Changes in distortion product otoacoustic emissions during prolonged noise exposure

The aim of this study was to evaluate the reduction in 2f1-f2 distortion product otoacoustic emission (DPOAE) amplitude resulting from prolonged noise exposures. A group of five chinchillas was exposed continuously to an octave-band noise centered at 4.0 kHz for a total of 42 days, 6 days at each of seven exposure levels. Exposure level increased in 8-dB steps from 48 to 96 dB SPL. DPOAE input-output (I/O) functions were measured at octave intervals over a range of primary tone f2 frequencies between 1.2 and 9.6 kHz. Measurements were obtained (1) pre-exposure, (2) during days 3-6 of each 6-day exposure, and (3) 4 weeks after the final exposure. Continuous noise exposure caused a reduction in DPOAE amplitude that was greatest at f2 frequencies within and above (3.4-6.8 kHz) the octave-band noise exposure. For these f2 frequencies, DPOAE amplitudes decreased as exposure level increased up to approximately 72-80 dB SPL; higher exposure levels failed to cause any further reduction in DPOAE amplitude. The noise level at which DPOAE amplitude began to decrease was approximately 50 dB SPL. Above this critical level, DPOAE amplitude decreased 1.3 dB for every dB increase in noise level up to approximately 75 dB SPL.     

The effect of noise exposure on the details of distortion product otoacoustic emissions in humans

The effect of noise exposure on amplitude and phase of distortion product otoacoustic emissions (DPOAEs) was examined by five different paradigms: across a wideband of frequency, microstructure, input/output function, primary frequency ratio tuning curve, and group delay. The aim was to investigate the vulnerability of these different features to moderate levels of noise exposure. Nine subjects were exposed to third-octave-band noise. The DPOAE amplitude was reduced frequency specifically with the greatest reduction approximately half an octave above the frequency of the noise. The degree of amplitude reduction was greatest at low stimulus levels. There were no observed effects on the shape of the primary ratio tuning curve. A weak tendency to a decrease was seen in group delays. Distinct microstructure was seen in the amplitude against frequency of five out of seven subjects. The maximum to minimum ratio of the microstructure decreased, and the whole pattern shifted toward lower frequencies after noise exposure. Evidence of multiple internal reflection or interference was seen in the periodicity of the microstructure. Using a simple model of the microstructure based on multiple reflections, the noise-induced changes were reevaluated. A reduction in maximum to minimum microstructure ratio could be interpreted as a decrease in the internal reflection coefficient. The implications of these observations for the interpretation of the DPOAE measurements are considered.     

Influence of spontaneous otoacoustic emissions on distortion product otoacoustic emission amplitudes

Although the influence of the levels and ratios of the primary stimulus on the amplitude of distortion product otoacoustic emissions (DPOAEs) has been studied intensely, the influence of the presence of spontaneous otoacoustic emissions (SOAEs) has been investigated less thoroughly. The present investigation analysed whether the unilateral presence of 58 SOAEs in 43 normal-hearing adults was related to larger DPOAEs in the ear with SOAEs compared to the contralateral ear having no SOAEs. The study was designed such that the only factor that could influence the amplitude of DPOAEs was the presence of SOAEs. Input/output (I/O) functions were collected in response to primary tones that were presented in 5-dB steps from 70 to 40 dB SPL at the frequency of the unilaterally recorded SOAE of each subject. The primary outcome was the demonstration of statistically significant (P < 0.05) larger DPOAEs in ears exhibiting SOAEs than in ears without measurable SOAEs, except at the highest stimulus level of 70 dB SPL. These results suggest that SOAEs play an additive role in the measurement of DPOAEs. The enhancing effect of the unilateral presence of SOAEs on DPOAEs was statistically significant for 65 dB SPL and lower levels of primary tones. The authors speculate that passive cochlear properties begin to participate in the generation of DPOAEs at primary-stimulus levels greater than 65 dB SPL.     

