Gunay Kirkim

The frequency of auditory neuropathy detected by universal newborn hearing screening program

OBJECTIVE Auditory neuropathy/auditory dyssynchrony (AN/AD) has become a well-accepted clinical entity. The combined use of oto-acoustic emissions (OAEs) and auditory brainstem response (ABR) testing in the universal newborn hearing screening (UNHS) has led to the easy recognition of this disorder. Although, we are now able to diagnose AN/AD reliably, little is known about its epidemiology, etiology, and especially the frequency of its occurrence. The primary goal of this study was to determine the frequency of AN/AD in the Western Anatolian region of Turkey. The secondary goal was to compare the detection rate of AN/AD before and after the implementation of the UNHS in the audiology department of Dokuz Eylul University Hospital. METHOD Between 2005 and 2007, among the 23,786 newborns who were screened by automated click evoked oto-acoustic emissions (a-CEOAE) and automated auditory brainstem responses (a-ABRs), 2236 were referred to our department. All necessary audiological tests were performed for all the referred newborns. Among them, babies with deficient or abnormal ABR in combination with normal OAEs were considered as having AN/AD. These babies were evaluated with additional diagnostic audiological tests. Furthermore, comparison of the incidence of children diagnosed with AN/AD before and after the implementation of UNHS in our audiology department was also performed. RESULTS Among the referred newborns, 65 had abnormal or deficient ABR test results. Ten of these 65 newborn babies (mean diagnostic age: 5.7 months) with hearing impairment showed electrophysiological test results that were consistent with AN/AD. The frequency of AN/AD in these 65 children with hearing loss was 15.38%. Moreover, the frequency of AN/AD within UNHS was found to be 0.044%. Seven of the 10 babies with AN/AD had hyperbilirubinemia as a risk factor, which is a high rate to be emphasized. On the other hand, the retrospective investigation of children diagnosed with AN/AD in the same audiology department between 1999 and 2005 (i.e. before the implementation of UNHS) revealed only 7 children, with an average diagnostic age of 34 months. CONCLUSION After implementing the UNHS, the incidence of AN/AD in the audiology department increased from 1.16 to 4.13. Furthermore, the age of diagnosis of AN/AD decreased from 34 months to 5.7 months. This study shows that AN/AD, when screened, is a comparatively common disorder in the population of hearing-impaired infants. While newborn hearing screening provides early detection of babies with hearing loss, it also helps to differentiate AN/AD cases when the screening is performed with both a-ABR and automated oto-acoustic emission (a-OAE) tests. Thus, the routine combined use of a-ABR and a-OAE tests in UNHS programs, especially for the high-risk infants, can provide better detection of newborns with AN/AD. Furthermore, hyperbilirubinemia is merely an association and maybe etiologically linked.

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity.

Background/Aims: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity. Methods: Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically. Results: In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3. Conclusions: Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

Protective effect of acetyl‐l‐carnitine against cisplatin ototoxicity: role of apoptosis‐related genes and pro‐inflammatory cytokines

Cisplatin is an anti‐neoplastic agent treatment with which causes many side effects including ototoxicity. The aim of this study was to investigate whether acetyl‐l‐carnitine would have protective effects on cisplatin‐induced ototoxicity in vitro, and if present, to reveal roles of apoptotic gene expressions and pro‐inflammatory cytokines.

Evaluation of the Effect of Acetyl L-Carnitine on Experimental Cisplatin Ototoxicity and Neurotoxicity

Introduction: Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent for pediatric tumors, and ototoxicity is one of the dose-limiting side effects. Objective: It was the aim of our study to investigate the effect of acetyl L-carnitine (ALCAR) on experimental CDDP ototoxicity by audiologic tests, histomorphologic, immunohistochemical and ultrastructural examinations and to investigate the apoptotic pathways. Materials and Methods: Wistar albino rats (n = 28) were studied. Baseline audiological tests were performed in 4 groups: group 1, control; group 2, ALCAR; group 3, CDDP; group 4, CDDP + ALCAR-administered rats. Control audiological tests were performed on the 3rd day, and then the rats were sacrificed. Ear and brain specimens were examined by transmission electron microscopy, and caspase 3, 8 and 9 activities were investigated. Results: The CDDP-administered rats showed significant auditory brainstem response threshold shifts using all stimuli (clicks, 6-kHz and 8-kHz tone burst) compared with the control groups. The CDDP + ALCAR-administered rats showed significant auditory brainstem response threshold shifts by only click stimuli compared with the control groups. In the brain, spiral ganglion and organ of Corti, ultrastructural damage was prominent in group 3; the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells and caspase 3, 8 and 9 immunostaining cells was significantly high in group 3. Conclusion: ALCAR improves CDDP-induced auditory impairment, and also antioxidative and antiapoptotic properties of ALCAR on CDDP ototoxicity were supported by the findings.

Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity

Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem.

Middle ear impedance measurements in large vestibular aqueduct syndrome

OBJECTIVE To assess the effect of inner ear pressure on middle ear impedance in patients with large vestibular aqueduct syndrome (LVAS). METHODS Data from admittance tympanometry and multifrequency tympanometry on 8 LVAS patients and control subjects were studied. RESULTS Static acoustic compliance (SAC) values for the ears with stable sensorineural hearing loss (SNHL) were within the limits of the mean values of control groups except for two ears. The resonance frequency (RF) values of the ears with stable SNHL were lower than the mean values of control groups except for three ears. SAC values for the two ears with fluctuating SNHL were lower and the RF values were higher than the mean values of control groups. CONCLUSION Decreased SAC values and increased RF values found in the ears with fluctuating SNHL might be an indirect indicator of increased inner ear pressure, while low RF values in the ears with stable SNHL might reflect the decreased inner ear impedance.

Feasibility of neonatal hearing screening program with two-stage transient otoacoustic emissions in Turkey

Background: The objective of this study was to investigate the incidence of hearing loss in neonates and evaluate the feasibility of a two‐stage Transient Evoked Otoacoustic Emission (TEOAE) screening test. Maternal concerns about hearing screening were also studied.

Results of multiple-frequency tympanometry measures in normal and otosclerotic middle ears

Tympanometry is a non-invasive, quick, and inexpensive method for examining the middle-ear function. Its limited value in differentiating otosclerotic from normal middle ears caused researchers to develop new methods for evaluation of middle ears. Resonant frequency had been found to be higher in otosclerotic middle ears than normals. We conducted multiple-frequency tympanometry measurements in 25 surgically confirmed otosclerotic ears and 100 normal ears. Mean middle-ear resonant frequency for the otosclerotic group was found to be 1190 Hz and mean middle-ear resonant frequency of the control group was 934.6 Hz (p<0.001). With a cut off value of 1025 Hz (based on 95% confidence interval), sensitivity was 80% and specificity was 82%. The present findings confirm the advantage of the resonant frequency estimation over conventional tympanometry in detecting middle-ear status and mechanics in patients with otosclerosis. As a conclusion, detecting resonant frequency when evaluating patients for otosclerosis must be an essential part of examination. Nevertheless, further investigation is necessary for better diagnosis of otosclerosis preoperatively.

Analysis of genetic and non genetic risk factors for cisplatin ototoxicity in pediatric patients

OBJECTIVE The aim of this study was to analyse the genetic and non genetic risk factors for cisplatin ototoxicity. METHODS This study was conducted on 72 children who received cisplatin based chemotherapy. Brock and Muenster classifications were used to evaluate ototoxicity seen in these children. 6 single nucleotide polymorphisms (SNP); ERCC1 rs 11615, GSTP1 rs1138272, GSTP1 rs1695, LRP2 rs 2075252, TPMT rs 12201199, COMT rs 9332377, were evaluated as genetic factors by real time PCR. Non genetic factors such as cranial irradiation, cumulative doses of cisplatin, age, gender, administration of other ototoxic drugs were analysed as well. By using Chi-square test, risk factors were matched with the ototoxicity classifications. Significant risk factors were reevaluated using logistic regression modelling. RESULTS According to univariate analyses, male gender, co-treatment with aminoglycosides and mutant genotype of GSTP1 rs1695 were significantly related with cisplatin ototoxicity. Logistic regression modelling analyses also showed that male gender, co-treatment with aminoglycosides were found to be significantly related with cisplatin ototoxicity. Mutant genotype of GSTP1 rs1695 was not found to be significant, but close to the level of statistical significance. CONCLUSION Male gender, co-treatment with aminoglycosides are significant risk factors for cisplatin ototoxicity in pediatric patients. Mutant genotype of GSTP1 rs1695 seems to be a genetic risk factor in univariate analyses, although not confirmed by multivariate analyses. Therefore, GSTP1 rs1695 SNP needs to be studied in larger series.

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

OBJECTIVE The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained. In groups I, II, and III, only saline, KRG, and CDDP, respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP injections were administered on day 11. On day 14, final DPOAEs and ABR measurements were completed. The rats were then sacrificed, and their inner ear structures were evaluated by transmission electron microscopy. RESULTS In the first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP ototoxicity. This protection was mainly due to a decline in apoptotic gene expression and an increase in antiapoptotic gene expression. In the in vivo part of the study, we found that both KRG doses had otoprotective effects. This protection was more prominent at the lower dose, especially on the spiral ganglion and the brainstem. CONCLUSION KRG was shown to be an otoprotective agent against CDDP-induced ototoxicity both in vivo and in vitro.