The feasibility of hospital-based universal newborn hearing screening in the United Kingdom.

Current hearing screening programmes in the United Kingdom are performing unacceptably poorly. Davies et al. (1997) suggested that universal newborn hearing screening (UNHS) would be more effective and cheaper to run. However, there is concern that hospital-based UNHS would not be feasible because of early postnatal discharge, and thus babies not staying in hospital long enough to be screened. Two studies were designed to determine the viability of hospital-based UNHS in a district general hospital in the United Kingdom. Study 1 retrospectively determined the discharge age and time of discharge of all 3021 well babies born at St Helier hospital, Carshalton, and the number of babies born at home in the area, from 19 October 1997-18 October 1998. Most well babies were found to pass through hospital at a convenient time for predischarge hearing screening, and the optimal protocol was screening from 9 am-2 pm, 7 days a week. The predicted maximal screening coverage was 92.68%. Study 2 tested the calculated optimal protocol over 1 week. It was found that UNHS with otoacoustic emissions on the maternity ward from 9 am-2 pm, 7 days a week, achieved a coverage of 89.06%, with an acceptable false positive rate of 6.2%. It is likely that a similar protocol with slight modifications could be implemented successfully in other hospitals in the United Kingdom.

Wave and place fixed DPOAE maps of the human ear.

Human intermodulation distortion product otoacoustic emissions (DPOAE) can be a mixture of low and high latency components. They have different level, phase, and suppression characteristics, which indicate that emissions arise both from the frequency region of the primary tones directly and indirectly via the DP frequency place. Which component dominates the measured DPOAE in the ear canal depends on the stimulus parameters, especially the frequency ratio, f2/f1. Interference between the two emissions adds complexity to measurements of DPOAE. The behavior and even existence of whichever emission route is lower in level often cannot directly be deduced from the raw DPOAE data because the other emission covers it. It is therefore not known whether both emissions are present for all stimulus parameters or whether the trends seen in each emission when they are the dominant emission route continue under stimulus conditions when they are not dominant. In this study, the two DPOAE components are separated by a post-processing method. Previously, maps of raw DPOAE data against f2/f1 and DP frequency have been obtained. To separate the components, sets of data consisting of f2/f1 sweeps were transformed by an inverse Fourier transform into the time domain. The low and high latency components appeared as two distinct peaks because of their different phase gradients. These peaks were separated by windowing in the time domain and two frequency domain maps were reconstructed, representing the low and high latency DPOAEs. It was found that the low latency component of the 2 f1-f2 DP was only emitted strongly with f2/f1 between approximately 1.1 and 1.3. The removal of the high latency component revealed the low ratio edge of this region, at which the level falls sharply. However, the low latency emission has been traced at reduced amplitude over a wide range of stimulus parameters. Although previously only observed at small frequency ratios, the high latency component was found to be present widely in the lower sideband, its level reducing slowly at larger f2/f1. Its phase behavior changes in the lower sideband, being approximately constant with DP frequency at small ratios of f2/f1, but deviating from this at wider ratios. These results support the hypothesis that a DPOAE component which propagates to and is re-emitted from the DP frequency place (place fixed emission) is present across a wide parameter range. However, for all but the close primary condition the lower sideband DPOAE is dominated by direct emission from the region of f2 and f1 wave interaction (wave fixed emission). A simple transmission line model is presented to illustrate how the observed DPOAE maps can arise on the basis of this hypothesis.

Indications of different distortion product otoacoustic emission mechanisms from a detailed f1,f2 area study.

