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Tuberculous epididymo-orchitis presenting within the setting of a sexually transmitted disease clinic.

BACKGROUND: Tuberculous epididymo-orchitis (TBEO) is uncommon in Western cities in the modern era. A case series of 3 patients with TBEO presenting to a sexually transmitted diseases (STD) clinic has never previously been reported. GOAL: The goal of this study was to report all known cases of TBEO attending a London STD clinic within the last 6 years. STUDY DESIGN: We conducted a case analyses. RESULTS: The 3 patients aged 30, 42, and 47 years were all HIV-negative and immigrants (2 black Africans, 1 Middle Eastern). The median duration of scrotal swelling was 3 months (range, 2-4 months). Mycobacterium tuberculosis was isolated from early-morning urine specimens in 2 of 3 cases. All had grade IV Heaf test (equivalent to greater than 15 mm Mantoux induration), unilateral TBEO without renal tract disease, and responded to antituberculous chemotherapy. CONCLUSION: The changing epidemiology of TB and demography of Western countries could lead to an increase in such patients presenting at STD clinics. The early diagnosis of TBEO, which is aided by clinical acumen and conventional diagnostic tools, can prevent complications.

Adult↗

The direct medical cost of epididymitis and orchitis: evidence from a study of insurance claims.

BACKGROUND: Epididymitis and orchitis (EO) are the primary sequelae of acute chlamydia and gonorrhea in men. Existing estimates of the cost per episode of epididymitis are over 10 years old or are based on limited data. OBJECTIVE: The objective of this study was to estimate direct medical costs of EO from insurance claims data. STUDY DESIGN: We used 1998 and 1999 insurance claims taken from a national database. We used International Classification of Diseases, 9th Revision codes to identify inpatient and outpatient claims for EO treatment. Prescription drug claims were identified with National Drug Codes. To capture episodes of EO that were most likely sequelae of sexually transmitted diseases, we categorized claims based on age at the time of the initial EO claim. RESULTS: The total cost per episode was US dollars 368 for males <13 years of age, US dollars 242 for those > or =13 and <41 years of age, and US dollars 291 for those > or =41 years of age. The cost for both younger and older men was significantly different from men > or =13 and <41 years of age. Inpatient claims were relatively rare, occurring in < or =1.2% of total episodes. CONCLUSION: The cost per episode we calculated was lower than previously published estimates and can be attributed to a lower rate of inpatient care than previously observed or estimated.

Adolescent↗

A new murine model of autoimmune orchitis induced by immunization with viable syngeneic testicular germ cells alone. I. Immunological and histological studies.

Experimental autoimmune orchitis (EAO) was produced in C3H/He mice with as high as 100% incidence by two or three s.c. injections of 1 x 10(7) viable syngeneic testicular germ cells (TC) without resorting to adjuvants, Bordetella pertussis vaccine, or other immunological manipulations. On day 40 after the first injection of TC, the lesions induced were characterized by interstitial infiltration of inflammatory cells and severe hypospermatogenesis in the testis with resulting whole organ atrophy and, in contrast, by a complete lack of epididymitis. Immunological studies revealed that this form of immunization caused both delayed-type hypersensitivity and humoral antibody responses to syngeneic TC. We compared the susceptibilities to the induction of this type of EAO among six different strains of inbred mice comprising A/J, AKR, BALB/c, C3H/He, C57BL/6 and DBA/2 mice. All strains except for DBA/2 mice developed lesions of EAO to a greater or lesser extent, and severe disease was induced with high frequency in two strains, C3H/He and A/J. As this murine model of EAO can be induced without the use of Freund's complete adjuvant and B. pertussis vaccine, it is simply 'autoimmune' in nature and may provide new ways for further investigation into the immunological mechanisms which regulate deleterious autoimmune reactions to germ cell antigens leading to the male infertility.

Animals↗

Generation and characterization of a continuous line of CD8+ suppressively regulatory T lymphocytes which down-regulates experimental autoimmune orchitis (EAO) in mice.

