Management of the incus body in ossiculoplasty.

OBJECTIVE: (1) Evaluate the sound transfer impact of removal of the incus body in ossicular chain reconstruction (OCR) using an incus strut prosthesis. (2) Provide basic science data to assist clinical decision making in ossiculoplasty. STUDY DESIGN: Basic science. SETTING: Cadaveric temporal bone research laboratory. SUBJECTS AND METHODS: Ossicular chain reconstruction with an incus strut prosthesis was performed on 7 human temporal bones with and without the incus body. The difference in round window membrane (RWM) peak-to-peak displacements (90-dB sound pressure level, 250-8000 Hz) using single-point laser Doppler vibrometry (LDV) was compared with observed baseline, intact ossicular chain values. RESULTS: Comparing OCR using an incus strut prosthesis to an intact ossicular chain across all 7 temporal bones, the largest differences in RWM velocity occurred at 1011 and 2011 Hz. With increasing frequencies, RWM velocities of the OCR approached the intact ossicular chain. Using a Wilcoxon rank-sum test comparing the ossicular chain with and without the incus body showed no statistically significant difference across all frequencies (P = .925). Removing the incus body resulted in improved median RWM velocity (× 10(-2) mm/s) by 0.6 at 1011 Hz and a decrease of 0.6 at 2011 Hz. A rank-sum test to evaluate the difference at 1011 and 2011 Hz did not demonstrate statistical significance. CONCLUSION: Removal of the incus body in OCR using an incus strut prosthesis did not significantly change sound transfer function of the middle ear relative to its preservation. Our data suggest the impact of the retained mass in OCR to be minimal.

Effects of tympanomeatal blunting on sound transfer function.

OBJECTIVE: (1) To measure the peak-to-peak displacement of the round window membrane (RWM) prior to blunting procedure. (2) To evaluate the impact of blunting the anterior tympanomeatal angle (ATA) on middle ear sound transfer function. STUDY DESIGN: Basic science study. Setting. Cadaveric temporal bone research laboratory. SUBJECTS AND METHODS: Six fresh human temporal bones were prepared using a mastoidectomy and facial recess approach. Baseline RWM peak-to-peak displacements were obtained by single-point laser Doppler vibrometry (LDV) at 90-dB sound pressure level over a spectrum of 250 to 8000 Hz. Temporalis muscle was harvested and then fashioned into a graft for each temporal bone, mimicking ATA blunting. RWM displacement responses with the blunted ATA were measured using the LDV to judge the impact on middle ear transfer function. RESULTS: For each of the 6 temporal bones, the average displacement decreased across all sound frequencies with the ATA blunting when compared with baseline (no blunting). Baseline velocity measurements for all sound signals averaged 4.5 × 10(-3) ± 1.892 × 10(-3) (mean ± SEM) mm/s, while measurements averaged 2.2 ± 6.62 × 10(-4) mm/s with blunting of the ATA (P < .001). This amounted to a 52% decrease in velocity of the RWM following blunting of the ATA. CONCLUSION: Blunting of the ATA decreases the sound transfer function of the tympanic membrane and middle ear. Prevention of blunting at the ATA during tympanoplasty should be emphasized.

Distribution of PLGA nanoparticles in chinchilla cochleae.

OBJECTIVES: To study the distribution of polylactic/glycolic acid-encapsulated iron oxide nanoparticles (PLGA-NPs) in chinchilla cochleae after application on the round window membrane (RWM). STUDY DESIGN AND SETTING: Six chinchillas (12 ears) were equally divided into controls (no treatments) and experimentals (PLGA-NP with or without magnetic exposure). After 40 minutes of PLGA-NP placement on the RWM, perilymph was withdrawn from the scala tympani. The RWM and cochleae were fixed with 2.5% glutaraldehyde and processed for transmission electron microscopy. RESULTS: Nanoparticles were found in cochleae with or without exposure to magnet forces appearing in the RWM, perilymph, endolymph, and multiple locations in the organ of Corti. Electron energy loss spectroscopy confirmed iron elements in nanoparticles. CONCLUSION: The nanoparticles were distributed throughout the inner ear after application on the chinchilla RWM, with and without magnetic forces. SIGNIFICANCE: PLGA-NP applied to the RWM may have potential for sustained therapy to the inner ear.

The permeability of SPION over an artificial three-layer membrane is enhanced by external magnetic field.

