Auditory adaptation testing as a tool for investigating tinnitus origin: two patients with vestibular schwannoma.

OBJECTIVE: To enhance the understanding of tinnitus origin by disseminating two case studies of vestibular schwannoma (VS) involving behavioural auditory adaptation testing (AAT). DESIGN: Retrospective case study. STUDY SAMPLE: Two adults who presented with unilateral, non-pulsatile subjective tinnitus and bilateral normal-hearing sensitivity. At the initial evaluation, the otolaryngologic and audiologic findings were unremarkable, bilaterally. Upon retest, years later, VS was identified. RESULTS: At retest, the tinnitus disappeared in one patient and was slightly attenuated in the other patient. In the former, the results of AAT were positive for left retrocochlear pathology; in the latter, the results were negative for the left ear although a moderate degree of auditory adaptation was present despite bilateral normal-hearing sensitivity. Imaging revealed a small VS in both patients, confirmed surgically. CONCLUSION: Behavioural AAT in patients with tinnitus furnishes a useful tool for exploring tinnitus origin. Decrease or disappearance of tinnitus in patients with auditory adaptation suggests that the tinnitus generator is the cochlea or the cochlear nerve adjacent to the cochlea. Patients with unilateral tinnitus and bilateral, symmetric, normal-hearing thresholds, absent other audiovestibular symptoms, should be routinely monitored through otolaryngologic and audiologic re-evaluations. Tinnitus decrease or disappearance may constitute a red flag for retrocochlear pathology.

Binaural Interference: Quo Vadis?

The reality of the phenomenon of binaural interference with speech recognition has been debated for two decades. Research has taken one of two avenues; group studies or case reports. In group studies, a sample of the elderly population is tested on speech recognition under three conditions; binaural, monaural right and monaural left. The aim is to determine the percent of the sample in which the expected outcome (binaural score-better-than-either-monaural score) is reversed (i.e., one of the monaural scores is better than the binaural score). This outcome has been commonly used to define binaural interference. The object of group studies is to answer the "how many" question, what is the prevalence of binaural interference in the sample. In case reports the binaural interference conclusion suggested by the speech recognition tests is not accepted until it has been corroborated by other independent diagnostic audiological measures. The aim is to attempt to determine the basis for the findings, to answer the "why" question. This article is at once tutorial, editorial and a case report. We argue that it is time to accept the reality of the phenomenon of binaural interference, to eschew group statistical approaches in search of an answer to the "how many" question, and to focus on individual case reports in search of an answer to the "why" question.

Parental restriction of children's access to cochlear implants: case studies.

This article reports on four retrospective case studies in which parental behavioral management of the implanted child included withholding the cochlear implant or activities associated with it as a disciplinary measure or as a means of preventing device loss or damage. The need for parental counseling by health care and educational professionals as to the importance of a child's connection to the hearing world all day long through the implant for optimal speech, language, academic, and psychosocial development is emphasized.

Self-stigma and empowerment in combined-CMHA and consumer-run services: two controlled trials.

OBJECTIVE: Self-help agencies (SHAs) are consumer-operated service organizations managed as participatory democracies involving members in all management tasks. Hierarchically organized board- and staff-run consumer-operated service programs (BSR-COSPs) are consumer managed, but they afford members less decision-making power. This study considered the relative effectiveness of SHAs and BSR-COSPs working jointly with community mental health agencies (CMHAs) and the role of organizational empowerment in reducing self-stigma. METHODS: Clients seeking CMHA services were assigned in separate randomized controlled trials to a trial of combined SHA and CMHA services versus regular CMHA services (N=505) or to a trial of combined BSR-COSP and CMHA services versus regular CMHA services (N=139). Self-stigma, organizational empowerment, and self-efficacy were assessed at baseline and eight months with the Attitudes Toward Persons With Mental Illness Scale, the Organizationally Mediated Empowerment Scale, and the Self-Efficacy Scale. Outcomes were evaluated with fully recursive path analysis models. RESULTS: SHA-CMHA participants experienced greater positive change in self-stigma than CMHA-only participants, a result attributable to participation in the combined condition (b=1.20, p=.016) and increased organizational empowerment (b=.27, p=.003). BSR-COSP-CMHA participants experienced greater negative change in self-stigma than CMHA-only participants, a result attributable to participation in the combined service (b=-4.73, p=.031). In the SHA-CMHA trial, participants showed positive change in self-efficacy, whereas the change among BSR-COSP-CMHA participants was negative. CONCLUSIONS: Differential organizational empowerment efforts in the SHA and BSR-COSP appeared to account for the differing outcomes. Members experienced reduced self-stigma and increases in self-efficacy when they were engaged in responsible roles.

