N-Acetyl-L-cysteine Affects Ototoxicity Evoked by Amikacin and Furosemide Either Alone or in Combination in a Mouse Model of Hearing Threshold Decrease.

Drug-induced ototoxicity resulting from therapy with aminoglycoside antibiotics and loop diuretics is one of the main well-known causes of hearing loss in patients. Unfortunately, no specific protection and prevention from hearing loss are recommended for these patients. This study aimed at evaluating the ototoxic effects produced by mixtures of amikacin (AMI, an aminoglycoside antibiotic) and furosemide (FUR, a loop diuretic) in the mouse model as the hearing threshold decreased by 20% and 50% using auditory brainstem responses (ABRs). Ototoxicity was produced by the combinations of a constant dose of AMI (500 mg/kg; i.p.) on FUR-induced hearing threshold decreases, and a fixed dose of FUR (30 mg/kg; i.p.) on AMI-induced hearing threshold decreases, which were determined in two sets of experiments. Additionally, the effects of N-acetyl-L-cysteine (NAC; 500 mg/kg; i.p.) on the hearing threshold decrease of 20% and 50% were determined by means of an isobolographic transformation of interactions to detect the otoprotective action of NAC in mice. The results indicate that the influence of a constant dose of AMI on FUR-induced hearing threshold decreases was more ototoxic in experimental mice than a fixed dose of FUR on AMI-induced ototoxicity. Moreover, NAC reversed the AMI-induced, but not FUR-induced, hearing threshold decreases in this mouse model of hearing loss. NAC could be considered an otoprotectant in the prevention of hearing loss in patients receiving AMI alone and in combination with FUR.

Vitamin C alleviates ototoxic effect caused by coadministration of amikacin and furosemide.

BACKGROUND: Drug-induced ototoxicity is still a main clinical problem in otolaryngology. It is widely known that aminoglycoside antibiotics combined with loop diuretics significantly contribute to permanent ototoxicity. The aim of this study was to find out whether ascorbic acid (vitamin C) is able to reverse or alleviate ototoxicity evoked by systemic (ip) administration of combination of amikacin and furosemide in experimental male albino Swiss mice. METHODS: Ototoxic combination of amikacin and furosemide was isobolographically evaluated based on the hearing threshold decreasing doses by 20% and 50% (TDD20 and TDD50), respectively. Linear regression analysis was used to determine the TDD20 and TDD50 values for amikacin, furosemide, vitamin C administered alone and in combination (at the fixed-ratio of 1:1). RESULTS: Vitamin C (in a dose of 500 mg/kg, ip) alleviated the impairment in hearing threshold evoked by combined ip administration of amikacin and furosemide (at the fixed-ratio of 1:1) in mice by reducing TDD50 values from 49.82 to 21.56 (p < 0.01). In contrast, vitamin C (500 mg/kg, ip) had no significant effect on TDD20 values for the combination of amikacin and furosemide at the fixed-ratio of 1:1. CONCLUSIONS: Vitamin C administered together with ototoxic drug combination of amikacin and furosemide reduced ototoxicity evoked by this two-drug combination in the experimental mice.

Patient-Related Benefits for Adults with Cochlear Implantation: A Multicultural Longitudinal Observational Study.

OBJECTIVES: To assess subjectively perceived, real-world benefits longitudinally for unilateral cochlear implant (CI) recipients in a multinational population treated routinely. To identify possible predictors of self-reported benefits. DESIGN: This was a prospective, multicenter, repeated-measures study. Self-assessment of performance at preimplantation and postimplantation at 1, 2, and 3 years using standardized, validated, local language versions of the Speech, Spatial, and Qualities of Hearing Scale (SSQ), and the Health Utilities Index Mark 3 (HUI3) was performed. Outcomes were analyzed using a longitudinal mixed-effects model incorporating country effect. Patient demographics were explored for associations with change over time. SUBJECTS: Two hundred ninety-one routinely treated, unilateral CI recipients, aged 13-81 years, from 9 clinics across 4 countries. RESULTS: Highly significant improvements were observed for all outcome measures (p < 0.0001). Postimplantation, mean outcome scores remained stable beyond 1 year, with notable individual variability. A significant association for one or more outcomes with preimplantation contralateral hearing aid use, telephone use, age at implantation, implantation side, preimplantation comorbidities, dizziness, and tinnitus was observed (p < 0.004). CONCLUSIONS: Longitudinal benefits of CI treatment can be measured using clinically standardized self-assessment tools to provide a holistic view of patient-related benefits in routine clinical practice for aggregated data from multinational populations. Self-reported outcomes can provide medical-based evidence regarding CI treatment to support decision-making by health service providers.

