Auditory learning and adaptation after cochlear implantation: a preliminary study of discrimination and labeling of vowel sounds by cochlear implant users.

This study examined two possible reasons underlying longitudinal increases in vowel identification by cochlear implant users: improved labeling of vowel sounds and improved electrode discrimination. The Multidimensional Phoneme Identification (MPI) model was used to obtain ceiling estimates of vowel identification for each subject, given his/her electrode discrimination skills. Vowel identification scores were initially lower than the ceiling estimates, but they gradually approached them over the first few months post-implant. Taken together, the present results suggest that improved labeling is the main mechanism explaining post-implant increases in vowel identification.

The effects of BW755C and other anti-inflammatory drugs on eicosanoid concentrations and leukocyte accumulation in experimentally-induced acute inflammation.

BW755C (3-amino-1-[m-trifluoromethyl)phenyl]-2-pyrazoline HCl) reduced the concentration of leukotriene B4 (LTB4), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) in exudate derived from the subcutaneous implantation in rats of 0.5% carrageenan-impregnated polyester sponges. Polymorphonuclear leukocyte (PMN) migration into the inflammatory exudate was also decreased. The inhibition of LTB4 may, in part, account for the lower number of cells in the exudate since LTB4 is a potent leukotactic agent. Inhibition of LTB4-formation and cell migration by BW755C was dose-related, but the two dose-response curves were not parallel. Cell influx still occurred at doses of BW755C that completely inhibited formation of LTB4: this indicates that, although LTB4 may have a chemotactic role in-vivo, other factors must also contribute to cell migration into the inflammatory exudate. Treatment of rats with dexamethasone also caused a reduction in leukocytes and eicosanoids in the exudate. As with BW755C, there was a differential effect on PMN and LTB4: dexamethasone (1 mg kg-1) reduced PMN accumulation by 40% but LTB4 formation was inhibited by 70%. Leukocyte accumulation was also inhibited by the non-steroidal anti-inflammatory drugs (NSAID's), indomethacin and flurbiprofen. These drugs reduced the concentration of both PGE2 and TXB2 in exudate but that of LTB4 was unchanged. This suggests that reduction of PMN accumulation by indomethacin and flurbiprofen is mediated by a mechanism other than inhibition of LTB4-synthesis. Aspirin also reduced the levels of PGE2 and TXB2 in the exudate but did not consistently affect PMN influx, thereby confirming that inhibition of cyclo-oxygenase does not reduce cell migration in inflammation.

The release of leukotriene B4 during experimental inflammation.

Leukotriene B4 (LTB4) has been detected by radioimmunoassay in inflammatory exudates obtained following the implantation of saline- or carrageenan-soaked polyester sponges in rats. The immunoreactive material was confirmed as LTB4 after extraction and purification by high pressure liquid chromatography. The peak concentration (6.9 +/- 0.5 ng/ml) was detected 6 hr after implantation of sponges soaked in 0.5% carrageenan; thereafter the level declined and was undetectable after 16-24 hr. The concentration of LTB4 during the early phase of the inflammatory response (4-8 hr) is sufficient to induce leukocyte aggregation, chemotaxis and degranulation of polymorphonuclear leukocytes (PMN) in vitro. Therefore, LTB4 may mediate, at least in part, the influx of PMN and contribute to other events which characterise the inflammatory response. The level of thromboxane B2 (TXB2) in the inflammatory exudate followed a similar time-course to that of LTB4 although the maximum concentration was higher (15-30 ng/ml). However, prostaglandin E2 (PGE2) exhibited a different time-course; the maximum level (20-30 ng/ml) was also reached 6-8 hr after implantation but remained elevated at 24 hr. The PMN count in the sponges and the concentrations of both LTB4 and TXB2, but not PGE2, were significantly reduced by prior treatment of the animals with colchicine. This suggests that PMN are the major source of LTB4 and TXB2 in the inflammatory exudate whereas PGE2 is produced in significant amounts by other tissues.

A radioimmunoassay for leukotriene B4.

A radioimmunoassay for leukotriene B4 has been developed. The assay is sensitive; 5 pg LTB4 caused significant inhibition of binding of [3H]-LTB4 and 50% displacement occurred with 30 pg. The specificity of the assay has been critically examined; prostaglandins, thromboxane B2 and arachidonic acid do not exhibit detectable cross-reactions (less than 0.03%). However, some non-cyclic dihydroxy- and monohydroxy-eicosatetraenoic acids do cross-react slightly (e.g. diastereomers of 5,12-dihydroxy-6,8,10-trans-14-cis-eicosatetraenoic and 12-hydroxy-5,8,10,14-eicosatetraenoic acids cross-react 3.3% and 2.0% respectively). The assay has been used to monitor the release of LTB4 from human neutrophils in response to the divalent cation ionophore, A23187. The immunoreactive material released during these incubations was confirmed as LTB4 by reverse phase high pressure liquid chromatography following solvent extraction and silicic acid chromatography.