Biomedical subjects
R A Dobie
Publications and source records attributed to R A Dobie.
Antidepressant treatment of tinnitus patients. Interim report of a randomized clinical trial.
Previous studies have shown that severe tinnitus is associated with current major depression, and that tricyclic antidepressant therapy reduces tinnitus disability, at least compared to brief placebo treatment. We are completing a randomized clinical trial of nortriptyline, stratified by presence or absence of current major depression, in 100 patients with severe chronic tinnitus. Preliminary analysis of global outcome on the first 52 patients reveals that those receiving nortriptyline were more likely to feel that their drug had been helpful (74% vs. 36%, p less than 0.01), but were equally likely to report that their tinnitus was improved (37% vs. 32%, NS). So far, neither audiometric nor self-report measures of tinnitus have demonstrated statistically significant differences between active drug and placebo. Simply administered visual rating scales, if externally-referenced, correlated better with global outcome than did the Iowa Tinnitus Handicap Questionnaire. As expected, nortriptyline was significantly superior to placebo with respect to reductions in the Hamilton Depression Scale, especially in depressed patients. Paradoxically, depressed patients reported more disability and loudness on all scales, but had lower 1 kHz tinnitus intensity matches and dynamic ranges. Our preliminary conclusions are that: 1) nortriptyline reduces depression in patients with severe tinnitus, 2) placebo effects are very important in the treatment of tinnitus, 3) depression may be associated with decreased tolerance for both internal and external sounds, and 4) it is still difficult to specify the appropriate measures of tinnitus loudness and disability for use in therapeutic trials.
The relative contributions of occupational noise and aging in individual cases of hearing loss.
A method is proposed for allocation of hearing handicap between noise and aging in individual cases when noise exposure level and duration are known or can be estimated. A recently published international standard (ISO-1999, 1990) provides statistical models for hearing threshold changes associated with aging and noise exposure. When an individual's hearing threshold level exceeds the sum of the median levels expected given that individual's age, gender, exposure level, and exposure duration, the appropriate allocation depends on the correlation between age-related and noise-induced changes. However, the differences in allocation between assumptions of perfect and absent correlation are small. Only very small errors result from calculating the allocation based on median expectations for noise and aging. In most cases, age-related changes exceed noise-induced changes for the 0.5, 1, 2, and 3 kHz pure-tone average; for men age 65, this is true for all exposure levels below 100 dBA.
Hearing threshold differences and risk of acoustic tumor.
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cis-platinum ototoxicity in children.
Despite the recognized ototoxicity of cis-platinum, a clinical outline for the audiologic evaluation of patients receiving this drug has not been clearly defined. In a practical approach to this problem, the audiograms of 48 pediatric patients referred for monitoring during planned cis-platinum therapy were reviewed. Eleven patients tested with auditory brain-stem response (ABR) audiometry demonstrated several limitations of this modality. Fourteen children underwent initial ABR testing followed by at least two pure-tone audiograms. The remaining 23 patients had their hearing evaluated by pure-tone audiometry only. Various factors such as patient age, cis-platinum dosage, and cranial radiation exposure were analyzed for apparent effect. Younger patients tended to be more susceptible to audiologic changes with the administration of cis-platinum. The proportion of patients who demonstrated a hearing loss increased with successive dosing as did the severity of the hearing loss. Prior exposure to cranial radiation was strongly linked to the development of hearing loss following cis-platinum therapy. Guidelines are presented regarding the use of clinical audiometry in the screening of these pediatric oncology patients.
A method for allocation of hearing handicap.
A three-stage method is proposed for allocation of hearing handicap. First, for a given injury or noise exposure period, the percentage of loss allocable for each ear is calculated as a simple ratio of hearing change (after age correction) to final hearing level. Second, final hearing handicap is divided between the two ears using a formula derived from the 1979 AAO-HNS/AMA standard. The percentage of hearing handicap allocable to a given period for each ear is simply the product of that ear's scores from the first two steps.
