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Objectives: UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Instrument is a comprehensive, self-administered survey for the assessment of gastrointestinal involvement in scleroderma patients, developed and validated in English. Our objective was to translate and validate a Romanian version of UCLA SCTC GIT 2.0., Methods: Translation from English into Romanian has been made using the forward-backward method. Sixty-four patients, attending a referral centre as part of an extensively studied cohort, were approached in a consecutive manner over a period of two years for administration of the questionnaire. We evaluated the reproducibility, internal consistency, construct validity and discriminative capacity of the translation (Romanian GIT)., Results: Fifty-four patients returned completed questionnaires. Internal consistency was demonstrated by Cronbach's alpha coefficient (0.931). Construct validity is supported by moderate, but significant correlations of Romanian GIT total score with the Mental Component Summary (MCS) of SF-36 (r=0.541, Spearman correlation) and among subscales, by significant correlations with SHAQ total score (r=0.559, Spearman correlation) and by strong correlations with gastrointestinal subscale of SHAQ (SHAQ GI) (r=0.726, Spearman correlation). Reproducibility was good as well. Divergent validity was supported by significant differences between patients with or without a clinical diagnosis of gastrointestinal disease. Other differences in the Romanian GIT total score were tested among subgroups of patients., Conclusions: The Romanian GIT has acceptable reliability and validity. This questionnaire can be used for the assessment of gastrointestinal involvement in scleroderma patients.

Daphnia magna individuals were transplanted across 12 sites from three Spanish river basins (Llobregat, Ebro, Jucar) showing different sources of pollution. Gene transcription, feeding and biochemical responses in the field were assessed and compared with those obtained in re-constituted water treatments spiked with organic eluates obtained from water samples collected at the same locations and sampling periods. Up to 166 trace contaminants were detected in water and classified by their mode of action into 45 groups that included metals, pharmaceuticals, pesticides, illicit drugs, and other industrial compounds. Physicochemical water parameters differentiated the three river basins with Llobregat having the highest levels of conductivity, metals and pharmaceuticals, followed by Ebro, whereas the Jucar river had the greatest levels of illicit drugs. D. magna grazing rates and cholinesterase activity responded similarly than the diversity of riparian benthic communities. Transcription patterns of 13 different genes encoding for general stress, metabolism and energy processes, molting and xenobiotic transporters corroborate phenotypic responses differentiated sites within and across river basins. Principal Component Analysis and Partial Least Square Projections to Latent Structures regression analyses indicated that measured in situ responses of most genes and biomarkers and that of benthic macroinvertebrate diversity indexes were affected by distinct environmental factors. Conductivity, suspended solids and fungicides were negatively related with the diversity of macroinvertebrates cholinesterase, and feeding responses. Gene transcripts of heat shock protein and metallothionein were positively related with 11 classes of organic contaminants and 6 metals. Gene transcripts related with signaling paths of molting and reproduction, sugar, protein and xenobiotic metabolism responded similarly in field and lab exposures and were related with high residue concentrations of analgesics, diuretics, psychiatric drugs, β blockers, illicit drugs, trizoles, bisphenol A, caffeine and pesticides. These results indicate that application of omic technologies in the field is a promising subject in water management., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The environmental presence of chemicals capable of affecting the endocrine system has become a matter of scientific and public concern after certain endocrine disruptor compounds (EDCs) have been detected in the aquatic environment. In this work, 31 different EDCs and related compounds (suspect EDCs) belonging to different contaminant classes were studied: 10 estrogens, natural and synthetic, 8 alkylphenolic compounds, bisphenol A, triclosan and triclorocaraban, 4 parabens, 2 benzotriazoles, 3 organophosphorous flame retardants and the chemical marker caffeine, in river water and sediment of four Iberian rivers (Ebro, Llobregat, Júcar and Guadalquivir). An extensive sampling has been undertaken in two monitoring campaigns (2010 and 2011). A total of 77 samples of water and 75 sediments were collected. For this propose two different multiresidue analytical methods were applied, using the automated online EQuan/TurboFlow™ liquid chromatography coupled to mass spectrometry detection in tandem. In terms of concentrations the compounds found at the highest average concentrations were: nonylphenol monocarboxylate (NP1EC), tolyltriazole (TT), tris(chloroisopropyl)phosphate (TCPP) found at average concentrations above 100 ng/L, followed by 1H-benzotriazole and tris(butoxyethyl)phosphate (TBEP) found at average concentration higher than 50 ng/L. Natural and synthetic hormones were found at low levels not exceeding 16 ng/L and 7 ng/g for water and sediment, respectively, however they contributed to more than 80% of the total estrogenicity of the samples (expressed as the equivalents of estradiol EEQ, ng/L). Regarding the spatial distribution of these contaminants, the Llobregat river was found to be the most contaminated river basin, having sites near the mouth of the river the ones with the highest contaminant load. In the Ebro river basin several hot spots were identified and Júcar showed to be the least contaminated. Overall, the study confirmed the presence of complex mixtures of unregulated contaminants, thus raising concern about their potential interactive effects., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Hospital effluents contribute to the occurrence of emerging contaminants in the environment due to their high load of pharmaceutical active compounds (PhACs) and some endocrine disruptor compounds (EDCs). Nowadays, hospital wastewaters are co-treated with urban wastewater; however, the dilution factor and the inefficiency of wastewater treatment plants in the removal of PhACs and EDCs make inappropriate the co-treatment of both effluents. In this paper, a new alternative to pre-treat hospital wastewater concerning the removal of PhACs and EDCs is presented. The treatment was carried out in a batch fluidized bed bioreactor under sterile and non-sterile conditions with Trametes versicolor pellets. Results on non-sterile experiments pointed out that 46 out of the 51 detected PhACs and EDCs were partially to completely removed. The total initial PhAC amount into the bioreactor was 8185 μg in sterile treatment and 8426 μg in non-sterile treatment, and the overall load elimination was 83.2% and 53.3% in their respective treatments. In addition, the Microtox test showed reduction of wastewater toxicity after the treatment. Hence, the good efficiency of the fungal treatment regarding removal of the wide diversity of PhACs and EDCs detected in hospital effluents is demonstrated., (Copyright © 2014. Published by Elsevier B.V.)

