Background and purpose: Ototoxicity is a known adverse effect of cisplatin (CDDP). Since apoptosis is involved in the development of some pathological conditions associated with the administration of anticancer drugs, we examined, using immunohistochemical and electrophysiological techniques, the apoptotic changes in the cochlea of Sprague-Dawley (SD) rats after an injection of CDDP (5 mgkg -1 body weight). Experimental approach: Luciferase assays were used to determine the different caspase activities and ATP levels in protein extracts of whole cochleae. The expression of several apoptotic-related proteins was measured by means of Western blotting. These analyses were performed 2, 7 and 30 days after the CDDP injection. The auditory brain stem response was obtained before and at the different times after the injection of CDDP, before the animals were killed. Key results: CDDP significantly increased the levels of caspase-3/7 activity and active caspase-3 protein expression and caspase-3 immunofluorescence staining, caspase-9 activity, and Bax protein expression but decreased Bcl-2 protein expression within the rat cochleae. Threshold shifts were significantly elevated 2 days after CDDP treatment. Conclusions and implications: These findings support the hypothesis that cisplatin-related apoptosis evokes an intrinsic pathway of pro-apoptotic signalling within the rat cochleae. Thus, selective inhibition of the sequence of events involved in the intrinsic apoptotic pathway could provide a strategy to minimize cisplatin-induced ototoxicity.

A retrospective study was done to assess the incidence and factors associated with neurological complications in patients who have undergone a functional neck dissection (FND). Four hundred forty-two epidermoid cancer patients operated on from January 1984 to December 2002 were included in the study. Clinical parameters, neurological sequelae, and other complications were evaluated in all cases. The incidence of neural damage was calculated on the nerves at risk (n =714). Paralysis of the 11th nerve occurred in 12 cases (1.68%). A lesion of the marginal branch of the 7th cranial nerve was observed in nine cases (1.26%). Bernard-Horner's syndrome and hypoglossal nerve paralysis were noted in four and three cases (0.56 and 0.42%), respectively. Thus, the incidence of neurological sequelae after FND is low. Neurological complications were not associated with either clinical parameters or non-neurological complications (P >0.05). None of the factors studied can predict the appearance of neural problems in the postoperative period.

IAntitumoral Pt-containing drugs present side effects like nephrotoxicity and ototoxicity. Several systematic experiments have been carried out with Wistar rats treated with cisplatin, carboplatin, and oxaliplatin to study Pt-drugs accumulation and elimination, and Pt-biomolecule distribution in the cells and cytosols of ear, kidney, and liver. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis shows a cisplatin accumulation capability between oxaliplatin (the highest) and carboplatin (the lowest). The maximum concentration of Pt in all the organs studied was achieved around the first week after cisplatin treatment. During the first 30 days, the elimination was very fast, decreasing in the subsequent 60 days in all the organs. Analysis of cytosols by liquid chromatography (LC)-ICP-MS showed an analogous behavior. In most samples, the distribution of the three drugs in the cellular and cytosolic fractions was similar for all the tissues. For kidney and ear, approximately 60% and 30%, respectively, of the metal accumulated was present in the cytosol, the cytosolic fractions smaller than 50 KDa being especially important. Cisplatin-biomolecule interaction strength under denaturing conditions was evaluated by LC-ICP-MS and showed a quite strong bond.

Immune-mediated inner ear disease (IMIED) is one of the few forms of reversible sensorineural hearing loss. Corticosteroids-responsive patients are usually associated with hearing improvement. Due to the long clinical course of IMIED that frequently present recurrences (hearing loss and vertigo), alternatives to corticosteroids such as methotrexate and recently TNF-alpha blockers have been proposed. Likewise new procedures for delivering corticosteroids to the inner ear have been developed. The aim of this article is to assess the efficacy of methotrexate and transtympanic 6-methylprednisolone in refractory IMIED. From a database of 200 patients affected by IMIED, 16 selected patients with refractory disease were included in the present study. Five patients were treated with methotrexate and 11 by means of transtympanic injection of 6-methylprednisolone. All patients treated with methotrexate had an improvement in their vestibular symptoms. However, hearing loss did not improve. Most patients treated with local 6-methylprednisolone (68.75%) showed an improvement in hearing loss and vestibular symptoms. Methotrexate has been shown to be ineffective in maintaining long-term remissions of hearing relapses although patients presented an improvement in vestibular symptoms. However, transtympanic 6-methylprednisolone has been shown to be a safe, easy and useful therapy in refractory IMIED and it may actually become the first-line treatment for these patients based on the existence of glucocorticoid receptors and the possible targets of immune-mediated damage within the inner ear.