Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in patients with head and neck cancer

Conclusions: Intra-arterial high-dose cisplatin chemoradiation (CRT-IA) with sodium thiosulfate (STS) causes relatively less severe cisplatin ototoxicity than intravenous cisplatin chemoradiation without STS (CRT-IV). The results of this study also suggest that early detection of ototoxicity is possible by testing the hearing loss at ultra-high frequencies. Objectives: To investigate protective effects of STS against cisplatin ototoxicity. Methods: Between 2011 and 2013, 18 patients with head and neck carcinomas were treated with intra-arterial infusions of high-dose cisplatin (range 100–180 mg/body, mean 111 mg/body; range 2–5 courses, mean 3.6 courses) and systemic administration of cisplatin (range 66–185 mg/body, mean 130 mg/body; range 1–3 courses, mean 2.6 courses) and concurrent radiation therapy (range 60–70 Gy, mean 69 Gy). Cisplatin was neutralized by STS in CRT-IA but not in CRT-IV. Results: Intra-arterial infusion in the high-dose cisplatin group caused significant hearing loss at ultra-high frequencies of 10 and 12 kHz (p = 0.028, 0.039, respectively), whereas the group receiving systemic administration of cisplatin had significant hearing loss at high frequencies of 8 and 10 kHz (p = 0.016, 0.027, respectively).     

Cisplatin ototoxicity and otoprotection with sodium salicylate

Cisplatin is a potent antineoplastic drug widely used for the treatment of cancer in both adults and children. One of its most important side effects is ototoxicity, which leads to irreversible bilateral hearing loss for high frequencies (4–8 kHz). Several studies have tried to identify drugs that, when combined with cisplatin, may act as otoprotectors. The mechanism of ototoxicity of cisplatin is known to be related to changes in the antioxidant mechanisms of hair cells, especially the outer hair cells of the cochlea. Our proposal was to assess the action of sodium salicylate, which has a known antioxidant property, as a possible otoprotector of outer hair cells against the action of cisplatin, using distortion product otoacoustic emissions (DPOAEs) and scanning electron microscopy. The study was conducted on albino guinea pigs divided into two groups: group 1 (n = 9, 18 cochleae) receiving a cisplatin dose of 8.0 mg/kg/day by the intraperitoneal (ip) route for 3 days, group 2 (n = 10, 20 cochleae) receiving 100 mg/kg sodium salicylate by the subcutaneous route followed 90 min later by cisplatin, 8.0 mg/kg/day ip for 3 days, and group 3 (n = 3, six cochleae) treated with 100 mg/kg day sodium salicylate for 3 days. In group 1, there was damage with the absence of cilia in all three rows of outer hair cells in the basal turn, followed by turns 2 and 3. In group 2, hair cells were present in all cochlear turns, but exhibited disarrangement of the ciliary structure, especially in row 1, and the DPOAEs were absent after 3 days of treatment. We conclude that drugs such as sodium salicylate, because of their antioxidant properties, may protect, at least partially, the outer hair cells against cisplatin ototoxicity.     

Investigation of the ototoxicity of gadoteridol (ProHance) and gadodiamide (Omniscan) in mice

Conclusion: In the mouse, when a tympanic perforation is present, gadoteridol does not seem to cause ototoxicity. Gadodiamide may cause mild ototoxicity other than toxicity to the outer hair cells of the cochlea.

Objectives: Endolymphatic hydrops have been visualized through intra-tympanic injection of gadolinium-based contrast agents (GBCAs) and three-dimensional fluid-attenuated inversion recovery (3-D FLAIR) magnetic resonance imaging. However, reports on the safety of GBCAs are limited. This study aimed to assess ototoxicity of gadoteridol and gadodiamide.

Method: In a prospective, randomized, controlled trial, myringotomies in the left ear were performed in 20 male C57 BL/6 mice. After testing the baseline auditory brainstem response (ABR) (range?=?8–32?kHz), the test solution (gadoteridol, gadodiamide, saline, or cisplatin) was injected into the left ear. ABR testing was repeated 14 days after test solution application. In morphological experiments, images of post-mortem surface preparations were assessed for cochlear hair cell status.

