Derin Wester

Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla

The effects of a combination of two antioxidant compounds were studied in a chinchilla model of noise-induced hearing loss. After obtaining baseline hearing thresholds using inferior colliculus evoked potentials, chinchillas were exposed for 6 h to octave band noise centered at 4 kHz (105 dB SPL). Post-noise thresholds were obtained 1 h after the noise exposure, and then animals received either saline or salicylate and N-L-acetylcysteine combination. Another group received antioxidant treatment 1 h prior to noise. Hearing was tested at 1, 2 and 3 weeks post-noise. Subsequently, the cochleae were harvested, and cytocochleograms were prepared. There was a 20-40 dB SPL threshold shift at 3 weeks for tested controls. Permanent threshold shifts (PTS) were significantly reduced (P<0.05) to approximately 10 dB for the pre-treatment group at week 3. The PTS for the post-treatment group at week 3 was similar to the pre-treatment group at 1 and 2 kHz (0-10 dB) but was intermediate between the control and pre-treatment groups at 4 and 8 kHz (23 dB). Animals pre-treated with antioxidant had a significant reduction in hair cell loss but those post-treated with antioxidant had no protection from hair cell loss. These findings demonstrate the feasibility of reduction of noise-induced hearing loss using clinically available antioxidant compounds.

Targeted topical steroid therapy in sudden sensorineural hearing loss

Objective To treat patients with sudden sensorineural hearing loss (SSNL) who failed oral prednisone therapy by using a round window membrane (RWM) microcatheter. This topical delivery strategy sought to improve effectiveness of steroid treatment to the inner ear by targeting drug delivery to the RWM. Study Design Nonrandomized prospective design. Setting Tertiary care facility. Patients Six patients with severe unilateral SSHL, five of whom were refractory to a course of oral steroid therapy treated within 6 weeks of SSHL and three additional patients treated more than 6 weeks after SSHL. Intervention Therapeutic use of RWM catheter. Main Outcome Measures Pure-tone averages (PTAs) and word identification scores (WIS). Results Five of the six patients treated within 6 weeks of SSHL improved their WIS. Of the six, four returned to baseline hearing, one recovered hearing that could benefit by hearing amplification, and one regained moderate improvement in PTA but not WIS. Conclusion Targeted topical steroid administration avoids the significant systemic side effects of oral steroids and may offer more effective dosing than simple transtympanic injection of medicine. Although these findings are preliminary, it is possible that after further study, targeted drug delivery may be a useful technique to consider in patients with severe to profound hearing loss that have failed all other management options.

Characterizing and treating dizziness after mild head trauma.

Objective: The objectives of this study were to characterize patterns of dizziness seen after mild head trauma and to examine the diagnosis and treatment of this disorder. Study Design: Prospective patient registry. Setting: Tertiary referral center. Patients: Fifty-eight cases of active duty and retired military personnel who sustained mild head trauma and had resultant dizziness. Interventions: Vestibular evaluation, characterization by group, and treatment. Main Outcome Measures: Outcome measures include characterization of diagnosis types, patient distribution by diagnosis type, and patient outcome. Results: Individuals suffering from dizziness after mild head injury were divided into three diagnostic groups. Forty-one percent of the individuals suffered from posttraumatic vestibular migraines, 28% of the individuals had posttraumatic positional vertigo, and 19% of the individuals were classified as posttraumatic spatial disorientation. The remaining 12% of the patients could not be characterized. The positional group had objective physical examination findings, which cleared with treatment in all cases. The migraine group of patients and the disorientation group of patients had distinct abnormalities of the vestibulo-ocular reflex (VOR) and the vestibulo-spinal reflex (VSR). Eighty-four percent of the migraine group demonstrated an improvement of these test results as compared with 27% of the disorientation group. Mean time to return to work was less than 1 week for the positional group, 3.8 weeks for the migraine group, and greater than 3 months for the disorientation group. Conclusions: Using our patient registry of individuals suffering from dizziness after mild head trauma, we were able to characterize the majority of these cases into one of three more specific diagnostic groups. We present diagnostic criteria, suggested treatment guidelines, and our prognostic data.

Transtympanic versus sustained-release administration of gentamicin: kinetics, morphology, and function.

Objectives/Hypothesis Transtympanic gentamicin therapy has become a popular treatment modality for Menieres disease, but questions regarding the ideal dose of medicine, the best administration paradigm, and the safest treatment end‐point remain unanswered. The goal of this study is to examine the inner ear kinetics of transtympanic gentamicin and compare this with the kinetics of sustained‐release delivery in a basic science model. In addition, we plan to examine the relationship of these kinetics curves to the effect of the two treatment modalities on inner ear function and morphology. It is hoped that this analysis will help clinicians to better apply local medical therapy to the ear.

