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Reversibility of azoospermia induced by bacillus Calmette-Guerin.

A single intratesticular injection of bacillus Calmette-Guerin induces azoospermia within 3 to 6 weeks in a variety of animals without loss of androgens. After a period of azoospermia, the return of spermatogenesis was observed in dogs and monkeys. Seven dogs that showed aspermatogenesis after a local instillation of bacillus Calmette-Guerin (20-110 units per testis) again demonstrated spermatogenesis after a period of 153 to 325 days of azoospermia. Sperm counts and motility were restored to preimmunization levels within 6 weeks after initiation of spermatogenesis. In one dog, systemic treatment with antimycobacterial drugs helped to clear the bacillus Calmette-Guerin from the testis, thus hastening the reinitiation of spermatogenesis. In two monkeys injected with 110 and 160 units of bacillus Calmette-Guerin, azoospermia lasted up to 150 days. Subsequently, fertility was restored and the treated animals sired healthy offspring. A second injection of bacillus Calmette-Guerin of a lesser dose (5-20 units per testis) in these fertile dogs and monkeys again produced azoospermia. Histologically, the monkeys having a second period of azoospermia demonstrated aspermatogenic orchitis in the testis and leukocyte infiltration in the interstitium. A majority of the tubules had intact basement membranes, with a block of spermatogenesis at the spermatocyte stage. In dogs, the second azoospermia lasted for 113 to 277 days with a subsequent restoration of sperm counts and sperm motility to preimmunization levels. There were no circulating antisperm antibodies detected in sera of these animals during the azoospermic period or during its reversal. These observations suggest that the bacillus Calmette-Guerin-induced azoospermia is reversible, both in terms of sperm count and fertility.

Animals↗

Enlargement and hypervascularity of both the epididymis and testis do not exclude involvement with lymphoma or leukemia.

We present 3 cases of diffuse infiltration of the testes and epididymides by malignant lymphoma and leukemia. Gray-scale and color Doppler sonograms showed diffuse hypoechoic enlargement and hypervascularity of the involved testes and epididymides. The authors emphasize that enlargement and hypervascularity of both the epididymis and testis can be caused by lymphomatous/leukemic involvement and is not always indicative of epididymo-orchitis.

Adult↗

The blood-testis barrier and Sertoli cell junctions: structural considerations.

In this review, a few well-established axioms have been challenged while others were viewed from a new perspective. The extensive literature on the blood-testis barrier has been scrutinized to help probe its mechanics and hopefully to promote understanding of the constant adaptation of the barrier function to germ cell development. Our principal conclusions are as follows: (1) Although the barrier zonule is topographically located at the base of the seminiferous epithelium it actually encircles the apex of the Sertoli cell. Consequently the long irregular processes specialized in holding and shaping the developing germ cells should be considered as apical appendages analogous to microvilli. (2) The development of the barrier zonule does not coincide with the appearance of a particular class of germ cells. (3) The barrier compartmentalizes the epithelium into only two cellular compartments: basal and lumenal. (4) Although the blood-testis barrier does sequester germ cells usually considered antigenic, immunoregulator factors other than the physical barrier seem to be involved in preventing autoimmune orchitis. (5) Structurally, a Sertoli cell junctional complex is composed of occluding, gap, close, and adhering junctions. The Sertoli cell membrane segments facing germ cells are presumably included in the continuum of the Sertoli cell junctional complex that extends all over the lateral and apical Sertoli cell membranes. (6) The modulation (i.e., formation and dismantling) of the junctions in a baso-apical direction is characteristic of the seminiferous epithelium and may be dictated by germ cell differentiation. The formation of tubulobulbar complexes and the following internalization of junction vesicles conceivably represent sequential steps of a single intricate junction elimination process that involves junction membrane segments from different cell types as part of a continual cell membrane recycling system. (7) The preferential association of junctional particles with one or the other fracture-face reflect a response to various stimuli including seasonal breeding. Changes in the affinity of the particles are generally coincidental with cytoskeletal changes. However, changes in the cytoskeleton are not necessarily accompanied by permeability changes. The number of strands seems to reflect neither the junctional permeability nor the transepithelial resistance. The diverse orientation of the strands seems to be related to the plasticity of the Sertoli cell occluding zonule. (8) Cooperation between all constituents (Sertoli cells, myoid cells, cell substratum, and germ cells) of the epithelium seems essential for the barrier zonule to function in synchrony with the germ cell differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Gadolinium-enhanced T1-weighted versus T2-weighted imaging of scrotal disorders: is there an indication for MR imaging?

