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Purpose:Guidelines recommend treating women who have symptoms of an uncomplicated urinary tract infection with antimicrobials without performing a urine culture. However, 10% to 50% of women with u...

Poor semen quality is associated with reduced somatic health and increased cancer risk. Infertility and cancer are increasingly being linked by epidemiologists and basic scientists. We sought to identify semen parameters associated with an increased childhood cancer risk in the family members of subfertile men.We performed a retrospective cohort study in men from the SHARE (Subfertility Heath and Assisted Reproduction) study who underwent semen analysis between 1994 and 2011. We used fertile population controls from the Utah Population Data Base. Our primary outcome was the risk of any childhood (18 years or younger) cancer in the siblings and cousins of men who underwent semen analysis compared to fertile, age matched controls. Cox proportional hazard regression models were used to test the association between semen quality and childhood cancer incidence.We selected 10,511 men with complete semen analysis and an equal number of fertile controls. These men had a total of 63,891 siblings and 327,753 cousins. A total of 170 and 958 childhood cancers were identified in siblings and cousins, respectively. The 3 most common cancers diagnosed in siblings were acute lymphoblastic leukemia in 37, brain cancer in 35 and Hodgkin lymphoma in 15. Oligozoospermia was associated with a twofold increased risk of any childhood cancer and a threefold increased risk of acute lymphoblastic leukemia in the siblings of subfertile men compared to fertile controls (HR 2.09, 95% CI 1.18-3.69 vs HR 3.07, 95% CI 1.11-8.46).Siblings of men with oligozoospermia are at increased risk for any-site cancer and acute lymphoblastic leukemia. This suggests a shared genetic/epigenetic insult or an environmental exposure that merits further investigation.

Clinical phenotyping of urological chronic pelvic pain syndromes (UCPPSs) in men and women have focused on end organ abnormalities to identify putative clinical subtypes. Initial evidence of abnormal brain function and structure in male pelvic pain has necessitated large-scale, multisite investigations into potential UCPPS brain biomarkers. We present the first evidence of regional white matter (axonal) abnormalities in men and women with UCPPS, compared with positive (irritable bowel syndrome, IBS) and healthy controls. Epidemiological and neuroimaging data were collected from participants with UCPPS (n = 52), IBS (n = 39), and healthy sex- and age-matched controls (n = 61). White matter microstructure, measured as fractional anisotropy (FA), was examined by diffusion tensor imaging. Group differences in regional FA positively correlated with pain severity, including segments of the right corticospinal tract and right anterior thalamic radiation. Increased corticospinal FA was specific and sensitive to UCPPS, positively correlated with pain severity, and reflected sensory (not affective) features of pain. Reduced anterior thalamic radiation FA distinguished patients with IBS from those with UCPPS and controls, suggesting greater microstructural divergence from normal tract organization. Findings confirm that regional white matter abnormalities characterize UCPPS and can distinguish between visceral diagnoses, suggesting that regional axonal microstructure is either altered with ongoing pain or predisposes its development.

Purpose: Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction.Materials and Methods: Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I α I) and α-SMA (α-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen.Results: Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and α-SMA in the prostate...

INTRODUCTION AND OBJECTIVE:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating condition of chronic pelvic pain. We previously linked a locus encoding acyloxyacyl hydrolase (Aoah)...

INTRODUCTION AND OBJECTIVE:Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating condition of chronic pelvic pain often co-morbid with voiding dysfunction and depression. We have p...

