Artemisone uptake in Plasmodium falciparum-infected erythrocytes.

Artemisone is one of the most promising artemisinin derivatives in clinical trials. Previous studies with radiolabeled artemisinin and dihydroartemisinin have measured uptake in Plasmodium falciparum-infected erythrocytes. Uptake is much greater in infected than in uninfected erythrocytes, but the relative contributions of transport, binding, and metabolism to this process still await definition. In this study, we characterized mechanisms by which [(14)C]artemisone is taken up into uninfected and P. falciparum-infected human erythrocytes in vitro. Radiolabeled artemisone rapidly enters uninfected erythrocytes without much exceeding extracellular concentrations. Unlabeled artemisone does not compete in this process. Radiolabeled artemisone is concentrated greatly by a time- and temperature-dependent mechanism in infected erythrocytes. This uptake is abrogated by unlabeled artemisone. In addition, the uptake of artemisone into three subcellular fractions, and its distribution into these fractions, is examined as a function of parasite maturation. These data are relevant to an understanding of the mechanisms of action of this important class of drugs.

Laboratory sample turnaround times: do they cause delays in the ED?

OBJECTIVES: Blood tests are requested for approximately 50% of patients attending the emergency department (ED). The time taken to obtain the results is perceived as a common reason for delay. The objective of this study was therefore to investigate the turnaround time (TAT) for blood results and whether this affects patient length of stay (LOS) and to identify potential areas for improvement. METHODS: A time-in-motion study was performed at the ED of the John Radcliffe Hospital (JRH), Oxford, UK. The duration of each of the stages leading up to receipt of 101 biochemistry and haematology results was recorded, along with the corresponding patient's LOS. RESULTS: The findings reveal that the mean time for haematology results to become available was 1 hour 6 minutes (95% CI: 29 minutes to 2 hours 13 minutes), while biochemistry samples took 1 hour 42 minutes (95% CI: 1 hour 1 minute to 4 hours 21 minutes), with some positive correlation noted with the patient LOS, but no significant variation between different days or shifts. CONCLUSIONS: With the fastest 10% of samples being reported within 35 minutes (haematology) and 1 hour 5 minutes (biochemistry) of request, our study showed that delays can be attributable to laboratory TAT. Given the limited ability to further improve laboratory processes, the solutions to improving TAT need to come from a collaborative and integrated approach that includes strategies before samples reach the laboratory and downstream review of results.