How to measure cerebrospinal fluid pressure invasively and noninvasively.

We describe tympanic membrane displacement (TMD) testing for non-invasive estimation of intracranial pressure (ICP). With the TMD test, displacement of the tympanic membrane of the middle ear is recorded during elicitation of the acoustic middle-ear reflex (AR). Increased intracranial/perilymphatic pressure displaces the resting stapes footplate laterally so that TMD during the acoustic reflex is medial. Decreased intracranial/perilymphatic pressure displaces the baseline stapes footplate position medially (inward) so that TMD during the AR is lateral. The TMD typically is bidirectional when intracranial/perilymphatic pressure is normal. Discrepant findings have been reported for the sensitivity of the TMD test to ICP as the regression of TMD on invasive measurement of the ICP reveals substantial intersubject variability and overlap among patient and control groups. Large-sample research on TMD test performance in healthy persons and patients with various disorders affecting the ICP is needed using direct, invasive measures of the ICP as the gold standard. Research also is needed to examine whether non-invasive TMD testing can be used to investigate the trans-lamina cribrosa pressure difference in glaucoma.

Are All Consumer-Operated Programs Empowering Self-Help Agencies?

The literature on consumer-operated-service programs (CQSPs) distinguishes two organizational types based on their leadership styles: the self-help agency (SHA)-participant democracy and the board-staff-run COSP. This study considers whether the characteristics of these two organizational leadership styles are recognized by members and whether these characteristics are associated with membership degree of empowerment. Two-hundred and fifty new entrants to five COSP drop-in centers rated the programs' leadership style using the COPES System Maintenance Scale and assessed their own empowerment on four empowerment measures. ANOVA with Bonferroni post-hoc tests were used to evaluate differences between settings; MANCOVA to assess differences in member empowerment. COSP system maintenance differences distinguished the two organizational types (p < .000). SHA-participant democracy members scored significantly better than board-staff-run program members on three of the four empowerment measures. SHA-participant democracies, with a lower focus on system maintenance, and an emphasis on power sharing between staff and non-staff members, appeared to more effectively use organizational decision-making processes to empower their members.

Outcomes from consumer-operated and community mental health services: a randomized controlled trial.

OBJECTIVE: Hierarchically organized board-and-staff-run consumer-operated service programs (COSPs) are viewed as organizations that promote recovery while working in concert with community mental health agencies (CMHAs). This study's objective was to determine the effectiveness of such combined services for people with serious mental illness. METHODS: A board-and-staff-run consumer-operated drop-in center and colocated CMHA provided the context for the randomized clinical trial. In a weighted sample, 139 new clients seeking help from the CMHA were randomly assigned to agency-only service or to a combination of COSP and CMHA services. Client-members were assessed at baseline and eight months on a measure of symptom severity and on four recovery-focused outcome measures: personal empowerment, self-efficacy, independent social integration, and hopelessness. All scales used have high reliability and well-established validity. Differences in outcome by service condition were evaluated with multivariate analysis of covariance via dummy variable regression. Change scores on the five outcomes were the dependent variables. The covariates for the multivariate analysis included baseline status on each outcome measure and service condition between-group demographic differences. RESULTS: Results indicated that significant changes in three recovery-focused outcomes were associated with service condition across time: social integration (p<.001), personal empowerment (p<.006), and self-efficacy (p<.001). All changes favored the CMHA-only condition. Neither symptomology nor hopelessness differed by service condition across time. CONCLUSIONS: Hierarchically organized board-and-staff-run COSPs combined with CMHA service may be less helpful than CMHA service alone.