The primary site of generation on the basilar membrane for the 2f1-f2 distortion product (DP) is generally considered to be near where the higher-frequency stimulus tone peaks. This site has also been shown to be a source of DP otoacoustic emission (DPOAE) in the ear canal, but a second source of emission is known to exist in the region of the DP frequency place. The DPOAE phase versus frequency gradient provides a means of investigating the emission mechanisms. "Wave-fixed" and "place-fixed" mechanisms have been proposed to account for the very different phase gradients found depending on whether the 2f1-f2 DPOAE is evoked by a small or large stimulus-frequency ratio. DPOAE phase versus frequency gradients can be investigated either by sweeping f1,f2 or by sweeping both frequencies maintaining a constant frequency ratio. Each manipulation gives only a partial description of DP behavior. In this study, the place-fixed/ wave-fixed dichotomy is analyzed using extensive 2f1-f2 and 2f2-f1 DP stimulus-frequency sweep data presented on matrices of f1 vs f2 and f2/f1 ratio versus DP frequency. These show how the DPs are related and provide a more complete picture of 2 f1-f2 and 2f2-f1 DPOAE phase and amplitude versus frequency behavior. The phase data contain evidence for a systematic variation in the proportions of wave- and place-fixed emission. The results suggest that 2f1-f2 DPOAEs with a wide stimulus frequency ratio are wave fixed, while all other DPOAEs are place fixed. A transition occurs within the 2 f1-f2 DP data region at a frequency ratio of about f2/f1 = 1.1. The 2f1-f2 DP and 2 f2-f1 DP phase behavior is continuous across the f2/f1 = 1 boundary. As the 2 f2-f1 DP generation region must be strongly influenced by the DP frequency place, the results imply that the place-fixed component of the 2 f1-f2 DP is also linked to its frequency place. A similar pattern was obtained with the 3f1-2f2 and 3f2-2f1 DPs. The results support the following model: For the limited set of stimulus conditions that gives rise to 2 f1-f2 wave-fixed emissions, DP energy is largely generated in the f2 region and is emitted directly. All other DPOAEs are place-fixed emissions, and while nonlinearity within the f2 stimulus envelope remains the generator, the DP is not directly emitted but travels apically until it is re-emitted basally via a separate reflection mechanism in the region of the DP place.

Basic characteristics of distortion product otoacoustic emissions in infants and children.

Distortion-product otoacoustic emissions at the 2 f1-f2 frequency (DPOAEs) are being advocated as a clinical tool for diagnosis of peripheral auditory pathology. Because they can be measured quickly and noninvasively, they may be an excellent method for identifying hearing loss in infants and children. However, few studies have examined the characteristics of DPOAEs in infants and children or detailed if, and how, their responses differ from those of adults. The purpose of the current study was to determine basic characteristics of DPOAEs in infants, toddlers, children, and young adults and to define any differences among age groups. An additional goal was to ensure that the presence of spontaneous otoacoustic emissions (SOAEs) did not confound any developmental effect. DPOAE input/output (I/O) functions at seven f2 frequencies and SOAEs were measured from one ear of 196 subjects. Children aged less than 1 yr had significantly higher mean DPOAE levels than older children and adults, and children aged 1-3 yr had higher mean DPOAE levels than teens and adults. These differences were dependent on frequency but were independent of f2 level and SOAE status. At every f2 frequency, groups of individuals having SOAEs had higher mean DPOAE levels than those not having SOAEs.

Multicomponent acoustic distortion product otoacoustic emission phase in humans. II. Implications for distortion product otoacoustic emissions generation.

Phase characteristics and latency of 2f1-f2, 3f1-2f2, and 2f2-f1 acoustic distortion product otoacoustic emissions (DPOAEs) recorded in normally hearing adults have been described in a companion paper [Moulin and Kemp, "Multicomponent acoustic distortion product otoacoustic emission phase in humans. I. General characteristics," J. Acoust. Soc. Am. 100, 1617-1639 (1996)]. Phase-versus-frequency functions (PFF) have been recorded using two methods, depending whether f1 or f2 was swept in frequency, defining, respectively, an "f1 sweep" and an "f2 sweep" method. The present study compares 2f1-f2, 3f1-2f2, 4f1-3f2, and 2f2-f1 DPOAEs phase characteristics, and latencies obtained by these two methods. For lower sideband DPOAEs, the f2 sweep gave consistently longer latencies than the f1 sweep method, whereas no difference was obtained for the 2f2-f1 DPOAE. This suggests that the lower sideband DPOAEs and the 2f2-f1 DPOAE do not come from the same aspect of the traveling wave. The longer delay obtained with an f2 sweep is suggested to be due to an additional delay added by the proximity of the peak of the f2 traveling wave. The place-fixed and the wave-fixed models of DPOAE generation are discussed, and an "intermediate" model of DPOAE generation is introduced to explain such additional delay and the existence of phase irregularities which were observed in the PFF. The ratio of the latencies obtained by the two sweep methods is frequency dependent and a relation to cochlear frequency selectivity is suggested. Finally, analysis of the differences in latency of the different lower sideband DPOAE components allowed an estimation of the return latency of DPOAEs.

Multicomponent acoustic distortion product otoacoustic emission phase in humans. I. General characteristics.

