These data suggest that the olfactory nerve is the route of entry into the brain and that this route of entry may be paralleled in cases of human neurologic melioidosis. This study focuses attention on the upper respiratory tract as a portal of entry, specifically focusing on NALT as a route for the development of systemic infection via the bloodstream and on the olfactory epithelium as a direct route to the brain.

Melioidosis is a potentially fatal disease that is endemic to tropical northern Australia and Southeast Asia, with a mortality rate of 14 to 50%. The bacterium Burkholderia pseudomallei is the causative agent which infects numerous parts of the human body, including the brain, which results in the neurological manifestation of melioidosis. The olfactory nerve constitutes a direct conduit from the nasal cavity into the brain, and we have previously reported that B. pseudomallei can colonize this nerve in mice. We have now investigated in detail the mechanism by which the bacteria penetrate the olfactory and trigeminal nerves within the nasal cavity and infect the brain. We found that the olfactory epithelium responded to intranasal B. pseudomallei infection by widespread crenellation followed by disintegration of the neuronal layer to expose the underlying basal layer, which the bacteria then colonized. With the loss of the neuronal cell bodies, olfactory axons also degenerated, and the bacteria then migrated through the now-open conduit of the olfactory nerves. Using immunohistochemistry, we demonstrated that B. pseudomallei migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24 h. We also found that the bacteria colonized the thin respiratory epithelium in the nasal cavity and then rapidly migrated along the underlying trigeminal nerve to penetrate the cranial cavity. These results demonstrate that B. pseudomallei invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier.

The small mean benefit was lower than the MCID. However, the marked variability in the individual patient responses revealed that a proportion of patients did benefit clinically, with an estimated NNT of 5.

SummaryAnaerobic threshold (AT), determined by cardiopulmonary exercise testing (CPET), is a well-documented measure of pre-operative fitness, although its reliability in patient populations is uncertain. Our aim was to assess the reliability of AT measurement in patients with abdominal aortic aneurysms. Eighteen patients were recruited. CPET was performed four times over a 6-week period. We examined shifts in the mean AT to evaluate systematic bias with random measurement error assessed using typical within-patient error and intraclass correlation coefficient (ICC, 3,1) statistics. There was no significant or clinically substantial change in mean AT across the tests (p = 0.68). The typical within-patient error expressed as a percentage coefficient of variation was 10% (95% CI, 8-13%), with an ICC of 0.74 (95% CI, 0.55-0.89). We consider the reliability of the AT to be acceptable, supporting its clinical validity and utility as an objective marker of pre-operative fitness in this population.

In contrast to its effect on spinal plain levobupivacaine, we did not find rostral spread of spinal hyperbaric bupivacaine to be less with prophylactic phenylephrine than with ephedrine. We observed an unexpectedly high incidence of fetal acidosis with ephedrine and found evidence that longer spinal-delivery intervals increase the risk of fetal acidosis developing with ephedrine, but not phenylephrine.