A novel fully automated method based on dual column switching using turbulent flow chromatography followed by liquid chromatography coupled to tandem mass spectrometry (TFC-LC-MS/MS) was applied for the determination of endocrine disruptors (EDCs) and related compounds in sediment and sewage sludge samples. This method allows the unequivocal identification and quantification of the most relevant environmental EDCs such as natural and synthetic estrogens and their conjugates, antimicrobials, parabens, bisphenol A (BPA), alkylphenolic compounds, benzotriazoles, and organophosphorus flame retardants, minimizing time of analysis and alleviating matrix effects. Applying this technique, after the extraction of the target compounds by pressurized liquid extraction (PLE), sediment and sewage sludge extracts were directly injected to the chromatographic system and the analytes were concentrated into the clean-up loading column. Using six-port switching system, the analytes were transferred to the analytical column for subsequent detection by MS-MS (QqQ). In order to optimize this multiplexing system, a comparative study employing six types of TurboFlow™ columns, with different chemical modifications, was performed to achieve the maximum retention of analytes and best elimination of matrix components. Using the optimized protocol low limits of quantification (LOQs) were obtained ranging from 0.0083 to 1.6 ng/g for sediment samples and from 0.10 to 125 ng/g for sewage sludge samples (except for alkylphenol monoethoxylate). The method was used to evaluate the presence and fate of target EDCs in the Ebro River which is the most important river in Spain with intensive agricultural and industrial activities in the basin that contribute to deteriorating soil and water quality., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A study was performed to assess exposure of the Spanish population to hexabromocyclododecane (HBCD). Based on consumption data statistics, food items from six food groups, i.e., fish and seafood, meat, animal fat, dairy products, eggs, and vegetable oils, were sampled and analyzed for HBCD followed by per capita intake calculations. The highest levels of HBCD were found in the fish and seafood samples (mean value of 11.6 ng/g lw), followed by meat samples (mean value of 2.68 ng/g lw), eggs (mean value of 1.75 ng/g lw), dairy products (mean value of 0.78 ng/g lw), animal fat (mean value of 0.74 ng/g lw), and vegetable oils (mean value of 0.45 ng/g lw). The daily ingestion rate of HBCD was estimated at 2.58 ng (kg of body weight)(-1) day(-1). HBCD mainly came from fish and seafood (56%), but also dairy products (14%) and meat (12%) contributed.

In the present study the occurrence of emerging hydrophobic organic pollutants in sediment samples from South America (Chile and Colombia) was investigated for the first time. Nineteen Chilean and thirteen Colombian sediment samples were analyzed in order to determine their content of brominated flame retardants (BFRs) (including PBDEs and emerging BFRs) as well as UV filters (UV-F). Samples were collected from neighboring aquatic ecosystems highly urbanized and industrialized in Colombia (Magdalena River area) and Chile (Biobio region). Different analytical procedures were applied depending on the selected analytes, based on chromatographic and mass spectrometric methodologies (GC-MS and LC-MS-MS). In general, concentration levels of both BFRs (up to 2.43 and 143ngg(-1) dw of PBDEs in Chile and Colombia, respectively) and UV-F (nd-2.96 and nd-54.4ngg(-1) dw in Chile and Colombia, respectively) were in the low range of published data, and the contribution of BFRs was higher than that of UV-F for almost all the sampled sediments., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The present study describes a novel, fully automated method, based on column switching using EQuan™ columns for an integrated sample preconcentration and liquid chromatography coupled to tandem mass spectrometry (LC-LC-MS/MS). The method allows the unequivocal identification and quantification of the most relevant environmental endocrine disruptors compounds (EDCs) and compounds suspected to be EDCs, such as natural and synthetic estrogens and their conjugates, antimicrobials, parabens, bisphenol A, alkylphenolic compounds, benzotriazoles, and organophosphorus flame retardants, in surface river water and wastewater samples. Applying this technique, water samples were directly injected into the chromatographic system and the target compounds were concentrated into the loading column. Thereafter, the analytes were transferred into the analytical column for subsequent detection by MS-MS (QqQ). A comparative study employing three types of columns, with different chemical modifications, was performed in order to determine the optimal column that allowed maximum retention and subsequent elution of the analytes. Using this new optimized methodology a fast and easy online methodology for the analysis of EDCs in surface river water and wastewater with low limits of quantification (LOQ) was obtained. LOQs ranged from 0.008 to 1.54 ng/L for surface river water and from 0.178/0.364 to 12.5/25.0 ng/L (except for alkylphenol monoethoxylates) for effluent/influent waste water. Moreover, employing approximately 1h, a complete analysis was performed which was significant improvement in comparison to other methods reported previously. This method was used to track the presence and fate of target compounds in the Ebro River which is the most important river in Spain whose intensive agricultural and industrial activities concentrate mainly close to the main cities in the basin, deteriorating soil and water quality., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The objective of this study was to determine different brominated flame retardants (BFRs) in sewage sludge produced in 17 wastewater treatment plants (WWTPs) located in the Northeast of Spain. A total of eight polybrominated diphenyl ether (PBDE) congeners, from tri- to deca-BDEs, were analyzed. The emerging BFR compounds, hexabromobenzene (HBB), pentabromoethylbenzene (PBEB) and decabromodiphenylethane (DBDPE) were also analyzed. The instrumental methodology for the analysis was based on gas chromatography coupled to mass spectrometry with negative chemical ionization (GC-NICI-MS). Moreover, liquid cromathography-quadrupole linear ion trap mass spectrometry (LC-QqLIT-MS/MS) was applied for the determination of hexabromocyclododecanes (HBCDs), tetrabromobisphenol A (TBBPA) and their related compounds, bisphenol A (BPA), monobromobisphenol A (MonoBBPA), dibromobisphenol A (DiBBPA) and tribromobisphenol A (TriBBPA). The most abundant PBDE congener in these sewage sludge samples was BDE-209, with levels ranging from nd to 2303 ng/g dw. In addition, a significant concentrations of DBDPE were also detected, nd-257 ng/g dw, due to their increase production as a Deca-BDE substitute. The emerging compounds HBB and PBEB were detected in 4 WWTPs and their concentrations ranged between nd-5.71 and nd-2.33 ng/g, respectively. TBBPA was detected in quantifiable levels in 15 of the 17 WWTPs analyzed, in concentration range of nd-472 ng/g dw, whereas HBCDs were only found in 8 WWTPs in lower concentrations, between nd and 97.5 ng/g dw. Based on the analysis of sewage sludge samples from different WWTPs and in order to evaluate the impact of these contaminants in the environment, an estimation of BFRs accumulated in the total sewage sludge produced in Catalonia was carried out, with values of 57.8 kg/year, 6.76 kg/year, 13.5 kg/year, 1.56 kg/year, 0.18 kg/year and 0.02 kg/year for PBDEs, DBDPE, TBBPA, HBCDs, HBB and PBEB respectively., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Liver samples from 53 Franciscana dolphins along the Brazilian coast were analyzed for organobrominated compounds. Target substances included the following anthropogenic pollutants: polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), pentabromoethylbenzene (PBEB), hexabromobenzene (HBB), decabromodiphenylethane (DBDPE), as well as the naturally-generated methoxylated-PBDEs (MeO-PBDEs). PBDE concentrations ranged from 6 to 1797 ng/g lw (mean 166 ± 298 ng/g lw) and were similar to those observed in cetaceans from Northern Hemisphere. PBBs were found in all sampling locations (