To evaluate the use of gadopentetate dimeglumine in magnetic resonance (MR) imaging of scrotal disorders, the clinical, ultrasound, and MR imaging data of 29 patients (age range, 19-75 years) with various intra- and extratesticular disorders were retrospectively analyzed. T1- and T2-weighted spin-echo images (T1-T2 group) were compared with T1-weighted spin-echo images before and after intravenous administration of gadopentetate dimeglumine (T1-Gd group). A receiver operating characteristic (ROC) analysis of the findings was undertaken. Better contrast between tumor and parenchyma and a clearer demonstration of the tunica albuginea were noted in the T1-T2 group (although not of diagnostic relevance). ROC analysis revealed no differences between the two imaging groups in the diagnosis of tumor, trauma, hydrocele, or hemorrhage; however, epididymitis was diagnosed more easily with contrast enhancement (0.8834 vs 0.7759, P = .04) and the diagnosis of orchitis was expressed more strongly (0.8221 vs 0.7184, P = .17). Four of the five observers were more confident in making the diagnosis with contrast enhancement. With MR imaging, the diagnosis was correctly suggested in three patients in whom clinical and ultrasound data were inconclusive. Gadolinium-enhanced MR imaging gives additional information in scrotal disorders and facilitates diagnosis. It may be helpful when findings at physical examination and ultrasound differ and when plain T1- and T2-weighted images are equivocal.

Adult↗

Antigen-presenting function of murine gonadal epithelial cell lines.

Murine Leydig (TM3) and Sertoli (TM4) cell lines were studied as nonprofessional antigen-presenting cells using the antigen model of human choriogonadotropin (hCG alpha/beta) and specific T-cell hybridomas. Both cell lines were treated with IFN-gamma to induce I-A(d) and I-E(d) molecules expression. Only the TM3 cell line, which expressed MHC-class II molecules upon IFN-gamma stimulation, was able to uptake, process, and present the human choriogonadotropin beta subunit to related T-cell hybridomas. Interestingly, the TM3 cell line was incapable of presenting the human choriogonadotropin alpha subunit, the presentation of which, by classical APC, is highly efficient. Using T-cell hybridomas directed against the immunogenic regions of hCG alpha/beta previously described in BALB/c mice, we showed that the TM3 cell line generated a narrower peptide repertoire than classical APC (i.e., B cells, macrophages, and dendritic cells). This experimental system suggests that Leydig cells could initiate, in vivo, an autoimmune process directed against gonadal tissues. In particular, such a mechanism has been evoked in experimental autoimmune orchitis.

Animals↗

Birth order and risk of testicular cancer.

To explore the etiology of testicular cancer, cases of testicular cancer were identified among members of a cohort of Danish boys born between 1941 and 1957 (inclusive), who had attended schools in Copenhagen and Gentofte and whose school health records were contained in an archive under the supervision of the Danish Cancer Registry. One hundred and eighty-three cases of testicular cancer diagnosed before 31 December 1984 were identified; 366 controls, matched to cases by sex and age, were selected from the same cohort. Information on potential risk factors and confounders was obtained from two sources: school health records and midwife protocols, both of which were recorded prior to the diagnosis of testicular cancer in cases. Relative risks (RR) approximated by the odds ratios were calculated and, in logistic regression analyses, adjustments were done for known or suspected confounders. A decreasing risk of testicular cancer with increasing birth order was observed (P = 0.020). Compared with being firstborn, being number four or more in birth order was associated with a significantly decreased RR for all testicular cancers (RR = 0.3, 95 percent confidence interval [CI] = 0.3-0.8) and testicular seminoma (RR = 0.1, CI = 0.02-0.9). No association was observed between high social class and the risk of testicular cancer (RR = 1.4, CI = 0.8-2.3); neither was age at which the study subjects had mumps or measles related to risk of testicular cancer. No cases of mumps orchitis were observed before or during school years. A slightly increased RR for testicular cancer among boys from small families could be explained by the association between family size and birth order.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.