Phase characteristics and latency of 2f1-f2, 3f1-2f2, and 2f2-f1 acoustic distortion product otoacoustic emissions (DPOAEs) have been analyzed in 12 adults with normal hearing. Phase-versus-frequency functions (PFF) have been recorded at each of ten pairs of primary frequencies, by two methods, depending on which one of the primary frequencies f1 or f2 was swept in frequency. Whichever sweep method was used, local phase irregularities were found in the PFF and were shown to be independent of the phase variability due to the measured noise, to be reproducible and frequency specific. Phase irregularities were significantly greater in subjects exhibiting spontaneous otoacoustic emissions. The latency calculation was unaffected by phase irregularities provided that a suitably large range of f2/f1 ratio was used. The DPOAE latencies that were obtained at low ratios of primaries were significantly longer than those obtained at higher ratios. For all DPOAE components and sweep methods used, the latency decreased as frequency increased from 750 Hz to 6 kHz. Substantial intersubject differences were found. They might be due to two main factors: differences in middle ear acoustic properties and in cochlea mechanical characteristics. The influence of pressure in the outer ear canal increased the DPOAE latencies recorded with both the f1 and f2 sweep methods at low frequencies. Men showed significantly longer 2f2-f1 DPOAE latencies than women, especially at low frequencies, which can be attributed to the difference in length of the cochlea according to gender. Lastly, the latencies measured using the f2 sweep were consistently longer than the latencies obtained using an f1 sweep for lower sideband DPOAEs, but no difference was observed for upper sideband DPOAEs.

The influence of evoking stimulus level on the neural suppression of transient evoked otoacoustic emissions.

This study concerns the suppression of transient evoked otoacoustic emissions (TEOAEs) by contralateral noise. The suppression is interpreted as neurally induced changes in cochlear mechanics. The magnitude of TEOAE suppression is explored in response to a single level of contralateral noise, in 20 normal subjects, and as a function of TEOAE evoking stimulus power in 6 subjects. TEOAE were found to be relatively more susceptible to contralateral suppression when the TEOAE evoking stimulus was low. This suggests that saturation of the TEOAE generator by the evoking stimulus reduces the susceptibility of the generator to neural suppression. However, this relation did not hold between ears. Those ears in which the TEOAE seemed easier to saturate were easier to suppress by contralateral noise. We have concluded that TEOAE generators can differ in their susceptibility to neural suppression. Ears in which the TEOAE generating mechanism is less dependent on the ipsilateral evoking stimuli power level, are also naturally more susceptible to efferent suppression.

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.

Binaural noise suppresses linear click-evoked otoacoustic emissions more than ipsilateral or contralateral noise.

We studied the efferent suppression of click-evoked otoacoustic emissions with 65 dB SPL of white noise presented to left, right, or sometimes both, ears for 408 ms. Each burst of noise preceded a series of four unipolar 80 microseconds 65 dB peak Sound Pressure clicks, presented to the left ear only. The first click of the four-click group followed the end of the noise by either 1, 2, 5, 10, 20, 50, 100 or 200 ms; each subsequent click was offset by 20 additional ms via an ILO88 system with special programming modifications. Conditions were alternated so that a 'without noise' condition preceded a 'with noise' condition for three repetitions of 600 clicks per trial. Seven subjects with normal hearing participated in the study, and three of the seven participated in a test-retest reliability study. Results showed the greatest suppression followed binaural stimulation ending within one to five ms of the first click in the pulse train. Somewhat less suppression was seen following ipsilateral stimulation. The least amount of suppression was seen following contralateral stimulation, suggesting that previous research using contralateral stimulation may underestimate efferent effects. We saw no effects when the end of the noise was 100 ms or more away from the beginning of the click train.

Distortion product otoacoustic emission delay measurement in human ears.

The measurement of distortion product otoacoustic emission (DPOAE) delay using the phase gradient method is discussed. A short f2 sweep paradigm is described. Its merits are discussed and comparisons made with other methods. Using sweeps of less than 4%, consistent and reliable measurements were obtained from 12 normal ears, except for a few isolated measurements. Investigation of these apparent anomalies indicated that the short f2 sweep method was sensitive to the localized effects of narrow distortion product intensity notches and spontaneous emissions. It is possible that middle ear pressure instability or some local change in the cochlea sometimes compounded the situation. The intersubject range (63% of the mean) of DPOAE delay values was greater than the range of values observed due to measurement variability (5.6% of the mean) or intrasubject variability (8.5% of the mean) demonstrating that the method can detect real differences between ears. However, comparison with previous work shows that caution is needed in interpreting these data, as all DPOAE phase methods provide only partial latency values. The physical interpretation depends on both the stimulus sweep used and the origin of DPOAES. Our data shows that f1 sweep derived latency is lower than f2 sweep data by more than 20%. Caution also needs to be exercised when comparing cochlear traveling wave delay, as inferred from electrophysiological data, with that obtained from DPOAE delay measurements.

