Audiological Monitoring in Children Treated with Platinum Chemotherapy.

Platinum compounds constitute the standard treatment for solid tumors in pediatric oncology. The purpose of this study is to assess the impact of platinum compounds in the development of ototoxicity in children following chemotherapy. This study included 160 patients treated with cisplatin and carboplatin for malignant solid diseases from 2007 to 2014. Their audiograms were classified according to the Boston SIOP ototoxicity scale. Twenty-five percent of the children treated with platinum compounds developed ototoxicity. The incidence of ototoxicity was correlated with the type of platinum derivative (i.e. cisplatin vs. carboplatin), coadministration of both drugs and concomitant cranial radiotherapy, but not with sex and age. Cumulative dose was correlated only with the cisplatin administration. Nine patients (8.6%) showed further progression of hearing impairment after the end of chemotherapy. The low rate of ototoxicity suggests the pivotal role of auditory monitoring in children treated with platinum compounds in order to be able to identify hearing loss at an early stage and to provide, jointly with pediatric oncologists, strategies to reduce further progression of cochlear toxicity.

Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling.

BACKGROUND: In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo. METHODS: The effects of curcumin and/or cisplatin treatment have been evaluated in head and neck squamous cell carcinoma as well as in a rat model of cisplatin-induced ototoxicity by using immunofluorescence, western blot, and functional and morphological analysis. RESULTS: This study demonstrates that curcumin attenuates all stages of tumour progression (survival, proliferation) and, by targeting pSTAT3 and Nrf-2 signalling pathways, provides chemosensitisation to cisplatin in vitro and protection from its ototoxic adverse effects in vivo. CONCLUSIONS: These results indicate that curcumin can be used as an efficient adjuvant to cisplatin cancer therapy. This treatment strategy in head and neck cancer could mediate cisplatin chemoresistance by modulating therapeutic targets (STAT3 and Nrf2) and, at the same time, reduce cisplatin-related ototoxic adverse effects.

Role of inflammation in non-allergic rhinitis.

OBJECTIVE: To investigate the role of inflammation in non-allergic rhinitis (NAR) patients in a large series to establish the prevalence of different NAR-subtypes, clinical features and the role of nasal cytology in the diagnostic algorithm. METHODOLOGY: Patients were selected out of 3650 individuals who spontaneously presented at our institution. We consecutively enrolled 519 NAR-patients in an analytical cross-sectional study between November 2007 and June 2013 (level of evidence: 3b). All patients underwent rhinological evaluation including symptoms questionnaire, endoscopy, CT scan, allergy tests and nasal cytology. RESULTS: The inflammatory cell infiltrate affects the severity of symptoms differently, allowing for identification of different phenotypes of NAR. We distinguished two groups: "NAR without inflammation"(NAR-) and "NAR with inflammation"(NAR+), in addition to different NAR-subtypes with inflammation. A significant difference was observed in terms of clinical symptoms and association with comorbidities (previously diagnosed asthma and aspirin intolerance) between NAR­, NAR+ and between different NAR+ subtypes. CONCLUSION: Our data suggest that NAR- and NAR with neutrophils behave similarly, showing lower symptom score values and a lower risk of association with comorbidities compared to NAR with eosinophils and mast cells (singularly or mixed). In our belief it is very important to establish the presence and type of inflammation in non-allergic rhinitis patients and nasal cytology is a very useful test in correct differential diagnosis.

Congenital toxoplasmosis and audiological outcome: from a case series to a suggestion of patient-based schedule.

Introduction: Sensorineural hearing loss (SNHL) has been suggested to be possibly related to congenital toxoplasmosis (CT), although its prevalence varies from 0% to 26%. This variance appears to be dependent especially on early timing of treatment. However, the available data are based on outdated studies conducted on small groups of patients that lack homogeneity. Therefore, to establish evidence-based guidelines for audiologic monitoring in CT, we conducted a comprehensive evaluation of a large case series over a long period of time. Patients and methods: This is a single-center, retrospective cohort that enrolled all infants and children who were exposed in utero to Toxoplasma gondii and/or congenitally infected between September 1980 and December 2022. They underwent standard serial audiological evaluations to detect possible SNHL at an early stage. The first evaluation was performed during the initial assessment to define the onset of congenital toxoplasmosis, with another evaluation conducted at least at 12 months of life. Results: We collected data from 1,712 patients, and 183 (10.7%) were diagnosed with CT. Among these cases, 78 children (42.6%) presented with symptomatic CT at the onset, exhibiting ocular findings (21.1%), clinical cerebral manifestations (6.1%), and/or abnormal findings on neuroimaging (35.5%). Therapy was administrated at the onset in 164 patients (89.6%) with 115 of them starting treatment prior to 2.5 months of age (0-388, median 32.00 ± 92.352 days of life). Only one patient presented with SNHL at the onset, but this was apparently unrelated to CT. The median number of audiological assessments was 2.2 ± 1.543 (2-10). No patients developed any grade of delayed hearing loss, both in treated and untreated groups. The median age at last audiological evaluation was 2.3 ± 2.18 years (1-8), although the median follow-up period was 12.4 years (±6.3), ranging from 1 to 27 years. Conclusions: Based on these data, it appears that SNHL may be less frequent in CT than previously assumed. We recommend conducting an audiological assessment at the onset (within the first 2.5 months of life) to comprehensively define the type of CT onset, and then conducting another evaluation within 9 months of life.

