Human cancer cells are irradiated by laser-driven quasimonoenergetic protons. Laser pulse intensities at the 5×1019 W/cm2 level provide the source and acceleration field for protons that are subsequently transported by four energy-selective dipole magnets. The transport line delivers 2.25 MeV protons with an energy spread of 0.66 MeV and a bunch duration of 20 ns. The survival fraction of in vitro cells from a human salivary gland tumor is measured with a colony formation assay following proton irradiation at dose levels of up to 8 Gy, for which the single bunch dose rate is 1×107 Gy/s and the effective dose rate is 0.2 Gy/s for 1 Hz repetition of irradiation. Relative biological effectiveness at the 10% survival fraction is measured to be 1.20±0.11 using protons with a linear energy transfer of 17.1 keV/μm.

No abstract

Although antibiotic-loaded hydroxyapatite blocks have been used for the treatment of chronic osteomyelitis, their long-term potential for releasing antibiotic into human bones is not well known. Five patients with chronic osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) infection were effectively treated with local implantation of vancomycin-loaded hydroxyapatite blocks. Blocks were removed during the following reconstructive surgeries when the releasing capability of the blocks, and the bacteriocidal activity of the remaining vancomycin in these blocks could be evaluated. Vancomycin was rapidly released within 1 month after implantation, and by 3 months 90% of vancomycin had leaked from the blocks. At 18 months vancomycin still remained in a bacteriocidal form in the hydroxyapatite blocks, though the blocks had no releasing potential or the eluted vancomycin had been changed to a different form. Vancomycin-loaded porous hydroxyapatite blocks would be useful for the treatment of chronic osteomyelitis or implant-associated osteomyelitis due to MRSA.

The objective of this study was to investigate the relationship between pharmacokinetic and pharmacodynamic parameters, on the basis of the mutant prevention concentration (MPC) concept, and the emergence of resistant mutants of Streptococcus pneumoniae to fluoroquinolone antibacterials. Some clinical isolates with various MIC and MPC values of moxifloxacin and levofloxacin were exposed under conditions simulating the time-concentration curves observed when moxifloxacin (400 or 80 mg, once a day) or levofloxacin (200 mg, twice a day) was orally administered by using an in vitro pharmacodynamic model. The decrease in susceptibility was evaluated by altering the population analysis profiles after moxifloxacin or levofloxacin treatment for 72 h. When the area under the concentration-time curve from 0 to 24 h (AUC 0-24 )/MPC and peak concentration (C max )/MPC were above 13.41 and 1.20, respectively, complete eradication occurred and no decrease in susceptibility was observed. On the other hand, when AUC 0-24 /MPC and C max /MPC were below 0.84 and 0.08, respectively, the susceptibility decreased. However, the time inside the mutant selective window and the time above the MPC did not show any correlation with the decrease in susceptibility. These results suggest that AUC 0-24 /MPC and C max /MPC are important parameters for predicting the emergence of resistant mutants and that higher values indicate greater effectiveness.