Role of gram-positive bacteria in chronic pelvic pain syndrome (CPPS).

INTRODUCTION: Chronic pelvic pain syndrome (CPPS) is a complex disorder that affects a large proportion of all men. A limited understanding of its etiology and pathogenesis is reflected by the absence of effective therapies. Although CPPS is deemed clinically non-infectious with no well-defined etiological role for microbes, bacteria is readily isolated from both healthy and patient prostate secretion and urine samples. Our laboratory has previously demonstrated that a specific gram-negative bacterial isolate can induce CPPS-like symptoms in mice. Here we aimed to expand on these findings examining the role of gram-positive patient-derived bacteria in CPPS. METHODS: A retrospective analysis of bacterial cultures from CPPS patients from a single center was performed. Gram-positive bacteria were isolated from the expressed prostatic secretion (EPS) of three CPPS-patients (pain inducers, PI) and one from a healthy volunteer (non-pain inducer, NPI). These bacteria were inoculated intra-urethrally in two mouse backgrounds and analyzed for their ability to induce tactile allodynia, voiding dysfunction, and colonize the murine prostate. Host immune responses to bacterial instillation were analyzed by flow cytometry. RESULTS: PI strains (Staphylococcus haemolyticus 2551, Enterococcus faecalis 427, and Staphylococcus epidermidis 7244) induced and maintained tactile allodynia responses (200% increase above baseline) for 28 days in NOD/ShiLtJ mice. Conversely the healthy subject derived strain (Staphylococcus epidermidis NPI) demonstrated no significant pelvic allodynia induction. Intra-urethral inoculation of the four bacterial strains into C57BL/6 mice did not induce significant increases in pain responses. Infected NOD/ShiLtJ displayed significant voiding dysfunction compared to their control counterparts. Colony counts of prostate tissues from both NOD/ShiLtJ and C57BL/6 mice at day 28 demonstrated that bacterial strains colonized equally well, including NPI. We also determined that mechanistically, the patient-isolates induced prostate inflammation specifically involving T-cells and monocytes. CONCLUSIONS: Gram-positive isolates from CPPS patients showed enhanced ability to induce tactile allodynia compared to a single taxonomically similar gram-positive strain isolated from a healthy control. Responses were shown to be dependent on host genetic background and not on colonization differences between strains.

Condyloma Acuminata of the Urethra in a Male Renal Transplant Recipient: A Case Report.

BACKGROUND: Condyloma acuminatum (CA) is a common sexually transmitted disease associated with human papilloma virus (HPV). CA occurring in the urethra is rare and has not been reported in male renal transplant recipients. In addition, despite immunosuppressive conditions and increased risk of HPV-related malignant neoplasms in transplant recipients, HPV testing in male transplant recipients has been uncommon. Here we report a case of urethral CA in a male deceased donor renal transplantation recipient and discuss the importance of HPV testing in male transplant recipients. CASE PRESENTATION: A 33-year-old male deceased donor renal transplant recipient presented with miction pain 5 years after the transplantation. He reported repeated urinary tract infections with no sexual contact since the renal transplantation. Multiple papillary tumors in his penile urethra were detected by cystoscopy, and a biopsy sample was pathologically diagnosed with CA. Transurethral tumor resection was performed, and the tumors were completely resected. Additional HPV risk type screening with a urethral smear sample showed the prevalence of low-risk HPV. Although tacrolimus was switched to everolimus and imiquimod cream was administered, the tumors recurred 6 months after the resection, and a second resection was performed. No further recurrence has been observed for 1 year to date. CONCLUSION: As the urethral CA was possibly related to immunosuppressive conditions and a risk for HPV-related malignant neoplasm, the case required careful diagnosis, including HPV risk type. The methodology of sampling for HPV testing in men has not been established. This case suggests the necessity for further discussion about HPV testing in male transplant recipients.

Urethral caruncle: a lesion related to IgG4-associated sclerosing disease?

