Cobalt toxicity in humans-A review of the potential sources and systemic health effects.

Cobalt (Co) and its compounds are widely distributed in nature and are part of numerous anthropogenic activities. Although cobalt has a biologically necessary role as metal constituent of vitamin B12, excessive exposure has been shown to induce various adverse health effects. This review provides an extended overview of the possible Co sources and related intake routes, the detection and quantification methods for Co intake and the interpretation thereof, and the reported health effects. The Co sources were allocated to four exposure settings: occupational, environmental, dietary and medical exposure. Oral intake of Co supplements and internal exposure through metal-on-metal (MoM) hip implants deliver the highest systemic Co concentrations. The systemic health effects are characterized by a complex clinical syndrome, mainly including neurological (e.g. hearing and visual impairment), cardiovascular and endocrine deficits. Recently, a biokinetic model has been proposed to characterize the dose-response relationship and effects of chronic exposure. According to the model, health effects are unlikely to occur at blood Co concentrations under 300µg/l (100µg/l respecting a safety factor of 3) in healthy individuals, hematological and endocrine dysfunctions are the primary health endpoints, and chronic exposure to acceptable doses is not expected to pose considerable health hazards. However, toxic reactions at lower doses have been described in several cases of malfunctioning MoM hip implants, which may be explained by certain underlying pathologies that increase the individual susceptibility for Co-induced systemic toxicity. This may be associated with a decrease in Co bound to serum proteins and an increase in free ionic Co2+. As the latter is believed to be the primary toxic form, monitoring of the free fraction of Co2+ might be advisable for future risk assessment. Furthermore, future research should focus on longitudinal studies in the clinical setting of MoM hip implant patients to further elucidate the dose-response discrepancies.

'Standard' versus 'nose reference' electrode placement for measuring oVEMPs with air-conducted sound: Test-retest reliability and preliminary patient results.

OBJECTIVES: This study compared two electrode placements ('standard' versus 'nose reference' placement) for measuring oVEMPs, elicited by air-conducted 500Hz tone bursts. The test-retest reliability of both positions was evaluated and additionally both electrode placements were applied on a group of vestibular patients. METHODS: Eighteen healthy volunteers (range of 20-25years) participated in the first part and were retested after one week for evaluation of the test-retest reliability. Eleven patients (range of 41-74years) with a variety of vestibular pathologies were tested once. RESULTS: In the normal group, the nose reference electrode placement resulted in significantly larger peak-to-peak amplitudes (p<0.001), shorter n10 (p=0.001) and p15 (p<0.001) latencies and smaller 95% prediction intervals for the Inter-Ocular Ratio (IOR) ([-68, 68] for the standard position versus [-32, 32] for the nose reference position). Furthermore, an excellent amplitude and IOR test-retest reliability was observed with the nose reference configuration, as shown by the intraclass correlation coefficient (ICC), the coefficient of variation of the method error (CVME) and the minimal detectable differences (MDD). In the patient group, the same significant amplitude difference was found. Moreover, three patients presented with absent oVEMPs when recorded with the standard placement, whereas the nose reference placement could evoke a detectable oVEMP response. CONCLUSIONS: This study demonstrated that a nose reference electrode position results in larger oVEMP amplitudes and achieves a better reliability for the most important clinical parameters (amplitude and IOR). Our patient data substantiate the possible clinical benefit of this position, but further systematic patient verification is required. SIGNIFICANCE: The nose reference electrode position facilitates the detection of generally very small oVEMP responses and shows a high test-retest reliability, showing promising potential for future use in the vestibular clinic.

Speech recognition in noise with active and passive hearing protectors: a comparative study.

The perceived negative influence of standard hearing protectors on communication is a common argument for not wearing them. Thus, "augmented" protectors have been developed to improve speech intelligibility. Nevertheless, their actual benefit remains a point of concern. In this paper, speech perception with active earplugs is compared to standard passive custom-made earplugs. The two types of active protectors included amplify the incoming sound with a fixed level or to a user selected fraction of the maximum safe level. For the latter type, minimal and maximal amplification are selected. To compare speech intelligibility, 20 different speech-in-noise fragments are presented to 60 normal-hearing subjects and speech recognition is scored. The background noise is selected from realistic industrial noise samples with different intensity, frequency, and temporal characteristics. Statistical analyses suggest that the protectors' performance strongly depends on the noise condition. The active protectors with minimal amplification outclass the others for the most difficult and the easiest situations, but they also limit binaural listening. In other conditions, the passive protectors clearly surpass their active counterparts. Subsequently, test fragments are analyzed acoustically to clarify the results. This provides useful information for developing prototypes, but also indicates that tests with human subjects remain essential.

Determination and evaluation of clinically efficient stopping criteria for the multiple auditory steady-state response technique.

