Predicting and diagnosing abacavir and nevirapine drug hypersensitivity: from bedside to bench and back again

There is a growing discussion surrounding the issue of personalized approaches to drug prescription based on an individual's genetic makeup. This field of investigation has focused primarily on identifying genetic factors that influence drug metabolism and cellular disposition, thereby contributing to dose-dependent toxicities and/or variable drug efficacy. However, pharmacogenetic approaches have also proved valuable in predicting drug hypersensitivity reactions in selected patient populations, including HIV-infected patients receiving long-term antiretroviral therapy. In this instance, susceptibility has been strongly linked to genetic loci involved in antigen recognition and presentation to the immune system--most notably within the major histocompatibility complex (MHC) region--consistent with the notion that hypersensitivity reactions represent drug-specific immune responses that are largely dose independent. Here the authors describe their experiences with the development of pharmacogenetic approaches to hypersensitivity reactions associated with abacavir and nevirapine, two commonly prescribed antiretroviral drugs. It is demonstrated that prospective screening tests to identify and exclude individuals with a certain genetic makeup may be largely successful in decreasing or eliminating incidence of these adverse drug reactions in certain populations. This review also explores the broader implications of these findings.

Detection of back-to-back proton pairs in charged-current neutrino interactions with the ArgoNeuT detector in the NuMI low energy beam line

Short range nucleon-nucleon correlations in nuclei (NN SRC) carry important information on nuclear structure and dynamics. NN SRC have been extensively probed through two-nucleon knock- out reactions in both pion and electron scattering experiments. We report here on the detection of two-nucleon knock-out events from neutrino interactions and discuss their topological features as possibly involving NN SRC content in the target argon nuclei. The ArgoNeuT detector in the Main Injector neutrino beam at Fermilab has recorded a sample of 30 fully reconstructed charged current events where the leading muon is accompanied by a pair of protons at the interaction vertex, 19 of which have both protons above the Fermi momentum of the Ar nucleus. Out of these 19 events, four are found with the two protons in a strictly back-to-back high momenta configuration directly observed in the final state and can be associated to nucleon Resonance pionless mechanisms involving a pre-existing short range correlated np pair in the nucleus. Another fraction (four events) of the remaining 15 events have a reconstructed back-to-back configuration of a np pair in the initial state, a signature compatible with one-body Quasi Elastic interaction on a neutron in a SRC pair. The detection of these two subsamples of the collected (mu- + 2p) events suggests that mechanisms directly involving nucleon-nucleon SRC pairs in the nucleus are active and can be efficiently explored in neutrino-argon interactions with the LAr TPC technology.