Animals↗

Transurethral laser ablation of the prostate--long-term results.

Continuing experience with the use of Nd:YAG laser-fibre prostatectomy over the past 4 years has produced encouraging results. Of the 198 patients we treated with the 60-W/60-s technique, 74 were available for evaluation after undergoing laser ablation of the prostate between October 1990 and July 1994. In all, 29/74 and 9/74 patients were available for 24 and 36 months of follow-up, respectively. The American Urological Association (AUA) symptom scores, peak uroflow (Qmax) rates and post-void residual urinary volumes show marked improvement. Following laser ablation of the prostate (LAP), complications have included 16 patients with post-procedural recurrent obstructive symptoms requiring revision. Three patients developed urinary tract infection, two developed bladder-neck stenosis, four fully anticoagulated patients with clot retention required blood transfusion and three patients had epididymo-orchitis. The results show a sustained reduction in AUA symptom scores and maintained improvement in peak flow rates and residual volumes, with stabilization of the above-mentioned parameters occurring within 12-36 months. The results demonstrate the continued durability of the outcome of LAP.

Aged↗

Genetic susceptibility to post-thymectomy autoimmune diseases in mice.

The strain distribution pattern of five different post-thymectomy autoimmune diseases was determined in 21 inbred and two congenic, resistant strains of mice. The results indicated that susceptibility genes outside the H-2 complex may be involved in the development of localized autoimmune diseases in neonatally thymectomized mice. Studies of recombinant inbred strains also showed that susceptibility to gastritis was not associated with the H-2 haplotype but appeared to be influenced by a minor histocompatibility locus. Possible linkage to the H-2 complex was suggested only in the development of coagulating gland adenitis. Although one experiment showed that susceptibility to orchitis and coagulating gland adenitis was inherited as a recessive trait, further studies are required to determine the exact mode of inheritance in each disease system.

Animals↗

Indium 111 white blood cell imaging of epididymitis.

The clinical diagnosis of epididymitis is frequently substantiated radiographically with pertechnetate 99m (99mTc) testicular scintigraphy and scrotal sonography. Indium 111 (111In) autologous leukocyte imaging in a patient with epididymitis has to our knowledge not been reported previously. The case presented is an elderly man with epididymitis. An 111In-labelled white blood cell scan demonstrated increased tracer accumulation in the region of the right epididymis. This suggests that 111In-labelled leukocyte scanning may be helpful in evaluating an inflammatory process involving the epididymis or testis and potentially may allow for differentiation of epididymitis and orchitis from missed torsion, tumour or cystic lesions.

Bone and Bones↗

[Mumps epidemiology--worldwide].

Mumps is an acute viral infection that is endemic worldwide and that occurs primarily in school-age children and adolescents. The most prominent manifestation is tender swelling of the parotid gland. The course of the disease is usually mild and selflimited. Meningitis and orchitis, the latter more common in postpubertal persons, are less frequent manifestations of this disease. As characteristic of many viral infections the severity of the illness increases with age. In the present review first the most important epidemiologic parameters of mumps are presented, as well as the various clinical manifestations and complications. Further the epidemiology of mumps in developing and in industrialized countries is discussed. Breakthrough infections with mumps occurring with either low or high vaccination coverage are described.

Adolescent↗

Complications of mumps requiring hospitalization in children.

