Ureteral stents are an integral part of urological practice. However, stents that migrate, fragment or are forgotten pose a management and legal dilemma. Our series consists of 31 patients, 22 with forgotten stents that were left indwelling for more than 6 months (mean 22.7) and 9 migrated stents. Of the forgotten stents 15 (68%) were calcified, 10 (45%) were fragmented, and 3 (14%) were calcified and fragmented. Procedures to render the patient stent-free were ureteroscopy in 16 (52%), percutaneous nephroscopy in 8 (26%), cystoscopic electrohydraulic lithotripsy in 6 (19%), extracorporeal shock wave lithotripsy in 10 (32%), open cysto-litholapaxy in 1 (3%) and simple nephrectomy in 1 (3%). Multiple procedures were required in 6 patients (19%). Management of such complicated ureteral stents requires a multimodal therapeutic approach incorporating the latest in extracorporeal shock wave lithotripsy and endourological techniques. These patients are at increased risk for loss of renal function. A computerized tracking registry of ureteral stents may help prevent this urological travesty.

Xenotropic murine leukemia virus-related virus (XMRV) is a new human gammaretrovirus identified inprostate cancer tissue from patients homozygous for a reduced-activity variant of the antiviral enzyme RNase L. Neither a casual relationship between XMRV infection and prostate cancer nor a mechanism of tumorigenesis has been established. To determine the integration site preferences of XMRV and the potential risk of proviral insertional mutagenesis, we carried out a genome-wide analysis of viral integration sites in the prostate cell line DU145 after an acute XMRV infection and compared the integration site pattern of XMRV with those found for murine leukemia virus and two human retroviruses, human immunodeficiency virus type 1 and human T-cell leukemia virus type 1. Among all retroviruses analyzed, XMRV has the strongest preference for transcription start sites, CpG islands, DNase-hypersensitive sites, and gene-dense regions; all are features frequently associated with structurally open transcription regulatory regions of a chromosome. Analyses of XMRV integration sites in tissues from prostate cancer patients found a similar preference for the aforementioned chromosomal features. Additionally, XMRV integration sites in cancer tissues were associated with cancer breakpoints, common fragile sites, microRNA, and cancer-related genes, suggesting a selection process that favors certain chromosomal integration sites. In both acutely infected cells and cancer tissues, no common integration site was detected within or near proto-oncogenes or tumor suppressor genes. These results are consistent with a model in which XMRV may contribute to tumorigenicity via a paracrine mechanism.Prostate cancer is the most common noncutaneous cancer diagnosed in men in developed countries and is responsible for the deaths of approximately 30,000 men per year in the United States (43). Despite its impact on male health, the molecular mechanisms involved in the pathogenesis of prostate cancer, particularly the events contributing to initiation and progression, remain relatively unknown in comparison with those for other common cancers. Epidemiological studies of kindreds with hereditary prostate cancer, who often display early-onset disease and account for 9% of all cases (16), identified HPC1 as a susceptibility locus for prostate cancer (94). HPC1 is linked to RNASEL, which encodes a regulated endoribonuclease for single-stranded RNA and functions in the antiviral action of interferon (IFN) (15, 17). In response to stimulation by viral double-stranded RNA, IFN treatment of cells induces a family of 2Ј-5Ј oligoadenylate synthetases that produce 2Ј-5Ј-linked oligoadenylates, which then activate the latent and ubiquitous protein RNase L, resulting in degradation of viral and cellular RNA and apoptosis induction (112). Several germ line variants of HPC1 and RNASEL have been observed in hereditary prostate cancer (91), including a common (35% allelic frequency) missense variant of RNase L in which a G-to-A transition at nucleotide position 13...

