Larry G. Duckert

Possible precursors of regenerated hair cells in the avian cochlea following acoustic trauma

Hair cell regeneration following acoustic trauma to the avian cochlea has been documented using DNA labeling with tritiated thymidine. The goal of this study was to identify potential precursor cell populations for regenerating hair cells. Chicks were exposed in pairs to a 1500 Hz pure tone at 120 dBSPL for 18 h. The animals received repeated injections of 3H-thymidine over a survival period of 6, 15, or 24 h, 3 days or 30 days after the completion of noise exposure. One cochlea from each animal was processed for autoradiography and the other for scanning electron microscopy. Labeled, regenerated hair cells were present by 3 days after exposure and recovery from injury was nearly complete by 30 days. Examination of animals in short survival groups suggest that two precursor populations may exist. For inferior sensory epithelial damage, cuboidal or hyaline epithelial cells appear to serve as the precursor cell population for the regeneration of both hair cells and supporting cells. With isolated superior damage, however, supporting cells may be the precursor population.

Utility of Laboratory Testing in Autoimmune Inner Ear Disease

Objectives: To assess the utility of various laboratory tests used to diagnose autoimmune inner ear disease.

Visual impairment and cognitive dysfunction in Alzheimer's disease.

Objective:To determine whether impaired visual acuity is associated with dementia and cognitive dysfunction in older adults.Design:Paired case-control comparisons of the relative frequencies of visual impairment in demented cases and nondemented controls. Cohort analyses of correlation between visual acuity and cognitive functioning in demented cases.Setting:Internal medicine clinics at two academically affiliated medical centers.Participants:Eighty-seven consecutively selected patients ≥65 years of age with mild-to-moderate, clinically diagnosed Alzheimer’s disease (cases) and 87 nondemented controls matched to the cases by age, sex, and education.Measurements and main results:The prevalence of visual impairment was higher in cases than in controls [unadjusted odds ratio for near-vision impairment =2.7 (95% CI=1.4, 5.2); unadjusted odds ratio for far-vision impairment =2.1 (95% CI=1.02, 4.3); odds ratios adjusted for family history of dementia, depression, number of medications, and hearing loss were 2.5 (95% CI=1.1, 10.5) for near-vision impairment and 1.9 (95% CI=0.8, 4.6) for far-vision impairment]. When further stratified by quartiles of visual acuity, no statistically significant “dose-response” relationship between vision impairment and dementia risk was observed. Among cases, the degree of visual impairment was significantly correlated with the severity of cognitive dysfunction for both near and far vision (adjusted ps<0.001).Conclusions:Visual impairment is associated with both an increased risk and an increased clinical severity of Alzheimer’s disease, but the increased risk may not be consistent with a progressive dose-response relationship. Further studies are needed to determine whether visual impairment unmasks and exacerbates the symptoms of dementia or is a marker of disease severity.

Acute Morphological Changes in Guinea Pig Cochlea following Electrical Stimulation A Preliminary Scanning Electron Microscope Study

A major area of concern in the development of the cochlear prosthesis involves the effects of the implant on inner ear anatomy and function. This study examined one aspect of host-implant interaction — the effects of cochlear implantation with and without electrical stimulation on cochlear morphology in the guinea pig. To accomplish this, a series of normal guinea pigs were acutely implanted bilaterally with a scala tympani multiple electrode prosthesis. One ear was stimulated with continuous 1 kHz sinusoidal current of constant intensity for a period of three hours. The contralateral control ear was not stimulated. Current intensities tested ranged from 0.1 mA to 1 mA rms. After stimulation the animals were sacrificed, perfused with fixative and the temporal bones were microdissected for examination using the scanning electron microscope. Morphological changes observed in the stimulated ear ranged from hair cell and supporting cell degeneration to complete destruction of the basilar membrane and organ of Corti overlying the electrode. These changes occurred at current intensities ranging from 0.4 mA to 1 mA and were conspicuously absent in the implanted but unstimulated control ears. The current intensities employed in this experiment were within operating ranges presently used in long-term behavioral studies in other animal models. To what degree the morphological changes observed in this study may effect the function of the prosthesis or host responses on a long-term basis cannot be determined from this experiment. However, our observations do demonstrate that electrical stimulation of the cochlea is not benign and point out the need for further evaluation to help define safe standards for use of the prosthesis.

Ototoxicity of Topical Otomicrobial Agents

Topical antimicrobial solutions are used commonly for prevention or treatment of purulent otorrhea even though most solutions contain ototoxic agents. This study compares the cochlear and middle ear toxicity of cortisporin otic solution (COS), 0.3% gentamicin ophthalmic solution (GOS), benzalkonium chloride (0.026% and 0.05%), and 1.0% Ofloxacin, a new quinolone antibiotic. Saline 0.9% was used as a control. The agent was instilled daily for 7 days into the bulla of juvenile guinea pigs. The animals were sacrificed on the 14th day. The organ of Corti was examined using surface preparation light microscopy and scanning electron microscopy. The tympanic membrane (TM) and adjacent middle ear mucosa were examined with light microscopy. The average cochlear hair cell damage was 66% for COS, 6.5% for GOS, and 1% for Ofloxacin, benzalkonium and saline. COS and benzalkonium 0.05% produced moderate mucosal thickening and inflammation. However, this was not statistically different from the mild mucosal thickening produced by saline, GOS, Ofloxacin and 0.026% benzalkonium. There was statistically significant mild to moderate thickening of the TM for all agents compared to the saline control.