Osteopetrosis of the Temporal Bone Treated with Cochlear Implant.

Osteopetrosis is a heterogeneous group of skeletal disorders. It is a rare genetic disease caused by osteoclast dysfunction, leading to invalid bone desorption and remodeling and an increase in skeletal mass and density. We present the case of a 52-year-old female with osteopetrosis of the temporal bone. She reported loss of hearing in her left ear 14 years ago because of a head trauma. Four months ago, she was conservatively treated because of sudden sensorineural hearing loss in her right ear with no improvement. Her pure tone average audiogram was bilaterally 90 dB with 10% speech recognition. The patient was implanted with a cochlear implant. Except for the extremely thick and dense cortical bone of the mastoid, surgery was uneventful. Speech recognition 6 months after the surgery showed 75%. The results were stable for 3 years follow-up. Patients with profound hearing loss caused by osteopetrosis may benefit from cochlear implantation.

Quality of life and hearing after cochlear implant placement in patients over 60 years of age.

OBJECTIVE: Multicenter evaluation of the quality of life and quality of hearing after Nucleus® cochlear implant placement in patients over 60 years of age. REFERENCE AND METHOD: Evaluation was performed in patients receiving cochlear implants after the age of 60 years as a part of the Cochlear-Implanted Recipient Observational Study (Cochlear-IROS). This study is a prospective, international and long-term assessment which enables observation of recipients for up to three years after implantation. Data regarding subjective evaluation of the quality of life and quality of hearing were gathered before the first switch-on of the sound processor and one year afterwards. Standardized questionnaires were used in this evaluation, including Health Utility Index (HUI mk. III) and Speech, Spatial and Qualities of Hearing (SSQ) Scale. Data were also gathered regarding the aetiology of hearing loss, hearing aid usage, tinnitus and vertigo, as well as on the telephone usage and the professional status of recipients. RESULTS: Included in the evaluation, were 20 subjects who were over 60 years old at the moment of the cochlear implant surgery. The study group consisted of 12 men and 8 female patients. The average age of CI recipients at the moment of implantation was 67.8 years (min. 60, max. 80 years). The SSQ questionnaire outcomes regarding self-assessment in the field of ability to hear in everyday situations one year after the surgery indicate that speech understanding increased by 180%, spatial hearing increased by 135 % and quality of hearing increased by 98%. Overall quality of life before the first sound processor switch-on as assessed using the HUI questionnaire was at the level of 0.38 (on 0-1 scale, where 0 equals death, and 1 equals full health). One year after the implantation, this assessment increased by 33% (up to 0.5 on the scale). CONCLUSION: The effectiveness of the cochlear implantation in patients with severe hearing loss after 60 years of age with respect to the quality of life and hearing was confirmed. Statistically significant improvement was demonstrated in the self-assessment of patients in relation to the speech understanding, spatial hearing and quality of hearing, as well as quality of life.

The influence of incudostapedial joint separation on the middle ear transfer function.

OBJECTIVES: One of the risks in middle ear surgery is high frequency hearing loss. It is believed that manipulations on the middle ear ossicles with the instruments may cause overstimulation of the inner ear and damage of the hear cells. Controversy arises whether temporary separation of the ossicles has any impact on middle ear transfer function and hearing threshold after surgery. The aim of the study is to evaluate the influence of incudostapedial joint (ISJ) separation on middle ear function in an experimental model. METHODS: With the use of single point laser Doppler vibrometer (LDV) stapes velocity in the intact chain and after ISJ separation was measured in 5 fresh human cadaver temporal bones. RESULTS: In all cases there was a decrease in stapes velocity after ISJ separation. Mead stapes velocity was reduced for 1 dB in 800 Hz to 9 dB in frequencies above 1,000 Hz. The decrease of velocity was greater in higher frequencies. CONCLUSION: Separation of the ISJ does not reduce significantly the middle ear function.