Effect of temperature on the transient evoked and distortion product otoacoustic emissions in rats

In order to study the energy dependence of the cochlear amplifier, transient evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) were recorded in rats during gradual cooling to 27 degrees C and heating to 40 degrees C. In the range 33-39 degrees C, the TEOAEs and DPOAEs were maximal in amplitude and almost insensitive to temperature. However, they were significantly depressed (reversibly) at higher and lower temperatures. Intensity functions were plotted at 37, 27 and 40 degrees C for both types of oto-acoustic emissions. At 37 degrees C intensity functions were nonlinear, with a notch at mid-intensity regions. At 27 degrees C, the magnitudes were depressed more at the lower intensities and threshold elevations were observed. As a result, the intensity functions were more linear and the notch was no longer seen. This result provides further evidence for a more active, energy-dependent component of the otoacoustic emissions at lower intensities for both TEOAEs and DPOAEs. The cooling probably affects the lower intensity otoacoustic emissions by inducing a depression in the endocochlear potential, by reducing the motility of the outer hair cells and by introducing a small conductive hearing loss.     

Statistical evaluation of hearing screening by distortion product otoacoustic emissions

The aim of this study was to provide a statistical evaluation of the screening properties of distortion product otoacoustic emissions (DPOEs) in individuals with clinically normal hearing and in patients with pure sensorineural deafness of various degrees. The main informational parameters used were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the analysis of receiver operating characteristic (ROC) curves. For each frequency tested, ears were classified as a function of their audiometric threshold. Two groups were defined relative to an arbitrary reference, the "audiometric criterion." The PPV decreased and NPV increased with increases in the audiometric criterion. Each point of the ROC curve represents the relationship between the false alarm rate and the hit rate for each audiometric criterion ranging between 10 and 75 dB hearing level: the lower the audiometric criterion, the lower the hit rate value, and the lower the false alarm value. The audiometric criterion giving the highest hit rate and the lowest false alarm rate was 55 to 60 dB hearing level for primaries at 60 and 70 dB sound pressure level, or 25 to 30 dB hearing level for primaries at 30, 40, and 50 dB sound pressure level. These two different behaviors of ROC curves are consistent with the hypothesis that DPOEs do not represent activity at a single location along the basilar membrane.     

Adaptive Wiener filtering for improved acquisition of distortion product otoacoustic emissions

An innovative acoustic noise canceling method using adaptive Wiener filtering (AWF) was developed for improved acquisition of distortion product otoacoustic emissions (DPOAEs). The system used one microphone placed in the test ear for the primary signal. Noise reference signals were obtained from three different sources: (a) pre-stimulus response from the test ear microphone, (b) post-stimulus response from a microphone placed near the head of the subject and (c) post-stimulus response obtained from a microphone placed in the subject's nontest ear. In order to improve spectral estimation, block averaging of a different number of single sweep responses was used. DPOAE data were obtained from 11 ears of healthy newborns in a well-baby nursery of a hospital under typical noise conditions. Simultaneously obtained recordings from all three microphones were digitized, stored and processed off-line to evaluate the effects of AWF with respect to DPOAE detection and signal-to-noise ratio (SNR) improvement. Results show that compared to standard DPOAE processing, AWF improved signal detection and improved SNR.     

Vulnerability and adaptation of distortion product otoacoustic emissions to endocochlear potential variation

The endocochlear potential (EP) was reversibly decreased in adult gerbils by the intraperitoneal injection of furosemide, while cochlear functioning was monitored by measurement of distortion production otoacoustic emissions (DPE) at a range of stimulus intensities. Stimulus frequencies for DPEs were f1 = 6.8 and f2 = 8 kHz (f2/f1 = 1.18). Emissions monitored in the ear canal and scala media were 2f1-f2, 3f1-2f2, 2f2-f1, and f2-f1. Typically, the EP decreased smoothly, reached a minimum one-half hour after injection, then recovered slowly over several hours. Emissions at 2f1-f2 and 3f1-2f2 at low stimulus levels were particularly vulnerable to the change in EP. These vulnerable emissions showed characteristic trajectories in which the amplitudes changed little with the initial EP decrease, then dropped sharply as the EP continued to decrease. However, the amplitudes then began to recover even before the EP reached minimum, and recovered completely while the EP remained subnormal. The trajectories of the other odd order emissions were similar, but lacked the abrupt decrease. The variation of the even order (f2-f1) component was completely different, but appeared related to the odd order trajectories in a complex fashion. During the initial decrease for the vulnerable components, the decrease in emission amplitude (in dB) was found to be proportional to the square of the change in EP (in mV). The recovery with a subnormal EP was interpreted as an adaptive effect with a time constant of about 15 min.     