Results: At 14 days following gadoteridol application, there was no significant change in ABR thresholds at 8, 16, or 32?kHz. Gadodiamide application caused a significant change in the ABR threshold at 8?kHz. Apparent cochlear hair cell loss was not observed in the surface preparation after gadoteridol or gadodiamide application.     

Protective effect of N-acetylcysteine against cisplatin ototoxicity in rats: a study with hearing tests and scanning electron microscopy

IntroductionOtotoxicity is a health problem appearing after powerful treatments in serious health conditions. It is sometimes inevitable when treatment of the serious disease is required. Cisplatin is an antineoplastic agent which was investigated previously to reveal increased nitrogen and reactive oxygen radicals that damages hair cells, resulting in ototoxicity. N-acetylcysteine, previously shown to decrease ototoxicity caused by different agents, is known to be a powerful in vitro antioxidant. Probably N-acetylcysteine, in addition to its antioxidant effect, blocks a cascade where reactive oxygen species result in apoptosis in the cochlea.ObjectivesThe possible preventive effect of N-acetylcysteine in cisplatin ototoxicity was studied with auditory brain stem responses, otoacoustic emissions, and histopathological investigation of the cochlea in a scanning electron microscopy.MethodsThis study was conducted on 21 Wistar Albino rats in four groups. 1 mL/kg/day three times in total intraperitoneal (i.p.) Saline (n = 5), 500 mg/kg/day i.p. three times in total N-acetylcysteine (n = 5), i.p. 15 mg/kg cisplatin alone (single dose) (n = 5) and i.p. 15 mg/kg cisplatin plus 500 mg/kg/day N-acetylcysteine (n = 6) were administered. The rats were anesthetized to study the hearing tests before and after the experiment. The rats were sacrificed to investigate the cochleas by scanning electron microscopy.ResultsAuditory brain stem responses and otoacoustic emissions values were attenuated in the cisplatin group. The group that received N-acetylcysteine in addition to cisplatin had better auditory brain stem responses thresholds and otoacoustic emissions. The samples obtained from the cisplatin group showed surface irregularities, degeneration areas, and total or partial severe stereocilia losses. The changes were milder in the cisplatin + N-acetylcysteine group.ConclusionCisplatin ototoxicity can be detected by auditory brain stem responses and otoacoustic emissions testing in rats. N-acetylcysteine may protect the cochlear cells from histopathological changes. We concluded that N-acetylcysteine given 4 h after cisplatin injection has a potential otoprotective effect against cisplatin ototoxicity. which suggests it could be used in clinical trials.     

Systemic dexamethasone for the prevention of cisplatin-induced ototoxicity

Ototoxicity is a common side effect of cisplatin chemotherapy. This study was undertaken to determine the potential protective effects of a systemic administration of dexamethasone against cisplatin-induced ototoxicity. A prospective controlled trial conducted in an animal model. The setting was Animal care research facilities of the Montreal Children’s Hospital Research Institute. An experimental guinea pig model was used. The animals were divided as follows: group 1 (n = 10): 12 mg/kg intraperitoneal (IP) cisplatin, group 2 (n = 14): 15 mg/kg/day dexamethasone IP for 2 days followed by cisplatin 12 mg/kg IP, group 3 (n = 14): 10 mg/kg/day dexamethasone IP for 2 days, on day 3, they received cisplatin 12 mg/kg IP followed by 20 mg/kg/day dexamethasone for 2 days and group 4 (n = 5): 10 ml of saline IP twice a day for 3 days. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (8, 16, 20 and 25 kHz) for groups 1, 2 and 3. Histological changes in the organ of Corti, the stria vascularis, the spiral ligament and the spiral ganglion neurons as well as scanning electron microscopy for outer hair cells were completed. Immunohistochemistry for tumour necrosis factor-alpha (TNF-α) was performed. ABR threshold shifts were similar in all groups. Histological and scanning electron findings demonstrate that dexamethasone has greater protective effect on the stria vascularis. Systemic dexamethasone administration in a guinea pig model did not provide significant protection against cisplatin-induced ototoxicity. Dexamethasone may be useful in future applications as a complementary treatment.     

