Urethral Inflammation Research Articles

Chlamydial and Gonococcal Infection in Men Without Polymorphonuclear Leukocytes on Gram Stain: Implications for Diagnostic Approach and Management

Gram stain is used to detect urethral inflammation, suggestive of infection, in men and guide therapeutic decisions. In the absence of signs, symptoms, or polymorphonuclear leukocytes (PMNs) on urethral Gram stain, treatment and sometimes testing is deferred. Determine the proportion of men with chlamydia or gonorrhea diagnosed by nucleic acid amplification testing (NAAT) or culture who lack Gram stain evidence of inflammation and compare their clinical characteristics to men with inflammation. Records from 2629 men presenting for routine sexually transmitted disease care with urethral PMN count and NAAT data were retrospectively analyzed. A subpopulation tested by NAAT and culture was analyzed. Men receiving antibiotics within the prior month or those reporting a sexual partner with trichomoniasis were excluded. Among 2266 eligible men, 353 (16%) had chlamydia and 462 (20%) had gonorrhea. Among chlamydia-infected men, PMNs per oil-immersion field (oif) on Gram stain were > or =5 in 291 (82%), 1 to 4 in 20 (6%), and none in 42 (12%). In men with gonorrhea, PMNs/oif were > or =5 in 433 (94%), 1 to 4 in 6 (1%), and none in 23 (5%). Urethral symptoms, discharge, and/or > or =5 PMNs/oif were absent in 47 (13%) and 22 (5%) of chlamydial and gonococcal infections, respectively (including no PMNs/oif and 1-4 PMNs/oif). None of these 47 chlamydial-infected men and only 4 of 22 men with gonorrhea received therapy at the time of initial examination. Twelve percent of chlamydial and 5% of gonococcal infections had no Gram stain evidence of urethral inflammation. Absence of symptoms and discharge is not uncommon in chlamydial infection detected by NAAT, and without testing, many infections will go untreated, furthering the possibility of complications or partner transmission.

HIV-Specific CD8+ Lymphocytes in Semen Are Not Associated with Reduced HIV Shedding

Sexual contact with HIV-infected semen is a major driving force behind the global HIV pandemic. Little is known regarding the immune correlates of virus shedding in this compartment, although HIV-1-specific CD8+ T cells are present in semen. We collected blood and semen from 27 chronically HIV-infected, therapy-naive men without common sexually transmitted infections or urethral inflammation and measured HIV-1 RNA viral load and cytokine/chemokine levels in both compartments. HIV-1 RNA levels were 10-fold higher in blood than semen, but discordantly high semen shedding was associated with higher semen levels of the proinflammatory cytokines IL-6, IL-8, IL-12, and IFN-gamma. Virus-specific CD8+ T cell epitopes were mapped in blood by IFN-gamma ELISPOT, using an overlapping HIV-1 clade B peptide matrix, and blood and semen CD8+ T cell responses were then assayed ex vivo using intracellular IFN-gamma staining. HIV-specific CD8+ responses were detected in 70% of semen samples, and their frequency was similar to or higher than blood. There was no correlation between the presence of virus-specific CD8+ T cells in semen and levels of HIV-1 RNA shedding. Among participants with detectable CD8+ IFN-gamma semen responses, their relative frequency was not associated with reduced HIV-1 RNA shedding, and their absolute number was correlated with higher levels of HIV-1 RNA semen shedding (r = 0.6; p = 0.03) and of several proinflammatory cytokines. Neither the presence nor the frequency of semen HIV-specific CD8+ T cell IFN-gamma responses in semen correlated with reduced levels of HIV RNA in semen.