Frequency analysis of the contralateral suppression of evoked otoacoustic emissions by narrow-band noise

Yeast cells defective in the GGS1 (FDP1/BYP1) gene are unable to adapt to fermentative metabolism. When glucose is added to derepressed ggs1 cells, growth is arrested due to an overloading of glycolysis with sugar phosphates which eventually leads to a depletion of phosphate in the cytosol. Ggs1 mutants lack all glucose-induced regulatory effects investigated so far. We reduced hexokinase activity in ggs1 strains by deleting the gene HXK2 encoding hexokinase PII. The double mutant ggs1 delta, hxk2 delta grew on glucose. This is in agreement with the idea that an inability of the ggs1 mutants to regulate the initiation of glycolysis causes the growth deficiency. However, the ggs1 delta, hxk2 delta double mutant still displayed a high level of glucose-6-phosphate as well as the rapid appearance of free intracellular glucose. This is consistent with our previous model suggesting an involvement of GGS1 in transport-associated sugar phosphorylation. Glucose induction of pyruvate decarboxylase, glucose-induced cAMP-signalling, glucose-induced inactivation of fructose-1,6-bisphosphatase, and glucose-induced activation of the potassium transport system, all deficient in ggs1 mutants, were restored by the deletion of HXK2. However, both the ggs1 delta and the ggs1 delta, hk2 delta mutant lack detectable trehalose and trehalose-6-phosphate synthase activity. Trehalose is undetectable even in ggs1 delta strains with strongly reduced activity of protein kinase A which normally causes a very high trehalose content. These data fit with the recent cloning of GGS1 as a subunit of the trehalose-6-phosphate synthase/phosphatase complex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiologic changes in preterm neonates: auditory brain stem response and distortion product otoacoustic emissions

The purposes of this investigation were to determine 1) if auditory peripheral maturity is present in the newborn; 2) if not, at what age maturational changes occur in the peripheral auditory system from preterm to full-term; and 3) how results of tests used to identify auditory dysfunction in neonates, such as distortion product otoacoustic emissions (DPEs) and auditory brain stem responses (ABRs), change during this period. Longitudinal DPE amplitude and ABR wave I latency measurements were obtained from a single ear of 18 preterm neonates. The DPEs were evoked at f2s of 2, 3, 4, and 5 kHz. The longitudinal data revealed that in general, DPE amplitude increased and ABR wave I latency decreased as a function of postconceptional age. These findings suggest that 1) the peripheral auditory system has not reached maturity in the preterm neonate; 2) maturational changes continue from preterm to full-term; and 3) these changes are reflected in ABR and DPE measurements.     

Effects of background noise on click-evoked otoacoustic emissions

OBJECTIVE: To investigate the effect of increased levels of background noise on click-evoked otoacoustic emission (CEOAE) recordings and to compare the effectiveness of the default CEOAE program with the QuickScreen CEOAE program in increased levels of noise, using an Otodynamics ILO88 recording device. DESIGN: The right ears of 40 young adult women with normal hearing were assessed using CEOAEs under four different noise conditions and with two different methods of data collection. The noise conditions were in quiet, 50 dB A, 55 dB A, and 60 dB A of white noise. Data were collected at each noise level in the default mode and also using the ILO88 QuickScreen program. RESULTS: There was a significant change in a number of important CEOAE output parameters with increased noise. In the default mode, mean whole wave reproducibility was 89.2% in quiet but declined to 85% with 50 dB A of white noise, 65% at 55 dB A and 20% at 60 dB A. The QuickScreen program proved more robust to the effects of noise than the default. In that mode, mean whole wave reproducibility was 91.7% in quiet, 92.5% with 50 dB A of white noise, 82.5% at 55 dB A and 45% at 60 dB A. CONCLUSIONS: The findings of the study indicate ambient noise levels for accurate CEOAE recording should not exceed 50 to 55 dB A of noise and alternatives to the default program should be considered in non-sound-treated situations.     