Validity and reliability of auditory screening tests in demented and non-demented older adults.

The validity and reliability of auditory screening tests were evaluated in 34 demented and 31 non-demented elderly outpatients. In reference to an audiometric gold standard (40-dB HL bearing loss in speech frequencies), 512-Hz and 1024-Hz tuning forks, finger rub, and whispered voice tests performed well (ROC curve areas =0.82 to 0.94). Simultaneously high (>0.80) sensitivities and specificities were achievable for all these tests in demented patients. In non-demented patients, however, only the whispered voice test achieved simultaneously high specificity and sensitivity. The most accurate rule for air conduction screening audiometry was the inability to bear ≥ two of four 40-dB HL speech frequencies (sensitivity =1.0, specificity =0.75 in non-demented patients; sensitivity =0.97, specificity =0.74 in demented patients). Interobserver/test-retest reliability was generally high for tuning forks, finger rub, and whispered voice tests (range of intraclass correlation coefficients =0.38 to 0.90), and was somewhat higher in demented than in non-demented patients. These results suggest that some of the simple, traditional methods of auditory screening may have considerable validity and reliability in demented and non-demented older adults.

Cochlear Prostheses: Stimulation-Induced Damage

The effects of 4 weekly, three-hour exposures to continuous sinusoidal (1 kHz) electrical stimulation of the inner ear at various current levels were assessed in the chronically implanted guinea pig. With scala tympani stimulation, histopathological damage, including new bone growth, was observed for currents at and above 100 μA rms. No changes were observed in similarly implanted, but not stimulated cochleas. At equal current levels, less damage was found in subjects stimulated via electrodes placed on the round window and promontory, as compared to the scala tympani. Consistent reversible changes in threshold and suprathreshold features of the electrically evoked auditory brainstem response (EABR) were found. The magnitude of EABR change was directly related to exposure stimulus current level and to cochlear stimulation site. Suprathreshold features of the EABR were more sensitive to continuous stimulation exposures than threshold measures. Reversible EABR changes were found in the presence and absence of stimulation-induced histopathology.

Placebo Effect in Tinnitus Management

Masking devices, lidocaine, and analog oral forms of lidocaine have all been reported as being effective forms of therapy to relieve tinnitus. Many studies, however, have used single-blind protocols and were possibly biased by placebo effects. To investigate the contributions of a placebo effect in clinical tinnitus studies, 25 tinnitus patients who had received a placebo injection in a previous double-blind lidocaine study were contacted on the pretense that they would receive a test dose of lidocaine; the 20 who responded were included in this study. A 5 cc bolus of placebo saline solution instead of lidocaine was then administered to each patient. Forty percent of the patients reported a change in their tinnitus following the placebo injection. The results of this study serve to point out the inherent flaws in straight clinical trials, and that the success rates achieved in such uncontrolled clinical investigations may be biased by the placebo effects.

Treatment of tinnitus with intravenous lidocaine: A double-blind randomized trial

Several recent reports have suggested that intravenous (IV) lidocaine is an effective form of therapy to relieve tinnitus; however, many of these studies were not well controlled. A double-blind randomized trial to assess the effectiveness of IV lidocaine on tinnitus was conducted at the University of Washington-affiliated hospitals on a total of 50 patients. Tinnitus was evaluated before and after injection by subjective assessment and audiometric matching. Although 40% of the lidocaine group reported a decrease in tinnitus, over 30% of the lidocaine group reported increased tinnitus after administration of the drug. There was also a high incidence of side effects, including disequilibrium, slurred speech, numbness, and tingling of the extremities in the drug group. The results of the study suggest that the clinical usefulness of IV lidocaine in relieving tinnitus may be less than was previously reported.

Morphological changes in the normal and neomycin-perfused guinea pig cochlea following chronic prosthetic implantation.†

The effects of chronic prosthetic implantation and interval electrical stimulation were studied in the normal and neomycin‐perfused cochlea of the guinea pig. One group of guinea pigs was implanted with a multiple‐electrode prosthesis in the scala tympani. During a 4‐week period, the device was stimulated for 3 hours weekly with a continuous, 1 kHz sinusoidal current of constant intensity. A second group of guinea pigs underwent identical implantation and stimulation except that cochlear perfusion with .1 M neomycin was performed at the time of implantation. Current intensities ranged from .1 to .6 mA RMS. Two complementary control groups were implanted but not stimulated. The animals were sacrificed, the cochleae were perfused with a fixative, and the temporal bones were prepared for examination under a light, transmission, or scanning electron microscope.