The use of the effective antineoplastic agent cisplatin is limited by its serious side effects , such as oto-and nephrotoxicity. Ototoxicity is a problem of special importance in children , because deafness hampers their language and psychosocial development. Recently , organic cation transporters (OCTs) were identified in vitro as cellular uptake mechanisms for cisplatin. In the present study , we investigated in an in vivo model the role of OCTs in the development of cisplatin oto-and nephrotoxicity. The functional effects of cisplatin treatment on kidney (24 hours excretion of glucose , water , and protein) and hearing (auditory brainstem response) were studied in wildtype and OCT1/2 double-knockout (KO) mice. No sign of ototoxicity and only mild nephrotoxicity were observed after cisplatin treatment of knockout mice. Comedication of wild-type mice with cisplatin and the organic cation cimetidine protected from ototoxicity and partly from nephrotoxicity. For the first time we showed that OCT2 is expressed in hair cells of the cochlea. Furthermore , cisplatin-sensitive cell lines from pediatric tumors showed no expression of mRNA for OCTs , indicating the feasibility of therapeutic approaches aimed to reduce cisplatin toxicities by competing OCT2-mediated cisplatin uptake in renal proximal tubular and cochlear hair cells. These findings are very important to establish chemotherapeutical protocols aimed to maximize the antineoplastic effect of cisplatin while reducing the risk of toxicities.

Although the influence of long-term musical training on the processing of heard music has been the subject of many studies, the neural basis of music imagery and the effect of musical expertise remain insufficiently understood. By means of magnetoencephalography (MEG) we compared musicians and nonmusicians in a musical imagery task with familiar melodies. Subjects listened to the beginnings of the melodies, continued them in their imagination and then heard a tone which was either a correct or an incorrect further continuation of the melody. Only in musicians was the imagery of these melodies strong enough to elicit an early preattentive brain response to unexpected incorrect continuations of the imagined melodies; this response, the imagery mismatch negativity (iMMN), peaked approximately 175 ms after tone onset and was right-lateralized. In contrast to previous studies the iMMN was not based on a heard but on a purely imagined memory trace. Our results suggest that in trained musicians imagery and perception rely on similar neuronal correlates, and that the musicians' intense musical training has modified this network to achieve a superior ability for imagery and preattentive processing of music.

Human representational cortex may fundamentally alter its organization and (re)gain the capacity for auditory processing even when it is deprived of its input for more than two decades. Stimulus-evoked brain activity was recorded in post-lingual deaf patients after implantation of a cochlear prosthesis, which partly restored their hearing. During a 2 year follow-up study this activity revealed almost normal component configuration and was localized in the auditory cortex, demonstrating adequacy of the cochlear implant stimulation. Evoked brain activity increased over several months after the cochlear implant was turned on. This is taken as a measure of the temporal dynamics of plasticity of the human auditory system after implantation of cochlear prosthesis.

Though brainstem audiometry is one of the most important investigations in pediatric audiology, it often necessitates sedation or general anaesthetics, especially in newborns and infants. Melatonin, inducing natural sleep without the risks of sedation, has been successfully used to induce sleep prior to EEG investigations. 250 children (142 male, 108 female) with suspected hearing loss underwent ABR (auditory brainstem responses) tests in melatonin-induced sleep. Click-induced and notched-noise ABR tests were performed. Click tests were successfully performed in 216 of 249 children or 86.7% (123 male, 93 female), notched-noise tests in 115 of 155 children or 74.2%. Failure rates showed an age dependence increasing from 4% in children <1 year to 25%>3 years, but no gender difference. In conclusion, melatonin-induced sleep is a good alternative to sedation, especially in children younger than 3 years. This method is widely accepted by parents and permits earlier diagnosis of hearing impairment in a routine clinical setting. The number of children undergoing general anaesthesia for ABR investigation was reduced from over 60 per year in 2000-2002 to 12 in 2005, which means >80% less general anaesthesia.