Objectives/hypothesis: Compare the accuracy of wideband acoustic transfer functions (WATFs) measured in the ear canal at ambient pressure to methods currently recommended by clinical guidelines for predicting middle-ear effusion (MEE)., Study Design: Cross-sectional validating diagnostic study among young children with and without MEE to investigate the ability of WATFs to predict MEE., Methods: WATF measures were obtained in an MEE group of 44 children (53 ears; median age, 1.3 years) scheduled for middle-ear ventilation tube placement and a normal age-matched control group of 44 children (59 ears; median age, 1.2 years) with normal pneumatic otoscopic findings and no history of ear disease or middle-ear surgery. An otolaryngologist judged whether MEE was present or absent and rated tympanic-membrane (TM) mobility via pneumatic otoscopy. A likelihood-ratio classifier reduced WATF data (absorbance, admittance magnitude and phase) from 0.25 to 8 kHz to a single predictor of MEE status. Absorbance was compared to pneumatic otoscopy classifications of TM mobility., Results: Absorbance was reduced in ears with MEE compared to ears from the control group. Absorbance and admittance magnitude were the best single WATF predictors of MEE, but a predictor combining absorbance, admittance magnitude, and phase was the most accurate. Absorbance varied systematically with TM mobility based on data from pneumatic otoscopy., Conclusions: Results showed that absorbance is sensitive to middle-ear stiffness and MEE, and WATF predictions of MEE in young children are as accurate as those reported for methods recommended by the clinical guidelines., (Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.)

Albumin dialysis using the molecular adsorbent recirculating system (MARS) is a new therapeutic approach for liver diseases. To gain insight into the mechanisms involved in albumin dialysis, we analyzed the peptides and proteins absorbed into the MARS strong anion exchange (SAX) cartridges as a result of the treatment of patients with cholestasis and resistant pruritus. Proteins extracted from the SAX MARS cartridges after patient treatment were digested with two enzymes. The resulting peptides were analyzed by multidimensional liquid chromatography coupled to tandem mass spectrometry. We identified over 1,500 peptide sequences corresponding to 144 proteins. In addition to the proteins that are present in control albumin-derived samples, this collection includes 60 proteins that were specific to samples obtained after patient treatment. Five of these proteins (neutrophil defensin 1 [HNP-1], secreted Ly-6/uPAR-related protein 1 [SLURP1], serum amyloid A, fibrinogen alpha chain and pancreatic prohormone) were confirmed to be removed by the dialysis procedure using targeted selected-reaction monitoring MS/MS. Furthermore, capture of HNP-1 and SLURP1 was also validated by Western blot. Interestingly, further analyses of SLURP1 in serum indicated that this protein was 3-fold higher in cholestatic patients than in controls. Proteins captured by MARS share certain structural and biological characteristics, and some of them have important biological functions. Therefore, their removal could be related either to therapeutic or possible adverse effects associated with albumin dialysis.

HSA solutions account for 14% of the world market for plasma products. Albumin is indicated for reestablishing and maintaining circulatory volume in situations resulting from traumatic shock, surgery, or blood loss. Albumin is also used in extracorporeal liver support devices that perform blood dialysis against this protein. However, the protein composition of therapeutic albumin is only partially known. We performed an exhaustive analysis of albumin composition using a proteomic approach. Low abundance proteins and peptides in these samples were concentrated using a strong anion exchange resin. The absorbed material was eluted with a stepwise gradient of ammonium trifluoroacetate and the protein fraction was digested and analyzed by multidimensional liquid chromatography coupled to ESI-MS/MS using a linear ion trap. A total of 1219 peptides corresponding to 141 proteins different from albumin were identified with a false discovery rate <1%. Near 50% of these proteins have been described previously as forming part of the albuminome. Some of these proteins are proteases (kallikrein) or protease inhibitors (kininogen and SRPK1) or have relevant functions in cell surface adhesion (selectin, cadherins, and ICAMs) or in immunity and defense (molecules of the complement system and attractin). Characterization of these proteins and peptides is crucial in order to understand the therapeutic and possible deleterious effects of albumin therapies, in which this solution is infused to treat different pathological conditions.

DPOAE input/output (I/O) functions were measured at 7f2 frequencies (1 to 8 kHz; f2/f1 = 1.22) over a range of levels (-5 to 95 dB SPL) in normal-hearing and hearing-impaired human ears. L1-L2 was level dependent in order to produce the largest 2f1-f2 responses in normal ears. System distortion was determined by collecting DP data in six different acoustic cavities. These data were used to derive a multiple linear regression model to predict system distortion levels. The model was tested on cochlear-implant users and used to estimate system distortion in all other ears. At most but not all f2's, measurements in cochlear implant ears were consistent with model predictions. At all f2 frequencies, the ears with normal auditory thresholds produced I/O functions characterized by compressive nonlinear regions at moderate levels, with more rapid growth at low and high stimulus levels. As auditory threshold increased, DPOAE threshold increased, accompanied by DPOAE amplitude reductions, notably over the range of levels where normal ears showed compression. The slope of the I/O function was steeper in impaired ears. The data from normal-hearing ears resembled direct measurements of basilar membrane displacement in lower animals. Data from ears with hearing loss showed that the compressive region was affected by cochlear damage; however, responses at high levels of stimulation resembled those observed in normal ears.

Primary and secondary sources combine to produce the 2f1-f2 distortion product otoacoustic emission (DPOAE) measured in the ear canals of humans. DPOAEs were obtained in nine normal-hearing subjects using a fixed-f2 paradigm in which f1 was varied. The f2 was 2 or 4 kHz, and absolute and relative primary levels were varied. Data were obtained with and without a third tone (f3) placed 15.6 Hz below 2f1-f2. The level of f3 was varied in order to suppress the stimulus frequency otoacoustic emission (SFOAE) coming from the 2f1-f2 place. These data were converted from the complex frequency domain into an equivalent time representation using an inverse fast Fourier transform (IFFT). IFFTs of unsuppressed DPOAE data were characterized by two or more peaks. Relative amplitudes of these peaks depended on overall primary level and on primary-level differences. The suppressor eliminated later peaks, but early peaks remained relatively unaltered. Results are interpreted to mean that the DPOAE measured in humans includes components from the f2 place (intermodulation distortion) and DP place (in the form of a SFOAE). These findings build on previous work by providing evidence that multiple peaks in the IFFT are due to a secondary source at the DP place.

