Efficacy over time of LHRH analogs in the treatment of PCa--a prospective analysis using serum testosterone to determine dosing intervals.

OBJECTIVES: To examine the duration of serum testosterone and prostate-specific antigen suppression after each dose of a 4-month depot leuprolide acetate for 18 months and to assess the potential for using serum testosterone as a guide for redosing the luteinizing hormone-releasing hormone analogs instead of using fixed dosing intervals. Luteinizing hormone-releasing hormone analogs are well established for the treatment of prostate cancer (PCa). However, many open questions remain regarding the optimal dosing. METHODS: Thirteen patients with PCa were enrolled in a longitudinal study. Serum testosterone levels were obtained at baseline and then monthly beginning 4 months after the first injection and every 2 months after the subsequent injections, for a total of 18 months. The median number of days from injection to the first serum testosterone level > or = 50 ng/dL was estimated using the Kaplan-Meier product-limit method. RESULTS: The median duration of effect was 159, 189, and 163 days for the first, second, and third treatment cycle, respectively. The prostate-specific antigen values from entry to completion decreased in all subjects. The total number of injections was reduced in all but one subject who completed the 18-month trial. One patient developed hormone-refractory PCa. CONCLUSIONS: Serum testosterone measurement might be a useful method for redosing luteinizing hormone-releasing hormone analogs. Using testosterone levels to determine the time of reinjection has a significant economic impact. Monitoring serum testosterone not only helps to identify patients who fail to achieve testosterone suppression but also provides close monitoring for the potential development of hormone-refractory PCa.

Yersinia enterocolitica leads to transient induction of TNF-alpha and activates NF-kappaB in synovial fibroblasts.

OBJECTIVE: The importance of the presence of bacterial antigen or even living bacteria for the pathogenesis of reactive arthritis has been discussed increasingly ever since bacterial antigen was found in inflamed joints. Bacteria may persist in the body and drive the local immune response, maintaining arthritis. Cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) are essential for bacterial elimination. In reactive arthritis, the course of the disease is influenced by several cytokines, including TNF-alpha. TNF-alpha expression can be mediated by transcription factor nuclear factor-kappa B (NF-kappaB). Moreover, TNF-alpha is also one of the strongest activators of NF-kappaB. METHODS: In vitro expression of TNF-alpha and activation of NF-kappaB in synovial fibroblasts after infection with Yersinia enterocolitica or Salmonella enteritidis was analysed by electrophoretic mobility shift assay, Western blot assay and real-time PCR. RESULTS: We found that infection of synovial fibroblasts with yersinia and salmonellae lead to the transient expression of TNF-alpha mRNA and induction of NF-kappaB. CONCLUSION: Induction of TNF-alpha in synovial fibroblasts after infection with yersiniae or salmonellae might be insufficient to eliminate bacteria, and this could allow the intracellular persistence of these bacteria. Our results therefore support the hypothesis that a permissive cytokine pattern might contribute to the pathogenesis of reactive arthritis.