We have previously shown that two injections with viable syngeneic testicular germ cells (TC) alone developed experimental autoimmune orchitis (EAO) in C3H/He mice, and that the induction of antigen-specific tolerance in this EAO model is associated with the generation of antigen-specific suppressively regulatory T (Ts) cells. For the elucidation of the nature of these Ts cells, a murine Ts cell line (designated Ts-A) was established. This line was generated from the spleen cells of C3H/He mice which had received three i.v. injections of a soluble (deaggregated) form of murine testicular antigen (mTA), followed by the repeated selection of these spleen lymphocytes in vitro by stimulation with mTA. Adoptive transfer of Ts-A cells into naive syngeneic mice immediately before the first TC injection was found to downgrade EAO in actively immunized recipients. The transferred Ts-A cells significantly inhibited the cellular immune response to TC in the recipients in an antigen-specific manner, but these cells had no inhibitory effect on the humoral immune response to TC. This line could also inhibit in vitro syngeneic TC-driven proliferation of orchitogenic lymphocytes. Surface phenotype of this line was CD8+, CD4-, Thy-1.2+, CD3+, and TCR alpha beta+. These findings may suggest an in vivo role for suppressively regulatory lymphocytes, capable of inhibiting helper T cells, in the regulation of EAO.

Animals↗

Phenotypic characterization of lymphocytic cell infiltrates into the testes of rats undergoing autoimmune orchitis.

Experimental autoimmune orchitis (EAO) was induced in adult Wistar rats by active immunization with a testicular homogenate (TH) and adjuvants. Fifty per cent of the immunized rats developed EAO. Testicular damage became evident at 50 days after the primary immunization and increased in severity at 80 days. Phenotypic characterization of T-cell subsets (CD4+ and CD8+) and Ia+ cells was performed on cryostat sections of testis obtained from normal rats, rats immunized with adjuvant (control group) and rats immunized with TH and adjuvants (experimental group) at 50 and 80 days. Labelled cells were only detected in the interstitial area; no labelled cells were observed inside the seminiferous tubules with any of the monoclonal antibodies used (W3/25, OX-8, OX-6). A significant increase in the numbers of CD4+ and CD8+, as well as of Ia+ cells, were observed in the testis of rats with severe EAO at 80 days after the first immunization. Rats of the same experimental group without testicular damage showed no major differences compared to rats from the control group, with the exception of a lower number of CD8+ cells. Variations in the lymphocyte subsets in lymph nodes draining the site of immunization showed the opposite pattern to that observed in the testis. In conclusion, these data suggest the traffic of specifically sensitized lymphocytes from lymph nodes to the testis and an active role of CD4+, CD8+ and Ia+ cells in the pathogenesis of EAO in the rat.

Animals↗

Immunologic and testicular response in guinea pigs after unilateral traumatic orchitis.

An acute and intense trauma was inflicted in one of the testes of adult guinea pigs. The immunological response and histological changes developed both in the injured and contralateral glands were studied at different intervals of time. It was observed: 1) Necrotic seminiferous tubules and a granulomatous cell reaction were seen in the injured gonad at 15 days. This was followed by a reduction of the mononuclear cell infiltration at 48 days. Finally a fibrotic tissue replaced the damaged areas at around 100 days. 2) Foci showing the classical picture of immunologic orchitis appeared in the contralateral gland at 15 and 48 days. Less frequent lesions were detected in the final period of the experiment. 3) These lesions were accompanied by cellular immunity detectable by the macrophage migration inhibition test at 15 and 48 days. With the exception of cytophilic activity also detected in same periods, no antibodies of hemagglutinating and sperm-agglutinating types could be found.

Acute Disease↗

Immunological studies in patients with mumps orchitis.

Seventy patients with mumps orchitis were investigated. Serological tests for antitesticular antibodies, using four different techniques showed positive results in 25 patients. Antivirus antibodies were detected and they reached higher values during the remission period of acute cases. Delayed hypersensitivity was studied by means of skin tests using homologous antigenic material. Several patients gave definite positive reactions. Testicular biopsies performed in some patients showed a histological picture similar to that obtained in experimental human or animal auto- or iso-sensitization. All patients in whom testicular damage was present also showed positive skin tests, ascertained by histology of the site of reaction, but none of them exhibited circulating antibodies in meaningful titers. The skin hypersensitivity suggest some correlation between this type of reaction and the development of the testicular lesions as shown in several other diseases in which an immune mechanism could be involved.

Acute Disease↗

Antigen non-specific tissue damage in T cell-mediated experimental autoimmune orchitis: preliminary characterization of a testis-specific T-cell line by using dermal tissue and cells.