Previous studies of animals observed a phenomenon of adaptation of distortion product otoacoustic emission (DPOAE) and found that the phenomenon was mediated to a large extent by the medial olivocochlear (MOC) reflex. The present study investigated DPOAE adaptation in humans. The following stimuli were used: f2/f1 = 1.2; f2 = 2, 4, or 5.65 kHz; L2 = 50-65 dB SPL re 20 microPa rms, L1 - L2 = 0-15 dB, where L1 and L2 represent levels of the f1 and f2 tones, respectively; duration of two-tone burst = 5.5 s; interburst gap = 20 or 30 s; number of repetitions = 40 or 64. We analyzed the 2f1 - f2 DPOAE as a function of time using a method of heterodyne envelope detection. The subjects were 20 humans aged from 15 to 54 years (median = 21 years) with normal hearing. We observed that (1) humans exhibited DPOAE adaptation phenomenon; (2) the time course of DPOAE level was characterized by a 2-exponential function; (3) distributions of the fast and slow time constants were well separated with their median values being 69 ms and 1.51 s, respectively; (4) distributions of the magnitudes of the fast and slow adaptation components were largely overlapped with their median values being 0.65 and 0.40 dB, respectively; and (5) the combined magnitude of the adaptation ranged from 0.4 to 3.0 dB with a median of 1.10 dB. To our knowledge, the present study is the first published article to describe adaptation of DPOAE in humans. These results should help advance the basic knowledge of human cochlear mechanics operating under the control of the MOC feedback system and contribute to the development of practical applications such as identifying people at high risk of acoustical injury and a clinical test of the functional status of the MOC system.

This article describes some of the factors relevant to the establishment of a universal newborn hearing screening (UNHS) program. First, the difficulty in providing precise estimates of test sensitivity and specificity are reviewed. This section is followed by hypothetical estimates of overall programmatic costs, first for a fixed number of babies to be screened and then as a function of the number of babies to be screened in a year. Included in these estimates are the costs for equipment, disposables, personnel, and follow-up testing. These estimates are provided for three different screening protocols: auditory brainstem response (ABR) alone, otoacoustic emission (OAE) alone, and OAE followed by ABR only for those babies who failed the OAE screening. If follow-up costs are not included, it is less expensive to screen newborns with OAEs compared with the other two protocols. However, once follow-up testing is included as part of the program costs and there are at least 400 births per year, procedures in which OAEs are performed first, followed by an ABR on those infants who do not pass the OAE test, result in the lowest costs. Hospitals with as few as 400 births per year should expect per-baby costs not exceeding $30, regardless of which protocol is used. For all three protocols, the unit costs decrease as the number of babies screened increases. The final section describes data from a local UNHS program in which all infants are screened first with an OAE test, followed by an ABR test on infants not passing the OAE screening. Idiosyncratic features to this program are described, including the fact that all screening tests are performed by audiologists, who are paid on a part-time basis, adding cost to the program. Even under these circumstances, the unit cost is under $30. These data lead us to conclude that all infants can be screened in a cost-effective manner.

Objectives: 1) To describe the hearing status of the at-risk infants in the National Institutes of Health-Identification of Neonatal Hearing Impairment study sample at 8 to 12 mo corrected age (chronologic age adjusted for prematurity). 2) To describe the visual reinforcement audiometry (VRA) protocol that was used to obtain monaural behavioral data for the sample., Design: All neonatal intensive care unit infants and well babies with risk factors (including well babies who failed neonatal tests) were targeted for follow-up behavioral evaluation once they had reached 8 mo corrected age. Three thousand one hundred and thirty-four (64.4%) of the 4868 surviving infants returned for at least one behavioral hearing evaluation, which employed a well-defined VRA protocol. VRA thresholds or minimum response levels (MRLs) were determined for speech and pure tones of 1.0, 2.0, and 4.0 kHz for each ear using insert earphones., Results: More than 95% of the infants were reliably tested with the VRA protocol; 90% provided complete tests (four MRLs for both ears). Ninety-four percent of the at-risk infants were found to have normal hearing sensitivity (MRLs of 20 dB HL) at 1.0, 2.0, and 4.0 kHz in both ears. Of the infants, 2.2% had bilateral hearing impairment, and 3.4% had impairment in one ear only. More than 80% of the impaired ears had losses of mild-to-moderate degree., Conclusions: This may be the largest study to attempt to follow all at-risk infants with behavioral audiometric testing, regardless of screening outcome, in an effort to validate the results of auditory brain stem response, distortion product otoacoustic emission, and transient evoked otoacoustic emission testing in the newborn period. It is one of only a few studies to report hearing status of infants at 1 yr of age, using VRA on a clinical population. Successful testing of more than 95% of the infants who returned for the VRA follow-up documents the feasibility of obtaining monaural behavioral data in this population.