Analysis of auditory evoked potentials by magnitude-squared coherence.
Evoked potentials are usually analyzed in the time domain (voltage versus time). The most familiar frequency-domain measure, the power spectral density function, displays power as a function of frequency but doesn't distinguish signal power from noise power. The coherence function estimates, for each frequency, the ratio of signal power to total (signal plus noise) power and, thus, indicates the degree to which system output (scalp potential) is determined by input (acoustic stimulus). Coherence ranges from 0 to 1; values above specified critical values can be accepted as demonstrating statistically significant system response. In this paper, we present coherence analysis of human scalp responses to clicks and amplitude-modulated tones. In both cases, this analytic method provides insight into the spectral character of the response (for example, assisting in specifying desirable filter characteristics). Threshold sensitivity is also improved: statistically significant responses can be detected at lower intensity by coherence analysis than by inspection of time-domain waveforms.
Treatment of depressed tinnitus patients with nortriptyline.
Patients disabled by tinnitus show a high prevalence of major depression. Furthermore, tinnitus produces patterns of disability similar to those produced by major depression. To explore further this link between tinnitus and depression, and to investigate the efficacy of treating depression in the treatment of tinnitus, a single-blind, placebo-washout, nonrandomized pilot study of the tricyclic antidepressant nortriptyline (hydrochloride) was undertaken in disabled tinnitus patients who also met diagnostic criteria for major depression. Nineteen patients began the study, two responded to placebo, and two dropped out prior to completion. Fourteen considered their tinnitus improved, and 12 chose to continue taking nortriptyline after the study. Depression severity decreased, on the average, by 65% (p less than .0001). Tinnitus loudness measured by audiometric matching decreased by a mean of 10 dB or 50% (p less than .02). Self-reports of tinnitus loudness and severity, somatic and psychologic symptoms, and psychosocial dysfunction all showed significant improvement with treatment. These results suggest that what initially appears to be an irreversible otologic disability in these patients may be in large part a reversible psychiatric disability.
The effect of unilateral corneal anesthesia on the Schirmer test.
Unilateral corneal anesthesia (or hypesthesia) caused by trigeminal nerve disease has an unknown effect on the Schirmer test. Using topical anesthesia, we found that unilateral corneal anesthesia reduces tearing bilaterally, with a greater decrease on the anesthetized side. Clinicians should be aware that trigeminal nerve deficit may alter Schirmer test results, and use bilateral topical corneal anesthesia or alternative methods to stimulate tearing in these cases.
Electrophysiologic assessment of low-frequency hearing: sedation effects.
Sixteen normal-hearing adults were tested in both awake and sedated states for several evoked responses to low-frequency stimuli. Responses obtained by cross-correlation function, middle latency responses, and the 40-Hz response proved most sensitive; all had mean thresholds of less than 20 dB normal hearing level for the awake-alert state, but 40-Hz and middle latency response mean thresholds were shifted about 10 dB under sedation. The cross-correlation method seems to offer promise for pediatric auditory assessment.
Auditory responses to the envelopes of pseudorandom noise stimuli in humans.
Averaged scalp potentials evoked by continuous pseudorandom noise can be cross-correlated with the evoking stimulus, yielding a cross-correlation function (CCF) which reflects neural phase-locking and is quite sensitive for low-frequency stimulus components [M.J. Wilson and R.A. Dobie (1987) Electroencephalogr. Clin. Neurophysiol. 66, 529-538]. However, for higher frequency signals, replicable CCFs can only be obtained at moderate to high intensities. Since auditory neurons also respond to envelopes of complex sounds, even for high-frequency carriers, we compared scalp responses evoked by band-limited complex sounds to the envelopes of these sounds; the resultant envelope cross-correlation functions (ECCFs) contained replicable response components primarily below 1,000 Hz, regardless of the evoking stimulus spectrum. ECCF thresholds for three octave-band stimuli (830-1,562, 1,611-3,125, and 3,174-6,201 Hz) were more sensitive than CCF thresholds (P = 0.006), averaging 35 dB spectrum level for 10 normal subjects. When stimuli with only odd harmonics were used, replicable odd-component scalp responses were seen only in the spectral range of the stimuli, while even-component responses (presumably to stimulus envelope) were seen only in low-passed scalp responses.