AIMS: Urethral caruncle is a benign, polypoid urethral mass that occurs almost exclusively in postmenopausal women. Despite that these lesions are routinely managed with topical medications or excision, their pathogenesis is not well understood. We investigated the possibilities of autoimmune, viral and inflammatory myofibroblastic proliferations as possible aetiologies. METHODS: In 38 patients with urethral caruncle, we utilised immunohistochemistry for immunoglobulin G (IgG) and IgG4 to assess for a potential autoimmune aetiology. Immunohistochemistry was performed in nine patients for Epstein-Barr virus, BK virus, human herpesvirus 8, human papillomavirus, adenovirus and anaplastic lymphoma kinase. RESULTS: Four patients (11%) showed infiltrates of ≥50 IgG4-positive plasma cells per high power field, of which all showed an IgG4 to IgG ratio greater than 40%. A statistically significant difference (p<0.01) was detected in the mean number of IgG4-positive cells (14.73 per high power field) compared with control benign urethral specimens (mean, 1.19). One patient with increased counts below this threshold had rheumatoid arthritis; none had documented autoimmune pancreatitis or other known manifestations of systemic IgG4-related sclerosing disease. All lesions showed negative reactions for the viral and inflammatory myofibroblastic markers. CONCLUSIONS: Urethral caruncle is a benign inflammatory and fibrous polypoid urethral mass of unclear aetiology. It appears unrelated to viral infection and lacks the abnormal expression of anaplastic lymphoma kinase protein, as seen in inflammatory myofibroblastic tumours. Increased numbers of IgG4-positive plasma cells in a subset of lesions raise the possibility that some cases may be related to the autoimmune phenomena of IgG4-associated disease.

Immunoglobulin G4-related sclerosing disease involving the urethra: case report.

Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration in various organs. We described the imaging findings of an IgG4-related inflammatory pseudotumor in the urethra. The urethral mass showed isoattenuation on unenhanced CT images, delayed enhancement on enhanced CT images, iso- to slight hyper-intensity on T1 and T2 weighted magnetic resonance images, diffusion restriction on diffusion weighted images, and heterogeneously low echogeneity on ultrasonography.

Urethral cytokine and immune responses in Chlamydia trachomatis-infected males.

Penile urethral swabs collected from PCR-confirmed Chlamydia trachomatis-infected, C. trachomatis-uninfected, and non-C. trachomatis-infected, nongonococcal urethritis-infected males were analyzed for cytokine, total immunoglobulin (Ig), and specific antibody levels by enzyme-linked immunosorbent assay. Differential cellular components of the swab transport medium were also enumerated for the same groups. Although low, the levels of C. trachomatis-specific IgA and IgG antibodies and interleukin 8 cytokine were significantly higher in C. trachomatis-infected individuals. There were no significant differences in the levels of seven additional cytokines evaluated.

Induction of mucosal antibody responses by microsphere-encapsulated formalin-inactivated simian immunodeficiency virus in a male urethral challenge model.

Male rhesus macaques were immunized mucosally with microsphere-encapsulated formalin-inactivated simian immunodeficiency virus (SIV) particles in a test of immunogenicity and protection against mucosal SIV challenge. Tracheal boosting of animals that had been primed intramuscularly resulted in strong serum ELISA titers to SIV, and evidence of local IgA responses in broncho-alveolar washes. The bulk of the antibody response was against non-envelope epitopes. No neutralizing antibody was observed, and intraurethral challenge with cell-free rhesus-grown virus showed no evidence of protection against infection. Microsphere-based immunization efficiently raises local and system responses, but the resulting immunity to SIV is apparently not sufficient to protect against mucosal challenge.

Immunity to reinfection and immunization of male guinea pigs against urethral infection with the agent of guinea pig inclusion conjunctivitis.

BACKGROUND AND OBJECTIVES: There is little information available on immunity of males to chlamydial infection after recovering from a primary urethral infection or after immunization with chlamydial antigen. The guinea pig model of genital infection using the chlamydial agent of guinea pig inclusion conjunctivitis was utilized to evaluate the protective immune response in these circumstances. GOAL: To determine whether immunity to reinfection develops after a primary urethral infection and whether immunity develops as a result of immunization with inactivated chlamydiae. STUDY DESIGN: Groups of five male guinea pigs each in two separate experiments were infected in the urethra with chlamydiae and challenged with a fresh inoculum at either 30, 75, or 150 days after infection. The course of the challenge infection was then determined. Similarly, guinea pigs were immunized subcutaneously with ultraviolet-inactivated chlamydial elementary bodies and the course of urethral infection was determined when inoculated 2 weeks after immunization. RESULTS: Male guinea pigs were highly resistant to reinfection after a primary urethral infection. Animals that were immunized with inactivated chlamydiae generally became infected upon challenge, but the intensity of the infection was markedly reduced. CONCLUSIONS: Male guinea pigs possess protective mechanisms that make them more resistant to repeat chlamydial genital infection for a longer period of time than is seen in female guinea pigs. In addition, immunization of males with inactivated chlamydial antigen by a parenteral route is able to elicit a protective response to urethral infection with chlamydiae.