The objective of this study was to determine whether distortion product otoacoustic emission (DPOAE) test performance, defined as its ability to distinguish normal-hearing ears from those with hearing loss, can be improved by examining response and noise amplitudes at 2 f1-f2 and 2f2-f1 simultaneously. In addition, there was interest in knowing whether measurements at both DPs and for several primary frequency pairs can be used in a multivariate analysis to further optimize test performance. DPOAE and noise amplitudes were measured at 2f1-f2 and 2 f2-f1 for 12 primary levels (L2 from 10 to 65 dB SPL in 5-dB steps) and 9 pairs of primary frequencies (0.5 to 8 kHz in 1/2-octave steps). All data were collected in a sound-treated room from 70 subjects with normal hearing and 80 subjects with hearing loss. Subjects had normal middle-ear function at the time of the DPOAE test, based on standard tympanometric measurements. Measurement-based stopping rules were used such that the test terminated when the noise floor around the 2 f1-f2 DP was < or = -30 dB SPL or after 32 s of artifact-free averaging, whichever occurred first. Data were analyzed using clinical decision theory in which relative operating characteristics (ROC) curves were constructed and areas under the ROC curves were estimated. In addition, test performance was assessed by selecting the criterion value that resulted in a sensitivity of 90% and determining the specificity at that criterion value. Data were analyzed using traditional univariate comparisons, in which predictions about auditory status were based only on data obtained when f2 = audiometric frequency. In addition, multivariate analysis techniques were used to determine whether test performance can be optimized by using many variables to predict auditory status. As expected, DPOAEs were larger for 2f1-f2 compared to 2 f2-f1 in subjects with normal hearing. However, noise amplitudes were smaller for 2f2-f1, but this effect was restricted to the lowest f2 frequencies. A comparison of signal-to-noise ratios (SNR) within normal-hearing ears showed that the 2f1-f2 DP was more frequently characterized by larger SNRs compared to 2f2-f1. However, there were several subjects in whom 2f2-f1 produced a larger SNR. ROC curve areas and specificities for a fixed sensitivity increased only slightly when data from both DPs were used to predict auditory status. Multivariate analyses, in which the inputs included both DPs for several primary frequency pairs surrounding each audiometric frequency, produced the highest areas and specificities. Thus, DPOAE test performance was improved slightly by examining data at two DP frequencies simultaneously. This improvement was achieved at no additional cost in terms of test time. When measurements at both DPs were combined with data obtained for several primary frequency pairs and then analyzed in a multivariate context, the best test performance was achieved. Excellent test performance (ROC) curve areas >0.95% and specificities >92% at all frequencies, including 500 Hz, were achieved for these conditions. Although the results described should be validated on an independent set of data, they suggest that the accuracy with which DPOAE measurements identify auditory status can be improved with multivariate analyses and measurements at multiple DPs.

Distortion product otoacoustic emission (DPOAE) frequency functions were measured in normal-hearing and hearing-impaired ears. A fixed-f2/swept-f1 paradigm was used with f2 fixed at half-octave intervals from 1 to 8 kHz. L1 was always 10 dB greater than L2, and L2 was varied from 65 to 10 dB SPL in 5-dB steps. The responses were quantified by the frequency and amplitude of the peak response. Peak responses were closer to f2 in higher frequency regions and for lower intensity stimulation. Results from hearing-impaired subjects suggest that audiometric thresholds at the distortion product frequency, fdp, in addition to hearing status at f2, can affect DPOAE results. Results are discussed in terms of several manifestations of a second resonance model, as well as a dual source model for the generation of DPOAEs as measured in the ear canal of humans. It appears that a dual source model accounts for the data better than second filter models.

This study evaluated the accuracy of acoustic response tests in predicting conductive hearing loss in 161 ears of subjects from the age of 2 to 10 yr, using as a "gold standard" the air-bone gap to classify ears as normal or impaired. The acoustic tests included tympanometric peak-compensated static admittance magnitude (SA) and tympanometric gradient at 226 Hz, and admittance-reflectance (YR) measurements from 0.5 to 8 kHz. The performance of individual, frequency-specific, YR test variables as predictors was assessed. By applying logistic regression (LR) and discriminant analysis (DA) techniques to the multivariate YR response, two univariate functions were calculated as the linear combinations of YR variables across frequency that best separated normal and impaired ears. The tympanometric and YR tests were also combined in a multivariate manner to test whether predictive efficacy improved when 226-Hz tympanometry was added to the predictor set. Conductive hearing loss was predicted based on air-bone gap thresholds at 0.5 and 2 kHz, and on a maximum air-bone gap at any octave frequency from 0.5 to 4 kHz. Each air-bone gap threshold ranged from 5 to 30 dB in 5-dB steps. Areas under the relative operating characteristic curve for DA and LR were larger than for reflectance at 2 kHz, SA and Gr. For constant hit rates of 80% and 90%, both DA and LR scores had lower false-alarm rates than tympanometric tests-LR achieved a false-alarm rate of 6% for a sensitivity of 90%. In general, LR outperformed DA as the multivariate technique of choice. In predicting an impairment at 0.5 kHz, the reflectance scores at 0.5 kHz were less accurate predictors than reflectance at 2 and 4 kHz. This supports the hypothesis that the 2-4-kHz range is a particularly sensitive indicator of middle-ear status, in agreement with the spectral composition of the output predictor from the multivariate analyses. When tympanometric and YR tests were combined, the resulting predictor performed slightly better or the same as the predictor calculated from the use of the YR test alone. The main conclusion is that these multivariate acoustic tests of the middle ear, which are analyzed using a clinical decision theory, are effective predictors of conductive hearing loss.

Objective: This retrospective study describes the phenotype associated with the single most common cause of genetic hearing loss. The frequency of childhood deafness is estimated at 1/500. Half of this hearing loss is genetic and approximately 80% of genetic hearing loss is nonsyndromic and inherited in an autosomal recessive manner. Approximately 50% of childhood nonsyndromic recessive hearing loss is caused by mutations in the connexin 26 (Cx26) gene (GJB2/DFNB1), making it the most common form of autosomal recessive nonsyndromic hearing loss with a carrier rate estimated to be as high as 2.8%. One mutation, 35delG, accounts for approximately 75% to 80% of mutations at this gene., Methods: Hearing loss was examined in 46 individuals from 24 families who were either homozygous or compound heterozygous for Cx26 mutations. A subset of these individuals were examined for vestibular function, otoacoustic emissions, auditory brainstem response, temporal bone computed tomography, electrocardiography, urinalyses, dysmorphology, and thyroid function., Results: Although all persons had hearing impairment, no consistent audiologic phenotype was observed. Hearing loss varied from mild-moderate to profound, even within the group of families homozygous for the common mutation 35delG, suggesting that other factors modify the phenotypic effects of mutations in Cx26. Furthermore, the hearing loss was observed to be progressive in a number of cases. No associations with inner ear abnormality, thyroid dysfunction, heart conduction defect, urinalyses, dysmorphic features, or retinal abnormality were noted., Conclusion: Newborns with confirmed hearing loss should have Cx26 testing. Cx26 testing will help define a group in which approximately 60% will have profound or severe-profound hearing loss and require aggressive language intervention (many of these patients will be candidates for cochlear implants).