Low Sensitivity of the Leukocyte Esterase Test (LET) in Detecting Chlamydia trachomatis Infections in Asymptomatic Men Entering a County Jail

Objectives: To determine the test performance characteristics of the leukocyte esterase test (LET) in detecting Chlamydia trachomatis (CT) infections in asymptomatic men entering a county jail. Methods: First-void urine of 2,176 men was simultaneously tested for urethral inflammation by the LET and for CT by the ligase chain reaction (LCR). Results: Using the LCR as reference standard, the sensitivity, specificity, and positive and negative predictive values of the LET with confidence intervals were 6.1% (2.7, 12.7), 98.5% (97.9, 99.0), 18.4% (8.3, 34.9), and 95.1% (94.0, 95.9), respectively. Conclusion: The LET lacks sensitivity in detecting asymptomatic chlamydial infection among men entering a correctional facility. Alternatives should be sought as cost-saving strategies.

Do all men attending departments of genitourinary medicine need to be screened for non-gonococcal urethritis?

We investigated the influence of symptoms and signs on the detection of Chlamydia trachomatis, Mycoplasma genitalium and Ureaplasma urealyticum organisms (ureaplasmas) in men with non-gonococcal urethritis (NGU). Two hundred and forty-two men attending the Jefferiss Wing at St Mary's Hospital for a sexual health assessment were evaluated, of whom 169 had NGU. Urethral inflammation was diagnosed if there were either > or =5 polymorphonuclear leucocytes (PMNLs) per high-power field (HPF) in five or more microscope fields of a Gram-stained urethral smear, or > or =10 PMNLs per HPF in five or more fields of a Gram-stained thread from 15-20 mL of a first-passed urine (FPU) specimen. C. trachomatis was diagnosed by direct immunofluoresence, M. genitalium by a polymerase chain reaction assay and ureaplasmas by culture. On multivariate analysis, to control for potential confounding by age, ethnicity, sexual lifestyle and co-infection, an urethral discharge remained significantly associated with the detection of C. trachomatis and M. genitalium in men with acute urethritis [OR 12.3, 95% CI (2.39-63.5) and OR 35.2, 95% CI (3.9-319.6), respectively], but dysuria or penile irritation did not. The detection of ureaplasmas was not associated with any clinical feature. In addition, on multivariate analysis men with NGU who were either symptomatic or had an observable discharge were more likely to have C. trachomatis or M. genitalium detected [(OR 6.92, 95% CI 1.41-33.9) and (OR 5.18, 95% CI 0.99-27.1), respectively], but not ureaplasmas (OR 1.19, 95% CI 0.33-4.35). The findings suggest that in men with acute NGU, symptoms or signs, and in particular a urethral discharge, are associated with the detection of C. trachomatis and M. genitalium, but not ureaplasmas. Currently, there is no precise answer to the question of whether all men attending a GUM clinic need to be screened for NGU, but if clinically asymptomatic NGU is found not to be associated with a sexually transmitted pathogen, the UK clinical guidelines requiring the preparation of a urethral smear from such men would need to be revised.

Leukocyte and Bacterial Counts Do Not Correlate With Severity of Symptoms in Men With Chronic Prostatitis: The National Institutes of Health Chronic Prostatitis Cohort Study

We examine whether leukocytes and bacteria correlate with symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome. 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 present in expressed prostatic secretion, voided urine 3 or semen at 2 log concentrations higher than at voided urine 1 or 2. Associations between symptoms, and inflammation and infection were investigated using generalized Mantel-Haenszel methods. Of all participants 50% had urethral leukocytes and of 397 with expressed prostatic secretion samples 194 (49%) and 122 (31%) had 5+ or 10+ WBCs in expressed prostatic secretion, respectively. The prevalence of category IIIa ranged from 90% to 54%, depending on the composite set of cut points. None of the index measures were statistically different (p >0.10) for selected leukocytosis subgroups. Based on prostate and semen cultures, 37 of 488 men (8%) had at least 1 localizing uropathogen. None of the index measures were statistically different (p >0.10) for selected bacterial culture subgroups. Although men with chronic prostatitis routinely receive anti-inflammatory and antimicrobial therapy, we found that leukocytes and bacterial counts as we defined them do not correlate with severity of symptoms. These findings suggest that factors other than leukocytes and bacteria also contribute to symptoms associated with chronic pelvic pain syndrome.