[Epidemiological and demographic analysis of indications for Baha® surgery in Poland--multicenter study]. / Analiza epidemiologiczna i demograficzna wskazan do implantacji systemu Baha® w Polsce--badanie wieloosrodkowe.

AIM OF THE STUDY: To collect and analyze epidemiological and demographical data of patients qualified for and implanted with the Baha® system in Poland. MATERIAL AND METHOD: 17 out of 28 otolaryngology departments performing Baha® implantation in Poland participated in the study. Up to date there were 286 patients registered in database. Data were obtained from the preoperative questionnaires including information such as age and gender, indications for the implantation, previous hearing aid use as well as data regarding the surgical technique. RESULTS: The most frequent indication for the Baha® system was bilateral mixed hearing loss (51%), followed by SSD (18%), bilateral conductive hearing loss (17%), unilateral mixed (8%) and conductive (6%) hearing loss. In 11% of subjects hearing impairment was congenital versus 89% cases of acquired. The mean age was 44 years with the slight prevalence of women (52%). 63% of patients did not have previous experience with hearing aids. The most frequent surgical technique was classic dermatome single stage procedure performed under general anesthesia (65%). CONCLUSIONS: Data gather in this multicentre research serve as a valuable source of information on qualifications for the Baha®, shows demographic spectrum of adult recipients in Poland. It also presents the preferences of surgical procedures. Outcomes of the study may constitute a reference for each centre participating in this research as well as for new centers starting the Baha® procedure.

Vibrations in the human middle ear.

BACKGROUND: Middle ear surgery techniques can improve hearing destroyed by disease, but results of treatment are difficult to predict. Therefore, researchers use a Laser Doppler Vibrometer to measure vibrations of human middle ear ossicles. MATERIAL/METHODS: Measurements of ossicular chain vibrations are performed on fresh human temporal bone specimens using Laser Doppler Vibrometer. Vibrations of stapes are recorded in 3 cases: 1) for intact ossicular chain, 2) when incus long process is removed, and 3) after long process reconstruction with bone cement. A typical analysis of transfer function is completed by other methods applied in dynamics. RESULTS: Measurements and analysis of stapes vibrations in case of intact and damaged ossicular chain show regular and irregular behavior which can be recognize with the help of phase portraits, recurrence plots, correlation dimension, and Hurst and Lyapunov exponents. The long process reconstruction with bone cement gives good results in improving hearing. CONCLUSIONS: Recurrence plots, and Lyapunov and Hurst exponents used in the study complete information obtained from transfer function and can be employed to enrich the classical approach to ossicular chain vibrations.

[Impedance changes in cochlear implant users]. / Zmiany impedancji elektrod u uzytkowników implantów slimakowych.

UNLABELLED: Impedance measurements are routinely performed during the cochlear implantation. These measurements make possible to check, whether all electrodes work correctly and are useful in the monitoring of implant's functioning during rehabilitation. The analysis of the impedance's changes makes possible to estimate, what processes happen in tissues and liquids of the inner ear around the electrode. THE AIM OF THE STUDY: The aim of the study was to estimate changes of the electrodes' impedance in cochlear implants users. MATERIAL AND METHODS: Measurements of the impedance was performed on every electrode introduced into the cochlea. Impedance measurements were investigated in 42 adult persons operated at the Department of Otolaryngology Medical University of Lublin. The impedance of electrodes in cochlear implants users was measured during operation, during the activation of the speech processor and during following settings of the speech processor. RESULTS: During activation of the speech processor we observed elevated values of the impedance, higher then during intra-operating-measurement. On the second fitting impedances decrease and then were stable at this level during one year follow-up. CONCLUSIONS: Increasing values of impedance during first fitting of the speech processor support the hypothesis that a layer of fibrous tissue forms around the electrode because of the inflammatory changes or due to exudation of protein. Such changes could be observed after cochlear implantation. Impedance values decrease after first fitting and remain stable. This may suggest that electrical stimulation prevents from adverse changes in the cochlea.