A previous study demonstrated the establishment of a murine testicular antigen (mTA)-specific CD4+ T-cell line (designated BT.1) which was capable of transferring experimental autoimmune epididymo-orchitis to naive recipient mice. The disease transfer was antigen-specific, because no inflammatory lesion was observed in any other organs and tissues of the recipients. In this study, to investigate the local environment of BT.1 cells, the effect of the cells and their culture supernatant on a local tissue integrity was studied. When BT.1 cells were seeded on cultured fibroblastoid cell monolayers, the cells completely disrupted these monolayers in spite of the absence of the specific antigens. Moreover, the culture supernatant of BT.1 cells induced non-specific dermal inflammation when injected into skin tissue of normal syngeneic mice. Therefore, BT.1 cells were shown to devastate a tissue integrity and cause attraction and activation of inflammatory cells of the recipient origin in a local environment. These results suggest that the transferred BT.1 cells will specifically home to the testis and epididymis of recipients but the following devastation of seminiferous tubules and epididymal ducts might be non-specifically produced by the inflammatory cells of both donor and recipient origin in the lesion.

Animals↗

Epididymo-orchitis caused by intravesically instillated bacillus Calmette-Guérin: genetically proven using a multiplex polymerase chain reaction method.

The intravesical instillation of bacillus Calmette-Guérin (BCG) is a standard therapy for superficial bladder carcinoma. Tuberculosis-like inflammation in the genitourinary tract is a serious complication of BCG. It can occur after a long interval from the cessation of the intravesical BCG therapy. If inflammation occurs, it is necessary to test whether the BCG strain has caused it or another mycobacterium species has. However, there has never been a report that proves BCG causes the inflammation, because BCG is difficult to differentiate from other strains of Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex by conventional tests, including regular polymerase chain reaction (PCR). We first present a case of epididymo-orchitis, which developed 31 months after the cessation of BCG therapy, detected using a multiplex PCR method as having been caused by BCG. Our report illustrates the efficacy of this method to detect the responsible microbe that is thought to be transmitted from the instillated BCG strain.

Administration, Intravesical↗

The intravenous urogram in acute epididymo-orchitis.

In a series of patients presenting with acute epididymo-orchitis, the abnormalities detected on intravenous urography were analysed. Urography is recommended in patients aged over 50 and in pre-pubertal boys, but it did not prove useful in adult patients under 50 years of age without other symptoms.

Acute Disease↗

Tuberculous epididymo-orchitis. A review of 20 cases.

Twenty cases of tuberculous epididymo-orchitis, occurring in Glasgow from 1970 to 1979, were reviewed. Five gave a history of previous tuberculosis and 10 showed no evidence of tuberculous infection in their urine. In half of the cases the diagnosis was made from histological material. Only five patients had normal intravenous urograms and five required subsequent major surgery for upper urinary tract disease. Tuberculosis should be considered in the differential diagnosis of a scrotal swelling even in the absence of a history of previous tuberculosis.

Adult↗

Tuberculous epididymo-orchitis: clinical and ultrasound observations.

The clinical, radiological and ultrasound features of 3 patients presenting with tuberculous epididymo-orchitis are described and the relevant literature reviewed. Scrotal swelling, pain and sinuses are common features at presentation. The presence of a sterile pyuria is a useful sign, but intravenous urography may fail to identify active renal disease. Ultrasound examination revealed testicular involvement in 2 patients. Differentiation from tumour may not be possible, but the presence of epididymal involvement strongly suggests an infective cause. Early surgical biopsy may prove helpful if acid-fast bacilli are not initially identified in early morning urine samples.

Adult↗

Granulomatous orchitis. Review of 15 cases.

Granulomatous orchitis is a rare lesion of the testis which can clinically simulate malignancy. The clinical, radiological and pathological features of 15 patients are presented and discussed.

Adult↗

Partial inhibition of cell-mediated immunity (CMI) by niridazole: effect upon development of autoimmune aspermatogenic orchitis (AIAO) in guinea pigs.

The effects of Niridazole upon the development of autoimmune aspermatogenic orchitis (AIAO) was studied in guinea pigs. Niridazole administration before, during, or three days after alloimmunization with sperm cells emulsified in Freund's complete adjuvant (FCA) produced slight changes in some correlates of cell-mediated immunity. No significant changes in humoral immunity or testicular histopathology can be observed at these periods. When Niridazole was administered ten days after alloimmunization, a significant inhibition of all manifestations of cell-mediated immunity against spermatozoa was observed. Thirty days after alloimmunization, half of the animals studied failed to develop significant histopathological changes in testis or epididymis. However, the titer of cytotoxic antibodies to testicular cells increased from threefold to fourfold, when compared to those of alloimmunized animals not receiving Niridazole. The critical period for cell interactions concerned with the full expression of AIAO was found to be between ten and fifteen days after alloimmunization.