Self-help and community mental health agency outcomes: a recovery-focused randomized controlled trial.

OBJECTIVE: Self-help agencies (SHAs) are consumer-operated service organizations managed as participatory democracies. Members are involved in all aspects of organizational management, because a premise of SHAs is that organizationally empowered individuals become more empowered in their own lives, which promotes recovery. The study sought to determine the effectiveness of combined SHA and community mental health agency (CMHA) services in assisting recovery for persons with serious mental illness. METHODS: A weighted sample of new clients seeking CMHA services was randomly assigned to regular CMHA services or to combined SHA-CMHA services at five proximally located pairs of SHA drop-in centers and county CMHAs. Member-clients (N=505) were assessed at baseline and at one, three, and eight months on five recovery-focused outcome measures: personal empowerment, self-efficacy, social integration, hope, and psychological functioning. Scales had high levels of reliability and independently established validity. Outcomes were evaluated with a repeated-measures multivariate analysis of covariance. RESULTS: Overall results indicated that combined SHA-CMHA services were significantly better able to promote recovery of client-members than CMHA services alone. The sample with combined services showed greater improvements in personal empowerment (F=3.99, df=3 and 491, p<.008), self-efficacy (F=11.20, df=3 and 491, p<.001), and independent social integration (F=12.13, df=3 and 491, p<.001). Hopelessness (F=4.36, df=3 and 491, p<.005) and symptoms (F=4.49, df=3 and 491, p<.004) dissipated more quickly and to a greater extent in the combined condition than in the CMHA-only condition. CONCLUSIONS: Member-empowering SHAs run as participatory democracies in combination with CMHA services produced more positive recovery-focused results than CMHA services alone.

Repair issues associated with cochlear implants in children.

OBJECTIVE: To examine the number and type of repair issues associated with the use of cochlear implants in children who have worn either the body-level or ear-level style for 4 to 5 years. STUDY DESIGN: Retrospective review. SETTING: Specialty eye and ear institute. METHODS: Charts for all children who received cochlear implants from one of the authors between 1994 and 2002 and who received 4 to 5 years of follow-up for either the body or the ear-level style were examined. Based on the return merchandise authorizations and chart notes, implant problems were classified as external or internal. External problems were further subclassified as affecting the batteries, case, earhook, cords/cables, microphone, speech processor, coil, and/or external magnet; internal problems were subclassified as affecting the internal magnet, electrode(s), or other. MAIN OUTCOME MEASURES: Type and number of internal and external cochlear implant component breakdowns over time (including external component repair rates per year) and number of associated hospital visits. RESULTS: Of the 22 children, 4 (18.2%) had internal component problems. For the external components, the repair rate per year was 4.1 and 2.7 for the body style and ear-level style, respectively. For the group of children who was seen for each of 4 years, the mean number of repair problems declined 32% and 43% over that period for the body-worn and ear-level implants, respectively. The mean repair cost per year, based on Years 4 and 5 of use, was $794 and $317 for the body-worn and ear-level styles, respectively. CONCLUSION: The declines over time in repair problems and associated hospital visits suggest that children learn, over time, to better maintain and care for their cochlear implant. Although most had external component breakdowns, relatively few had internal component repair issues.

Temporal integration of the contralateral acoustic reflex threshold for a 1000 hz tonal activator and its age-related changes.