The Effect of Diltiazem on the Healing of Traumatic Urethral Inflammation

Objective: To investigate the effect of diltiazem, a calcium channel blocker, on healing of the traumatic urethral inflammation when applied systemically or locally. Materials and Methods: 21 adult male Wistar rats (230–250 g) were assigned to group 1 (n = 7) = control, group 2 (n = 7) = local application or group 3 (n = 7) = systemic application. In group 1, only a urethral injury was achieved at the 12-o’clock position by gently introducing and drawing a tiny hook in the urethra until urethral bleeding occurred. In group 2, after the same procedure, 10 mg/kg diltiazem was applied retrogradely via a 22-gauge Angiocath intraurethrally for 5 consecutive days, while the same account of the drug was administered intraperitoneally in group 3. After 21 days, the rats were sacrificed for urethrectomy. Pathologically, the thickness of connective tissue, the regularity of the epithelial lining, the presence of the inflammation and the density of collagen were evaluated with Masson’s trichrome staining. The Mann-Whitney U test was used for statistical analyses. Results: The mean connective tissue thickness was 0.77 ± 0.39, 1.01 ± 0.77 and 0.93 ± 0.53 µm in groups 1, 2 and 3, respectively. The differences between the groups were insignificant (p > 0.05). The hyperplastic epithelial lining in the study groups, with both systemic and local applications, was markedly infrequent and the inflammation was less prominent. However, these differences did not reach statistical significance. Conclusions: Diltiazem appears not to have any preventive effect on connective tissue formation when applied locally or systemically in our urethral injury model.

Effects of perinatal exposure to flutamide on sex hormones and androgen-dependent organs in F1 male rats.

Flutamide, which has antiandrogenic properties, was administered to pregnant rats, and effects on male offspring were examined. Crj: CD (SD) IGS (SPF) females were administered flutamide (0.15, 0.6, 2.5, 10.0, 100 mg/kg, p.o.) from gestation Day 14 to post parturition Day 3. The number of pups, body weights, clinical features, anogenital distance (AGD), nipple retention, testicular descent, and urogenital malformation in F1 males were examined. Hormone measurement, necropsy and histopathological examination were carried out at post-neonatal Day 4 (PND 4) and PND 60. Sperm analysis was also carried out at PND 60. Decrease in body weight was seen in the 100 mg/kg group and the AGD was decreased at 2.5 mg/kg and above. Retention of nipples, hypospadia, vaginal pouches, penis malformation, unilateral ectopic testis, and decrease of organ weights (prostate, seminal vesicles, levator ani muscle plus bulbocavernosus muscle, testis) were observed at 10 mg/kg and above. Testicular testosterone (T) was increased significantly with 100 mg/kg at PND 4 and tendencies for increase were observed in serum T, LH and FSH at 10 mg/kg and more at the same time point. In contrast, elevated levels of LH and FSH were seen with 100 mg/kg at PND 60. Histopathological examination revealed defects or hypoplastic changes of genital organs (> or = 10 mg/kg), squamous metaplasia (10 mg/kg) or mucification (100 mg/kg) of the urethral diverticulum epithelium and inflammation of genital organs (100 mg/kg). Though only undescended testes lacked spermatogenesis at 10 mg/kg, atrophic change of seminiferous tubules and azoospermia were observed in the 100 mg/kg group, despite testicular descent. Perinatal administration of flutamide affected F1 male rats at 2.5 mg/kg and above. In addition to urogenital malformation, 100 mg/kg flutamide caused high LH and FSH levels at PND 60. This study indicates that the most sensitive parameter is AGD, whereby reduction was observed at 2.5 mg/kg. A clear no-effect level (NOEL: 0.6 mg/kg) was obtained in this perinatal study of an antiandrogenic chemical.