Animals↗

Requirement of B lymphocytes in local adoptive transfer of experimental allergic orchitis (EAO) by lymph node cells.

The necessity of T lymphocytes in local adoptive transfer of experimental allergic orchitis (EAO) is an established fact. The present study was undertaken to elucidate the participation of B lymphocytes in the local transfer system of EAO. The capacity of purified lymph node T and B cells to transfer EAO was compared. Donor strain 13 guinea pigs were sensitized with testicular antigen and complete Freund's adjuvant. We then injected 1 X 10(8) cells just under the tunica albuginea of the testis of a syngeneic recipient. The recipients were killed 5 days after cell transfer. Nylon-wool nonadherent T cells alone produced only minimal lesions, but could induce more severe mononuclear lesions with the addition of syngeneic, normal macrophages. In contrast, B-cell enriched populations either alone or combined with a small number of macrophages, were able to transfer extensive lesions. In the combined transfer of immune T and immune B cells the severity of transferred lesions was dependent upon the number of B cells. These results suggest that cooperative interactions among T cells, B cells, and macrophages are involved in the generation of transferred testicular lesions, with emphasis on the participation of B cells.

Animals↗

Sequential study of the histopathology and cellular and humoral immune response during the development of an autoimmune orchitis in Wistar rats.

Wistar rats immunized with an homologous testicular homogenate (TH) and complete Freund's adjuvant, followed by i.v. injection of Bordetella pertussis, developed an autoimmune orchitis (EAO). Animals were studied at 7, 16, 30, 50, and 80 days (d) after the first immunization. An important lesion of the testis only appeared at 50 d, increasing in severity and incidence (77%) at 80 d. Lesions were characterized by a prevalent aspermatogenesis with tubular atrophy and mild interstitial mononuclear infiltrates. Delayed-type hypersensitivity response (DTH) against TH was detected early at 7 d and, except for 16 d, it increased with time, reaching a maximum at 80 d. A good temporal relationship between DTH and histopathology was found. Circulating antibodies to TH, detected by ELISA, were only present in 64% of the animals with testis lesion, while no deposits of IgG or C3 in the seminiferous tubules were seen. We describe a sequence of immunological events, concomitant with pathological changes of the testis, during the development of a severe EAO in Wistar rats.

Animals↗

Characterization of autoantigens relevant to experimental autoimmune orchitis (EAO) in mice immunized with a mixture of syngeneic testis homogenate and Klebsiella O3 lipopolysaccharide.

Experimental autoimmune orchitis (EAO) in mice has been induced by repeated injection of a mixture of syngeneic testis homogenate and Klebsiella O3 lipopolysaccharide (KO3 LPS) as a potent adjuvant. The antisera obtained from mice with EAO lesions defined several antigens with apparent molecular weights (MW) of 38,000 (38 kd), 86 kd, 100 kd, and greater than 200 kd by the immunoblotting method. These antigens were organ-specific and exclusively present on the acrosome of spermatozoa, suggesting that these acrosomal antigens were highly relevant to EAO. It was found that the antigen with a fairly high MW (greater than 200 kd) was expressed on spermatozoa from the epididymis. Furthermore, the acrosomal 86 kd antigen was predominantly expressed in the testis, while the 100 kd antigen was dominant in the spermatozoa from the epididymis. It was therefore suggested that the 86 kd and 100 kd antigens in the acrosome were differentially expressed on the process of maturation of spermatozoa.

Adjuvants, Immunologic↗

Lymphocyte subsets in the lymph nodes of rats with autoimmune orchitis.

We determined temporal variations of cell subpopulations in the immunization draining lymph nodes during the development of an experimental autoimmune orchitis (EAO) induced in Wistar rats. A phenotypic characterization of T cells and their subsets (CD4+ and CD8+), B, and Ia+ cells was performed by immunofluorescent technique. At the end of the immunization period (30 days), rats injected with testicular homogenate plus adjuvants presented a considerable increase in absolute cell number but normal lymphocyte subset percentages. Testicular damage became evident at 50 days after the first immunization and increased its severity at 80 days: animals that developed EAO presented a lower number of CD8+ cells as compared with undamaged rats. This latter group showed a low CD4/CD8 ratio due to the high proportion of CD8+ cells, which could probably have a suppressor function. At 80 days massive testicular infiltration and decreased absolute cell number in lymph nodes suggest the possible migration of specific lymphocytes to the target organ.

Adjuvants, Immunologic↗