Cochlear implantation in recipients with single-sided deafness: Audiological performance

Objective: To examine the auditory benefit of cochlear implants (CI) in patients with single-sided deafness (SSD).

Material and methods: Twenty patients with a normal pure tone audiogram (n?=?8) or moderate hearing loss (n?=?12) in one ear and a CI system MED-EL SONATA/CONCERTO?+?OPUS2 (n?=?12), COCHLEAR CI24RE(ST)?+?CP810 (n?=?7) and Advanced Bionics HiRes90?K?+?Harmony (n?=?1) in the contralateral ear and with at least 6 months of CI experience were tested with respect to directional hearing, speech perception in noise, binaural loudness matching, and binaural pitch matching. Twenty-six normal hearing controls were included for normative reference.

Results: Addition of the CI significantly improves directional hearing (percentage of correct source identifications improved from 14.9 to 15.6%, root mean square error decreased from 125 to 93°) and improves speech perception in noise (speech perception threshold median improved from ?2.3 to ?6.0?dB signal to noise ratio, equivalent to a binaural intelligibility level difference?=?3.7?dB). Alternate binaural loudness balancing showed that matching takes place at levels between 48 and 55?dB HL (group averages). In the pitch matching experiment, the standard deviation of the relative interaural frequency difference at 500, 1000, and 2000?Hz was 24.5, 22.8, and 24.0%, respectively (compared to 11.7, 14.4, and 12.3% in the control group).

Conclusions: In SSD, cochlear implantation considerably improves audiological performance in terms of directional hearing, binaural signal equivalence, and speech perception.     

Protective effects of α-tocopherol and tiopronin against cisplatin-induced ototoxicity

Objective To investigate the possible protective effects of α-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 α-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+α-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+α-tocopherol acetate+tiopronin, (V) α-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. α-Tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with α-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 α-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of α-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed.

Conclusion This study supports the hypothesis that α-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.     

Effect of esterified hyaluronic acid as middle ear packing in tympanoplasty for adhesive otitis media

Objectives: The goal of this study was to evaluate the effects of middle ear packing agents (MEPA) on post-operative hearing improvement and complications after tympanoplasty in patients with adhesive otitis media (OM).

Materials and methods: Patients with adhesive OM who underwent tympanoplasty surgery were enrolled in the study between January 2012 and January 2015. A total of 205 patients who received canal wall-down tympanoplasty with ossicular chain reconstruction were randomized into one of the three groups with different MEPA. Group 1 (n?=?72) received MeroGel as the MEPA, Group 2 (n?=?64) cartilage, and Group 3 (n?=?69) both. Air conduction (AC) and bone conduction (BC) thresholds at 0.5, 1, 2, and 4?kHz were measured, and air-bone gaps (ABG) were analyzed before and after the surgery for each patient.

Results: Mean pre- and post-operative ABG was 30.9?dB and 17.6?dB in Group 1, 31.4?dB and 21.9?dB in Group 2, and 32.2?dB and 19.1?dB in Group 3. The ABG closure was 13.3?±?7.5 in Group 1, 9.5?±?5.9 in Group 2, and 13.1?±?9.3 in Group 3. The improvement of ABG after surgery was statistically significant in all three groups (p?p?Conclusions: Tympanoplasty using esterified hyaluronic acid (i.e. MeroGel) or cartilage as the MEPA resulted in improved hearing for patients with conductive hearing loss due to adhesive OM. Using MeroGel as the MEPA appeared to achieve a better post-operative outcome than using cartilage.     