© 2015 American Urological Association Education and Research, Inc. Purpose: Several chronic pain conditions may be distinguished by condition specific brain anatomical and functional abnormalities on imaging, which are suggestive of underlying disease processes. We present what is to our knowledge the first characterization of interstitial cystitis/bladder pain syndrome associated white matter (axonal) abnormalities based on multicenter neuroimaging from the MAPP Research Network. Materials and Methods: We assessed 34 women with interstitial cystitis/bladder pain syndrome and 32 healthy controls using questionnaires on pain, mood anddaily function. White matter microstructure was evaluated by diffusion tensor imaging to model directional water flow along axons or fractional anisotropy. Regions correlating with clinical parameters were further examined for gender and syndrome dependence. Results: Women with interstitial cystitis/bladder pain syndrome showed numerous white matter abnormalities that correlated with pain severity, urinary symptoms and impaired quality of life. Interstitial cystitis/bladder pain syndrome was characterized by decreased fractional anisotropy in aspects of the right anterior thalamic radiation, the left forceps major and the right longitudinal fasciculus. Increased fractional anisotropy was detected in the right superior and bilateral inferior longitudinal fasciculi. Conclusions: To our knowledge we report the first characterization of brain white matter abnormalities in women with interstitial cystitis/bladder pain syndrome. Regional decreases and increases in white matter integrity across multiple axonal tracts were associated with symptom severity. Given that white matter abnormalities closely correlated with hallmark symptoms of interstitial cystitis/bladder pain syndrome, including bladder pain and urinary symptoms, brain anatomical alterations suggest that there are neuropathological contributions to chronic urological pelvic pain.

Purpose: We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria.Materials and Methods: Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors.Results: Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome co...

We determined whether including a care coordination system to manage the referral process for hematuria would lead to improved quality of care.Inflection Navigator, a protocol based, electronic medical record enabled care coordination system, was developed to support primary care physicians evaluating newly discovered hematuria. We studied the system for patients referred for microscopic and gross hematuria from May 2009 to May 2010. We compared outcomes in these 106 patients and in 105 referred to our urology department for hematuria during the same period who did not use the system.Patients in the care coordination group completed the evaluation in a significantly shorter time with more than a 1-month difference in time between referral and the completion of the imaging and cystoscopy components of the assessment (mean 40.9 vs 74.1 days, p0.05). This system potentially lowered health care costs by decreasing the mean ± SD number of urology visits needed to complete an evaluation from 2.1 ± 1.5 in the standard referral group to 1.6 ± 1.4 in the care coordination group (p0.05).A protocol based care coordination system for hematuria decreased the time needed to complete an evaluation and decreased the number of overall visits required to make a final diagnosis. Thus, the Inflection Navigator system is an example of an electronic medical record enabled process innovation that can improve the efficiency of care while potentially lowering health care costs.

We evaluated targeted antimicrobial prophylaxis in men undergoing transrectal ultrasound guided prostate biopsy based on rectal swab culture results.From July 2010 to March 2011 we studied differences in infectious complications in men who received targeted vs standard empirical ciprofloxacin prophylaxis before transrectal ultrasound guided prostate biopsy. Targeted prophylaxis used rectal swab cultures plated on selective media containing ciprofloxacin to identify fluoroquinolone resistant bacteria. Patients with fluoroquinolone susceptible organisms received ciprofloxacin while those with fluoroquinolone resistant organisms received directed antimicrobial prophylaxis. We identified men with infectious complications within 30 days after transrectal ultrasound guided prostate biopsy using the electronic medical record.A total of 457 men underwent transrectal ultrasound guided prostate biopsy, and of these men 112 (24.5%) had rectal swab obtained while 345 (75.5%) did not. Among those who received targeted prophylaxis 22 (19.6%) men had fluoroquinolone resistant organisms. There were no infectious complications in the 112 men who received targeted antimicrobial prophylaxis, while there were 9 cases (including 1 of sepsis) among the 345 on empirical therapy (p=0.12). Fluoroquinolone resistant organisms caused 7 of these infections. The total cost of managing infectious complications in patients in the empirical group was $13,219. The calculated cost of targeted vs empirical prophylaxis per 100 men undergoing transrectal ultrasound guided prostate biopsy was $1,346 vs $5,598, respectively. Cost-effectiveness analysis revealed that targeted prophylaxis yielded a cost savings of $4,499 per post-transrectal ultrasound guided prostate biopsy infectious complication averted. Per estimation, 38 men would need to undergo rectal swab before transrectal ultrasound guided prostate biopsy to prevent 1 infectious complication.Targeted antimicrobial prophylaxis was associated with a notable decrease in the incidence of infectious complications after transrectal ultrasound guided prostate biopsy caused by fluoroquinolone resistant organisms as well as a decrease in the overall cost of care.