ENT function in a 14-days guinness scuba dive.

Scuba diving is known to affect the rhino-pharyngo-tubaric district (RPT unit). The aim of the study was to document function modifications of the RPT unit in 6 Italian divers (3 men and 3 women) who lived for 14 days consecutively at a depth of 8-10 m, breathing air (21% oxygen) at a pressure ranging between 1.8 and 2 ATA. RPT and inner ear assessment were carried out before the dive (TIME 0) and 24 h (TIME 1) after resurfacing, in order to investigate diving-related RPT and inner ear alterations. Physical examination after resurfacing revealed: fungal external otitis, otoscopic findings consistent with middle ear barotraumas and rhinosinusitis. Rhino-manometry showed a remarkable increase in inspiratory nasal flow and a substantial decrease in nasal resistance. No epithelial cell disruption was retrieved comparing pre and post resurfacing samples. Post-diving tubaric dysfunction was found. Pure tone audiometry revealed a bilateral 40 dB HL hearing loss at 4 kHz in 1 diver. Relevant PTA functions did not seem to be affected by the experiment, no remarkable changes were found at the Sensory Organisation Test and at the Motor Control Test. The 14-day underwater period had a positive effect on nasal flows and resistances.

Predictive role of audiological and clinical features for functional results after stapedotomy.

OBJECTIVE: To analyze and compare the preoperative factors that potentially influence the outcome of stapedotomy in our study group. MATERIALS AND METHODS: 161 cases were enrolled. Clinical variables considered to influence functional results - air conduction (AC) and bone conduction (BC) pure-tone average (PTA), air-bone gaps (ABG), sensorineural hearing loss (SNHL), ABG gain and DeltaSNHL - were gender, age, case type (unilateral vs. bilateral), ear side (right vs. left), pregnancy, vascular disease and family history of otosclerosis. The audiometric variables were preoperative AC- and BC-PTA, SNHL and ABG. RESULTS: Univariate logistic regression analysis showed that the probability of obtaining a > or =10 dB gain is significantly affected by the following factors: age <50 years, AC-PTA > or =50 dB and preoperative ABG > or =30 dB. All the other factors included into the registration (gender, familiarity, side, bilateral vs. unilateral, pregnancy, vascular diseases and preoperative BC-PTA) were not found to significantly affect postoperative gain (p > 0.05). Nevertheless, multivariate logistic regression analysis maintained a statistically significant correlation only between gain > or =10 dB and both preoperative ABG > or =30 dB and age <50 years. CONCLUSIONS: The accurate knowledge of predictive factors is a valuable tool that permits the surgeon to plan surgery with a better case selection as well as assisting in counseling the patient with regard to the likelihood of success of the procedure.

Giant deep lobe parotid gland pleomorphic adenoma involving the parapharyngeal space. Report of three cases and review of the diagnostic and therapeutic approaches.

Aim of the present report is to discuss and underline the diagnostic algorithm and the surgical approach to giant parotid pleomorphic adenomas arising in the deep lobe and growing in the parapharyngeal space. Three cases are described and a review is made of the international literature concerning giant deep lobe parotid gland pleomorphic adenoma. Diagnosis was based on imaging, computed tomography scan and magnetic resonance imaging and upon cytology, by means of fine needle aspiration biopsy. The surgical approach varied according to the location of the tumour. All patients were discharged without complications and no cases of permanent facial nerve palsy were observed. An exhaustive pre-operative diagnostic algorithm is required before approaching this lesion. Fine needle aspiration biopsy is, in our opinion, mandatory to avoid histological surprises. The surgical approach should provide excellent visibility with wide surgical exposure to secure local neurovascular structures.