THE NATURAL HISTORY OF IDIOPATHIC URETHRORRHAGIA IN BOYS

We describe the presenting symptoms, evaluation and natural history of urethrorrhagia in boys.The records of 27 consecutive toilet trained boys with idiopathic urethrorrhagia were retrospectively reviewed for information regarding age, symptoms, symptom duration, physical examination, and radiographic, endoscopic and laboratory data. Patient interviews were performed, and the resolution rate, symptom duration and associated urological abnormalities were evaluated.Mean age at presentation was 10.1 years. Symptoms included urethrorrhagia in 100% and dysuria in 29.6% of cases. Radiographic and laboratory evaluations were normal in all patients except for microscopic hematuria in 57%. Cystourethroscopy in 4 patients revealed bulbar urethral inflammation without stricture in 2. A total of 24 patients (89%) were followed an average of 37 months (range 10 to 106). Complete resolution developed in 46% of cases at 6 months, in 71% at 1 year and in 91.7% overall. The average duration of symptoms was 9.9 months (range 2 weeks to 38 months). In 2 boys (8.3%) urethrorrhagia persisted for 22 and 28 months, and in 1 cystoscopy revealed urethral stricture. Self-limiting urethrorrhagia recurred in 2 patients (8.3%) after initial resolution. Treatment consisted of watchful waiting in all patients except 1 with urethral stricture, who underwent urethral dilation. After urethrorrhagia resolved epididymo-orchitis recurred in 1 case.Routine radiographic, laboratory and endoscopic evaluation is unnecessary for evaluating urethrorrhagia. Watchful waiting is indicated because the condition resolves in 71% and 91.7% of patients at 1 and 2 years, respectively. Evaluation should be considered in patients with prolonged urethrorrhagia because urethral stricture may be identified.

Immunocytological Analysis of Leukocyte Subpopulations in Urine Specimens before and after Prostatic Massage

Objective: To evaluate the presence of leukocyte subpopulations in urine after prostatic massage (VB 3) in symptomatic patients with ≧10 leukocytes/high power field (magnification ×1,000) in expressed prostatic secretions, and who were classified as suffering from chronic bacterial prostatitis or inflammatory chronic pelvic pain syndrome. Methods: 115 consecutive patients were investigated. Granulocytes in centrifuged midstream urine (VB 2) and VB 3 were counted after Papanicolaou stain. Macrophages, B and T lymphocytes were analyzed after immunocytological staining with monoclonal antibodies according to the alkaline phosphatase anti–alkaline phosphatase method. The counts were quantified as the number of cells per view field at a magnification of ×400. In all patients, acute or chronic urethritis had been excluded before enrollment in the study. 16 men without signs or symptoms of urogenital inflammation served as controls. Results: Of the 115 patients, 101 men demonstrated ≧10 leukocytes/view field in VB 3. In comparison to VB 2, the leukocyte subpopulations in VB 3 demonstrated an increase in granulocytes (9.2–fold), macrophages (7.6–fold), T lymphocytes (7.6–fold), and B lymphocytes (4–fold). The increase was statistically significant (p<0.001 each). The proportion of these cells in VB 3 was 81.6, 11.1, 5.5, and 1.8%, respectively. As compared to controls, all leukocyte subsets in VB 3 were significantly elevated (p>0.001 each). Conclusion: Elevated numbers of leukocytes in VB 3 are indicative of prostatitis provided that urethral inflammation and leukocyturia in VB 2 are excluded. Granulocytes are the predominant cell type of inflammation. The increase in macrophages, T and B lymphocytes in prostatic secretions indicate the participation of both the cellular and humoral immune system in the inflammatory process.

Urethral syndromes in children.