BACKGROUND: Sensorineural hearing loss, a subset of all clinical hearing loss, may be correctable through the use of gene therapy. We are testing a delivery system of therapeutics through a 3 cell-layer round window membrane model (RWM model) that may provide an entry of drugs or genes to the inner ear. We designed an in vitro RWM model similar to the RWM (will be referred to throughout the paper as RWM model) to determine the feasibility of using superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) for targeted delivery of therapeutics to the inner ear. The RWM model is a 3 cell-layer model with epithelial cells cultured on both sides of a small intestinal submucosal (SIS) matrix and fibroblasts seeded in between. Dextran encapsulated nanoparticle clusters 130 nm in diameter were pulled through the RWM model using permanent magnets with flux density 0.410 Tesla at the pole face. The SIS membranes were harvested at day 7 and then fixed in 4% paraformaldehyde. Transmission electron microscopy and fluorescence spectrophotometry were used to verify transepithelial transport of the SPION across the cell-culture model. Histological sections were examined for evidence of SPION toxicity, as well to generate a timeline of the position of the SPION at different times. SPION also were added to cells in culture to assess in vitro toxicity. RESULTS: Transepithelial electrical resistance measurements confirmed epithelial confluence, as SPION crossed a membrane consisting of three co-cultured layers of cells, under the influence of a magnetic field. Micrographs showed SPION distributed throughout the membrane model, in between cell layers, and sometimes on the surface of cells. TEM verified that the SPION were pulled through the membrane into the culture well below. Fluorescence spectrophotometry quantified the number of SPION that went through the SIS membrane. SPION showed no toxicity to cells in culture. CONCLUSION: A three-cell layer model of the human round window membrane has been constructed. SPION have been magnetically transported through this model, allowing quantitative evaluation of prospective targeted drug or gene delivery through the RWM. Putative in vivo carrier superparamagnetic nanoparticles may be evaluated using this model.

Mitochondrial dysfunction in hearing loss.

Mitochondrial pathology plays an important role in both inherited and acquired hearing loss. Inherited mitochondrial DNA mutations have been implicated in both syndromic and non-syndromic hearing loss, as well as in predisposition to aminoglycoside ototoxicity. Acquired mitochondrial dysfunction in the absence of mitochondrial DNA mutations has also been proposed as playing an important role in noise-induced and toxin-induced hearing loss. Presbycusis, the hearing loss associated with aging, may be caused by mitochondrial dysfunction resulting from the accumulation of acquired mitochondrial DNA mutations and other factors. The pathophysiological mechanisms and clinical implications of these findings are discussed.

Transtympanic electrocochleography: a 10-year experience.

OBJECTIVE: To report the authors' experience with transtympanic electrocochleography during the past 10 years. STUDY DESIGN: Retrospective case review. SETTING: Otology/neurotology referral center. PATIENTS: Transtympanic electrocochleography was performed on 2,421 ears of 2,140 patients from May 1990 to April 2000. INTERVENTION: Clicks and tonebursts were used in electrocochleography testing. Summating potential/action potential ratio was calculated. Action potential latency shift by rarefaction and condensation clicks was measured. Cochlear microphonic was recorded. MAIN OUTCOME MEASURE: An enlarged summating potential/action potential ratio (>0.40), broadened action potential waveform (>3 msec) or prolonged action potential latency shift (>0.2 msec) was considered to be indicative of endolymphatic hydrops. The presence of cochlear microphonic indicated hair cell survival. RESULTS: In response to clicks, an enlarged summating potential/action potential ratio was found in 76.1% of ears and a broadened action potential waveform in 70%. Either an enlarged summating potential/action potential ratio or a broadened action potential waveform was observed in 78.4% of ears. In response to tonebursts, an enlarged summating potential/action potential ratio was found in 64.8%. The combined use of clicks and tonebursts yielded an enlarged summating potential/action potential ratio in 81.7%. Electrocochleography using tonebursts had the advantage of frequency selectivity. A prolonged action potential latency shift was found in 62.2% of ears with Ménière's disease. A significant association between an enlarged summating potential/action potential ratio and an action potential latency shift was noted (chi = 5.357, p = 0.021). An enlarged summating potential/action potential ratio was found 71% in Stage 1 of Ménière's disease, 82% in Stage 2, 85% in Stage 3, and 90% in Stage 4 (chi = 19.442, p = 0.000). An enlarged summating potential/action potential ratio was associated with the duration of the disease, 43% in the under 1-year group, and 100% in the more than 30-years group (chi = 33.555, p = 0.000). A large cochlear microphonic was present in 69% of ears with hearing levels greater than 40 dB. CONCLUSION: Transtympanic electrocochleography using clicks and tonebursts is a reliable test to detect the presence of endolymphatic hydrops in Ménière's disease. A prolonged action potential latency shift evoked by rarefaction and condensation clicks is a useful addition to the application of electrocochleography in the diagnosis of Ménière's disease.