Chronic perilymphatic fistula: experimental model in the guinea pig.
Chronic perilymphatic fistulas were created in guinea pig cochleas using silicone rubber tubing placed into the scala tympani through the round window. Fistula patency was determined by fluorescein perfusion into cerebral spinal fluid. Fistula were found to be patent in 6 of 6 animals at 7 days and 8 of 13 animals at 28 days. Analysis of ABRs revealed threshold increases of 10 to 15 dB across all frequencies at 1 hour and 7 days. However, thresholds returned to pre-fistula levels by 28 days. Animals with acute fistulas (simple laceration of the round window) had similar threshold increases at 1 hour; however, recovery to baseline levels occurred by day 7. Control animals with intact round windows did not have threshold shifts. Scanning electron microscopy revealed hair cell loss localized to the apical and basal turns of the cochlea. The morphologic changes observed occurred acutely (within 7 days) and were not progressive, despite the presence of a fistula. Hair cell loss or degeneration did not correlate with hearing loss.
Progression of hearing loss in bilateral Menière's disease.
Otologists may be reluctant to perform labyrinthectomy in unilateral Menière's disease, fearing the later development of bilateral disease and severe hearing loss in the previously normal ear. To illuminate this issue, we reviewed audiologic records for 85 patients diagnosed as having bilateral Menière's disease at the University of Washington Hospital from 1969 to 1986. The progression of hearing loss in each ear was noted, as well as interaural relationships. Nine patients experienced a significant reversal, in which the initially better ear surpassed the other ear in hearing deficit, but only one of these patients could at any time have been considered a labyrinthectomy candidate, according to hypothetically liberal audiometric criteria.
Human short-latency auditory responses obtained by cross-correlation.
Short-latency auditory responses were obtained by cross-correlation of continuous, pseudorandom noise stimuli with averaged scalp potentials from adults with normal hearing. Responses were recorded for spectrum levels of 14-74 dB for noise bandwidths from 800 to 6000 Hz. At the lowest intensity level of broadband noise, all 10 subjects showed replicable cross-correlation functions (CCFs), which were characterized by prominent positive peaks at delays (latencies) of 5-7 msec. Male subjects exhibited longer delays than females. Delay (latency) increased with decreasing stimulus intensity. Very early responses (less than 2 msec) attributable to cochlear microphonic, which were prominent in earlier work on guinea pigs, were not well seen in these human data. CCFs for responses to band-limited stimuli and off-line derivation of band-limited CCFs for responses evoked by broadband stimuli both showed that this technique is most sensitive to frequency-following behavior at low frequencies (less than 800 Hz). However, definite phase-locked responses to even the highest passband (3100-6200 Hz) were seen. These results support the use of the CCF technique as an efficient method of frequency-specific assessment of the auditory system.
Dichotic threshold tests.
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Intracranial facial nerve anastomosis.
A technique of intracranial facial nerve anastomosis using fenestrated collagen splints was used in eight patients operated upon for acoustic neuroma or glomus temporale tumor. This technique is rapid and simpler than suturing in the cerebellopontine angle. Clinical results are as good as or even better than those obtained with more peripheral facial nerve anastomosis or grafting. An animal study demonstrated no undue histologic reaction to the collagen splints.
Noise-induced hearing loss: the family physician's role.
Noise is an environmental health problem that has not received sufficient attention. Physicians should become knowledgeable about the medical consequences of excessive noise, support legislation to reduce the problem and promote programs aimed at noise control and prevention of hearing loss. Questions about noise and hearing should be incorporated into the medical history, and pure-tone audiometry should be a part of periodic physical evaluations.