UNLABELLED: During the years 1987-1988, an outbreak of mumps was reported among the paediatric population in Israel. Mumps immunization in Israel was not universal at that time and most of the population had not been immunized. During that period, 66 children with evidence of recent mumps parotitis with several complications, i.e. meningo-encephalitis, cerebellar ataxia, arthritis, orchitis, transverse myelitis, deafness and presternal oedema were treated in our department. All patients had recovered completely except one who had permanent hearing loss. CONCLUSION: This paper provides a reminder that mumps, while basically benign, has complications serious enough to lead to hospitalization without immunization.

Adolescent↗

[POEMS syndrome with chronic renal failure].

CASE HISTORY AND CLINICAL FINDINGS: A 43-year-old male was admitted to the hospital because of subfebrile temperatures since 3 months, weight loss of 9 kilogramms and lateral foot pains with bilateral leg edema. Over the last years, the patient had consulted a doctor several times for upper respiratory infections, orchitis and a spinal neck syndrome. At the physical examination, we found a temperature of 37.4 degrees C, no rales, no crackles at auscultation of the lung, bilateral ankle edema and livid, pressure-dolent skin changes at the lateral margins of both feet. The blood pressure was 170/100 mmHg. EXAMINATIONS: The following pathologically laboratory results were found: erythrocyte sedimentation rale (ESR) 35/55 mm n. W., C-reactive protein (CRP) up to 39 mg/l, leucocytes up to 13.5/nl, LH and FHS were elevated corresponding to hypergonadotropic hypogonadism, renal failure with at the beginning a selective glomerular proteinuria, as well as a monoclonal IgG-gammopathy. The bone marrow aspiration as well as the bone marrow biopsy revealed neither plasmocytoma nor a malignant systemic disease. The ultrasound examination showed enlarged liver, spleen, and kidneys. TREATMENT AND FOLLOW-UP: After excluding a connective tissue disease and an infection and with the missing proof of a malignant tumor treatment was started with parenteral methylprednisolon 500 mg on 3 consecutive days under the hypothesis of classic panarteriitis nodosa, even when multiple biopsies were negative. Under the treatment, the elevated inflammatory parameters and renal failure improved, but deteriorated quickly after discontinuation of the corticosteroid medication. The second kidney biopsy showed a chronic scaring glomerulopathy of the hemolytic uremic syndrome type. In the follow-up the renal insufficiency was improved by corticosteroids. With the manifestation of a bilateral sensory polyneuropathy in January 1994, the diagnosis of a POEMS syndrome was most likely. CONCLUSION: According to the literature, up to 50% of the cases with POEMS syndrome reveal renal failure. Most times a glomerular microangiopathy is shown histologically. A treatment trial with corticosteroids is justified.

Adult↗

[Filaria: a tropical disease as the etiology of acute scrotum].

In the diagnosis and treatment of acute scrotal pain and swelling it is important to differentiate between testicular torsion and epididymo-orchitis. A special case of a thirty-eight-year-old male asylant from Nepal was presented in the urological service with acute scrotal pain. To exclude testicular torsion, a diagnostic exploration of the scrotum was done with the findings of an acute funiculitis with abscess formation. Under surgical drainage of abscess together with medical treatment the acute inflammation disappeared. The diagnosis of filarial funiculitis was made after identifying the microfilariae in a blood vessel and in the peripheral blood smear. A filaricide medication with diethylcarbamacine citran was administered with good symptomatic relief.

Acute Disease↗

Clinical and sonographic criteria of acute scrotum in children: a retrospective study of 172 boys.