Assessment of hyperacusis with a newly produced Japanese version of the Khalfa hyperacusis questionnaire

Objectives: The purpose of this study was to determine the validity and reliability of a Japanese version of the Khalfa hyperacusis questionnaire (KHQ) and proposed a threshold KHQ score for classifying hyperacusis.

Methods: In total, 112 patients with hyperacusis (group A) and 103 patients without hyperacusis (group B). The patients in group A were further classified into the following subgroups: subjects with hyperacusis as their chief complaint (n?=?26, group A1) and subjects with hyperacusis accompanied by chief complaints of tinnitus and/or hearing loss (n?=?86, group A2).

Results: The average total questionnaire score for patients in group A was 11.8?±?9.7, which was statistically significantly higher than that of patients in group B, 5.7?±?4.8. Cronbach’s coefficients for internal consistency were high for the total score (0.92). The average total scores for groups A1 and A2 were 18.1?±?11.1 and 9.9?±?8.4, respectively, and the difference between the groups was statistically significant.

Conclusions: We developed a Japanese version of the KHQ. It showed high reliability and validity; suggesting its usefulness in clinical practice. We propose that a total KHQ score of 16 is an appropriate cutoff for classifying hyperacusis     

Comparative outcomes of active and passive hearing devices by transcutaneous bone conduction

Conclusion Bonebridge (BB) and Sophono (SP) devices improved hearing; with the BB implant showing a better performance at medium and high frequencies. Furthermore, the BB, as an active implant, showed higher functional gain and increased time of use, when compared to the SP, a passive system. Objectives This study aims to compare surgical and audiological outcomes of SP and BB devices in order to assess and further differentiate the indication criteria. Methods Fourteen patients with conductive and mixed hearing loss were evaluated pre- and post-operatively (BB or SP) (period 2013–2014). Age, gender, surgical history, cause and type of hearing loss, implant use per day, levels of bone and air conduction, and functional gain were recorded. Data was analysed by Wilcoxon singed-rank and Wilcoxon rank-sum tests. Results Fourteen patients (BB; n?=?10 and SP; n?=?4) with an average age?=?25.42 years (CI95?=?12.41–38.43) were evaluated. The gender relation was equal (1:1), with pre-implantation osseous thresholds of 20.42?dB (CI95?=?11.15–29.69), and pre-implantation aerial thresholds of 70.83?dB (CI95?=?62.52–79.14). The SP wearing time was significantly lower than that of the BB (SP?=?7–10?h/day, BB?=?8–12?h/day; p?=?0.0323). The functional gain did not differ significantly between the two devices (BB?=?40.00?±?13.19?dB, SP?=?34.06?±?15.63?dB; p?=?0.3434), but a significant improvement from pre- to post-implantation was observed (p?p?=?0.0140) and 4?kHz (p?相似文献   

l-N-acetylcysteine protects outer hair cells against TNFα initiated ototoxicity in vitro

Objective: The present study is aimed at determining the efficacy and exploring the mechanisms by which l-N-acetylcysteine (l-NAC) provides protection against tumor necrosis factor-alpha (TNFα)-induced oxidative stress damage and hair cell loss in 3-day-old rat organ of Corti (OC) explants. Previous work has demonstrated a high level of oxidative stress in TNFα-challenged OC explants. TNFα can potentially play a significant role in hair cell loss following an insult to the inner ear. l-NAC has shown to provide effective protection against noise-induced hearing loss in laboratory animals but mechanisms of this otoprotective effect are not well-defined.

Design: Rat OC explants were exposed to either: (1) saline control (N?=?12); (2) TNFα (2?μg/ml, N?=?12); (3) TNFα+l-NAC (5?mM, N?=?12); (4) TNFα+l-NAC (10?mM, N?=?12); or (5) l-NAC (10?mM, N?=?12). Outer hair cell (OHC) density, levels of reactive oxygen species (ROS), lipid peroxidation of cell membranes, gluthathione activity, and mitochondrial viability were assayed.