Interrelations between transiently evoked otoacoustic emissions, spontaneous otoacoustic emissions and acoustic distortion products in normally hearing subjects

Active cochlear mechanisms and especially outer hair cells seem to be involved in oto-acoustic emissions (OAEs) genesis. This study sought to investigate basic characteristics of spontaneous otoacoustic emissions (SOAEs), click-evoked otoacoustic emissions (TOAEs) and interrelations between SOAEs, TOAEs and 2f1-f2 and 2f2-f1 distortion product OAEs (DPOAEs) in 135 normally hearing subjects. A gender effect was shown on TOAEs and DPOAEs amplitude, and is attributed to the higher incidence of SOAEs in women (58%) than in men (22%). Moreover, SOAEs presence seems to mask the age effect found, especially at high frequency components, on TOAEs amplitude. A general influence of SOAEs on TOAEs and DPOAEs is shown, especially at frequencies ranging from 1 kHz to 3 kHz, collecting more than 66% of the SOAEs peaks recorded. Lastly, correlations between TOAEs frequency band amplitude and 2f1-f2 DPOAEs amplitude, shows frequency specificity, at least at low frequencies (i.e., from 0.5 to 2 kHz) in agreement with previous works suggesting that the 2f1-f2 DPOAEs generation site is at the geometric mean of the primaries. The same correlations calculated with 2f2-f1 DPOAEs amplitude show frequency specificity at low frequencies i.e., at 800 Hz and 1600 Hz. 2f2-f1 DPOAEs in humans are shown to be generated near the 2f2-f1 frequency region on the cochlear partition.     

Random noise in the spectra of evoked otoacoustic emissions

Adult male rats were given an oral dose of 10 mg/kg aspartame 14C-labelled in the methanol carbon. At timed intervals of up to 6 hours, the radioactivity in plasma and several organs was investigated. Most of the radioactivity found (>98% in plasma, >75% in liver) was bound to protein. Label present in liver, plasma and kidney was in the range of 1-2% of total radioactivity administered per g or mL, changing little with time. Other organs (brown and white adipose tissues, muscle, brain, cornea and retina) contained levels of label in the range of 1/12 to 1/10th of that of liver. In all, the rat retained, 6 hours after administration about 5% of the label, half of it in the liver. The specific radioactivity of tissue protein, RNA and DNA was quite uniform. The protein label was concentrated in amino acids, different from methionine, and largely coincident with the result of protein exposure to labelled formaldehyde. DNA radioactivity was essentially in a single different adduct base, different from the normal bases present in DNA. The nature of the tissue label accumulated was, thus, a direct consequence of formaldehyde binding to tissue structures. The administration of labelled aspartame to a group of cirrhotic rats resulted in comparable label retention by tissue components, which suggests that liver function (or its defect) has little effect on formaldehyde formation from aspartame and binding to biological components. The chronic treatment of a series of rats with 200 mg/kg of non-labelled aspartame during 10 days resulted in the accumulation of even more label when given the radioactive bolus, suggesting that the amount of formaldehyde adducts coming from aspartame in tissue proteins and nucleic acids may be cumulative. It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts.     