Assessment of an implementation of a narrow band, neonatal otoacoustic emission screening method.

OBJECTIVE: To validate a narrow band method for the detection of transient evoked otoacoustic emissions (TEOAEs) in neonates. DESIGN: A method for the assessment of TEOAEs was implemented. The method was based upon assessing the estimated signal to noise ratio of a narrow band of TEOAEs from 1.6 kHz to 2.8 kHz. This method was tested against a commercially available broad band TEOAE test, the Otodynamics ILO88 in quickscreen mode. Trials were performed on 162 ears from a group of normal neonates aged from 3 to 6 wk. RESULTS: The sensitivity of the method was 100% and its specificity was 92%, against the ILO88 test when looking for the absence of TEOAEs. When the ILO88 test was limited in time so that the number of undetected TEOAEs from both tests were similar, the narrow band test took 40% less time than the ILO88 test. CONCLUSIONS: The narrow band TEOAE detection method, as implemented here, did not miss any neonate ears without TEOAEs. However, the narrow band test did not detect TEOAEs in 8% of the group in which TEOAEs were detected by the ILO88. With a two-stage screening test and a 0.6% incidence of sensorineural hearing loss, it is predicted that 1.9% of neonates with TEOAEs would be misclassified, by the narrow band test. (It is predicted that the ILO88 quickscreen test would misclassify 1.1% under the same conditions.) The test is faster and easier to perform than the broad band ILO88 test.

The objective assessment of transient evoked otoacoustic emissions in neonates.

OBJECTIVE: To develop a simple objective method for assessing the presence or absence of a TEOAE in recordings from neonatal ears. DESIGN: Several simple, objective methods of transient evoked otoacoustic emissions (TEOAE) assessment were tested against a verified subjective assessment method, using 200 neonatal TEOAEs recorded under clinical conditions. RESULTS: Total TEOAE level did not correlate well with the subjective assessment. Total estimated signal to noise ratio correlated better with the subjective assessment. Filtering the response between 1.5 and 2.8 kHz and windowing it between 4 and 10 msec did not degrade the correlation. In a normal population of neonates the filterd, windowed estimated signal to noise ratio method miscategorized only 4.0% of the responses as having no TEOAEs. None of the population without TEOAEs were categorized as having TEOAEs by the objective test. CONCLUSIONS: An objective TEOAE assessment (based on the signal to noise ratio of a time limited midband section of the TEOAE) performed well at detecting the presence or absence of a TEOAE.

Quantitative assessment of methods for the detection of otoacoustic emissions.

OBJECTIVE: To compare the performance of various types of signal detector commonly used to detect otoacoustic emissions (OAEs). METHOD: The signal detectors were tested with signals in various types of noise, including noise with various amplitude distributions. Commonly utilized transient evoked OAE and distortion product OAE detectors were analyzed. RESULTS: In both cases it was found that detector performance increased as the measurement bandwidth was increased. Noises of different amplitude distributions were found to affect the performance of both types of detectors. The effect of different amplitude distributions decreased as the measurement bandwidth was increased. For a given power per spectral line, the transient evoked OAE detector could detect signals 6 dB farther into gaussian noise than the distortion product OAE detector. CONCLUSIONS: An analysis of the results of practical methods of OAE measurement show that distortion product OAEs can be measured with higher power per spectral line than transient evoked OAEs. This means that in adult humans distortion product OAEs can be reliably detected in about 1/14th of the time of transient evoked OAEs. In neonatal humans distortion product OAEs can be reliably detected in about two-thirds of the time of transient evoked OAEs.

Antimicrobial effect of combinations of EDTA-Tris and amikacin or neomycin on the microorganisms associated with otitis externa in dogs.

Combinations of EDTA-Tris and two aminoglycoside antibiotics (amikacin and neomycin) were tested for synergistic activities against the microorganisms associated with otitis externa in dogs and for the solutions' stability over time. Synergistic activity was observed when EDTA-Tris plus amikacin and EDTA-Tris plus neomycin were tested against Staphylococcus intermedius, Proteus mirabilis, Pseudomonas aeruginosa, and Escherichia coli, but not against Candida albicans. Stability studies over a 3-month period indicated that the test solutions were stable at room temperature and that their antimicrobial activity was maintained.

Analyses of Mössbauer mechanical measurements indicate that the cochlea is mechanically active.