The reasons for referral and treatment strategies in patients who underwent complete primary repair of bladder exstrophy elsewhere in the newborn period were evaluated.An institutionally approved database identified patients who underwent complete primary repair of exstrophy and were subsequently referred for continued care.A total of 10 females and 55 males were referred for treatment between 1996 and 2010. Six females and 23 males were referred for complications following initial complete primary repair of exstrophy. Female complications included dehiscence (3 patients), prolapse (2) and stricture (1). Male complications included dehiscence (10 patients), prolapse (9), pubic separation (1) and stricture (3). Nine males had posterior urethral loss and 13 had major penile soft tissue injuries. Grade V vesicoureteral reflux and severe hydronephrosis were seen in the 4 patients with urethral strictures. Patients with dehiscence or prolapse underwent successful reclosure with osteotomy. Cases with posterior urethral loss or strictures were repaired with grafts. Four females and 32 males were referred for incontinence. Nine of these patients had poor bladder capacity, of whom 5 underwent bladder augmentation with continent stoma and 4 are awaiting further bladder growth. A total of 27 patients underwent bladder neck repair, with 15 (56%) subsequently continent, 5 (19%) daytime continent with nocturnal incontinence and 7 (26%) continuously incontinent. At initial closure osteotomy had been performed in all patients who were continent following bladder neck reconstruction and in 4 of 5 who were daytime continent.Complications of complete primary repair of bladder exstrophy can result in undesired upper urinary tract changes and penile soft tissue loss. Surgical reconstruction of such complications and acceptable continence are attainable in select cases.

Research into the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome has primarily focused on markers of peripheral dysfunction. We present the first neuroimaging investigation to our knowledge to characterize brain function and anatomy in chronic prostatitis/chronic pelvic pain syndrome.We collected data from 19 male patients with chronic prostatitis/chronic pelvic pain syndrome, and 16 healthy age and gender matched controls. Functional magnetic resonance imaging data were obtained from 14 patients with chronic prostatitis/chronic pelvic pain syndrome as they rated spontaneous pain inside the scanner. Group differences (16 patients per group) in gray matter total volume and regional density were evaluated using voxel-based morphometry, and white matter integrity was studied with diffusion tensor imaging to measure fractional anisotropy. Functional and anatomical imaging outcomes were correlated with the clinical characteristics of chronic prostatitis/chronic pelvic pain syndrome.Spontaneous pelvic pain was uniquely characterized by functional activation within the right anterior insula, which correlated with clinical pain intensity. No group differences were found in regional gray matter volume, yet density of gray matter in pain relevant regions (anterior insula and anterior cingulate cortices) positively correlated with pain intensity and extent of pain chronicity. Moreover the correlation between white matter anisotropy and neocortical gray matter volume was disrupted in chronic prostatitis/chronic pelvic pain syndrome.We provide novel evidence that the pain of chronic prostatitis/chronic pelvic pain syndrome is associated with a chronic pelvic pain syndrome specific pattern of functional brain activation and brain anatomical reorganization. These findings necessitate further investigations into the role of central mechanisms in the initiation and maintenance of chronic prostatitis/chronic pelvic pain syndrome.

In the past numerous chemokines have been noted in the expressed prostatic secretions of patients with chronic prostatitis/chronic pelvic pain syndrome. We examined the functional effects of chemokines in expressed prostatic secretions of patients with chronic pelvic pain syndrome.We studied the functional effects of expressed prostatic secretions on human monocytes by examining monocyte chemotaxis in response to monocyte chemoattractant protein-1, a major chemoattractant previously identified in chronic prostatitis/chronic pelvic pain syndrome cases. We determined effects on cellular signaling by quantifying intracellular calcium increase in monocytes and nuclear factor-κB activation in normal prostate epithelial cells.Results show that the monocyte chemoattractant protein-1 in expressed prostatic secretions is nonfunctional with an inability to mediate human monocyte chemotaxis, or mediate signaling in monocytes or prostate epithelial cells. This lack of functionality could be extended to other proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, when incubated with expressed prostatic secretions from patients with chronic pelvic pain syndrome. The mechanism underlying this apparent ability to modulate proinflammatory cytokines involves heat labile extracellular proteases that mediate the inhibition of immune and prostate epithelial cell function.These results may have implications for the design of specific diagnostic and therapeutic methods targeted toward the complete resolution of prostate inflammatory insults.