Xenotropic murine leukemia-related virus (XMRV) was identified in association with human prostate cancer and chronic fatigue syndrome. To examine the infection potential, kinetics, and tissue distribution of XMRV in an animal model, we inoculated five macaques with XMRV intravenously. XMRV established a persistent, chronic disseminated infection, with low transient viremia and provirus in blood lymphocytes during acute infection. Although undetectable in blood after about a month, XMRV viremia was reactivated at 9 months, confirming the chronicity of the infection. Furthermore, XMRV Gag was detected in tissues throughout, with wide dissemination throughout the period of monitoring. Surprisingly, XMRV infection showed organ-specific cell tropism, infecting CD4 T cells in lymphoid organs including the gastrointestinal lamina propria, alveolar macrophages in lung, and epithelial/interstitial cells in other organs, including the reproductive tract. Of note, in spite of the intravenous inoculation, extensive XMRV replication was noted in prostate during acute but not chronic infection even though infected cells were still detectable by fluorescence in situ hybridization (FISH) in prostate at 5 and 9 months postinfection. Marked lymphocyte activation occurred immediately postinfection, but antigen-specific cellular responses were undetectable. Antibody responses were elicited and boosted upon reexposure, but titers decreased rapidly, suggesting low antigen stimulation over time. Our findings establish a nonhuman primate model to study XMRV replication/dissemination, transmission, pathogenesis, immune responses, and potential future therapies.Xenotropic murine leukemia-related virus (XMRV) is a novel gammaretrovirus, initially identified in human prostate cancer using a Virochip DNA microarray (43) in men with a low-activity variant of RNASEL, an enzyme involved in innate immunity via type I interferons (14). Although related to murine leukemia virus (MLV) and probably acquired by zoonotic infection, human tissue-derived XMRV clearly segregates from other gammaretroviruses, genotypically arguing against the hypothesis that such human infection is acquired via repeated zoonotic transmission (43). The association of XMRV with prostate cancer has since been confirmed by other laboratories, albeit with a potentially different cellular tropism (34). In addition, association with RNASEL deficiency has been variable (1, 7, 15, 34), suggesting that low levels of RNASEL may not be a requirement for productive infection or viral propagation in humans. Nevertheless, the association of RNASEL mutations and prostate cancer has been reinforced by the recent discovery that a prostate cell line, 22Rv1, was derived from a patient with a low-activity RNASEL genotype (15). RNASEL dysfunction has also been associated with another disease, chronic fatigue syndrome (CFS) (8,20,21,38,42), which prompted an investigation into a potential association of XMRV with CFS. In a geographically restricted cohort, up to 67% of CFS patients were found ...

BackgroundXenotropic Murine Leukemia Virus-related Virus (XMRV) is a human gammaretrovirus recently identified in prostate cancer tissue and in lymphocytes of patients with chronic fatigue syndrome. To establish the etiologic role of XMRV infection in human disease requires large scale epidemiologic studies. Development of assays to detect XMRV-specific antibodies would greatly facilitate such studies. However, the nature and kinetics of the antibody response to XMRV infection have yet to be determined.ResultsThree rhesus macaques were infected with XMRV to determine the dynamics of the antibody responses elicited by infection with XMRV. All macaques developed antibodies to XMRV during the second week of infection, and the predominant responses were to the envelope protein gp70, transmembrane protein p15E, and capsid protein p30. In general, antibody responses to gp70 and p15E appeared early with higher titers than to p30, especially in the early period of seroconversion. Antibodies to gp70, p15E and p30 persisted to 158 days and were substantially boosted by re-infection, thus, were identified as useful serologic markers. Three high-throughput prototype assays were developed using recombinant proteins to detect antibodies to these viral proteins. Both gp70 and p15E prototype assays demonstrated 100% sensitivity by detecting all Western blot (WB) positive serial bleeds from the XMRV-infected macaques and good specificity (99.5-99.9%) with blood donors. Seroconversion sensitivity and specificity of the p30 prototype assay were 92% and 99.4% respectively.ConclusionsThis study provides the first demonstration of seroconversion patterns elicited by XMRV infection. The nature and kinetics of antibody responses to XMRV in primates were fully characterized. Moreover, key serologic markers useful for detection of XMRV infection were identified. Three prototype immunoassays were developed to detect XMRV-specific antibodies. These assays demonstrated good sensitivity and specificity; thus, they will facilitate large scale epidemiologic studies of XMRV infection in humans.