Results: l-NAC (5 and 10?mM) provided protection for OHCs from ototoxic level of TNFα in OC explants. Groups treated with TNFα+l-NAC (5?mM) showed a highly significant reduction of both ROS (p?p?l-NAC (5?mM) treated explants (p?Conclusions: l-NAC is a promising treatment for protecting auditory HCs from TNFα-induced oxidative stress and subsequent loss via programmed cell death.     

The effectiveness of eugenol against cisplatin-induced ototoxicity

IntroductionOtotoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin.ObjectiveThe aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity.MethodsThe study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations.ResultsCisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection.ConclusionThe study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.     

Kinetic oscillatory stimulation of nasal mucosa in non-allergic rhinitis: comparison of patient self-administration and caregiver administration regarding pain and treatment effect. A randomized clinical trial

Conclusion: Patient self-administration of the Kinetic Oscillatory Stimulation (KOS)-catheter was a fully acceptable alternative to insertion of the catheter by physician with helmet fixation, in patients with non-allergic rhinitis (NAR). The approaches were equivalent regarding pain. The treatment effect in the patient self-administration group was not inferior.

Objectives: To evaluate whether self-administration of a KOS-catheter was different compared to insertion by a physician, assessed with patient reported pain on a visual analogue scale (VAS). Also, to evaluate the difference in nasal stuffiness with the Sino-Nasal Outcome Test (SNOT-22) and Peak Nasal Inspiratory Flow (PNIF).

Methods: Patients with NAR were randomized to group 1, patient insertion of catheter and manual fixation, and group 2, catheter insertion by physician and fixation with a helmet. Patients were treated once, 10?min in each nasal cavity, and followed up 14 days later.

Results: Twenty-nine patients were included (group 1, n?=?14; group 2, n?=?15). There was no statistical significant difference in patient reported pain between groups. There was a decrease in nasal stuffiness after treatment in the total study population (n?=?26, p?=?0.001). In group 1 nasal stuffiness was decreased and in group 2 there was no change (group 1, p?=?0.004; group 2, p?=?0.071). No statistical significant change in PNIF was observed.     

Microdrill stapedotomy for otosclerosis with small and large preoperative air-bone gap: a retrospective comparison of results

Abstract

Background: In otosclerosis mixed hearing loss is the most frequent symptom and arises when the focus involves the stapes footplate. Surgeons usually prefer to wait a minimum air-bone gap of 25 – 35?dB before surgery.

Objectives: To evaluate the outcome of microdrill stapedotomy for otosclerosis in patients with a preoperative air-bone gap (ABG) <25?dB versus patients with a preoperative gap ≥ 25?dB.

Material and methods: For this retrospective study, the outcomes and complications after microdrill stapedotomy were compared between adult patients with a preoperative small ABG (n?=?127, ABG <25?dB) and those with a large ABG (n?=?254, ABG ≥25?dB).

Results: The postoperative ABG was significantly smaller than the preoperative ABG (p?<?.05) in both groups; there were no differences in complications rates (severe sensorineural hearing loss, footplate fracture or early postoperative vertigo) between the two groups.

Conclusions: Our findings show that microdrill stapedotomy is safe and can be performed even in patients with a preoperative small ABG without increasing the risk of sensorineural hearing loss due to inner ear damage.     

WR-2721 (Amifostine) Ameliorates Cisplatin-Induced Hearing Loss But Causes Neurotoxicity In Hamsters: Dose-Dependent Effects