Purpose: We evaluated the efficacy and tolerability of pentosan polysulfate sodium (PPS) for the treatment of men with chronic pelvic pain syndrome (CPPS), National Institutes of Health (NIH) category III. Materials and Methods: In a 16-week double-blind study 100 men with a clinical diagnosis of CPPS were randomized to receive 300 mg PPS or placebo 3 times daily. Clinical Global Improvement (CGI) was the primary outcome measure. Additional outcome measures were the NIH-Chronic Prostatitis Symptom Index (CPSI), Subjective Global Assessment and Symptom Severity Index assessment tools. Results: Significantly more patients receiving PPS experienced moderate to marked improvement based on CGI assessment (18 or 37% vs 8 or 18%, p = 0.04). However, mean CGI scores were not significantly different between the PPS group (1.0) and placebo groups (1.0 vs 0.6, p = 0.107). All NIH-CPSI domains suggested a positive effect for PPS and for total NIH-CPSI the difference approached statistical significance (−5.9 or 22% vs −3.2 or 12%, p = 0.068). The PPS group showed significantly greater improvement in NIH-CPSI quality of life domain scores than the placebo group (−2.0 or 22% vs −1.0 or 12%, p = 0.031). Of patients receiving PPS 67% and 80% of those receiving placebo completed the 16-week study. Diarrhea, nausea and headache were the most common adverse events. Conclusions: Pentosan polysulfate (900 mg daily) was more likely than placebo to provide relief for CPPS symptoms.

Chronic pelvic pain syndrome (CPPS) is the most common form of prostatitis, accounting for 90-95% of all diagnoses. It is a complex multi-symptom syndrome with unknown etiology and limited effective treatments. Previous investigations highlight roles for inflammatory mediators in disease progression by correlating levels of cytokines and chemokines with patient reported symptom scores. It is hypothesized that alteration of adaptive immune mechanisms results in autoimmunity and subsequent development of pain. Mouse models of CPPS have been developed to delineate these immune mechanisms driving pain in humans. Using the experimental autoimmune prostatitis (EAP) in C57BL/6 mice model of CPPS we examined the role of CD4+T-cell subsets in the development and maintenance of prostate pain, by tactile allodynia behavioral testing and flow cytometry. In tandem with increased CD4+IL17A+ T-cells upon EAP induction, prophylactic treatment with an anti-IL17 antibody one-day prior to EAP induction prevented the onset of pelvic pain. Therapeutic blockade of IL17 did not reverse pain symptoms indicating that IL17 is essential for development but not maintenance of chronic pain in EAP. Furthermore we identified a cytokine, IL7, to be associated with increased symptom severity in CPPS patients and is increased in patient prostatic secretions and the prostates of EAP mice. IL7 is fundamental to development of IL17 producing cells and plays a role in maturation of auto-reactive T-cells, it is also associated with autoimmune disorders including multiple sclerosis and type-1 diabetes. More recently a growing body of research has pointed to IL17's role in development of neuropathic and chronic pain. This report presents novel data on the role of CD4+IL17+ T-cells in development and maintenance of pain in EAP and CPPS.