Transient-evoked otoacoustic emissions and contralateral suppression in patients with unilateral tinnitus

OBJECTIVE: Finding an optimal soldering system for a titanium prosthesis has become increasingly important with the successful introduction of titanium and titanium alloys to dentistry. This study examined the effect of corrosion on the strength of the soldered joints of pure titanium and Ti-6Al-4V alloys joined using various solders. METHODS: Commercially pure titanium and Ti-6Al-4V alloy rods (2 mm in diameter; 25 mm long) were soldered in an argon atmosphere using four solders: two kinds of titanium-based solder, a gold-based solder, and a silver-based solder. Tensile strengths were examined before or after immersion treatments. Specimens were immersed in either a 0.9% NaCl or 1.0% lactic acid solution held at 35 degrees C for 3 and 8 wk. The amounts of various metal elements released were determined by atomic absorption photospectroscopy. The natural potentials and potentiodynamic polarization behavior of the soldered specimens in 0.9% NaCl or 1.0% lactic acid were determined by a computer-assisted corrosion measurement system. The results were analyzed by ANOVA and Student's t-test. RESULTS: The cp-titanium and Ti-6Al-4V samples soldered with titanium-based solders exhibited tensile strengths of 300-400 MPa and were not significantly affected by immersion in either solution (no significant difference at p < 0.05). The strengths of both the cp-titanium and titanium alloy specimens soldered with gold-based solder were significantly lower than for any of the other specimens and were affected by immersion in the 0.9% NaCl solution (p < 0.01). The cp-titanium and Ti-6Al-4V specimens that were soldered with titanium-based solders did not show any transpassive regions or breakdown in the natural electrode potential range. On the contrary, the specimens soldered with gold-based and silver-based solders showed transpassive regions or breakdown potentials at less than 0 mV in 0.9% NaCl solution. SIGNIFICANCE: It is recommended that titanium-based solder be employed for titanium and titanium alloys.     

Comparison of distortion product otoacoustic emissions with auditory brain-stem response for clinical use in neonatal intensive care unit

PURPOSE: Kainic acid (KA) has long been used in experimental animals to induce status epilepticus (SE). A mechanistic implication of this is the association between excitotoxicity and brain damage during or after SE. We evaluated KA-induced metabolic impairment and the potential mitigating effects of GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] in superfused rat cerebral cortical slices. METHODS: Interleaved [31P]/[1H] magnetic resonance spectroscopy (MRS) was used to assess energy metabolism, intracellular pH (pHi), N-acetyl-L-aspartate (NAA) level, and lactate (Lac) formation before, during, and after a 56-min exposure to 4 mM KA in freshly oxygenated artificial cerebrospinal fluid (oxy-ACSF). RESULTS: In the absence of GYKI 52466 and during the KA exposure, NAA, PCr, and ATP levels were decreased to 91.1 +/- 0.8, 62.4 +/- 3.9, and 59.1 +/- 4.3% of the control, respectively; Lac was increased to 118.2 +/- 2.1 %, and pH, was reduced from 7.27 +/- 0.02 to 7.13 +/- 0.02. During 4-h recovery with KA-free ACSF, pHi rapidly and Lac gradually recovered, NAA decreased further to 85.5 +/- 0.3%, and PCr and ATP showed little recovery. Removal of Mg2+ from ACSF during KA exposure caused a more profound Lac increase (to 147.1 +/- 4.0%) during KA exposure and a further NAA decrease (to 80.4 +/- 0.5%) during reperfusion, but did not exacerbate PCr, ATP, and pHi changes. Inclusion of 100 microM GYKI 52466 during KA exposure significantly improved energy metabolism: the PCr and ATP levels were above 76.6 +/- 2.1 and 82.0 +/- 2.9% of the control, respectively, during KA exposure and recovered to 101.4 +/- 2.4 and 95.0 +/- 2.4%, respectively, during reperfusion. NAA level remained at 99.8 +/- 0.6% during exposure and decreased only slightly at a later stage of reperfusion. CONCLUSIONS: Our finding supports the notion that KA-induced SE causes metabolic disturbance and neuronal injury mainly by overexcitation through non-N-methyl-D-aspartate (NMDA) receptor functions.     

Influence of contralateral noise on distortion product latency in humans: is the medial olivocochlear efferent system involved?