Kinetics of gentamicin uptake in the inner ear of Chinchilla langier after middle-ear administration in a sustained-release vehicle

The search for a safe, effective treatment for the vertigo associated with Menieres disease has long been an important topic in otolaryngology. In recent years many groups have begun using intratympanic gentamicin to treat this vertigo. Although reported cure rates are as high as 90%, many questions remain regarding this type of treatment. Current limitations are the necessity for repeated treatments and a lack of clear dosing guidelines. In addition, the gentamicin must be delivered in a manner that allows maximal vestibulotoxic effect without injury to hearing. Until investigators can control the exact amount of medicine that is placed in the ear and have an understanding of the kinetics of gentamicin absorption, adequate dosing guidelines will be difficult to establish, and therapy will continue to rely on empiric data. We describe the use of a fibrin-based sustained-release vehicle, impregnated with gentamicin, injected into the middle ear of chinchillas. This allows for a prolonged effect without repeated dosing. Using this model, we studied the absorption kinetics of gentamicin at time points ranging from 8 hours to 1 week after injection. We used our findings to create a kinetics curve of gentamicin absorption. We discuss the shape and characteristics of this kinetics curve and examine the effects of the fibrin-based sustained-release vehicle and gentamicin on the middle ear. We noted no absorption in the contralateral (untreated ear) or blood. Through better understanding of the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population and initiate programs for the use of this sustained-release vehicle in human beings.

Use of the round window microcatheter in the treatment of Meniere's disease.

Objectives/Hypothesis Transtympanic gentamicin is an increasingly popular treatment for Menieres disease. The present report examines the 2‐year follow‐up of our first 27 patients with Menieres disease treated with the use of microdose gentamicin through the Round Window Microcatheter. We applied the 1995 American Academy of Otolaryngology—Head and Neck Surgery criteria to this patient group to analyze the results of treatment.

Morphologic Changes in the Inner Ear of Chinchilla Laniger after Middle Ear Administration of Gentamicin in a Sustained-Release Vehicle

The use of transtympanic gentamicin has become a popular method of treating Menieres disease; nevertheless, many questions still remain regarding this therapy. Until investigators can control the exact amount of medicine that is administered to the ear and have an understanding of the kinetics of gentamicin, therapy will continue to rely on empirical data. Previously we described the use of a fibrin-based sustained-release vehicle impregnated with gentamicin in the middle ears of chinchillas. With this model a kinetics curve of gentamicin was defined. The inner ears of these animals were submitted for immunohistochemical and histologic analysis. We discuss the ultrastructural changes seen and correlate this to our kinetics data. We also examine measurement of hair cell damage with heat shock protein levels. By better understanding the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population.

Transtympanic management of tinnitus

Transtympanic therapy is becoming and important treatment modality for many inner ear disorders. The current therapies aimed at Menieres disease, sudden sensorineural hearing loss, noise-induced hearing loss, and the tinnitus associated with these disorders and idiopathic tinnitus, however, represents simply an evolutionary step in this treatment modality and must be validated by further scientific study. A number of promising developments including newer more targeted neuroactive medicines, a better understanding of medicine delivery, and the knowledge of the site, origin, and pathophysiology of the symptoms complex will make this therapy more effective. In the future it is possible that many inner ear disorders will be amenable to inner ear medical therapy. Ideally in the future with knowledge of the disease and its etiology the physician will simply pick the established medicine, the established dose, and the established route of administration and achieve a relatively predictable result.

Microdose gentamicin administration via the round window microcatheter: results in patients with Meniere's disease.

Abstract: Transtympanic gentamicin is becoming increasingly popular in the treatment of Menieres disease. In this report we examine our experience with the use of microdose gentamicin via the Round Window Microcatheter for the treatment of Menieres disease. Thirty‐six patients were treated with gentamicin administration via the Round Window Microcatheter between July 1997 and August 2000. The patients all underwent 10 days of continuous treatment with a total dose of 2.4–3.75 mg of gentamicin (10 mg/ml). All patients had extensive pre‐, intra‐, and post‐therapy auditory and vestibular testing. In this group, vertigo was eliminated in 89% of the patients, and tinnitus and pressure were significantly reduced in over 60% of the patients. Only one patient suffered a significant hearing loss and, most importantly, in all but one patient vestibular function was improved or normalized after treatment. Round Window Microcatheter‐administered microdose gentamicin is an exciting new treatment for Menieres disease. Preliminary results indicate that vertigo can be controlled without a significant reduction in cochlear or vestibular function in most patients. These results suggest that this therapy may be acting at a non‐hair cell site. Our results are compared to the published literature examining transtympanic injection. In addition, the underlying science supporting this type of treatment is examined.

Vestibular testing abnormalities in individuals with motion sickness.

Hypothesis The goal of this study was to compare the results of vestibular testing in individuals with motion sickness to a group of control subjects. Background Studying motion sickness is difficult, because no animal model has been developed and symptoms rarely occur outside motion environments. Tests that can be performed in normal laboratory settings, which help to identify individuals with motion sickness, may be valuable in characterizing this disorder. Methods Twenty active duty military individuals with well-documented motion sickness were tested. The test battery included sinusoidal rotational chair testing to calculate vestibulo-ocular reflex function, step-velocity testing to calculate vestibular time constants, and posturography testing to assess vestibulo-spinal reflex status. The results of this test battery were compared with a set of age- and sex-matched controls without motion sickness. Results Vestibular test abnormalities were demonstrated in individuals with motion sickness. Vestibulo-spinal reflex function on posturography was normal in the control group but abnormal in 70% of the individuals with motion sickness. In addition, 5% of the control group demonstrated a minimal shortening of the absolute time constant, whereas 60% of the individuals with motion sickness had abnormal absolute time constants. Conclusion A significant percentage of individuals with motion sickness demonstrate abnormalities in their time constant or vestibulo-spinal reflex function. These abnormalities can be detected using standard, land-based vestibular tests. These preliminary results have implications in understanding the etiology of motion sickness and may provide outcome measures to be used in treating motion sickness.