Acquired sensorineural hearing loss in children: current research and therapeutic perspectives.

The knowledge of mechanisms responsible for acquired sensorineural hearing loss in children, such as viral and bacterial infections, noise exposure, aminoglycoside and cisplatin ototoxicity, is increasing and progressively changing the clinical management of affected patients. Viral infections are by far the most relevant cause of acquired hearing loss, followed by aminoglycoside and platinum derivative ototoxicity; moreover, cochlear damage induced by noise overexposure, mainly in adolescents, is an emerging topic. Pharmacological approaches are still challenging to develop a truly effective cochlear protection; however, the use of steroids, antioxidants, antiviral drugs and other small molecules is encouraging for clinical practice. Most of evidence on the effectiveness of antioxidants is still limited to experimental models, while the use of corticosteroids and antiviral drugs has a wide correspondence in literature but with controversial safety. Future therapeutic perspectives include innovative strategies to transport drugs into the cochlea, such as molecules incorporated in nanoparticles that can be delivered to a specific target. Innovative approaches also include the gene therapy designed to compensate for abnormal genes or to make proteins by introducing genetic material into cells; finally, regenerative medicine (including stem cell approaches) may play a central role in the upcoming years in hearing preservation and restoration even if its role in the inner ear is still debated.

Vascular endothelial growth factor (VEGF) expression in noise-induced hearing loss.

Noise-induced hearing loss has been associated with alterations in cochlear blood flow. Our study analyzed the expression of Vascular Endothelial Growth Factor (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic agent, with multiple functions on vascular biology, ranging from vascular permeability to endothelial cell migration, proliferation, differentiation, and survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 min. Auditory function was evaluated by electrocochleographic recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes were studied by immunohistochemistry and scanning electron microscopy. The expression of VEGF and its receptors was examined by immunohistochemistry and western blotting analysis. The hearing threshold shift reached a level of 60 dB SPL on day 1 after trauma and underwent a partial recovery over time, reaching a value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the area located 14-16 mm from the apex. Increased cochlear VEGF expression was observed in noise-exposed animals, in particular at the level of stria vascularis, spiral ligament, and spiral ganglion cells. No changes were observed in the expression of VEGF-receptors. Our data suggest a role for VEGF in the regulation of the vascular network in the inner ear after acoustic trauma and during auditory recovery, with potentially important clinical and therapeutic implications.

Early definition of type, degree and audiogram shape in childhood hearing impairment.

In the context of permanent childhood hearing loss, early audiological diagnosis is a prerequisite for activation of an adequate rehabilitation program to prevent or limit the known effects that auditory deprivation determines on language development and cognitive skills in neonates. Audiological diagnosis consists schematically of three phases: identification of subjects at risk, definition of hearing loss and/or children features, verification of appropriateness of diagnosis itself and a rehabilitation programme. Strategies and methods of audiological diagnosis are well defined and include an integration of data coming from objective methods with clinical and behavioural data. Although the substantial effectiveness of procedures and a general consensus on their use and interpretation have been defined, there are several critical issues concerning the achievement of this objective, which will be discussed in this paper.

A review of new insights on the association between hearing loss and cognitive decline in ageing.

Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research.

Styrene enhances the noise induced oxidative stress in the cochlea and affects differently mechanosensory and supporting cells.

Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens. The mechanism of damage was studied by analyzing superoxide anion and lipid peroxidation expression and by computational analyses of immunofluorescence data to evaluate and compare the oxidative stress pattern in outer hair cells versus the supporting epithelial cells of the organ of Corti. The oxidative stress hypothesis was further analyzed by evaluating the protective effect of a Coenzyme Q10 analogue, the water soluble Qter, molecule known to have protective antioxidant properties against noise induced hearing loss and by the analysis of the expression of the endogenous defense enzymes. This study provides evidence of a reciprocal noise-styrene synergism based on a redox imbalance mechanism affecting, although with a different intensity of damage, the outer hair cell (OHC) sensory epithelium. Moreover, these two damaging agents address preferentially different cochlear targets: noise mainly the sensory epithelium, styrene the supporting epithelial cells. Namely, the increase pattern of lipid peroxidation in the organ of Corti matched the cell damage distribution, involving predominantly OHC layer in noise exposed cochleae and both OHC and Deiters' cell layers in the styrene or combined exposed cochleae. The antioxidant treatment reduced the lipid peroxidation increase, potentiated the endogenous antioxidant defense system at OHC level in both exposures but it failed to ameliorate the oxidative imbalance and cell death of Deiters' cells in the styrene and combined exposures. Current antioxidant therapeutic approaches to preventing sensory loss focus on hair cells alone. It remains to be seen whether targeting supporting cells, in addition to hair cells, might be an effective approach to protecting exposed subjects.

