No abstract

No abstract

Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.

Few population-based case-control studies have assessed etiologic factors for penile cancer. Past infection with high-risk human papillomavirus (HPV) is a known risk factor for penile cancer; however, few previous studies have related the HPV DNA status of the tumor to potential demographic and behavioral risk factors for the disease or evaluated whether in situ and invasive penile cancer share risk factors. Little information is available on the role and timing of circumcision in the etiology of penile cancer. We conducted a population-based case-control study in western Washington state that included 137 men diagnosed with in situ (n 5 75) or invasive (n 5 62) penile cancer between January 1, 1979, and December 31, 1998, and 671 control men identified through random digit dialing. Cases and controls were interviewed in person and provided peripheral blood samples. Case and control blood samples were tested for antibodies to HPV16 and HSV-2, and tumor specimens from cases were tested for HPV DNA. Men not circumcised during childhood were at increased risk of invasive (OR 5 2.3, 95% CI 1.3-4.1) but not in situ (OR 5 1.1, 95% CI 0.6-1.8) penile cancer. Approximately 35% of men with penile cancer who had not been circumcised in childhood reported a history of phimosis compared to 7.6% of controls (OR 5 7.4, 95% CI 3.7-15.0). Penile conditions such as tear, rash and injury were associated with increased risk of disease. Among men not circumcised in childhood, phimosis was strongly associated with development of invasive penile cancer (OR 5 11.4, 95% CI 5.0-25.9). When we restricted our analysis to men who did not have phimosis, the risk of invasive penile cancer associated with not having been circumcised in childhood was not elevated (OR 5 0.5, 95% CI 0.1-2.5). Cigarette smoking was associated with a 4.5-fold risk (95% CI 2.0-10.1) of invasive penile cancer. HPV DNA was detected in 79.8% of tumor specimens, and 69.1% of tumors were HPV16-positive. The proportion of HPV DNA-positive tumors did not vary by any risk factors evaluated. Many risk factors were common for both in situ and invasive disease. However, 3 factors that did not increase the risk for in situ cancer proved significant risk factors for invasive penile cancer: lack of circumcision during childhood, phimosis and cigarette smoking. The high percentage of HPV DNA-positive tumors in our study is consistent with a strong association between HPV infection and the development of penile cancer regardless of circumcision status. Circumcision in early childhood may help prevent penile cancer by eliminating phimosis, a significant risk factor for the disease. ' 2005 Wiley-Liss, Inc.

Purpose-Case series have shown a Fournier's gangrene mortality rate of 20% to 40% with an incidence of as high as 88% in some studies. Because to our knowledge there are no population based data, we used a national database to investigate the epidemiology of Fournier's gangrene.Materials and Methods-We used the State Inpatient Databases, the largest hospital based database available in the United States, which includes 100% of hospital discharges from participating states. Inpatients diagnosed with Fournier's gangrene (ICD-9 CM 608.83) who underwent genital/perineal débridement or died in the hospital were identified from 13 participating states in 2001 and from 21 in 2004. Population based incidence, regional trends and case fatality rates were estimated.Results-We identified 1,641 males and 39 females with Fournier's gangrene. Cases represented less than 0.02% of hospital admissions. The overall incidence was 1.6/100,000 males, which peaked in males who were 50 to 79 years old (3.3/100,000) with the highest rate in the South (1.9/100,000). The overall case fatality rate was 7.5%. Patients with Fournier's gangrene were rarely treated at hospitals (mean ± SD 0.6 ± 1.2 per year, median 0, range 0 to 23). Overall 0 to 4 and 5 or greater cases were treated at 66%, 17%, 10%, 4%, 1% and 1% of hospitals, respectively. Conclusions-Patients withFournier's gangrene are rarely treated at most hospitals. The population based mortality rate of 7.5% was substantially lower than that reported in case series from tertiary care centers. Keywordsurology; male; female; gangrene; mortality Fournier's gangrene is a urological emergency characterized by progressive necrotizing infection of the external genitalia or perineum. 1 Most studies indicate a mortality rate of 20% to 40% with some studies showing a fatality rate of as high as 88% (table 1). 2 These data are from tertiary referral centers with the largest series including only 80 patients. 3 The generalizability of these data is limited. Previous reports reflect differences in referral patterns, surgical management, clinical volumes and many other institutional differences.* Correspondence: Department of Urology, University of Washington School of Medicine, 1959 Northeast Pacific St., Box 356510, Seattle, Washington 98195 (telephone: 206-543-3640; FAX: 206-543-3272 For example, reports diverge widely in recommendations for urinary and fecal diversion, hyperbaric oxygen use and early skin grafting. [3][4][5][6][7] There are sparse data from community hospitals and to our knowledge no population based data on incidence, regional trends or case fatality rates.To better understand epidemiology and outcomes in patients with Fournier's gangrene we examined a large, population based database to determine patient characteristics, and the incidence of and hospital experience with Fournier's gangrene. We hypothesized that previous case series from tertiary referral centers do not reflect the clinical spectrum and outcomes in the general population. MATERIALS AND METHODS Popula...