BACKGROUND: Previous research has noted an age effect on the temporal integration of the acoustic reflex for a noise activator. PURPOSE: To determine whether the age effect earlier noted for a noise activator will be noted for a tonal activator. RESEARCH DESIGN: Comparison of ARTs of younger and older groups at activating stimulus durations of 12, 25, 50, 100, 200, 300, 500, and 1000 msec. STUDY SAMPLE: Two groups of adults with normal-hearing sensitivity: one group of 20 young adults (ten males and ten females, ages 18-29 years, with a mean age of 24 years) and one group of 20 older adults (ten males and ten females, ages 59-75 years, with a mean age of 67.5 years). RESULTS: A significant main effect for duration was obtained. That is, as the duration increased, the acoustic reflex threshold for the 1000 Hz tonal activator decreased. The interactions of duration x age group and duration x hearing level were not significant. There was a nonsignificant main effect (p = .889) for the between-subjects factor of age. CONCLUSION: Results contradict the findings for broadband noise.

Technical report: distortion product otoacoustic emissions that are not outer hair cell emissions.

PURPOSE: To present a case study in order to alert clinicians to the possibility of occurrence of intermodulation distortion during otoacoustic emissions testing that arises from the cavity formed by the external auditory meatus and tympanic membrane rather than from the inner ear, compromising the reliability and validity of otoacoustic emissions testing. RESEARCH DESIGN: Prospective case study. STUDY SAMPLE: A young (26-year-old) female adult with a longstanding, bilateral, essentially moderate to severe sensorineural hearing loss presented with robust distortion product otoacoustic emissions. RESULTS: Repeat otoacoustic emissions testing with another device of the same model revealed essentially absent distortion product otoacoustic emissions and transient otoacoustic emissions. Calibration of both otoacoustic emissions devices using a 1 cc membranous cavity indicated present intermodulation distortion for the device that yielded robust distortion product otoacoustic emissions for the patient but absent intermodulation distortion for the device that revealed absent distortion product otoacoustic emissions and absent transient evoked otoacoustic emissions for the patient. The calibration findings for the device yielding intermodulation distortion in the cavity were confirmed by an engineer of a technical instrumentation company. The device was shipped back to the manufacturer of the device for repair. The manufacturer's engineers diagnosed the problem as an interruption in the relay system. Following repair, calibration revealed the absence of intermodulation distortion in the 1 cc membranous cavity. CONCLUSIONS: The findings have implications for the reliability and validity of otoacoustic emissions. Clinicians should routinely calibrate otoacoustic emissions devices using 1.0 and 0.5 cc membranous cavities to rule out intermodulation distortion that could produce artifactual otoacoustic emissions in patients.

Efficacy of the bone-anchored hearing aid for single-sided deafness.

OBJECTIVES/HYPOTHESIS: The aim was to examine short- and long-term efficacy of the bone-anchored hearing aid (BAHA) on adults with single-sided deafness. STUDY DESIGN: Prospective investigation. METHODS: The outcome measures included the Hearing in Noise Test (HINT), Abbreviated Profile of Hearing Aid Benefit (APHAB), and Single-Sided Deafness Questionnaire (SSD). The BAHA group comprised seven adults with single-sided deafness and the control group comprised 20 adults with essentially normal-hearing sensitivity, bilaterally. The outcome measures were administered in the unaided, directional BAHA, and omnidirectional BAHA conditions after 1 month, 6 months, and 12 months of BAHA use. A repeated measures analysis of variance (ANOVA) model was used to evaluate the data (for the SSD, a nonparametric analog of ANOVA was employed). RESULTS: None of the factors (time, HINT condition, amplification status) or their interactions were significant predictors of change in signal-to-noise ratio (SNR) from baseline over time on the HINT. The mean SNR (non-baseline-subtracted) was significantly lower in the directional BAHA versus the unaided status and in the omnidirectional BAHA versus the unaided status, but only under the noise in front, speech lateralized to the bad ear HINT condition. Significant short- and long-term BAHA benefit was observed on the APHAB (all subscales except Aversiveness) and SSD (all questionnaire items). CONCLUSIONS: Our results show short- and long-term efficacy for the BAHA in adults with single-sided deafness for recognition of speech in noise (noise in front, speech lateralized to the bad ear) and on subjective measures of benefit.