The redox protein p66(shc) mediates cochlear vascular dysfunction and transient noise-induced hearing loss.

p66(shc), a member of the ShcA protein family, is essential for cellular response to oxidative stress, and elicits the formation of mitochondrial Reactive Oxygen Species (ROS), thus promoting vasomotor dysfunction and inflammation. Accordingly, mice lacking the p66 isoform display increased resistance to oxidative tissue damage and to cardiovascular disorders. Oxidative stress also contributes to noise-induced hearing loss (NIHL); we found that p66(shc) expression and serine phosphorylation were induced following noise exposure in the rat cochlea, together with markers of oxidative stress, inflammation and ischemia as indicated by the levels of the hypoxic inducible factor (HIF) and the vascular endothelial growth factor (VEGF) in the highly vascularised cochlear lateral region and spiral ganglion. Importantly, p66(shc) knock-out (p66 KO) 126 SvEv adult mice were less vulnerable to acoustic trauma with respect to wild type controls, as shown by preserved auditory function and by remarkably lower levels of oxidative stress and ischemia markers. Of note, decline of auditory function observed in 12 month old WT controls was markedly attenuated in p66KO mice consistent with delayed inner ear senescence. Collectively, we have identified a pivotal role for p66(shc) -induced vascular dysfunction in a common pathogenic cascade shared by noise-induced and age-related hearing loss.

Rosmarinic acid up-regulates the noise-activated Nrf2/HO-1 pathway and protects against noise-induced injury in rat cochlea.

Noise-induced hearing loss depends on progressive increase of reactive oxygen species and lipoperoxidative damage in conjunction with the imbalance of antioxidant defenses. The redox-sensitive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a critical role in the regulation of cellular defenses against oxidative stress, including heme oxygenase-1 (HO-1) activation. In this work we describe a link between cochlear oxidative stress damage, induced by noise exposure, and the activation of the Nrf2/HO-1 pathway. In our model, noise induces superoxide production and overexpression of the lipid peroxidation marker 4-hydroxy-nonenals (4-HNE). To face the oxidative stress, the endogenous defense system is activated as well, as shown by the slight activation of superoxide dismutases (SODs). In addition, we observed the activation of the Nrf2/HO-1 pathway after noise exposure. Nrf2 appears to promote the maintenance of cellular homeostasis under stress conditions. However, in this model the endogenous antioxidant system fails to counteract noise-induced cell damage and its activation is not effective enough in preventing cochlear damage. The herb-derived phenol rosmarinic acid (RA) attenuates noise-induced hearing loss, reducing threshold shift, and promotes hair cell survival. In fact, RA enhances the endogenous antioxidant defenses, as shown by decreased superoxide production, reduced expression of 4-HNE, and up-regulation of SODs. Interestingly, RA potentiates the Nrf2/HO-1 signaling pathway, as shown by immunohistochemical and Western blot analyses. Thus, protective effects of RA are associated with the induction/activation of the Nrf2-ARE signaling pathway in addition to RA direct scavenging capability.

Anti-endothelial autoantibodies in patients with sudden hearing loss.

OBJECTIVES/HYPOTHESIS: Sudden hearing loss (HL) can be caused by autoimmune disorders localized to the inner ear or secondary to systemic immune diseases. Studies in autoimmune animal strains showing HL have reported changes in the cochlear stria vascularis. The authors investigated the presence of antiendothelial cell antibodies (AECA) to see if immune-mediated vasculitis may play a role in human sudden HL. STUDY DESIGN: A prospective study in patients with sudden HL. METHODS: Fifteen consecutive patients (mean age, 32 y) affected by sudden HL and 14 normal subjects were included. Patients with familial deafness and metabolic diseases were excluded. Extensive audiovestibular, imaging, microbiological, immunological, and routine examinations were performed. AECA were detected on rat kidney tissue sections on the sera collected at -20 degrees C. RESULTS: AECA were positive in 8 of 15 patients (53%) (2 of 5 men and 6 of 10 women), thus differing significantly from the normal control population, in which only 2 of 14 tested AECA positive (P = .023). CONCLUSIONS: In patients with sudden HL, immune-mediated vascular damage can have a pathogenetic role and AECA might represent a serological marker of vasculitis.