To test the hypothesis of temporal modifications of cochlear responses when medial efferents are activated, otoacoustic emission latencies were estimated in 16 normal human subjects, in the presence and absence of a contralateral broadband noise, using measurements of the phase of the 2f1-f2 distortion product (group latency method). Significant decrease in the latency of lower frequency (0.8-2.7 kHz) emissions was found in the presence of increasing levels of contralateral sound, and this effect disappeared when the primary-tone levels increased to 60 dB SPL. To ensure that effects were not attributable to mechanisms involving middle ear structures, susceptible to activation by contralateral sound, latency measures were performed in seven subjects whose efferents were severed during a vestibular neurotomy and in two subjects with paralyzed stapedial muscle. Results in patients were compared to those obtained in three surgical control patients with intact efferent bundle, and in eight other normal subjects. All the subject groups exhibited a decrease in latency under contralateral sound except the patients with the severed efferent system who showed increased latencies.     

Distortion product otoacoustic emissions in healthy newborns: normative data

Distortion product otoacoustic emissions (DPOAE) offer an alternative to transiently evoked otoacoustic emissions (TEOAE) as an audiological test. The former can be used as a screening technique, and may also provide frequency-specific information about the functional state of the cochlea. We recorded DPOAE in a group of healthy newborns to establish the characteristics of a DPOAE "audiogram" (DP-gram) in this population. The DP-gram can be obtained with characteristics quite similar to those observed in adults, with two sharp peaks of maximum amplitude at F2 frequencies of 2 kHz and 5-6 kHz, and a decline in DPOAE amplitude in midfrequencies. The results confirm the limitations of DPOAE recording for testing parts of the basilar membrane where lower frequencies are coded.     

Transitory evoked and distortion products of otoacoustic emissions in absent auditory evoked potentials

Transient click-evoked otoacoustic emissions (TEOAE) and distortion-product otoacoustic emissions (DPOAE) are produced by an active biomechanical process in the cochlea, presumably related to outer hair-cell activity. Although it is generally accepted that in most cases of hearing loss with absent auditory evoked potentials neither TEOAE nor DPOAE can be found, some cases with such a constellation have been described. Here we report another four cases of children with severe to profound hearing loss where we discovered reproducible TEOAE and DPAOE, whereas auditory evoked potentials were missing. TEOAE and DPOAE recordings in these cases indicate substantially preserved outer hair-cell function independent of profound pre-sensineural hearing loss. Since the incidence of children with preserved otoacoustic emissions together with impairment of synaptic or postsynaptic function of the first neuron is not known, the unconditioned use of TEOAE nor DPOAE as a screening instrument must be seriously questioned. Secondly, in conjunction with subjective audiometry and brain-stem-evoked potentials, emission recordings is an indispensable measurement prior to cochlear implantation and use of high-power hearing aids.     

Distortion product otoacoustic emissions for the assessment of auditory sensitivity

Distortion product otoacoustic emissions (DPOAEs) were evaluated in 494 normal and 506 cochlear-impaired human ears, to determine whether DPOAEs depend on factors such as background noise, the shape of the pure tone audiogram, sex and aging, and whether a DPOAE test can perform well in distinguishing normal-hearing from hearing-impaired ears. The amplitudes of DPOAEs were measured at the frequency of 2f1-f2 (f1 < f2, f2/f1 = 1.22, f2 at 1, 2 and 4 kHz) using as stimuli two pure tones at level of 70 dB from an ILO92 Otoacoustic Emission Analyzer. The correlation coefficients between the DPOAE level and the auditory threshold decreased as the background noise levels at 1 kHz and 2 kHz increased. Therefore, it appeared that ears with large background noise levels would be inadequate for the study of DPOAEs predicting the hearing state. The sensitivity (normal-hearing ears identified as normal hearing) and the specificity (hearing-impaired ears identified as hearing impaired) at the equal-sensitivity-specificity condition were 80.7-86.7% at 1, 2 and 4 kHz, and the areas under the receiver operating characteristic (ROC) curves, which were used to estimate the test performance, were 0.88 for 1 kHz, 0.91 for 2 kHz and 0.92 for 4 kHz. Since these results suggest that a DPOAE can be used as a reliable technique for objective auditory tests, it is thought that actual values (DPOAE level: 4.3 dB at 1 kHz, 5.0 dB at 2 kHz and 2.9 dB at 4 kHz) of false-positive (hearing-impaired ears identified as normal hearing) rates corresponding to 5% can be used in clinical evaluation to separate normal hearing from hearing-impaired ears. There was, however, a significant age effect at 4 kHz on DPOAEs in the ears with the same pure tone hearing thresholds, and the areas of the ROC curves in subjects ranging from 10 to 29 years old were larger than in subjects over 50 years (1 kHz: 0.88 to 0.94 versus 0.83 to 0.84, 2 kHz: 0.95 versus 0.89, 4 kHz: 0.95 to 0.96 versus 0.88 to 0.89). Therefore, it is thought that age-adjusted norms may be necessary for the accurate interpretation of DPOAE results.     