The persistence of HIV replication in infected individuals may reflect an inadequate host HIV-specific CD8+ cytotoxic T lymphocyte (CTL) response. The functional activity of HIV-specific CTLs and the ability of these effector cells to migrate in vivo to sites of infection was directly assessed by expanding autologous HIV-1 Gag-specific CD8+ CTL clones in vitro and adoptively transferring these CTLs to HIV-infected individuals. The transferred CTLs retained lytic function in vivo, accumulated adjacent to HIV-infected cells in lymph nodes and transiently reduced the levels of circulating productively infected CD4+ T cells. These results provide direct evidence that HIV-specific CTLs target sites of HIV replication and mediate antiviral activity, and indicate that the development of immunotherapeutic approaches to sustain a strong CTL response to HIV may be a useful adjunct to treatment of HIV infection.

BackgroundThe “Multidisciplinary Approach to the Study of Chronic Pelvic Pain” (MAPP) Research Network was established by the NIDDK to better understand the pathophysiology of urologic chronic pelvic pain syndromes (UCPPS), to inform future clinical trials and improve clinical care. The evolution, organization, and scientific scope of the MAPP Research Network, and the unique approach of the network’s central study and common data elements are described.MethodsThe primary scientific protocol for the Trans-MAPP Epidemiology/Phenotyping (EP) Study comprises a multi-site, longitudinal observational study, including bi-weekly internet-based symptom assessments, following a comprehensive in-clinic deep-phenotyping array of urological symptoms, non-urological symptoms and psychosocial factors to evaluate men and women with UCPPS. Healthy controls, matched on sex and age, as well as “positive” controls meeting the non-urologic associated syndromes (NUAS) criteria for one or more of the target conditions of Fibromyalgia (FM), Chronic Fatigue Syndrome (CFS) or Irritable Bowel Syndrome (IBS), were also evaluated. Additional, complementary studies addressing diverse hypotheses are integrated into the Trans-MAPP EP Study to provide a systemic characterization of study participants, including biomarker discovery studies of infectious agents, quantitative sensory testing, and structural and resting state neuroimaging and functional neurobiology studies. A highly novel effort to develop and assess clinically relevant animal models of UCPPS was also undertaken to allow improved translation between clinical and mechanistic studies. Recruitment into the central study occurred at six Discovery Sites in the United States, resulting in a total of 1,039 enrolled participants, exceeding the original targets. The biospecimen collection rate at baseline visits reached nearly 100%, and 279 participants underwent common neuroimaging through a standardized protocol. An extended follow-up study for 161 of the UCPPS participants is ongoing.DiscussionThe MAPP Research Network represents a novel, comprehensive approach to the study of UCPPS, as well as other concomitant NUAS. Findings are expected to provide significant advances in understanding UCPPS pathophysiology that will ultimately inform future clinical trials and lead to improvements in patient care. Furthermore, the structure and methodologies developed by the MAPP Network provide the foundation upon which future studies of other urologic or non-urologic disorders can be based.Trial registrationClinicalTrials.gov identifier: NCT01098279 “Chronic Pelvic Pain Study of Individuals with Diagnoses or Symptoms of Interstitial Cystitis and/or Chronic Prostatitis (MAPP-EP)”. http://clinicaltrials.gov/show/NCT01098279

Both qualitative and quantitative virologic measurements were compared between blood and genital compartments for 128 men infected with human immunodeficiency virus type 1 (HIV-1) to address several controversial issues concerning HIV-1 shedding in semen and to obtain further information about the distribution of virus between these two compartments. Evidence for viral compartmentalization was suggested by earlier studies that noted the poor correlation between blood and seminal virus load, phenotype, and genotype. Further support for this viral compartmentalization was based on the following observations between semen and blood: lack of association between culturability of virus in semen and viral RNA level in blood, discordant distribution of viral phenotypes, discordant viral RNA levels, a weak correlation between viral RNA level in semen and CD4 cell count in blood, differences in the biologic variability of viral RNA levels, and differences in the virus load response to antiretroviral therapy.