Auditory deprivation in adults with asymmetric, sensorineural hearing impairment.

The purpose of this investigation was to prospectively examine performance on the pure-tone air-conduction threshold, speech-recognition threshold, and suprathreshold word-recognition tests over time in 21 monaurally aided (experimental group) and 28 unaided adults (control group) with asymmetric, sensorineural hearing impairment. The results revealed significant declines on the mean suprathreshold word-recognition scores over time at one and two years post-baseline for the worse ears of the control participants; no declines occurred in the worse ears of the experimental participants or in the better ears of either group. A slight, significant increase in the pure-tone average occurred for the better ears of both groups. The findings are consistent with the presence of an auditory deprivation effect on suprathreshold word-recognition ability in the control group, suggesting that lack of amplification leads to decline in word-recognition performance over time in the worse ears of adults with asymmetric sensorineural hearing impairment.

Temporal integration of the contralateral acoustic-reflex threshold and its age-related changes.

Although numerous studies have investigated temporal integration of the acoustic-reflex threshold (ART), research is lacking on the effect of age on temporal integration of the ART. Therefore the effect of age on temporal integration of the ART was investigated for a broad-band noise (BBN) activator. Subjects consisted of two groups of adults with normal-hearing sensitivity: one group of 20 young adults (ten males and ten females, ages 18-29 years, with a mean age of 24 years) and one group of 20 older adults (ten males and ten females, ages 59-75 years, with a mean age of 67.5 years). Activating stimulus durations were 12, 25, 50, 100, 200, 300, 500, and 1000 ms. Significant main effects for duration and age were obtained. That is, as the duration increased, the acoustic reflex threshold for BBN decreased. The interactions of duration x age group and duration x hearing level were not significant. The result of pair-wise analysis indicated statistically significant differences between the two age groups at durations of 20 ms and longer. The observed age effect on temporal integration of the ART for the BBN activator is interpreted in relation to senescent changes in the auditory system.

Objective computerized versus subjective analysis of facial synkinesis.

OBJECTIVES/HYPOTHESIS: To compare the sensitivity of an objective, computerized approach to measurement of facial synkinesis with that for a subjective approach and to examine the test-retest reliability of these approaches. STUDY DESIGN: Prospective, nonrandomized, and blinded. METHODS: Remote facial motion at the upper eyelids and oral commissures during a closed-lip smile and eyelid closure were measured using a commercially available computerized motion analysis system. Thirty healthy adults with normal facial nerve function were enrolled to establish normative data and a threshold value for synkinesis. Thirty consecutive patients were analyzed based on the synkinesis threshold value. Blinded subjective evaluations by two observers were also performed independently on the same patients. RESULTS: Facial synkinesis was detected significantly more frequently with objective than subjective analysis for eyelid closure; no significant differences between approaches were shown for the closed-lip smile. Interestingly, five (17%) patients developed early synkinesis within 3 months from the onset of the facial nerve injury. The test-retest reliability of all objective measures was excellent for both expressions. Close agreement in percent of patients with synkinesis between test and retest subjective evaluations was obtained for both observers for both expressions. CONCLUSIONS: The objective, computerized approach to detection of facial synkinesis has excellent reliability and is more sensitive than the subjective approach to assessment to the presence of facial synkinesis associated with eyelid closure. The finding of early synkinesis suggests that central nervous reorganization plays a role in regeneration of the facial nerve.

Mapping cooperative activity of the hepatitis C virus RNA-dependent RNA polymerase using genotype 1a-1b chimeras.