Effect of leukotriene inhibitor on otoacoustic emissions in salicylate ototoxicity

Our previous work showed that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Pretreatment with LT inhibitor was found to prevent salicylate ototoxicity. Other studies demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in cochlear outer hair cells, and decreased otoacoustic emissions. The purpose of our study was to determine the effect of LT blocker (Sch 37224) on transient-evoked otoacoustic emissions (TEOAEs) in salicylate or LT ototoxicity. Chinchillas were divided into five groups. Transient-evoked otoacoustic emissions were measured after salicylate application on the round window membrane (RWM), with (Group 1) and without (Group 2) LT blockade; after LTC4 (a type of leukotriene) application on the RWM, with (Group 3) and without (Group 4) LT blockade; and in the control group after saline application on the RWM. The overall response differences from the baseline measurements over time in each case were compared with each other. Both salicylate and LTC4 application on the RWM were followed by significant decreases in TEOAEs, and the decrease was prevented by pretreatment with LT blocker. There was no significant change in TEOAEs in the control group. Salicylate ototoxicity appears to be mediated by the elevated levels of leukotrienes as a consequence of cyclooxygenase inhibition. This study also provides further evidence that the site of action in salicylate ototoxicity is the outer hair cell.     

Effect of negative middle-ear pressure on transient-evoked otoacoustic emissions

OBJECTIVE: To seek an optimal treatment plan from the results of treatment for metastatic disease of the spine in children. DESIGN: An 8-year retrospective study of children with metastatic disease of the spine. Imaging studies were reviewed and treatment modalities analysed. SETTING: The divisions of pediatric orthopedics and pediatric neurosurgery at the Children's Hospital of Eastern Ontario, Ottawa. PATIENTS: All children seen between April 1980 and December 1987 who had lesions metastatic to the spine by hematogenous or direct extension. There were 20 children (15 boys, 5 girls) with a mean age at the time of diagnosis of 9.5 years. Follow-up ranged from 2 weeks to 108 months. One child was lost to follow-up. INTERVENTIONS: Eleven children underwent laminectomy and decompression. Of the 14 neurologically compromised children, 5 received chemotherapy and radiotherapy and 9 received chemotherapy, radiotherapy and surgery. MAIN OUTCOME MEASURES: Type of metastatic lesion, vertebrae involved and response to therapy. RESULTS: Vertebrae involved with metastases were as follows: cervical (3), thoracic (5), lumbar (8) and multilevel (2). Meninges were involved in 2 cases. The most common causes of metastatic spinal involvement were neuroblastoma (4 cases) and astrocytoma (6 cases). Pathologic fractures occurred in 4 children and kyphoscoliosis in 4. Spinal cord paresis developed in 14 of the 20 children. Of the 6 children who survived from 48 to 108 months, 5 had tumours of neural origin, 4 being astrocytomas. Children with neuroblastoma or leukemic infiltration had a good initial response to chemotherapy. Five of the 6 surviving children had astrocytomas, and 5 were treated by surgical decompression. CONCLUSIONS: Metastatic disease of the spine in children secondary to astrocytoma should be treated aggressively, but from the experience gained from this study it is impossible to devise a rigid treatment plan for each type of metastatic tumour. The choice of chemotherapy, radiotherapy or surgery depends on the type of tumour, the age of the child and whether or not the spinal cord is compromised.