In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Magnetic Resonance Imaging (MRI) methods were evaluated as a tool for the study of experimental meningitis. The identification and characterisation of pathophysiological parameters that vary during the course of the disease could be used as markers for future studies of new treatment strategies.</p> <p>Methods</p> <p>Rats infected intracisternally with <it>S. pneumoniae </it>(n = 29) or saline (n = 13) were randomized for imaging at 6, 12, 24, 30, 36, 42 or 48 hours after infection. T1W, T2W, quantitative diffusion, and post contrast T1W images were acquired at 4.7 T. Dynamic MRI (dMRI) was used to evaluate blood-brain-barrier (BBB) permeability and to obtain a measure of cerebral and muscle perfusion. Clinical- and motor scores, bacterial counts in CSF and blood, and WBC counts in CSF were measured.</p> <p>Results</p> <p>MR images and dMRI revealed the development of a highly significant increase in BBB permeability (P < 0.002) and ventricle size (P < 0.0001) among infected rats. Clinical disease severity was closely related to ventricle expansion (P = 0.024).</p> <p>Changes in brain water distribution, assessed by ADC, and categorization of brain 'perfusion' by cortex ΔSI_(bolus)were subject to increased inter-rat variation as the disease progressed, but without overall differences compared to uninfected rats (P > 0.05). Areas of well-'perfused' muscle decreased with the progression of infection indicative of septicaemia (P = 0.05).</p> <p>Conclusion</p> <p>The evolution of bacterial meningitis was successfully followed <it>in-vivo </it>with MRI. Increasing BBB-breakdown and ventricle size was observed in rats with meningitis whereas changes in brain water distribution were heterogeneous. MRI will be a valuable technique for future studies aiming at evaluating or optimizing adjunctive treatments</p

Sorry everyone, but it didn't work (p = 0.06)

The more or less ubiquitous use of Fisher-type statistics in quantitative/numeric evaluations of drug and alcohol education initiatives takes place within the context of a literature of long standing which suggests there are areas in which null hypothesis testing and the use of conventional cut-off points (i.e. the 1% and 5% probability levels) are inappropriate. This literature is largely ignored. The paper identifies some of these issues in terms of their relevance to the problems of evaluation of drug/alcohol programmes. The paper argues that the qualitative approach does not solve these problems but merely by-passes them, as well as being unsatisfactory in a number of ways. Thus, it is concluded that there is a pressing need for change in the type of quantitative approach adopted. Suggestions are made for a variety of exploratory methods, still involving broadly numerical analysis, which have a philosophical rather than a merely technical base, and which shed light on ‘what is going on’ rather than merely providing a binary decision (it worked/it did not work) derived from an arbitrary criterion for statistical significance and a null hypothesis which is usually known to be false from the start