1. Walid Farhat, MD* 2. Gordon McLorie, MD* 1. 2. *Division of Urology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Objectives After completing this article, readers should be able to: 1. Describe the evaluation of a child suspected of having urethritis. 2. Delineate the screening tests that have the highest yield for urethritis in young children. 3. List components of a behavioral modification approach to treating dysfunctional voiding. 4. Compare and contrast physical findings in gonococcal and nongonococcal urethritis. Inflammation of the urethra (urethritis) may be due to infection, trauma, allergy, foreign body, or an undetermined factor. Certain characteristics distinguish urethritis in the pediatric population from that in adults. First, urethritis in adults and adolescents has an infectious etiology and always is the result of sexual contact; infectious urethritis in the pediatric age group is uncommon, except in sexually active adolescents or children who have been sexually abused by an adult who has the disease. Second, the variability and nonspecificity of a variety of noninfectious urethral pathologies may mimic infectious urethritis in children. Children who have urethritis may present with irritative voiding symptoms, such as dysuria, urgency, or frequency; possible urethral discharge; initial hematuria; or blood spotting on the underwear. Patients suspected of having urethritis are evaluated with a detailed history, physical examination, urethral smear, or urine culture. In girls, examination may show evidence of vaginitis, which is a common cause of dysuria after urinary tract infection, labial adhesions, or even sexual abuse; in males, results of the examination frequently are inconclusive. In infants, young children, and sexually inactive adolescents, screening tests that have the highest yield include urinalysis and abdominal ultrasonography (US); uroflow is reserved for toilet-trained children. The urine should be examined for evidence of infection or hematuria. Abdominal US can diagnose a variety of abnormalities, including bladder stone or inflammation, ureterocele, foreign body, or tumor. Uroflow is a noninvasive urodynamics test that assesses the ability to initiate voiding on command, quantitates …

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Objectives. Diagnosis of urethral and prostatic inflammation can represent a challenge. We compare the accuracy of diagnostic methods for detecting inflammation in lower urinary specimens/samples. Methods. A standardized protocol was used to evaluate urethral smear, first-void urine (VB1), midstream urine (VB2), expressed prostatic secretions (EPS), and postmassage urine (VB3) in urologic patients with no symptoms or signs of urethritis who were attending our prostatitis clinic. Results. Of 235 subjects, 60 (26%) had leukocytes detected by the Gram-stained urethral smear, 44 (18%) by the VB1, and only 14 (6%) by the VB2. Compared with the urethral swab, VB1 had 0% to 22% sensitivity and 81% to 98% specificity, and VB2 had 8% to 11% sensitivity. Of 83 subjects with prostatic inflammation, the EPS detected 63 (76%) and the VB3 detected 68 (82%). Conclusions. VB1 or VB2 examinations had low sensitivity for detecting urethral inflammation. Examining both the EPS and VB3 proved best for detecting prostatic fluid inflammation. Combining the urethral smear with lower urinary tract localization (“four-glass test”) represents an optimal approach for detecting urethral and prostatic inflammation.

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Detecting urethral and prostatic inflammation in patients with chronic prostatitis

Screening urine samples by leukocyte esterase test and ligase chain reaction for chlamydial infections among asymptomatic men.

Urine samples from 358 asymptomatic males were screened for urethral inflammation by the leukocyte esterase (LE) test and for Chlamydia trachomatis by the ligase chain reaction (LCR). LE and LCR positivity rates were 7.5% (27 of 358 samples) and 2.8% (10 of 358 samples), respectively. Eight of the 10 LCR-positive samples were detected by the LE screening test. The urine LE prescreening test in combination with the LCR assay may be a reasonable approach for genitourinary chlamydial disease control.

Trichomoniasis in Men

Trichomoniasis is common among sexually active women, but its importance as a cause of morbidity among sexually active men remains uncertain. The article outlines areas of controversy and presents pertinent new data from case-control and natural history studies. Trichomonas vaginalis was documented in 11% of 447 men at risk for a sexually transmitted disease. Although 54% of infected men complained of urethral discharge, the discharge was only mild or moderately severe. Elimination of Trichomonas vaginalis was associated with resolution of urethritis. Trichomonas vaginalis is an important consideration in sexually active men with urethral symptoms or inflammation but with little or no evidence of discharge on physical examination.

