Intermittent LHRH therapy in the management of castrate-resistant prostate cancer (CRPCa): results of a multi-institutional randomized prospective clinical trial.

BACKGROUND: Patients who develop castration-resistant prostate cancer (CRPCa) typically continue on androgen deprivation therapy (ADT). Whether these patients need to remain on ADT has not been well studied. We conducted a multicenter randomized trial to compare an intermittent versus continuous approach to ADT in CRPCa patients. Overall survival, health-related quality of life (QOL), and cost were the main endpoints. METHODS: CRPCa patients were randomized 2:1 to intermittent or continuous luteinizing hormone-releasing hormone agonists (LHRHa). Patients were followed with clinical assessments, laboratory investigations, and QOL questionnaires (EORTC QLQ-C30 or PROSQOLI) every 2 months. If the serum testosterone rose above castrate levels (1.75 nmol/L), LHRHa were reinitiated. The study was designed to close if >50% of patients needed to restart ADT in the intermittent arm. RESULTS: Thirty-one patients were followed with a median follow-up of 26.8 months-18 in the intermittent arm and 13 in the continuous. Twelve of 18 patients on the intermittent arm were reinitiated on LHRHa at a median time of 17.9 months. There was no difference in overall or cancer-specific survival between the 2 arms. There was no statistically significant difference in QOL between the 2 arms at 0 and 12 months. The total mean costs at 24 months were significantly lower in the intermittent arm ($3135 vs. $8253 Canadian dollars, P=0.0167) compared with the continuous. The main limitation of this study is the small sample size. CONCLUSIONS: We have observed that intermittent ADT in patients with CRPCa, using a testosterone of >1.75 ngmol/L as a trigger to reinitiate LHRHa, results in a substantial cost savings with no negative impact on oncologic and QOL outcomes.

Identification of sulfate-reducing bacteria in methylmercury-contaminated mine tailings by analysis of SSU rRNA genes.

Sulfate-reducing bacteria (SRB) are often used in bioremediation of acid mine drainage because microbial sulfate reduction increases pH and produces sulfide that binds with metals. Mercury methylation has also been linked with sulfate reduction. Previous geochemical analysis indicated the occurrence of sulfate reduction in mine tailings, but no molecular characterization of the mine tailings-associated microbial community has determined which SRB are present. This study characterizes the bacterial communities of two geochemically contrasting, high-methylmercury mine tailing environments, with emphasis on SRB, by analyzing small subunit (SSU) rRNA genes present in the tailings sediments and in enrichment cultures inoculated with tailings. Novel Deltaproteobacteria and Firmicutes-related sequences were detected in both the pH-neutral gold mine tailings and the acidic high-sulfide base-metal tailings. At the subphylum level, the SRB communities differed between sites, suggesting that the community structure was dependent on local geochemistry. Clones obtained from the gold tailings and enrichment cultures were more similar to previously cultured isolates whereas clones from acidic tailings were more closely related to uncultured lineages identified from other acidic sediments worldwide. This study provides new insights into the novelty and diversity of bacteria colonizing mine tailings, and identifies specific organisms that warrant further investigation with regard to their roles in mercury methylation and sulfur cycling in these environments.

Comparison of changes in metal toxicity following exposure of water with high dissolved organic carbon content to solar, UV-B and UV-A radiation.

This study examines the effects of natural solar radiation on the metal-binding capacity of dissolved organic matter (DOM). Newington Bog water (35.5 mg L(-1) dissolved organic carbon [DOC]) was irradiated for 20 days under UV-B lamps in the laboratory and under natural solar radiation. In the presence of irradiated DOM, IC(50) (contaminant concentration required to reduce algal growth by 50%) was significantly decreased with UV-B treatment for four metals: Pb, 64%; Cu, 63%; Ni, 35% and Cd, 40%. Solar radiation also significantly decreased IC(50) of Pb (58%) and Cu (49%), DOC concentration (11%), DOM fluorescence (DOMFL, 33%) and DOC-specific UV absorbance. Further experiments on Raisin River water (20.7 mg DOC L(-1)) exposed to 20 days of artificial UV-A and UV-B radiation produced significant decreases in IC(50) for Cu (48%) with UV-A and for Pb (43%) with UV-B. DOC concentration was decreased 20% by UV-B and 24% by UV-A. DOMFL decreased 51.5% in the first 5 days of UV-A exposure, an effect that was not observed with the UV-B treatment. The UV-A treatment decreased UV absorbance more at longer wavelengths and over a broader wavelength band than did the UV-B treatment. Change in toxicity with UV irradiation was inconsistent among the metals tested in this study, indicating that some organic metal-binding ligands were more quickly removed or altered than others. The DOM remaining after irradiation appears to be qualitatively different from the unirradiated DOM. The much greater irradiance of UV-A makes its contribution to the removal and/or alteration of DOM at least as important as the influence of higher energy UV-B.

Increased metal bioavailability following alteration of freshwater dissolved organic carbon by ultraviolet B radiation exposure.

Dissolved organic carbon (DOC) is critically important in the chemistry of freshwater. It complexes heavy metals, making them less bioavailable to aquatic organisms, and absorbs and attenuates UVB radiation, undergoing degradation and alteration in the process. This study examined changes in metal toxicity to the freshwater green alga Pseudokirchneriella subcapitata in high- and low-DOC natural water samples after exposure to UVB radiation. Brown-water and clear-water samples were irradiated for 0, 5, and 10 days. The DOC concentrations of the samples were measured, and they were subsequently spiked with Cu, Ni, Zn, Cd, Co, and Pb and used in algal bioassays to measure changes in metal toxicity following irradiation. DOC concentrations declined only 20% with UVB irradiation in both samples, although DOC concentration was much higher in the brown-water sample than in the clear-water sample. In the brown-water sample metal toxicity increased up to 78% after 10 days of UVB irradiation for Cu, Zn, Co and Pb, but not for Ni and Cd. Changes were less evident in the clear-water sample. The differences observed between IC(50) values for relatively fresh, high-DOC water from the headwaters of the Raisin River and much "older," low-DOC water from Lake Simcoe point to the likelihood of the effects observed in this study being many times greater in the natural environment because of very long exposure to solar radiation. Alteration of DOC by UVB irradiation may influence primary productivity and species composition, especially in waters in which metal concentrations are high.