In-the-ear calibration of sound pressure level may be problematic at frequencies above 2 kHz, because the pressure can vary significantly along the length of the ear canal, due to reflection of sound waves at the eardrum. This issue has been investigated by measuring behavioral thresholds to tones in a group of human subjects (N = 61) for two different insertion depths of an insert earphone. The change in insertion depth was intended to alter the distribution of pressure in the ear canal, shifting the frequency at which spectral notches occur. The inset earphone or "probe" (Etymotic ER-10C) also contained a calibrated microphone, allowing the recording of sound pressure levels in the ear canal. Prior to the threshold measurements in each subject, the Thevenin acoustic source characteristics of the probe were determined by a special calibration procedure. This calibration allowed the expression of the sound level at threshold in terms of acoustic intensity (W/m2). The impact of changes in insertion depth was determined by measuring behavioral threshold at each depth. Because cochlear sensitivity remained constant, the level of sound entering the ear at threshold should have been the same (within measurement error) for both insertions. The difference in sound pressure level (SPL) at threshold between the two probe insertions was greatest at the notch frequency of the first insertion. At this notch frequency, the SPL at threshold increased by an average of 11.4 dB. The change in sound intensity level (SIL) at threshold was almost always less than the change in SPL. At the notch frequency, the SIL decreased, on average, by only 0.5 dB. These results suggest that SIL may be a better indicator than SPL of the sound level entering the ear, especially for frequencies in the 4-8 kHz range.

Objective: The current study sought to determine whether tone burst auditory brain stem response (ABR) latencies could be used to detect an increase in the cochlear traveling wave velocity in patients with Meniere's disease., Background: It has been proposed that the derived band ABR technique can be used to show an increase in cochlear traveling wave velocity in patients with Meniere's disease. The current study sought to replicate these findings using tone burst ABR at frequencies of 0.5, 1, 2, 4, and 8 kHz and intensities from 40-100 dB hearing loss (HL) in 10-dB steps., Methods: Wave V latency differences between adjacent frequencies were taken to represent the time it takes the traveling wave to travel between the "place" on the basilar membrane where these two frequencies are represented. Thirty-two subjects participated in the project consisting of 10 with normal hearing, 10 with cochlear HL (not caused by Meniere's disease), and 12 with Meniere's disease., Results: There were no significant differences in absolute wave V latencies or in wave V latency differences (travel time estimates) between the groups (repeated measures analysis of variance, p > 0.05)., Conclusion: These results suggest that wave V latencies and estimates of cochlear travel time cannot be used to distinguish Meniere's disease from other forms of cochlear HL or from normal-hearing ears. The results of this study differ from those using the derived band ABR technique. This difference may be because of the disease state of the authors' subjects or differences in stimulus paradigm.

Interactions among age, threshold, and frequency in relation to distortion product otoacoustic emissions (DPOAE) have yet to be resolved. The effects of these variables were explored by analyzing DPOAEs in ears with thresholds not exceeding 20 dB HL. Multivariate regression analyses were performed in two different ways. For data to be included in the first analysis, audiometric threshold had to be 20 dB HL or better only at the particular frequency under study, but might exceed 20 dB HL at other half-octave frequencies. Significant main effects were found for age, threshold, and frequency. There was also an age-by-frequency interaction, but a significant age-by-threshold interaction was not observed. DPOAE amplitudes decreased as either age, frequency, or threshold increased. In the second analysis, when a more stringent inclusion criterion was applied (normal thresholds at all frequencies), the main effects for age, threshold, and frequency were not significant. The significant age-by-frequency interaction remained, whereby DPOAE amplitudes decreased as age and frequency increased, but the age-by-threshold interaction again was not significant. The magnitude of DPOAE amplitude change across age, threshold, and frequency and for the age-by-frequency interaction was small but similar for both groups of subjects. Age in association with threshold did not account for observed changes in DPOAE amplitudes for either group. Importantly, the lack of a significant age-by-threshold interaction indicates that there may be processes intrinsic to aging alone that act on DPOAE generation.

This study examined the effect of primary stimulus level on the ability of distortion product otoacoustic emission (DPOAE) measurements to separate normal-hearing from hearing-impaired ears. Complete I/O functions were obtained for nine f2 frequencies on 210 people approximately evenly divided between normal hearing and hearing impaired. Clinical decision theory was used to assess both DPOAE amplitudes and DPOAE threshold as diagnostic indicators of hearing status. Moderate level primary stimuli elicited responses that separated normal from impaired better than either lower level or higher level stimuli. The two populations were differentiated for all frequencies above 500 Hz by DPOAE amplitude, given primary levels, L1 and L2, of 65 and 55 dB SPL. DPOAE threshold performed equally well, but threshold ambiguity in noise and longer testing times make it a less suitable DPOAE measure to use diagnostically.

Distortion product otoacoustic emission (DPOAE) input/output functions were measured at nine f2 frequencies ranging from 500 to 8000 Hz in 210 normal-hearing and hearing-impaired subjects. In a companion paper [Stover et al., J. Acoust. Soc. Am. 100, 956-967 (1996)], L1-L2 was held constant at 10 dB, and L2 was varied from 65 to 10 dB SPL in 5-dB steps. Based upon analyses using clinical decision theory, it was demonstrated that DPOAE amplitudes for 65/55 dB SPL primaries (L1/L2) and DPOAE thresholds resulted in the greatest separation between normal and impaired ears. In this paper, the data for these two conditions were recast as cumulative distributions, which not only describe the extent of overlap between normal and impaired distributions, but also provide the measured value (i.e., the specific DPOAE amplitude or threshold) for any combination of hit and false alarm rates. From these distributions, confidence limits were constructed for both DPOAE amplitude and threshold to determine the degree of certainty with which any measured response could be assigned to either the normal or impaired population. For these analyses, DPOAE measurements were divided into three categories (a) response properties that would be unlikely to come from normal ears, (b) response properties that would be unlikely to come from impaired ears, and (c) response properties for which hearing status was uncertain. Based upon DPOAE amplitude measurements, the region of uncertainty, defined between the 95 percentile for impaired ears and the 5 percentile for normal ears, was relatively narrow for f2 frequencies ranging from 707 to 4000 Hz. For DPOAE thresholds, this region was relatively narrow for F2 frequencies ranging from 1414 to 4000 Hz.

Click-evoked otoacoustic emission (COAE) and tone-burst-evoked otoacoustic emission (TBOAE) input/output (I/O) functions and group latencies were measured in normal-hearing and hearing-impaired ears to determine the extent to which these two types of transient-evoked otoacoustic emissions (TEOAEs) were similar. When stimulus levels measured in 1/3 octave bands centered at 500, 1000, 2000, and 4000 Hz were similar, TBOAE and COAE I/O functions were essentially identical in regions of normal hearing. This held true in subjects who had normal hearing from 250 to 8000 Hz as well as for subjects who had normal hearing across some frequency ranges but hearing impairment across others. The high degree of correlation offers support to the view that both types of transient emissions share common generators. There were no significant differences in group delay between TBOAEs measured from normal-hearing and hearing-impaired subjects.