OBJECTIVE: The present study aimed at establishing clinically efficient stopping criteria for a multiple 80-Hz auditory steady-state response (ASSR) system. METHODS: In Experiment 1, data of 31 normal-hearing subjects were analyzed off-line to propose stopping rules. Consequently, ASSR recordings will be stopped when (1) all 8 responses reach significance and significance can be maintained for 8 consecutive sweeps; or (2) the mean noise levels were 4nV (if p-values were between 0.05 and 0.1, measurements were extended once by 8 sweeps); or (3) a maximum amount of 48 sweeps was attained; whichever occurred first. In Experiment 2, these stopping criteria were applied on 10 normal hearing and 10 hearing-impaired adults to assess the efficiency. RESULTS: The application of these stopping rules resulted in ASSR threshold values that were comparable to other ASSR research. Furthermore, preliminary analysis of the response and noise amplitudes demonstrated slightly higher values for hearing impaired than normal-hearing subjects. CONCLUSIONS: The proposed stopping rules can be used in adults to determine accurate ASSR thresholds within a time-frame of about 1h. SIGNIFICANCE: The use of these a priori stopping criteria might assist the clinician in their decision to terminate ASSR recordings.

The effects of aging on evoked otoacoustic emissions and efferent suppression of transient evoked otoacoustic emissions.

OBJECTIVE: There is still controversy regarding the effects of aging on evoked otoacoustic emissions (EOAEs), as well as on the efferent system measured by contralateral acoustic stimulation of EOAEs. The purpose of this study was to investigate the deterioration in EOAEs and efferent suppression (ES) in a representative sample statistically controlling for the differences in hearing thresholds. METHODS: Seventy-one ears (20-79years) were included in the study, 47 of which had normal hearing thresholds, and 24 ears had a sensorineural high-frequency hearing loss caused by presbycusis. The effects of aging on transient evoked (TEOAEs) and distortion product OAEs (DPOAEs), and on ES were evaluated using multiple regression and correlation coefficients. RESULTS: EOAEs and ES were more strongly correlated with age, than with pure-tone thresholds (PTTs). Moreover, the increase in the amount of variance explained by the regression model using both predictors was larger for PTTs as compared to the variable age. CONCLUSIONS: The deterioration of EOAEs and ES with advancing age is caused mainly by pure age-effects, and additionally by the reduction in hearing thresholds. SIGNIFICANCE: The relative contribution of age and hearing thresholds on EOAEs, as well as on ES is important for their interpretation in clinical settings.

The clinical value of the multiple-frequency 80-Hz auditory steady-state response in adults with normal hearing and hearing loss.

OBJECTIVES: To determine the ability of the air-conduction multiple-frequency auditory steady-state response (ASSR) technique to diagnose normal hearing (NH) and mild and moderate degrees of sensorineural hearing loss (SNHL), to assess patients with conductive hearing loss (CHL), to evaluate flat and sloping configurations of hearing impairment, and to provide sensitivity and specificity values for various ASSR cutoff criteria. DESIGN: A comparative study between ASSR and criterion-standard behavioral thresholds. SETTING: Ear, nose, and throat department at a university hospital. PATIENTS: The study population comprised 40 adults with NH, 17 with SNHL, and 7 with CHL. MAIN OUTCOME MEASURES: The measure of interest was the difference between ASSR and behavioral thresholds at 0.5, 1.0, 2.0, and 4.0 kHz. The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency were calculated for several ASSR cutoff criteria. RESULTS: The ASSR technique clearly distinguished moderate SNHL from NH, but the "mild SNHL and NH" and "mild SNHL and moderate SNHL" differentiation was particularly difficult at 0.5 and 2.0 kHz, respectively. Air-conduction ASSR thresholds accurately predicted behavioral thresholds in CHL. The ASSR system precisely reflected the flat and sloping configurations. Finally, the most appropriate ASSR cutoff point for normality seems to be the 30-dB-or-lower criterion. CONCLUSIONS: In adults, the multiple-frequency 80-Hz ASSR technique can be used to determine the degree and configuration of hearing loss. Although air-conduction ASSR thresholds accurately predicted behavioral thresholds in CHL, future research with bone-conduction ASSRs is necessary to establish the type of hearing loss. Furthermore, the applicability of these findings still needs to be confirmed for infants.

Auditory steady-state responses to MM and exponential envelope AM(2)/FM stimuli in normal-hearing adults.

The present study utilized a commercially available multiple auditory steady-state response (ASSR) system to test normal hearing adults (n=55). The primary objective was to evaluate the impact of the mixed modulation (MM) and the novel proposed exponential AM(2)/FM stimuli on the signal-to-noise ratio (SNR) and threshold estimation accuracy, through a within-subject comparison. The second aim was to establish a normative database for both stimulus types. The results demonstrated that the AM(2)/FM and MM stimulus had a similar effect on the SNR, whereas the ASSR threshold results revealed that the AM(2)/FM produced better thresholds than the MM stimulus for the 500, 1000, and 4000 Hz carrier frequency. The mean difference scores to tones of 500, 1000, 2000, and 4000 Hz were for the MM stimulus: 20+/-12, 14+/-9, 10+/-8, and 12+/-8 dB; and for the AM(2)/FM stimulus: 18+/-13, 12+/-8, 11+/-8, and 10+/-8 dB, respectively. The current research confirms that the AM(2)/FM stimulus can be used efficiently to test normal hearing adults.