SifA was originally identified as a virulence factor required for formation of Salmonella‐induced filaments (Sifs), elongated tubules rich in lysosomal glycoproteins that extend from the Salmonella‐containing vacuole in infected epithelial cells. Here, we demonstrate that deletion mutants of ssaR, a component of the SPI‐2 type III secretion system, do not form Sifs in HeLa epithelial cells. This suggests that SifA is a translocated effector of this system, acting within host cells to form Sifs. In support of this hypothesis, transfection of HeLa cells with a vector encoding SifA fused to the green fluorescent protein caused extensive vacuolation of LAMP‐1‐positive compartments. Filamentous tubules that closely resembled Sifs were also observed in transfected cells, demonstrating that SifA is sufficient to initiate alteration of host cell endosomal structures. ΔsifA mutants were impaired in their ability to survive/replicate in RAW 264.7 murine macrophages, a phenotype similar to ssaR mutants. Our findings suggest that SifA is an effector of the SPI‐2 type III secretion system and allows colonization of murine macrophages, the host niche exploited during systemic phases of disease in these animals. A family of SifA‐related proteins and their importance to Salmonella pathogenesis is also discussed.
This initiative was undertaken in response to concerns regarding the variation in management and in outcomes of patients with bladder cancer throughout centres and geographical areas in Canada. Population-based data have also revealed that real-life survival is lower than expected based on data from clinical trials and/or academic centres. To address these perceived shortcomings and attempt to streamline and unify treatment approaches to bladder cancer in Canada, a multidisciplinary panel of expert clinicians was convened last fall for a two-day working group consensus meeting. The panelists included urologic oncologists, medical oncologists, radiation oncologists, patient representatives, a genitourinary pathologist, and an enterostomal therapy nurse. The following recommendations and summaries of supporting evidence represent the results of the presentations, debates, and discussions. Methodology
Medical and surgical complications of prostatectomy are significantly increased in the setting of prior radiotherapy. Understanding the magnitude of this increased risk is important for patient counseling.
Objectives: Lymphocele is the most common complication of pelvic lymphadenectomy (PLND). We sought to determine predictors of symptomatic lymphocele after radical prostatectomy (RP) and PLND, and in particular, to determine if the number of drains placed represents an independent predictor. Methods: Between January 1999 and June 2007, 4173 consecutive patients underwent bilateral PLND at the time of either open or laparoscopic RP. Lymphoceles were identified in patients undergoing imaging as a result of symptoms suspicious for lymphocele, such as fever, abdominal pain or lower extremity swelling. Routine postoperative imaging was not carried out. Cox proportional hazards analysis was carried out using forced variable entry to obtain maximum likelihood estimates of the hazard ratios and 95% confidence intervals using the number of drains placed , number of nodes removed , RP approach and use of prophylactic low-molecular-weight heparin (LMWH) as predictors of symptomatic lymphocele. Results: There were 164 patients (4%) with a symptomatic lymphocele on follow up, with a median time to presentation of 19 days. The primary presenting complaints were fever in 47%, abdominal pain in 40%, lower extremity swelling in 37%, genital swelling in 25%, groin pain in 22%, abdominal swelling in 9%, and back and flank pain in 6% and 5%, respectively. Median lymphocele diameter was 5 cm. Significant predictors of symptomatic lymphocele on multivariate analysis included number of nodes removed and use of LMWH, but not number of drains placed. Conclusions: Use of prophylactic LMWH and a higher node count are predictive of a higher incidence of symptomatic lymphocele after RP and PLND.
We found highest concordance for GR2 and GR5 and lowest for GR4. The baseline clinical variables associated with GR1 upgrades and GR2 downgrades may play a role in clinical decision-making.
Patient factors as well as technical factors influence the development of symptomatic anastomotic strictures following contemporary radical prostatectomy. The impact of these factors is influenced by the individual surgeon and the approach used.
The combined stone-free and fragmentation rate was 51%, lower than in other published reports. In patients with calculi greater than 1,000 HU shock wave lithotripsy achieved a stone-free rate of only 17%. Patients should be informed of the likelihood of treatment failure or need for auxiliary procedures if the Doli S lithotriptor is used, particularly for stones greater than 1,000 HU.
Testosterone suppression, achieved through orchiectomy or medically induced androgen-deprivation therapy (ADT), is a standard treatment for men with recurrent and metastatic prostate cancer. Current assay methods demonstrate the capacity for testosterone suppression to <0.7 nmol/l, and clinical data support improved outcomes from ADT when lower levels are achieved. Practical clinical guidelines are warranted to facilitate adoption of 0.7 nmol/l as the new standard castrate testosterone level.A pan-Canadian group of experts, representing diverse clinical specialties, identified key clinical issues, searched and reviewed relevant literature, and developed consensus statements on testosterone suppression for the treatment of prostate cancer. The expert panel found that current evidence supports the clinical benefit of achieving low testosterone levels during ADT, and encourage adoption of ≤0.7 nmol/l as a new castrate level threshold. The panel recommends regular monitoring of testosterone (e.g., every 3-6 months) and prostate-specific antigen (PSA) levels as clinically appropriate (e.g., every 3-6 months) during ADT, with reassessment of therapeutic strategy if testosterone is not suppressed or if PSA rises regardless of adequate testosterone suppression. The panel also emphasizes the need for greater awareness and education regarding testosterone assay specifications, and strongly promotes the use of mass spectrometry-based assays to ensure accurate measurement of testosterone at castrate levels.
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