Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved.

Locating whiteness in the academic production of "I Philosophy" in and of time and place

This review will critically evaluate two recent texts by white academics working across disciplines of cultural studies, history and anthropology and published by UNSW Press, which share a focus on the relationship between Aboriginality, Philosophy, Place and Time in Australia. I write from the position of a queer white academic committed to engaging politically and intellectually with the challenge of Indigenous sovereignties in this place while also aware that my position as a middle class white woman and intellectual imposes limits on what it is possible for me to know about Indigenous epistemologies (see Moreton-Robinson, 2000). In the course of this review I will demonstrate how anthropology's tendency to fix its objects of study within a circumscribed space of 'difference' limits the capacity of texts produced within this discipline to account for racialized struggles over sovereignty. While these struggles are equally embedded in the ethnographic context and the nation's constitution and political institutions, we will see that Muecke and Bird Rose confront problems in analysing the relationship between the intimate space of the 'field', in which one's research subjects quickly become one's 'friends' and/or 'classificatory kin'—on one hand—and the public space of the nation within which statements about Aboriginality by white academics circulate and are vested with an authority that escapes individual intentions and control—on the other.

An electrical heart model incorporating real geometry and motion

Abstract—This paper describes an electrical model of the ventricles incorporating real geometry and motion. Cardiac geometry and motion is obtained from segmentations of multipleslice MRI time sequences. A static heart model developed previously is deformed to match the observed geometry using a novel shape registration algorithm. The resulting electrocardiograms and body surface potential maps are compared to a static simulation in the resting heart. These results demonstrate that introducing motion into the cardiac model modifies the ECG during the T wave at peak contraction of the ventricles.