Chronic prostatitis has been traditionally characterized by inflammation and/or infection of the prostate gland, objectively categorized by white blood cells and cultured bacteria in prostate specific specimens. We compared leukocyte counts and localization rates for bacterial cultures of segmented urine samples (VB1, VB2, VB3), expressed prostatic secretion (EPS) and semen in men diagnosed with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) to men without pelvic pain (controls).A total of 463 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study and 121 age matched men without urinary symptoms had leukocyte counts performed and 5-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, EPS, VB3) and semen. All risk factor comparisons between case and control analyses were tested using generalized Mantel-Haenszel methods, and multivariable models were developed using logistic regression methods, adjusting for clustering by clinical center within both methods.Men with CP/CPPS had statistically higher leukocyte counts in all segmented urine samples and EPS, but not in semen compared to asymptomatic control men. However, the control population also had a high prevalence of leukocytes. Of the men with CP/CPPS 50% and 32% had 5 or more, or 10 or more white blood cells (WBCs) per high power field, respectively, in EPS compared to 40% and 20% of the control population. Similarly, 32% and 14% of the patients with CP/CPPS had 5 or more, or 10 or more WBCs per high power field in VB3 compared to 19% and 11% in the control population. Localization of uropathogenic bacteria in EPS, VB3 and/or semen was similar in men with CP/CPPS (8.0%) and asymptomatic men (8.3%).Men with CP/CPPS have significantly higher leukocyte counts in all segmented urine samples and EPS but not in semen as compared to controls. There is no difference in rates of localization of bacterial cultures for men with CP/CPPS compared to control men. The high prevalence of WBCs and positive bacterial cultures in the asymptomatic control population raises questions about the clinical usefulness of the standard 4-glass test as a diagnostic tool in men with CP/CPPS.

Purpose: We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome.Materials and Methods: All 488 men screened into the National Institutes of Health Chronic Prostatitis Cohort Study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, were used to measure symptoms. Urethral inflammation was defined as white blood cell (WBC) counts of 1 or more (1+) in the first voided urine. Participants were classified as category IIIa based on WBC counts of 5 or more, or 10 or more (5+, 10+) in the expressed prostatic secretion, or 1+ or 5+ either in the post-expressed prostatic secretion urine (voided urine 3) or semen. Uropathogens were classified as localizing if the designated bacterial species were absent in voided urine 1 and voided urine 2 but present in expressed prostatic secretion, voided urine 3 or semen, or prese...

Purpose: We describe the study design of the National Institutes of Health Chronic Prostatitis Cohort (CPC) study characterizing men with chronic prostatitis/the chronic pelvic pain syndrome.Materials and Methods: All 488 men screened into the CPC study before close of recruitment on August 22, 2001 were selected for analysis. The National Institutes of Health Chronic Prostatitis Symptom Index, including subscores, was used to measure symptoms. A comprehensive history, physical examination and demographic profile were obtained from each participant. Generalized Mantel-Haenszel procedures were used to investigate baseline associations between selected factors and symptoms.Results: Chronic prostatitis/chronic pelvic pain syndrome is a chronic syndrome affecting men over a wide age range. The majority of CPC study participants are white, well educated and affluent. However, lower education, lower income and unemployment were associated with more severe symptoms. Patients most frequently reported pain in the ...

Purpose: Mast cells have been implicated in bladder inflammation and pathogenesis. To determine if mast cell secretion products can modulate urothelial inflammatory responses we developed an in vitro model of mast cell-urothelial cell interactions.Materials and Methods: Cultures of the immortalized urothelial cell line TEU-2 were incubated in the conditioned medium of mast cell cultures. The urothelial inflammatory response to mast cell secretion products was then determined by quantifying nuclear factor κB activity, the expression of endogenous nuclear factor κB dependent genes and the protein expression of inflammation markers.Results: Conditioned medium from RBL-2H3 mast cells induced a 4-fold increase in TEU-2 nuclear factor κB activity that was independent of the activation state of the mast cells. In contrast, ribonuclease protection assays revealed that the nuclear factor κB dependent transcripts tumor necrosis factor-α (TNF-α), interleukin (IL) 8 and 1β, and intracellular adhesion molecule 1 (ICAM...

Purpose: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis.Ma...