Using the results of Mössbauer measurements, mechanical activity in the cochlea was tested for by comparing the measured basilar membrane (BM) transverse velocity amplitude with that calculated for a lossless mechanically passive system, derived from the measured BM velocity phase. If the cochlea is considered to be a lossless mechanically passive system, then the transverse velocity amplitude can be calculated from the group velocity and the relative variation of stiffness along the BM. The group velocity can be derived from the Mössbauer phase measurements, and the relative variation of stiffness along the BM can be derived from the frequency map of the cochlea. Making some general assumptions, the actual transverse velocity amplitudes are then compared from the Mössbauer amplitude data with those derived from the Mössbauer phase data, to determine if there is a significant transverse velocity gain. This operation was performed on several sets of Mössbauer data. From Mössbauer data showing sharp tuning, differences were found of up to 40 dB between the actual transverse velocity amplitude and the calculated lossless passive transverse velocity amplitude derived from the phase data. Examination of the assumptions made during the calculation of the lossless passive transverse velocity amplitude showed that none could account for a 40-dB transverse velocity gain. Thus, it is concluded that this transverse velocity gain can only be accounted for by the contribution to the amplitude of the transverse BM velocity by mechanically active elements along the cochlear duct. From Mössbauer data showing much less sharp tuning, it was found that the actual transverse velocity amplitude was approximately equal to the calculated lossless passive transverse velocity amplitude, basal to the characteristic place. This result is attributed to the disabling of the mechanically active elements along the cochlear duct. Apical to the characteristic place, the actual transverse velocity amplitude is shown to behave in a manner that suggests that the effective damping increases markedly in this region. This increase in effective damping is not necessarily due to an increase in viscous damping but could be due to any mechanism removing energy from the BM traveling wave. As an example, this paper discusses how this effective damping could be accounted for the transfer of energy to another mode of vibration at the characteristic place.

Suppression of stimulus frequency otoacoustic emissions.

Observations of the suppression of stimulus frequency evoked otoacoustic emissions (SFOAEs) by a second tone were made in human subjects. Measurements were made with the suppressor tone at frequencies and levels at, above, and below the stimulus tone generating the SFOAE. Data were collected with the stimulus tone at a range of levels (20-60 dB SPL), over a range of frequencies and in six different ears, in three subjects. The results were fitted to a phenomenological model, which allowed the data to be expressed as two parameters against the frequency of the suppressor tone. Characteristics of the suppression were examined, in particular the asymmetry between suppression by tones of higher and lower frequency than the tone evoking the SFOAE. At relatively low levels of suppressor tone, suppressors with frequencies higher than the stimulus tone were more effective suppressors than lower frequencies. At higher levels of suppressor tone, the situation was reversed, with lower frequencies being more effective than higher frequencies. These results were discussed in terms of nonlinear interaction between waves in the cochlea. This interpretation was used to estimate the shape of the traveling wave envelope produced by the stimulus tone, from the results of the suppression experiments. It was shown that the estimates of the shapes of the traveling wave envelope were nonlinear, the peak of the envelope becoming sharper at lower levels of stimulus. A simple quantitative model of SFOAE suppression was formulated using concepts of energy flow within the cochlea. This model produced SFOAE suppression results with all the major characteristics of SFOAE suppression from a real, human ear.

Pharmacokinetics of clindamycin phosphate in dogs after single intravenous and intramuscular administrations.

Clindamycin phosphate was administered to dogs at dosage of 11 mg/kg of body weight via IV and IM routes. The disposition curve for IV administration was best represented as a 2-compartment open model. Mean elimination half life was 194.6 +/- 24.5 minutes for IV administration and 234.8 +/- 27.3 minutes for IM administration. Bioavailability after IM administration was 87%. Dosage of 11 mg/kg, IV, given every 8 hours, provided serum concentration of clindamycin that exceeded the minimal inhibitory concentration for all Staphylococcus spp, as well as most pathogenic anaerobes, throughout the dosing interval. Intramuscular administration induced signs of pain and cannot be recommended.

The influence of contralateral acoustic stimulation on click-evoked otoacoustic emissions in humans.

Contralateral acoustic stimulation has the effect of reducing the amplitude and shifting the phase of click-evoked OAEs. This effect is thought to be mediated via the medial efferent system and, therefore, the presence of this effect could be used to test the integrity of the neural pathway from one cochlea to the other. With a clinical application in mind, a technique for demonstrating the influence of contralateral acoustic stimulation on click-evoked OAEs was designed to overcome fluctuations in patient and environmental noise. The results of this test on three normal subjects and a patient with a posterior fossa lesion are described.