[Vibrations of the human tympanic membrane measured with Laser Doppler Vibrometer]. / Drgania blony bebenkowej oceniane Dopplerowskim wibrometrem laserowym.

The knowledge of the physiology of the normal ear is important to understand the function of the ear. It is especially crucial in the reconstruction of the destroyed ear to apply the knowledge of the normal ear. We present results of tympanic membrane vibrations measurements using Laser Doppler Vibrometer in human temporal bone specimens. Six temporal bone specimens were harvested within 48 hours of death and stored cooled until preparation. The preparation included mastoidectomy with posterior tympanotomy and partial resection of the facial nerve to visualize the stapes with its footplate. We measured velocity and displacement of each quadrant of the tympanic membrane and the umbo with the laser Vibrometer equipped with velocity and displacement decoders. The sensor head OFV-534 produced and read the reflected laser beam directed at a measured point with a dedicated micromanipulator attached to an operating microscope. A retro-reflective tape was used to enhance the reflection of the laser beam. Vibrations were induced by a acoustic stimulation at the tympanic membrane. The results of the measurements were corrected to a sound pressure in the external ear canal. Laser Doppler Vibrometer system allows an undisturbed measurement of vibrations in the middle ear. Posterior quadrants of the tympanic membrane have greater velocity and displacement than anterior quadrants in lower frequencies up to 2 kHz.

[Recurrence in operated patients with laryngeal squamous cell carcinoma]. / Wznowy u pacjentów leczonych operacyjnie z powodu raka krtani.

PURPOSE: The aim of the present study was to investigate the recurrence prevalence in patients with laryngeal squamous cell carcinoma (LSCC) underwent surgery as primary treatment. MATERIAL: The assessed group consisted of 148 patients with operable LSCC underwent surgery as primary treatment between 1999-2002. Surgery was performed in all cases. Total laryngectomy was performed in 107 (72.3%) patients and laser endoscopic tumor resection was performed in 41 (27.7%) patients. RESULTS: Local recurrence occurred in 18 (12.2%) patients, nodal recurrence in 12 (8.1%) and both and/or remote metastases in 6 (4%) patients. Altogether, recurrence was present in 36 (24.3%) patients and 111 (75.7%) patients had no symptoms of recurrence. Recurrence prevalence in 3-year follow-up--prevalence of recurrence significantly increased with tumor's T feature (p=0.04), N feature (p=0.03), progression of clinical stage (p=0.008) and histological malignancy G stage (p=0.01). Recurrence prevalence in 5-year follow-up--prevalence of recurrence significantly increased with tumor's T feature (p=0.02), N feature (p=0.01), progression of clinical stage (p=0.003) and histological malignancy G stage (p=0.002). Tumors localized in glottic area had less recurrences than those localized in supraglottic area (p=0.05). There were no significant dependence between recurrence type (local or nodal) and tumor's clinicopathological features. Multiple factor analysis with logistic regression model did not revealed simultaneous influence of many variables on recurrence's presence and type. Using multiple factor analysis with Cox's regression model it was proved that recurrence presence (p<0.00001) is a significant independent prognostic factor in the analyzed group of patients with laryngeal carcinoma in 3-year follow-up. CONCLUSIONS: Recurrence prevalence depends on localization, systemic progression stage, clinical progression stage, cervical lymph nodes state and histological malignancy stage of tumor. Patients with local recurrence have statistically significantly worse prognosis than patients with no recurrence. Recurrence presence is significant independent prognostic factor in 3-year follow-up.

The motion of conventional and novel total ossicular replacement prostheses during changes in static pressure.

PURPOSE: To investigate the motion of prostheses used to reconstruct ears with an absent stapes arch. STUDY DESIGN: We have studied the motion of conventional total ossicular replacement prostheses (TORPs) and a novel incus-stapes replica prosthesis (ISRP), which connects the malleus head to the footplate, during changes in middle ear pressure (+400 to -400 dPa) in fresh human temporal bones using digital video clips and photographs. The pressure in the (sealed) external auditory meatus was varied using a manual tympanometer. The displacements of the prostheses in the medial to lateral plane have been measured using the dimensioning tool of Corel Draw. RESULTS: During changes in static pressure, TORPs move more in the lateral to medial plane than ISRPs. The motion of ISRPs is similar to that of the intact ossicular chain. CONCLUSION: The ISRP design is less likely to damage the cochlea during changes in static pressure than a conventional TORP, but the maximum medial displacement of the TORPs studied was less than 0.1 mm.