A novel analysis approach has been developed to examine the latency of distortion product otoacoustic emissions (DPOAEs). DPOAEs were measured in ten normal-hearing adults in a paradigm in which f2 was held constant and f1 was varied. This paradigm was used with a wide range of primary levels. Latency was estimated in two ways. In the first, a phase-slope delay measurement was used which showed a significant response latency increase as stimulus intensity was decreased. In the second approach, an inverse-FFT procedure was used to provide a temporal analysis of the data. Results of this analysis reveal a complex latency structure with multiple peaks in the envelope of the time waveform. The latencies of individual peaks remain constant across level, however, short latency peaks have the greatest amplitudes at higher levels, and longer latency peaks are largest at low levels. These results would be consistent with the idea that there are multiple intracochlear sources for distortion product generation; however, a simple model, in which generation is assigned to the f2 and the 2f1-f2 place, does not adequately explain the number of envelope peaks that were present in many ears.

This paper describes audiologic, electrophysiologic, and medical test results for a now 10-year-old girl who has had 45 episodes of reversible, sudden sensorineural hearing loss over the last 8 years. Episodes have lasted from 6 to 72 hours and often have been accompanied by a mild illness. Acoustic immittance measures have been consistent with normal middle-ear function with the exception of absent ipsilateral and contralateral acoustic reflexes. Mechanically evoked perioral reflex activity was markedly asymmetric following lower lip stimulation. The asymmetry of R1 activation between right and left side lower lip inputs raises questions about the integrity of central connections within the brain stem, including internuncial pathways coursing between trigeminal sensory relay nuclei and the facial motor nucleus. An electrocochleographic evaluation revealed cochlear microphonic but absent or markedly abnormal whole nerve action potentials. Auditory brainstem responses (ABR) have been either absent or poorly formed and significantly delayed, regardless of hearing sensitivity. Middle and late auditory evoked potentials were essentially normal. Both transient-evoked and distortion-product otoacoustic emissions were present regardless of peripheral auditory sensitivity. All medical tests have been essentially normal. Although no definitive diagnosis has been reached, beta blockers have been used with some success. Taken together, these data document a very unusual case of fluctuating hearing loss. The electrocochleographic and otoacoustic emission data suggest that the outer hair cells are functioning normally and that the loss is not cochlear in origin.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient-evoked (TEOAE) and distortion-product otoacoustic emissions (DPOAE) were measured in 51 graduates of an intensive care nursery and compared to data obtained from 80 normal-hearing children and adults. All infants had click-evoked auditory brainstem responses (ABR) at 30 dB nHL or less while the older subjects had pure-tone thresholds of 20 dB HL or less for octave frequencies from 250 to 8000 Hz. OAE data were collected using commercially available devices. All data were analyzed in terms of emission amplitude, emission-to-noise ratio, and response reproducibility as a function of frequency. DPOAEs were measured at three points per octave between f2 frequencies of approximately 500 and 8000 Hz. TEOAEs were elicited by clicks and were analyzed in both octave and 1/3-octave bands centered at frequencies from 500 to 4000 Hz, as well as in the broadband condition. In addition, stimulus amplitudes for the clicks used to elicit TEOAEs were analyzed within octave and 1/3-octave bands to determine whether any age-related differences in responses can be accounted for on the basis of stimulus differences. Both emission amplitude and noise amplitude were greater in neonates than adults, although there was variability across frequency. Emission-to-noise ratio and response reproducibility were more similar between groups. For TEOAEs, high-frequency emission-to-noise ratios were larger in neonates compared to older subjects, while the reverse was true in the lower frequencies. Less obvious frequency effects were observed for DPOAEs. These findings are discussed in relation to the potential use of OAEs as screening measures for neonatal hearing loss.

Distortion product otoacoustic emission (DPOAE) data were obtained with a custom-designed system from 20 subjects with normal hearing. Cavity measurements, using this system and an Etymotic ER-10B low-noise microphone system, resulted in estimates of recording system distortion of -20 dB SPL for f2 frequencies ranging from 500 to 8000 Hz, and primary levels ranging from 20 to 75 dB SPL (L2 = L1-10 dB). Using this system it was possible to automatically adjust averaging time in order to obtain the same residual noise levels across frequencies. In all subjects with normal hearing, DPOAEs were measurable over a wide range of primary levels for octave f2 frequencies from 1000 to 8000 Hz, but not at 500 Hz. At 500 Hz, only half of the normal-hearing subjects produced DPOAEs that were above the noise floor. When they did, DPOAE amplitude was less than that observed at higher f2 frequencies. While the cause for response absence in some normal ears may have been due to residual noise, the reduced amplitude suggests that the other factors influence the measurement of DPOAEs at low frequencies. This result may be due to reduced cochlear production of DPOAEs at lower frequencies or reduced transmission through the middle ear.

The ability of transient-evoked otoacoustic emissions (TEOAEs) and distortion product otoacoustic emissions (DPOAEs) to distinguish normal hearing from hearing impairment was evaluated in 180 subjects. TEOAEs were analyzed into octave or one-third octave bands for frequencies ranging from 500 to 4000 Hz. Decision theory was used to generate receiver operating characteristic (ROC) curves for each of three measurements (OAE amplitude, OAE/noise, reproducibility) for each OAE measure (octave TEOAEs, 1/3 octave TEOAEs, DPOAEs), for octave frequencies from 500 to 4000 Hz, and for seven audiometric criteria ranging from 10 to 40 dB HL. At 500 Hz, TEOAEs and DPOAEs were unable to separate normal from impaired ears. At 1000 Hz, both TEOAE measures were more accurate in identifying hearing status than DPOAEs. At 2000 Hz, all OAE measures performed equally well. At 4000 Hz, DPOAEs were better able to distinguish normal from impaired ears. Almost without exception, measurements of OAE/noise and reproducibility performed comparably and were superior to measurements of OAE amplitude, although the differences were small. TEOAEs analyzed into octave bands showed better performance than TEOAEs analyzed into 1/3 octaves. Under standard test conditions, OAE test performance appears to be limited by background noise, especially for the low frequencies.

