Hospital-associated bacterial meningitis

Eighteen of 349 cases (5.2 per cent) of bacterial meningitis seen between 1949 and 1973 were hospital-associated (developed after admission to the hospital). The patients were adults, usually males, and developed symptoms and signs of meningitis from 2 to 23 days (mean, 10.1 days) after hospital admission. The diagnosis of bacterial meningitis was made from less than 1 day to 15 days (mean, 4.8 days) after the onset of symptoms. Fourteen of the 18 patients had received antibiotics during the week prior to developing meningitis. Nine (50 per cent) had a chronic, noninfection, underlying illness. Diagnostic or surgical procedures involving the neuraxis or adjacent structures preceded the development of meningitis in 10 of the 18 patients (56 per cent). Only 6 of the 18 patients survived their infection. Prompt recognition, diagnosis, and therapy of hospital-associated meningitis in high-risk patients may reduce the significant mortality.     

Combating coevolutionary disengagement by reducing parasite virulence

While standard evolutionary algorithms employ a static, absolute fitness metric, coevolutionary algorithms assess individuals by their performance relative to populations of opponents that are themselves evolving. Although this arrangement offers the possibility of avoiding long-standing difficulties such as premature convergence, it suffers from its own unique problems, cycling, over-focusing and disengagement. Here, we introduce a novel technique for dealing with the third and least explored of these problems. Inspired by studies of natural host-parasite systems, we show that disengagement can be avoided by selecting for individuals that exhibit reduced levels of "virulence", rather than maximum ability to defeat coevolutionary adversaries. Experiments in both simple and complex domains are used to explain how this counterintuitive approach may be used to improve the success of coevolutionary algorithms.     

Middle and long latency auditory evoked potentials in cat. II. Component distributions and dependence on stimulus factors

The middle (10-50 ms) and long (50-600 ms) latency periods of the auditory evoked potential (AEP) were investigated in muscle-paralyzed, artificially respired cats with respect to two issues: (1) the distribution of components across the skull, and (2) the effects of changing stimulus intensity on component latencies and amplitudes. The distributional data were gathered during a behavioral study in which four behavioral tasks related to classical pupillary conditioning were used to vary attentional and arousal processes. The distributions across the skull surface (averaged across tasks) of 12 peaks and troughs (P10, N13, P17, N22, P31, N41, P55, N70, N100, N140, P260 and N520) and seven principal components derived from the set of waveforms collected during this experiment are reported. Both peak amplitudes and principal component scores were distributed differentially across the skull surface. In the second experiment, acoustic stimulus intensity was varied, and AEPs collected from a vertex and temporal electrode site. In general, increasing stimulus intensity had a stronger influence on the earlier portions of the AEP, where increased amplitude and decreased latency was the rule, than on later ones. The relationships between cat and human AEP components were discussed based on both the data presented in this paper and in previous papers.     

Blockade of accumbens 5-HT3 receptor down-regulation by ondansetron administered during continuous cocaine administration

The present experiment examined whether ondansetron, co-administered with continuous cocaine, would block the down regulation of accumbens 5-HT3 receptors. Rats were exposed to a 14-day pretreatment regimen that involved the continuous infusion of 40 mg kg(-1) day(-1) cocaine or 0.9% saline via a subcutaneously implanted osmotic minipump. In addition to the continuous cocaine or saline administration, all subjects received daily subcutaneous (s.c.) injections of either vehicle or 0.1 mg kg(-1) ondansetron for the entire 14-day pretreatment regimen. The rats were then withdrawn from this pretreatment regimen for seven days, and slices from the nucleus accumbens obtained. The slices were perfused with 25 mM K+ in the absence and presence of 0, 12.5, 25, or 50 microM m-Chlorophenyl-biguanide HCl (mCPBG). The efflux samples were assayed for dopamine content by high pressure liquid chromatography (HPLC) with electrochemical detection. Continuous cocaine administration significantly attenuated the ability of mCPBG to facilitate K+-induce dopamine overflow compared to saline control rats. In addition, the rats that received ondansetron and cocaine during the 14-day pretreatment period, the ability of mCPBG to enhance K+ stimulated dopamine release was not significantly different from the saline control subjects. For all groups except the cocaine alone group, the effects of mCPBG on K+ stimulated dopamine release were Ca2+ dependent, suggesting that these effects are receptor mediated. These results suggest that continuous cocaine administration functionally down-regulates 5-HT3 receptors in the nucleus accumbens, and that this down-regulation can be blocked by chronic ondansetron administration. Hence, a functional down regulation of accumbens 5-HT3 receptors represents a significant contribution to the tolerance induced by continuous cocaine administration.