Chemoprotective agents reduce the toxic side effects of chemotherapy agents such as cisplatin. The conventional belief is that the chemoprotective agent WR-2721 (Amifostine), while protecting against most cisplatin-induced side effects, does not protect against cisplatin-induced ototoxicity (i.e., hearing loss). There is no knowledge, however, about the efficacy of high doses of WR-2721 (WR) in possibly protecting against cisplatin-induced ototoxicity. Thus, the dose-dependent effects of WR in possibly ameliorating cisplatin-induced ototoxicity were investigated. Hamsters were given a series of 5 cisplatin injections (3 mg/kg/injection once every other day, i.p.) either alone or in combination with 18, 40, 80, or 400 mg/kg/injection of the rescue agent WR (n = 5 or 10/group). Other groups received either 80 mg/kg/injection WR alone (n = 5) or were untreated (n = 14). Ototoxicity was assessed by auditory brain stem responses (ABR). WR provided dose-dependent rescue from cisplatins ototoxicity with no protection at the low dose of 18 mg/kg, moderate protection at 40 mg/kg, and nearly complete protection at 80 and 400 mg/kg. However, WR doses of 40 mg/kg or higher caused neurotoxicity as evidenced by prolongations in the ABRs interpeak latencies. Thus, high doses of WR provided the beneficial effect of protecting against cisplatin-induced ototoxicity, but had the harmful side effect of neurotoxicity. Previous failures to find chemoprotection from cisplatin-induced ototoxicity were likely due to the use of WR doses that were too small. The clinical implications of the beneficial and harmful effects of high doses of WR are discussed.     

Effects of early intratympanic steroid injection in patients with acoustic trauma caused by gunshot noise

Conclusion: This study evaluated the efficacy of concurrent administration of ITSI and systemic steroids in delayed treatment of NIHL after gunshot noise exposure. The results showed additional hearing benefits with administration of ITSI. Further evaluation is warranted to confirm this efficacy.

Objective: This investigation evaluated the effects of early administration of an intratympanic steroid injection (ITSI) in combination with systemic steroids treatment in patients with acoustic trauma caused by gunshot noise.

Methods: Nineteen patients eligible under the criteria established concerning delayed treatment for noise-induced hearing loss (NIHL) were enrolled in this study. Patients were divided into two groups: those who received prednisolone (PD) only (n?=?8), and those who received PD with ITSI (n?=?11). ITSI treatment was initiated simultaneously alongside systemic PD administration. These patients received ITSI every other day for a total of four treatments. Pure-tone air conduction threshold audiometry, to record the pure-tone average (PTA) at 2, 4, and 8?kHz, was conducted upon each patient’s initial visit, and 1 month after starting treatment, to evaluate the degree of hearing gain (hearing gain (dB)?=?(initial PTA) – (final PTA)).

Results: The initial PTA in PD-only and PD with ITSI groups were 52.75?±?15.50?dB and 50.27?±?12.01?dB, respectively. There were no significant differences in the baseline characteristics of the two groups, which include age and the number of days that treatment was delayed. In the multivariable linear regression analysis, both the initial PTA and the treatment method showed a significant association (R^2?=^?0.41). The unstandardized regression coefficient of the initial PTA was 0.47 (p?=?0.02). Patients with additional ITSI showed significant improvement in the degree of hearing gain compared with the PD-only group (unstandardized regression coefficient =11.48, p?=?0.03)     

Comparison of auditory steady-state response and click-evoked auditory brain response in infants with different types and degrees of hearing loss

Abstract

Background: Auditory steady-state response (ASSR) and click-evoked auditory brain response (c-ABR) have been used for hearing assessment for decades years, the correlation of the two methods and the effects of type and degree of hearing loss (HL) to the correlation in infants younger than 6?months of age are unclear.

Objectives: To compare the correlation of ASSR and c-ABR and then to analyse the effects of type and degree of HL on the correlation in infants younger than 6?months of age.

Material and methods: Retrospective study comparing ASSR thresholds at various frequencies with c-ABR thresholds. 182 ears from 96 infants were assessed and classified according to types and degrees of HL.

Results: The correlation coefficients were: 0.823, 0.864, 0.891, 0.871, 0.908, 0.915 and 0.913 between ASSR thresholds at 0.5, 1, 2, 4, 2–4, 1–2–4, 0.5–1–2–4?kHz and c-ABR thresholds respectively. The correlation coefficients in the group of sensorineural HL (SHL) (r?=?0.763–0.900) were higher than conductive HL (r?=?0.309–0.619) across all frequencies. The coefficients of severe-profound SHL (r?=?0.595–0.790) were higher than mild-moderate SHL (r?=?0.434–0.687) across all frequencies.