Chlamydia trachomatis direct isolation, antibody prevalence and clinical symptoms in women attending outpatient clinics.

Two hundred and ninety-seven women with complaints of vaginal or urethral discharge and 100 women attending outpatient clinics for contraceptive or other advice (enrolled as controls) were studied and compared. A meticulous sampling for Chlamydia trachomatis was taken from one hundred and seventy-seven women enrolled in the study group (A1). Technical difficulties were encountered with the remaining 120 cases--study group (A2). It was found that ninety-three out of the 177 women (of group A1) were infected with either Chlamydia trachomatis or Neisseria gonorrhoeae (52.5%) compared to four out of 120 (3.4%) in the A2 subgroup. The overall prevalence of C. trachomatis antibodies was found to be 171/397 (43.1%) when all three groups studied were tested by immunoperoxidase (IPA). In comparison, by direct culture alone 92/397 (23.2%) were positive. The most significant clinical symptoms for chlamydial infection were purulent or mucoid discharge, bleeding and vaginitis (p = 0.005). This study demonstrates that immunoperoxidase (IPA) and ELISA techniques for C. trachomatis serology are helpful for the identification of infection by this agent. The possibility of using these serological methods in screening tests for vaginal infections in addition to C. trachomatis direct culture and clinical symptoms in outpatient clinics should be considered.

Localized amyloidosis of the lower genitourinary tract: a clinicopathological and immunohistochemical study of nine cases.

A series of nine cases of localized amyloidosis of the lower genitourinary tract are reported. The patients comprised six males and three females with an age range of 50-79 years at initial presentation. Clinically and on cystoscopy, the lesions were often diagnosed as neoplasms. Histologically, seven cases had typical features of localized amyloid deposits, while two cases had an unusual appearance with a florid histiocytic and giant cell reaction. Using an immunoperoxidase staining method the deposits were non-reactive with antibodies to serum amyloid A protein, prealbumin and beta 2 microglobulin, while equivocal immunoreactivity was seen with anti-light chain antibodies.

[Specific IgM and IgA antibodies in Chlamydia trachomatis infections in adults]. / Les anticorps spécifiques IgM et IgA dans les infections à Chlamydia trachomatis de l'adulte.

The authors have compared the prevalence of Chlamydia trachomatis specific serum IgM and IgA antibodies in two populations with Chlamydia positive total antibodies. The first population, P1 had a positive direct diagnosis, and the second had a negative one. IgM antibodies were found in 13.5 p. cent of P1 only. IgA were found in 51.9 p. cent of P1 versus 15.7 p. cent of P2. The interest of IgA detection is discussed, particularly towards deep infections where they could be an argument of an active infection.

Evaluation of chlamydiazyme for the detection of genital infections caused by Chlamydia trachomatis.

Chlamydiazyme is a 4-h enzyme-linked immunoassay that detects an antigen of Chlamydia trachomatis directly in clinical specimens. This immunoassay was compared with cell culture for the diagnosis of chlamydial infections of the genital tract. The assay was evaluated at five clinics with a total of 1,277 cervical specimens of which 239 were culture positive. At three of these clinics where urethral samples were taken from males, 99 of 363 samples were culture positive. The sensitivity of the assay averaged 89.5% for detecting cervical infections and 78.8% for detecting male urethral infections. Specificity was 97.0% when samples from either males or females were tested. Some patients who were culture negative were infected with chlamydiae according to both Chlamydiazyme and a monoclonal antibody test that detected a chlamydial antigen distinct from the antigen detected by Chlamydiazyme. If the 15 females and 2 males who were positive by both immunoassays but culture negative were considered positive for chlamydial infection, the specificity of the assay was 98.4% in females and 97.7% in males. Chlamydiazyme is a simple and relatively rapid immunoassay that has sufficient sensitivity and specificity to supplant culture in the detection of genital chlamydial infections.

Specific red cell adherence testing of benign and malignant lesions of the urethra.