Urethral cytology in spinal cord injury patients performing intermittent catheterisation

Local reactions of the urethral wall are known to occur by repeated introduction of a catheter in the urethra. Urethritis was found in 2-19% of patients practising intermittent catheterisation. Although the use of catheters of smaller size and the liberal use of lubricants may prevent urethral irritation and trauma, it was postulated that hydrophilic catheters (LoFric, Astra Tech Ltd, Stroud, England) induce significantly less trauma than PVC catheters because of the binding of the water molecules to the catheter surface which consists of polyvinylpyrrolidone and sodium chloride. Although urethritis and urethral stricture may represent one end of the spectrum of repeated urethral trauma, minor degrees of inflammation need to be quantitatively determined while assessing two different catheters for intermittent catheterisation. The degree of urethral inflammation in patients practising intermittent catheterisation was studied by urethral cytology and staining the smear by Papanicolaou's method. The number of neutrophil polymorphs and epithelial cells in three random high power fields in the urethral smear was counted and the percentage ratio of polymorphs to epithelial cells was calculated. Group 1 comprised 14 patients practising intermittent catheterisation with a PVC catheter and group 2 comprised 17 patients performing intermittent catheterisation with a LoFric catheter. There was no significant difference between the two groups as regards the age, diagnosis, size of the catheter used for intermittent catheterisation and the number of times that they performed catheterisation during a 24 hour period. Urethral cytology revealed a percentage (mean ratio) ratio of polymorphs to epithelial cells of 66 in group 1 and 0.04 in group 2. (< 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Epinephrine Reduces the Severity of Catheter‐induced Urethral Inflammation by Action at the α2‐adrenoceptors

We have studied the contribution of epinephrine to experimentally induced urethral inflammation in the rat. Inflammation was induced by inserting latex strips into the urethra. The effects of various experimental procedures were assessed according to a 4-point scale based on histological findings. The results showed that 0.5 mg/kg epinephrine decreased the severity of catheter-induced urethral inflammation. This effect was blocked by the alpha 2-adrenergic agonist, yohimbine, but not by alpha 1 (prazosin), beta 1 (M32 MTC), or beta 2 (butoxamine) antagonists. The results suggest that the suppressive effect of epinephrine is mediated by action at the alpha 2 adrenergic receptor.

Management of chronic urethral symptoms in men.

We describe 20 men who were referred because of chronic urogenital symptoms. They had been previously seen by zero to six physicians (mean, 1.8 physicians) and had been treated with zero to five courses of antimicrobial agents (mean, 2.4 courses) without relief of their symptoms. Results of physical examinations of all patients were normal. An extensive evaluation failed to reveal any objective evidence of urethral inflammation. Cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, Ureaplasma urealyticum, and Trichomonas vaginalis were uniformly negative. No additional antimicrobial agents were prescribed. Data from follow-up questionnaires filled out by 10 of these men 5-28 months later (mean, 11.8 months) disclosed the disappearance of symptoms in three and the reduction of symptoms in four. Chronic urethral symptoms may occur in the absence of objective evidence of inflammation and infection with known urethral pathogens. Observation without antimicrobial therapy is the treatment of choice for such patients.

The contribution of epinephrine to experimentally induced urethral inflammation in the rat

We have studied the effect of the adrenal medulla and epinephrine on experimentally induced urethral inflammation in the rat. Urethral inflammation was induced by inserting latex strips into the urethra. The effects of different experimental procedures were assessed by using a 4-graded inflammation scale based on histological findings. Adrenal medullectomy significantly reduced experimentally induced urethral inflammation. This effect was reversed if the rats were treated repeatedly with epinephrine or salbutamol. On the other hand high doses of epinephrine reduced the experimentally induced urethral inflammation.