BACKGROUND: Diagnosis of testicular torsion in children is challenging, as clinical presentation and findings may overlap with other diagnoses. OBJECTIVE: To define the clinical and ultrasound criteria that best predict testicular torsion. MATERIALS AND METHODS: The records of children hospitalized for acute scrotum from 1997 to 2002 were reviewed. The clinical and ultrasound findings of children who had a final diagnosis of testicular torsion were compared with those of children who had other diagnoses (torsion of the testicular appendix, epididymitis, and epididymo-orchitis). RESULTS: Forty-one children had testicular torsion; 131 had other diagnoses. Stepwise regression analysis yielded three factors that were significantly associated with testicular torsion: duration of pain < or =6 h; absent or decreased cremasteric reflex; and diffuse testicular tenderness. When the children were scored by final diagnosis for the presence of these factors (0-3), none of the children with a score of 0 had testicular torsion, whereas 87% with a score of 3 did. The ultrasound finding of decreased or absent testicular flow had a sensitivity of 63% and a specificity of 99%. Eight of ten children with testicular torsion and normal or increased testicular flow had a coiled spermatic cord on ultrasound. CONCLUSION: We suggest that all children with acute scrotal pain and a clinical score of 3 should undergo testicular exploration, and children with a lower probability of testicular torsion (score 1 or 2) should first undergo diagnostic ultrasound. Because the presence of testicular flow does not exclude torsion, the spermatic cord should be meticulously evaluated in all children with acute scrotum and normal or increased testicular blood flow.

Acute Disease↗

Spiral twist of the spermatic cord: a reliable sign of testicular torsion.

BACKGROUND: Colour Doppler sonography (CDS) has become the procedure of choice in evaluating testicular perfusion but false negative findings have been reported. OBJECTIVE: To determine if direct visualisation of the twisted spermatic cord using high resolution US is a reliable sign to assess testicular torsion. MATERIAL AND METHODS: Thirty patients (aged 2-26 years) with equivocal diagnosis of testicular torsion prospectively underwent high resolution and CDS. The results were correlated with surgical findings. Serial transverse and longitudinal scans were performed to compare the scrotal contents on each side and study the complete spermatic cord course, from inguinal canal to testis, to detect a spiral twist. RESULTS: In 14 of the 23 cases of torsion, the diagnosis was based on the colour Doppler findings in the scrotum because blood flow was absent in the symptomatic testis and detectable without difficulty on the normal side. In nine cases, CDS was unreliable; in six cases intratesticular perfusion was present in a twisted testis and in three small boys, no colour signal was obtained in either testis. In all cases of torsion, the spiral twist of spermatic cord was detected at the external inguinal ring. The twist induced an abrupt change in spermatic cord course, size and shape below the point of torsion. It appeared in the scrotum as a round or oval, homogeneous or heterogeneous extratesticular mass with or without blood flow, that could be connected cephalad with the normal inguinal cord. In the other seven cases (three late torsions of the appendix testis, one epididymo-orchitis and three torsions with spontaneous reduction), no spiral twist was detectable. CONCLUSION: The detection of spermatic cord spiral twist appears a reliable US sign of torsion whatever the testicular consequences.

Adolescent↗

The mouse p52 subunit of the transcription/DNA repair factor TFIIH is located in the class III region of the H2 complex: cloning and sequence polymorphism.

Loci controlling susceptibility to a number of diseases, including cortisone-induced cleft palate, experimental allergic orchitis, and chemically-induced transplacental lung tumors have been mapped to a 27 kilobase (kb) region within the class III region of the mouse major histocompatibility complex (H2). This region, contains three genes G7e, which resembles a viral envelope gene, Bat6 (G7a), which encodes a valyl-tRNA synthetase, and G7c, which has no known function. We cloned a set of overlapping cosmid clones containing 115 kb of DNA surrounding Bat6. Exon trapping has identified a new gene located telomeric of Bat6. Northern blot analysis detected a transcript of 1.7 kb with highest expression in the testis. DNA sequence analysis identified this gene as the mouse homologue of the human gene encoding the p52 subunit of the TFIIH transcription/DNA repair factor. Nucleotide sequence identity was 91% between mouse and human, and the protein sequence was 98% identical. Sequence analysis of p52 cDNA from congenic mouse strains detected an amino acid polymorphism at position 209, which results in the substitution of a threonine in the H2b haplotype to a methionine in the H2a,d haplotypes.

Amino Acid Sequence↗