We herein report the first application of the specific red cell adherence test in patients with benign and malignant lesions of the urethra. In an attempt to determine whether the specific red cell adherence test could have potential use in predicting malignant behavior of urethral carcinoma we applied this test on specimens from 17 patients with a urethral caruncle, 3 with chronic urethritis and 4 with primary urethral carcinoma. Of the 20 benign lesions 18 (90 per cent) were positive for adherence, while the 4 urethral carcinoma specimens were negative. The high positive rate obtained in specimens of benign urethral lesions, together with the uniformly negative tests in those of urethral carcinoma, indicate the possible use of the specific red cell adherence test in early detection of aggressive behavior of urethral carcinoma, as well as predictiveness in bladder cancer.

Chlamydial urethral infection in Teheran. A study of male patients attending an STD clinic.

The prevalence of chlamydial infection of the urethra was studied in 172 consecutive male patients attending a sexually transmitted disease clinic in Teheran. Chlamydia trachomatis was isolated in 8.8% of the patients with a valid culture result. Of the five isolates serotyped, two were serotype E and three were serotypes G, H, and K. Type-specific antibodies against C trachomatis serotypes D to K were found in 16% of patients, and IgM, indicating current infection, was detected in 12%. Type-specific antibodies against serotypes A to C (trachoma agent) were detected in 5.4%. The low chlamydial isolation rate may have been due to the inclusion of a large number of patients with a mild or trivial urethritis or a history of previous treatment with antichlamydial drugs. The results indicate that in Iran where trachoma is still endemic, chlamydial infection of the urethra does occur in the urban population and is caused by serotypes D to K.

Inapparent chlamydial infection in the urogenital tract of guinea-pigs.

Microbiologically inapparent urogenital infection appeared to be induced in male guinea-pigs inoculated intra-urethrally with low doses of the guinea-pig inclusion conjunctivitis strain (GP-IC) of Chlamydia psittaci. This state was indicated by the ability of inoculated animals to donate eye infection to normal animals caged with them. Donors failed to develop overt urogenital infection throughout the period of transmission judged by both absence of infected cells in urethral scrapings and failure to isolate GP-IC in cell culture; however, inoculation of donors with 5-iododeoxyuridine led to transient appearance of infectivity in scrapings. In distinction from overtly infected animals, donors failed to develop serum antibody and remained susceptible to urethral challenge with larger doses of GP-IC. Animals that had recovered from overt urethral infection were resistant to challenge and appeared unable to transmit eye infection.

Animal model studies of genital chlamydial infections. Immunity to re-infection with guinea-pig inclusion conjunctivitis agent in the urethra and eye of male guinea-pigs.

A previous report demonstrated that male guinea-pigs could be infected in the urethra with guinea-pig inclusion conjunctivitis (GPIC) agent and that the infection was transmitted during mating from infected males to females. In the experiments reported here, inoculation of male guinea-pigs in the urethra with GPIC organisms resulted in infection which subsided spontaneously in about 2 weeks. Males were demonstrated to be completely resistant to urethral challenge with 10(3)ID50 when tested 6 weeks after urethral infection. These guinea-pigs, immune to re-infection of the urethra, remained susceptible to infection of the eye, but this ocular infection was shorter in duration than that in previously uninfected control animals. Infection in the eye resulted in immunity to both ocular and urethral infection when animals were challenged 6 weeks after the ocular infection.

Immunity in infection with Neisseria gonorrhoeae: duration and serological response in the chimpanzee.

Relative and absolute resistance to urethral and pharyngeal infection with Neisseria gonorrhoeae persisted for up to two years in male chimpanzees parenterally immunized with a colony type 2 gonococcal antigen. Twelve additional adult males were immunized with either a colony type 1 gonococcal antigen or a sham diluent before being challenged with the immunizing isolate of N. gonorrhoeae. Serum specimens were obtained throughout the immunization procedure and tested for indirect fluorescent, bactericidal, microhemagglutinating, and complement-fixing antibody to the immunizing isolate of N. gonorrhoeae. The serological response measured by the indirect fluorescent antibody and serum bactericidal tests correlated most closely with the resistance of individual chimpanzees when they were challenged in the pharynx and urethra with graduated doses of N. gonorrhoeae one month after the last immunization. In this study, the resistance of the immunized chimpanzees to urethral infection with N. gonorrhoeae varied from one to greater than 1,000 times that of sham-injected controls.