Transient-evoked otoacoustic emissions (TEOAEs) were measured in 113 normal-hearing and hearing-impaired ears to examine repeatability within a test session, which TEOAE parameter (level, TEOAE level-to-noise or reproducibility) best identified hearing loss and if the TEOAE separated into frequency-specific bands identified hearing loss in a corresponding frequency region. TEOAEs and stimulus levels were found to be very repeatable. For broadband TEOAEs, TEOAE level, TEOAE-to-noise, and % reproducibility were found to identify hearing loss equally well, based on measurement of the area underlying relative operator characteristic curves. Analysis for frequency-specific bands showed that separation of normal-hearing and hearing-impaired ears depended on frequency, with best identification at 2000 and 4000 Hz, identification at 1000 Hz slightly worse, and virtually no separation between normal-hearing and hearing-impaired ears at 500 Hz. Again, all three parameters were essentially equal in identifying hearing loss. Subjective evaluations of presence or absence of TEOAEs was highly correlated between two judges, with good agreement for TEOAEs at 1000, 2000, and 4000 Hz. The findings from this study suggest that TEOAEs will be valuable for clinical use because of their repeatability and identification of hearing-impaired ears.

Distortion product otoacoustic emissions (DPOAE) were measured in normal-hearing and hearing-impaired human subjects. Analyses based on decision theory were used to evaluate DPOAE test performance. Specifically, relative operating characteristic (ROC) curves were constructed and the areas under these curves were used to estimate the extent to which normal and impaired ears could be correctly identified by these measures. DPOAE amplitude and DPOAE/noise measurements were able to distinguish between normal and impaired subjects at 4000, 8000, and, to a lesser extent, at 2000 Hz. The ability of these measures to distinguish between groups decreased, however, as frequency and audiometric criterion used to separate normal and hearing-impaired ears decreased. At 500 Hz, performance was no better than chance, regardless of the audiometric criterion for normal hearing. Cumulative distributions of misses (hearing-impaired ears incorrectly identified as normal hearing) and false alarms (normal-hearing ears identified as hearing impaired) were constructed and used to evaluate test performance for a range of hit rates (i.e., the percentage of correctly identified hearing-impaired ears). Depending on the desired hit rate, criterion values of -5 to -12 dB SPL for DPOAE amplitudes and 8 to 15 dB for DPOAE/noise accurately distinguished normal-hearing ears from those with thresholds greater than 20 dB HL for the two frequencies at which performance was best (4000 and 8000 Hz). It would appear that DPOAE measurements can be used to accurately identify the presence of high-frequency hearing loss, but are not accurate predictors of hearing status at lower frequencies, at least for the conditions of the present measurements.

Developmental changes in the peak latencies of auditory brainstem responses (ABR) recorded from humans and kittens were compared to test the hypothesis that developmental time courses among mammals are the same when appropriately normalized. Response latencies were computed as the difference from adult latency and conceptional ages were represented as percentages relative to the age that ABR wave latencies achieved a criterion value within 0.2 ms of asymptotic latency (i.e., adulthood). An underlying assumption of this exercise is that far-field response latency is an appropriate index of overall 'auditory development'. Results of this analysis suggest that developmental changes in latency of responses arising within the auditory periphery are similar between humans and cats, when appropriately normalized, and that more central changes show less correspondence. Consequently, absolute time course differences for specific developmental parameters must be considered and caution should be exercised when extrapolating results acquired from one species to the other.

Auditory brainstem responses were measured in response to 1000-Hz tone bursts from 115 patients with sensorineural hearing loss, presumably of cochlear origin. Mean wave V latencies and variability were comparable to those observed in normal hearing subjects for similar stimuli. The range of interaural differences in wave V latencies for 1000-Hz tone bursts were slightly greater than those observed for clicks, which may not be surprising, given the greater variability in wave V latencies for tonal stimulation, even in normal-hearing subjects. These differences, however, were not affected either by the magnitude or symmetry of hearing loss for frequencies at and above 1000 Hz. These data suggest that tone burst ABRs might be useful in otoneurologic evaluations, especially for patients with asymmetric hearing loss.

The present study describes the unexpected finding of evoked otoacoustic emissions (EOAEs) from the left ear of a subject with severe-to-profound bilateral sensorineural hearing loss. No EOAEs could be measured from the right ear. To ensure that the EOAEs were not artifacts, two different instrumentation systems were used and both provided similar results. It is suggested that the subject may have a group of surviving outer hair cells in some regions of her left cochlea with corresponding inner hair cell or neural damage.

The goal of early identification of hearing loss is being reached gradually. The technological options for assessing hearing loss in neonates and infants are expanding to the point that we are now capable of identifying hearing loss, regardless of developmental level. The latest revision of the JCIH (1991) risk criteria, in conjunction with an increasing number of statewide programs, provides optimism for meeting the goal of finding and remediating hearing loss early in the first year of life.

Auditory brainstem responses were measured in five normal-hearing subjects, using single-cycle sinusoids at octave frequencies ranging from 250 to 2000 Hz. These sinusoids, gated with Blackman functions, were presented either at 0 or 180 degree phase and were varied in level from 90 dB SPL to threshold in 10-dB steps. Stimulus phase affected wave V latencies for low-frequency stimuli, with the effect decreasing as frequency increased. These data are thought to represent an evoked potential manifestation of known phase-locking abilities within the auditory system.

Pediatric cochlear implantation is restricted to patients with stable, bilateral profound sensorineural hearing losses who derive no benefit from conventional amplification. Obtaining reliable audiologic thresholds in a young child with sudden or early-onset hearing loss can be challenging. This study examines the accuracy with which auditory brainstem response evaluation can predict unaided and aided behavioral thresholds in a child with severe-to-profound hearing loss. Reliable behavioral thresholds were obtained on 119 children who had no measurable click-evoked auditory brainstem responses at instrumentation limits of 100 dB HLn. These data show that an absent auditory brainstem response at 100 dB HLn does not necessarily indicate the absence of measurable unaided hearing for test frequencies ranging from 250 Hz to 4000 Hz. Average aided thresholds of better than 60 dB were present in 43% of the children for 500, 1000, and 2000 Hz and in 53% for 500 and 1000 Hz. Therefore, the absence of a click-evoked auditory brainstem response at 100 dB HLn in a young child is not prima facie evidence of the child's cochlear implant candidacy.

Temporal aspects of the acoustic reflex response were estimated for normally hearing subjects, subjects with noise-induced hearing loss and children with sensorineural hearing impairment. Onset latency and rise/fall times of admittance change were measured from the averaged responses (8 presentations) to tone bursts of 250 ms durations and 10 ms rise/fall time. Tone burst frequency was varied from 500 to 4 000 Hz. No differences between groups were observed for onset responses. Compared to the data from normally hearing subjects, the offset responses were slightly longer for subjects with noise-induced hearing loss and were considerably longer for hearing-impaired children. Due to the prolongation seen for noise-exposed subjects, it is difficult to interpret these data in terms of site of lesion. Still, the differences between hearing-impaired children and normal subjects suggest that acoustic reflex offset latency may be a useful screening device.