[Reconstruction of meatal wall with cartilage and perichondrium]. / Rekonstrukcja sciany przewodu sluchowego za pomoca chrzastki i ochrzestnej .

The aim of the study was evaluation of the use of cartilage and perichondrium for reconstruction of meatal wall. In the group of 27 patients transmeatal atticotomy was performed to remove cholesteatoma from epitympanic recess. Auricular or tragal perichondrium with cartilage island were used for reconstruction of meatal wall and tympanic membrane defect. Good closure of the defect was obtained in 24 (89%) patients in 3-6 years follow up. We had one failure and no follow up in 2 patients. Of 7 patients with intact ossicular chain 0-10 dB air-bone gap was obtained in 5 and 11-20 dB gap in 2 patients. Perichondrium and cartilage are very good for reconstruction of meatal wall and drum defect.

Trans-4-aminocrotonic acid (TACA), a potent agonist of GABA(A) and GABA(C) receptors, shows a proconvulsant action in the electroconvulsive threshold test in mice.

In the present study, we evaluated TACA (a potent agonist of GABA(A) and GABA(C) receptors) in the electroconvulsive threshold test in mice. Surprisingly, TACA (at 15 and 25 mg/kg) significantly decreased the threshold. The highest ineffective dose of TACA was estimated as 10 mg/kg. The obtained results indicate that the drug enhancing GABAergic transmission may possess proconvulsant properties in the electroconvulsive test. Such effect was completely opposite to our primary assumption and expectance.

Interaction of the neurosteroid alphaxalone with conventional antiepileptic drugs in different types of experimental seizures.

A number of neurosteroids exert antiseizure and/or neuroprotective properties. The aim of this study was to evaluate the effect of the neurosteroid alphaxalone on the protective action of conventional antiepileptics in four seizure tests. Alphaxalone (up to 5 mg/kg) did not exert a significant action against amygdala-kindled seizures in rats, or against pentetrazole- or aminophylline-induced convulsions in mice. The neuroactive steroid at the dose of 2.5 mg/kg significantly raised the threshold for electroconvulsions in mice. At 2.5 mg/kg, alphaxalone diminished the protective activity of valproate against maximal electroshock and at 2.5-5 mg/kg against pentetrazole-induced seizures in mice. However, alphaxalone (2.5 mg/kg) did not affect the protective activity of carbamazepine, diphenylhydantoin, phenobarbital or clonazepam against maximal electroshock and at 5 mg/kg did not affect that of phenobarbital, clonazepam and ethosuximide against pentetrazole-induced convulsions. Insignificant results were also obtained in the case of co-administration of alphaxalone with phenobarbital, valproate, clonazepam and carbamazepine against aminophylline-evoked seizures in mice. Also, in the kindling model of epilepsy, combinations of the neuroactive steroid (2.5 mg/kg) with valproate, carbamazepine, phenobarbital, diphenylhydantoin or clonazepam at their subprotective doses did not result in pro- or anticonvulsant activity. Valproate (284 mg/kg; the dose used in combination with alphaxalone) produced significant memory deficits in mice. Alphaxalone (2.5 mg/kg), valproate (at its ED(50) value of 226 mg/kg) and the combination of valproate (284 mg/kg) with alphaxalone (2.5 mg/kg) did not affect long-term memory, evaluated in the passive avoidance task with mice. Alphaxalone administered alone or in combination with valproate caused no motor impairment in experimental animals. Finally, alphaxalone (2.5 and 5 mg/kg) significantly increased the free plasma levels of valproate, strongly indicating that the neuroactive steroid-induced reduction of the protective activity of valproate is not related to pharmacokinetic phenomena. Summing up, alphaxalone does not seem to be a promising candidate for adjunctive treatment of epilepsy.