Cinnarizine is pharmaceutically used in conditions with vestibular vertigo such as Meniere's disease. It is thought to act on extra-vestibular targets. We hypothesized that cinnarizine, as a blocker of L-type Ca2+ channels, may directly target vestibular hair cells where Ca2+ currents are important for the mechano-electrical transduction and transmitter release. Our aim was to clarify whether cinnarizine affected voltage-dependent Ca2+ currents in vestibular type II hair cells. Such cells were isolated from inner ears of guinea pigs by enzymatic and mechanical dissection from the gelatinous otolithic membrane and studied with the patch-clamp technique in conventional whole-cell mode. Ca2+ currents were elicited by depolarizing pulses in a solution containing 1.8 mM Ca2+ and 40 mM Ba2+. These currents resembled L-type currents (I(Ca,L)) with respect to their voltage-dependence and their inhibition by nifedipine and Cd2+ but did not show time-dependent inactivation. The currents were inhibited by cinnarizine in a concentration-dependent and reversible manner. The IC50 was 1.5 microM. A block exceeding 80% was achieved with 10 microM. The onset of current block was faster with higher concentrations but the reversibility after wash-out was less, suggesting accumulation in the membrane. We conclude that these direct actions of cinnarizine on hair cells should be considered as molecular mechanisms contributing to therapeutic effects of cinnarizine in vertigo.

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We conducted a study to evaluate speech recog nition soft ware in an otorhino laryngo logy unit and to assess its imp act on p roductivity pri or to gene ral impl ementation. Current speech recognition sof tware (IBM ViaVoice, version 10) was impl emented on a personal computer with a 2-GHz central pro cessing unit , 256 MB of RAM, and a 30-GB hard disk drive, with and without add-on professional vocabularyforotorhino laryngo logy. This vocabulary was added by the automated analysis ofan additional 12,25 7 docum ents from our department. We compared the word recog nition error rates f or three different text typ es and determin ed their impact on the amount ofsurgeon : time that was invested in the p roduction ofan error-f ree docum ent. Although error rates without any professional vocabulary dat abase we re rather high (operation report s: 38.72 %; consultation notes: 2 7.77%), the patient inf ormation was edited with a satisf actory result (10.65 %). Best results were obtained with the specialty-related vocab ulary database added by the analysis of our ow n documents (operation reports: 5.45 %; consultation notes: 5.21%). An increase in p roductivity compa red with that of conventional tran scription was fo und at an error rate of less than 16%.

In vestibular hair cells, K+ currents induced by rises in hydrostatic pressure have recently been demonstrated. These currents are inhibited by charybdotoxin, a blocker of Ca2+-dependent K+ channels. On the other hand, cinnarizine is a blocker of voltage-gated Ca2+ currents in hair cells and is used as a drug in conditions with vestibular vertigo. Our aim was to test in patch-clamp experiments (conventional whole-cell mode) whether cinnarizine, by reducing Ca2+ influx, inhibited Ca2+ and pressure-sensitive K+ currents in vestibular type-II hair cells of guinea pigs. A quantitatively similar inhibition of K+ currents was evoked by extracellular Ca2+ removal, cinnarizine (0.5 microM), and the L-type Ca2+ channel blocker nifedipine (3 microM). Cinnarizine abrogated increases of K+ currents induced by increases in the hydrostatic pressure (from 0.2 to 0.5 cm H2O). At a higher concentration (1 microM), cinnarizine elicited K+ current inhibitions larger than those elicited by Ca2+ removal. Moreover, it reduced K+ currents in the absence of Ca2+, in contrast to nifedipine. However, charybdotoxin abolished these effects of cinnarizine. We thus conclude that cinnarizine inhibits, by two mechanisms, pressure-induced currents that are sensitive to charybdotoxin and Ca2+. It reduces Ca2+ influx and exerts a Ca2+-independent inhibition, with a lower IC50 than that required for Ca2+ channel blockade. These two actions may importantly contribute to its therapeutic effects.

For daily clinical routine, counting nystagmus beats leads to the same diagnostic precision as the analysis of slow-phase velocities. In contrast, multivariate analysis of several nystagmus parameters can distinguish between distinct diseases with fairly high precision. This stepwise analysis of nystagmographic data could create the basis for an expert-system tool in the near future.