Conclusions and significance: ASSR was one valuable cross-check measure by providing frequency specific information in auditory assessment.     

Negative hearing effects of a single course of IV aminoglycoside therapy in cystic fibrosis patients

Abstract

Objective: Identify hearing effects of a single course of intravenous (IV) aminoglycoside antibiotics (AGs) therapy in adult cystic fibrosis (CF) patients. Determine whether the change is large enough to enable a proof-of-concept study of a new drug preventing AG-associated hearing loss.

Design: Retrospective case review of CF patients with sequential audiograms?±?an intervening course of IV AG therapy.

Study sample: 84 patients with no intervening IV AG treatment, 38 patients undergoing a single course of IV AGs.

Results: Using ASHA ototoxicity metrics, 45% of adult CF patients in the Single-IV group met the criteria for ototoxicity compared to 23% of the No-IV patients. Other hearing metrics including the average maximal threshold shift (TS) and average high frequency TS showed highly significant differences between groups. Testing only participants with mild or greater pre-therapy high frequency hearing loss further increased the differences between the two groups by every metric tested.

Conclusion: Adult CF patients exposed to a single course of IV AGs have significantly greater TS than patients without IV AG exposure. Patients with mild to moderate hearing loss prior to AG-IVs are at increased risk of developing ototoxicity from subsequent parenteral AG therapy.     

Distortion product otoacoustic emissions: An objective technique for the screening of hearing loss in children treated with platin derivatives

In order to develop a sensitive audiometric protocol for identifying ototoxicity in children, a retrospective study of 16 children treated with cisplatin and/or carboplatin was performed. Audiometric testing was done by means of pure-tone threshold audiometry (PTA), high-frequency audiometry (HFA), and distortion product otoacoustic emissions (DPOAEs).

Cisplatin caused a sensorineural high-frequency hearing loss in the study group compared to the controls (p?<?0.01). Sixty-six percent of the cisplatin patients had a grade 2 or 3 ototoxicity. However, ototoxicity was not found in the patients treated with carboplatin. An excellent correlation was found between DPOAE levels and results obtained by audiometry (r?=?0.82).

Patients exposed to cisplatin are at significant risk for the development of drug-induced sensorineural hearing loss. Because of the several advantages of DPOAEs (noninvasive, objective, rapid, easy to use, sensitive) this method should be added in the audiological follow-up in infants and toddlers.     

Effect of sodium thiosulfate on cisplatin-induced ototoxicity

The effect of sodium thiosulfate (STS) on cisplatin (CDDP)-induced ototoxicity in the guinea pigs was studied by surface preparation, outer hair cell counting, electrocochleographic, light and electron microscopic techniques. Seventy-eight guinea pigs were divided into five groups. Group I received intraperitoneal CDDP (2.5 mg/kg/day) alone: group V as control; the other three groups were given the same doses of CDDP as group I with intramuscular STS (600 mg/kg/day) administered 30 min before (group II) or 30 min (group III) and 6 hr (group IV) after CDDP. The results showed that CDDP produced serious ototoxicity both functionally and histologically when given without STS. The first row of outer hair cells (OHC) in basal turn was first damaged. The inner hair cells (IHC) were more resistant than the OHC. The pattern of destruction is similar to that produced by aminoglycosides. Concomitant use of STS, however, significantly reduced CDDP-induced ototoxicity. Transmission electron microscopy showed the degeneration of mitochondria to be the major and earliest sign of OHC damage induced by CDDP. Our present study documented the good protective efficacy of STS against CDDP cochleotoxicity. STS did not reverse the pathological changes already caused by CDDP. This study provided some experimental evidence for the prevention of CDDP ototoxicity in clinical cancer chemotherapy.