Purpose: Adherence of type 1 piliated Escherichia coli to vaginal mucosa plays a major role in the pathogenesis of ascending urinary tract infections (UTIs) in women. Progress in understanding the mechanism of adherence to the vaginal surface could be enhanced by the utilization of well-characterized vaginal epithelial cells. The objective of this study was to immortalize vaginal epithelial cells and study their bacterial adherence properties.Materials and Methods: Primary vaginal cells were obtained from a normal post-menopausal woman, immortalized by infection with E6/E7 genes from human papillomavirus 16 (HPV 16) and cultured in serum free keratinocyte growth factor medium.Results: Positive immunostaining with a pool of antibodies to cytokeratins 1, 5, 10 and 14 (K1, K5, K10 and K14) and to K13 confirmed the epithelial origin of these cells. The immortalized cells showed binding of type 1 piliated E. coli in a pili specific and mannose sensitive manner.Conclusion: This model system should facilitate st...

Purpose:: The role of bacteria in the chronic pelvic pain syndrome (nonbacterial prostatitis and prostatodynia) is controversial and difficult to assess because the bacterial flora of the prostate is not well defined. Polymerase chain reaction (PCR) is a highly sensitive molecular method of bacterial detection. It confirms the sterility of tissue with a high level of confidence and detects small numbers of microbial agents that may represent pathogens. We performed PCR to determine bacterial colonization of the prostate in presumably healthy men and in those undergoing simple or radical prostatectomy.Materials and Methods:: We analyzed 28 prostate samples from 18 organ donors from whom prostate tissue was obtained under sterile surgical conditions at organ withdrawal, 14 sterile surgical prostate specimens from 7 patients undergoing radical prostatectomy for prostate cancer who previously underwent transrectal biopsy and 6 sterile surgical specimens from 2 men who underwent simple prostatectomy for benign...

Purpose: We evaluated the efficacy of self-start therapy in women with recurrent urinary tract infections.Materials and Methods: Women with recurrent urinary tract infections received a dip slide urine culture kit and 6 tablets of norfloxacin (400 mg.). At each symptomatic urinary tract infection episode the patient performed a culture and initiated therapy. The culture was returned and the patient was resupplied with another kit and norfloxacin. Patients were seen 5 to 9 days and 4 to 6 weeks after therapy to assess treatment outcome.Results: A total of 34 women were enrolled in the study and were evaluable for treatment outcomes. Six women followed for 74 months were asymptomatic and 9 followed for 103 months had no infections. A total of 28 women followed for 355 months had 84 symptomatic episodes and 25 had 67 urinary tract infections. Patients had symptomatic episodes at a rate of 2.8 per patient-year (range 0 to 9) and infections at a rate of 2.3 per patient-year (range 0 to 9). The greatest...

THE potential role of bacteria, and particularly uropathogenic bacteria, in the pathogenesis of urologic chronic pelvic pain syndrome (UCPPS), is debatable. The presence of normal bacterial flora or uropathogens in the prostate tissue of apparently healthy men is extremely unlikely. 1 Conversely, 5% of controls and 8% of patients with UCPPS harbor uropathogenic bacteria in their prostatic secretions or post-prostatic massage voided urine, or semen specimens that were not present in the urethral or bladder specimens. In this issue of The Journal Nickel et al (page 127) demonstrate that 4.8% of controls and 3% of patients had evidence of uropathogens localized to the prostate’s secretion, which supports this observation. 2 One could conclude that since the rate of prostate localization was similar, the presence or absence of pathogenic bacteria has no bearing on this syndrome. However, the data on bacterial colonization with uropathogenic bacterial colonization of the bladder argue that this simplistic approach is not always true. More than 100,000 uropathogenic bacteria and pyuria are routinely identified in the bladder urine of patients with symptomatic cystitis and women with asymptomatic bacteriuria. Clearly the difference is not the presence, much less the number, of bacteria or white blood cells, but rather the virulence characteristics of the bacteria and/or the host susceptibility factors. Thus, the possibility that uropathogenic bacteria associated with UCPPS are different from those associated with traditional cystitis or asymptomatic bacteriuria has been documented, associated with chronic pelvic pain syndrome in humans, and able to cause tactile allodynia (pelvic pain) in a mouse model while the