The nonstructural protein 5B (NS5B) of hepatitis C virus (HCV) encodes an RNA-dependent RNA polymerase (RdRp) which is essential for viral replication. NS5B expression in bacteria generated 20- to 50-fold lower yield and 100-fold less product per mol of enzyme for gentoype 1a RdRp than type 1b. Further, unlike type 1b RdRp, type 1a enzyme failed to exhibit cooperative properties in the assays described herein. Differences in thermal stability may partially account for the inability to efficiently oligomerize. Superose gel filtration analyses confirm differences between these RdRp preparations, although affinity for the column rather than size may account for the differences in migration. To further address this complexity, a panel of RdRp type 1a-type 1b chimeras were evaluated and implicate a role for the thumb subdomain of genotype 1b RdRp as critical for cooperative function.

Enzymatic activities of the GB virus-B RNA-dependent RNA polymerase.

The GB virus-B (GBV-B) nonstructural protein 5B (NS5B) encodes an RNA-dependent RNA polymerase (RdRp) with greater than 50% sequence similarity to the hepatitis C virus (HCV) NS5B. Recombinant GBV-B NS5B was reported to possess RdRp activity (W. Zhong et al., 2000, J. Viral Hepat. 7, 335-342). In this study, the GBV-B RdRp was examined more thoroughly for different RNA synthesis activities, including primer-extension, de novo initiation, template switch, terminal nucleotide addition, and template specificity. The results can be compared with previous characterizations of the HCV RdRp. The two RdRps share similarities in terms of metal ion and template preference, the abilities to add nontemplated nucleotides, perform both de novo initiation and extension from a primer, and switch templates. However, several differences in RNA synthesis between the GBV-B and HCV RdRps were observed, including (i) optimal temperatures for activity, (ii) ranges of Mn(2+) concentration tolerated for activity, and (iii) cation requirements for de novo RNA synthesis and terminal transferase activity. To assess whether the recombinant GBV-B RdRp may represent a relevant surrogate system for testing HCV antiviral agents, two compounds demonstrated to be active at nanomolar concentrations against HCV NS5B were tested on the GBV RdRp. A chain terminating nucleotide analog could prevent RNA synthesis, while a nonnucleoside HCV inhibitor was unable to affect RNA synthesis by the GBV RdRp.

First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling.

The first cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor is reported. The inhibitor was obtained by rational modification of a high throughput screening lead with the aid of a S. pneumoniae FabH homology model. This homology model was used to design analogues that would have both high affinity for the enzyme and appropriate aqueous solubility to facilitate cocrystallization studies.

Mechanism of de novo initiation by the hepatitis C virus RNA-dependent RNA polymerase: role of divalent metals.

We functionally analyzed the role of metal ions in RNA-dependent RNA synthesis by three recombinant RNA-dependent RNA polymerases (RdRps) from GB virus-B (GBV), bovine viral diarrhea virus (BVDV), and hepatitis C virus (HCV), with emphasis on the HCV RdRp. Using templates capable of both de novo initiation and primer extension and RdRps purified in the absence of metal, we found that only reactions with exogenously provided Mg(2+) and Mn(2+) gave rise to significant amounts of synthesis. Mg(2+) and Mn(2+) affected the mode of RNA synthesis by the three RdRps. Both metals supported primer-dependent and de novo-initiated RNA by the GBV RdRp, while Mn(2+) significantly increased the amount of de novo-initiated products by the HCV and BVDV RdRps. For the HCV RdRp, Mn(2+) reduced the K(m) for the initiation nucleotide, a GTP, from 103 to 3 micro M. However, it increased de novo initiation even at GTP concentrations that are comparable to physiological levels. We hypothesize that a change in RdRp structure occurs upon GTP binding to prevent primer extension. Analysis of deleted proteins revealed that the C terminus of the HCV RdRp plays a role in Mn(2+)-induced de novo initiation and can contribute to the suppression of primer extension. Spectroscopy examining the intrinsic fluorescence of tyrosine and tryptophan residues in the HCV RdRp produced results consistent with the protein undergoing a conformational change in the presence of metal. These results document the fact that metal can affect de novo initiation or primer extension by flaviviral RdRps.