Transient evoked otoacoustic emissions (TEOAEs) in new-borns: normative data.

OBJECTIVE: Early diagnosis and rehabilitation of congenital hearing loss are mandatory in order to achieve a satisfactory linguistic and cognitive development. A universal hearing screening in order to identify congenital hearing losses before 3 months of age is required. METHODS: TEOAEs are an easy to perform, short lasting, not invasive and low-cost test with a high sensitivity. 320 at term new-borns (640 ears) without any risk factor for hearing loss underwent TEOAEs. The new-borns were screened 3 days after birth. Those who failed the first test were retested when possible before the discharge from the hospital. ABR was performed 3 months later in cases who failed TEOAE. RESULTS: The median TEOAE sampling time was 98 s, the median test duration was 14 min. The mean stimulus amplitude was 80 dB peSPL in the left ear and 81 dB peSPL in the right ear, noise levels within the external meatus during sampling were 44 dB SPL on the right ear and 43 dB SPL on the left one, noise contained within the response (A-B difference) was 8.65 dB SPL in the left ear and 8.74 dB SPL in the right ear, mean TEOAEs amplitudes were 21.49 dB SPL and 21.78 dB SPL in the right and left ear respectively, the mean lower and upper limit of the spectrum being 678 and 5720 Hz. According to these criteria 494/640 ears (77.2%) passed the test at the first recording, while TEOAEs resulted to be absent in 146/640 ears (22.8%). A retest was performed successfully before the discharge from the Hospital in 30/640 ears (4.7%). An ABR recording within the third month of life was scheduled as out-patient in the 58 new-borns (116 ears, 18.2%) who failed the test. 18 of them (36 ears, 5.6%) did not complete the program, 19 new-borns (38 ears, 11.8%) showed a normal ABR, while two new-borns (four ears, 0.6%) failed ABR after 3 months. A second ABR performed after 6 months was normal. CONCLUSIONS: TEOAEs recording seems at now the test of choice for a universal hearing screening. However, a greater standardization of criteria both in performing the test and in evaluating the results is needed.

Protective effects of alpha-tocopherol and tiopronin against cisplatin-induced ototoxicity.

OBJECTIVE: To investigate the possible protective effects of alpha-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as alpha-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage. MATERIAL AND METHODS: Hartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+alpha-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+alpha-tocopherol acetate+tiopronin, (V) alpha-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. RESULTS: Cisplatin induced progressive high-frequency hearing loss of 40-50 dB SPL. Alpha-tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with alpha-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both alpha-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of alpha-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed. CONCLUSION: This study supports the hypothesis that alpha-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss.

The role of antioxidants in protection from ototoxic drugs.

A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus α-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20°. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by α-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. In conclusion, antioxidants such as α-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.

Can chronic nasal obstruction cause dysfunction of the paratubal muscles and otitis media? An experimental study in developing Wistar rats.

OBJECTIVE: To quantitatively analyze modifications of the paratubal muscles in developing Wistar rats following nasal obstruction. MATERIAL AND METHODS: Twenty-four Wistar rats were used. Twelve were examined at 6, 8 and 12 weeks after birth and were considered normal controls. The nostrils of the remaining 12 rats were bilaterally obstructed by means of a synthetic resin 28 days after birth. The animals were sacrificed at either 2, 4 or 8 weeks after nostril occlusion. Serial sections were made in the dorsoventral plane and stained with hematoxylin-eosin. Four 5 x 5 microm2 areas, selected within the paratubal muscles, were histologically analyzed and the number of muscular fibers was counted manually. RESULTS: The number of tensor veli palatini muscle fibers progressively decreased in the obstructed rats compared with age-matched normal controls and in those that had been obstructed for 4 and 8 weeks these reductions were statistically significant. CONCLUSION: The correct development of the paratubal muscles seems to be linked to physiological nasal breathing and is negatively affected by oral breathing.

An unusual complication of cochlear implant: benign paroxysmal positional vertigo.

Three days after the initial fitting of the cochlear device a 40-year-old woman complained of severe rotational vertigo following head movements associated with neurovegetative symptoms. Otoneurological evaluation revealed a horizontal paroxysmal positional nystagmus beating towards the lowermost ear, induced by rolling the patient's head from supine both to the right or to the left lateral position suggesting the diagnosis of benign paroxysmal positional vertigo of the left horizontal semicircular canal. The nystagmus characteristics were the same whether the cochlear device was switched on or off. The hypothesis of an otolith dislodging due to the electrical stimulation during the initial fitting is discussed.