacity to a greater extent in Eln(+/-) mice compared with Wt mice. • Bladder strips from Eln(+/-) -sham mice showed a significantly heightened contractile response to both EFS and carbachol compared with Wt-sham mice. • A significantly increased contractile response to carbachol was detected in Wt-pBOO vs Wt-sham but not between Eln(+/-) -pBOO and Eln(+/-) -sham mice.
• The results that elastin-deficient mice had decreased bladder compliance and capacity and increased bladder contractility; and that Wt-pBOO mice showed an enhanced contractile response to carbachol, but Eln(+/-) -pBOO mice did not, suggest that elastin is critical for normal bladder function and is involved in bladder response to pBOO.
BJU International 11/2011; 110(3):413-9. · 3.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : The objective of this study was to examine the histologic features of the labia minora, within the context of the female sexual response.
: Eight cadaver vulvectomy specimens were used for this study. All specimens were embedded in paraffin and were serially sectioned. Selected sections were stained with hematoxylin and eosin, elastic Masson trichrome, and S-100 antibody stains.
: The labia minora are thinly keratinized structures. The primary supporting tissue is collagen, with many vascular and neural elements structures throughout its core and elastin interspersed throughout.
: The labia minora are specialized, highly vascular folds of tissue with an abundance of neural elements. These features corroborate previous functional and observational data that the labia minora engorge with arousal and have a role in the female sexual response.
Journal of Pelvic Medicine and Surgery 07/2011; 17(4):180-3.
[Show abstract][Hide abstract] ABSTRACT: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome.
A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries.
Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls.
In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.
The Journal of urology 03/2011; 185(3):901-6. · 4.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to describe the distal pathway of the dorsal nerve of the clitoris (DNC) from gross anatomical and histological studies of cadaver specimens.
We performed dissections on 14 intact adult cadaver vulva specimens using 2× loupe magnification and microscopy. The DNC was identified by gross dissection and confirmed histologically by staining with hematoxylin and eosin (H&E), Masson's trichrome (MT), and S100 antibody. The DNC pathway and its branches were followed from the pubic rami to the glans clitoris.
The DNC travels inferior to the inferior pubic ramus along the superior/posterior edge of the clitoral crus. At the angle of the clitoral body, inferior to the pubic symphysis, the DNC enters the deep component of the suspensory ligament, which attaches to the clitoral body and to the pubic symphysis. The dorsal nerves, at the angle of the clitoral body, travel along the dorsal aspect of the clitoral body at the 11 and 1 o'clock positions. At the base of the clitoral body, the DNC is suspended superiorly away from the tunica. Distally along the clitoral body, the DNC descends and runs along the tunica and enters the glans. Within the glans, the terminal fibers are widely dispersed, and numerous receptors populate the supporting tissue of the glans beneath the epithelium.
The detailed description of the distal course of the nerve presented here has not been previously described in adult humans and is pertinent for surgical procedures involving the clitoris.
Neurourology and Urodynamics 02/2011; 30(3):412-6. · 2.67 Impact Factor