Distortion product otoacoustic mapping measured pre- and post-loud sound exposures.

OBJECTIVE: Sampling distortion product otoacoustic emissions (DPOAEs) at multiple f2/f1 ratios and f2 frequency values produces a DPOAE "map." This study examined the efficacy of DPOAE mapping compared with pure tone audiometry and standard DPOAEs for detecting noise effects in subjects exposed to loud sound. DESIGN: A map significance score was developed as a single measure of map change. Significance scores were evaluated before and after exposure to: loud music (LM), controlled noise (CN), and firing range noise (FR) in three separate sets of subjects. Scores were compared to audiometry and standard DPOAE results in the LM study. STUDY SAMPLE: The LM and CN exposure studies involved 22, and 20 healthy young subjects respectively with normal hearing. Eight Marines were studied before and after FR exposure. RESULTS: After LM exposure, audiometry showed significant changes at 1, 2, 4, and 6 kHz. Standard DPOAE measures were also significantly different at several frequencies. Map significance scores detected changes more effectively and showed the distribution of DPOAE alterations. CONCLUSIONS: Map significance scores detected changes after noise exposure more reliably than audiometry and standard DPOAEs. Additionally, maps showed a diffuse response to sound exposure perhaps explaining why individual DP-grams appear less sensitive.

Fixed-Level Frequency Threshold Testing for Ototoxicity Monitoring.

OBJECTIVES: Hearing loss from ototoxicity is often most pronounced at high frequencies. To improve patient monitoring and compliance, high-frequency testing methods should be short and easy to administer. We evaluated the repeatability and accuracy of a Békésy-like, fixed-level frequency threshold (FLFT) technique. This test takes less than a minute and could provide a rapid and effective way to determine the highest audible frequency. We hypothesized the FLFT test would be repeatable in normal-hearing subjects, and accurate when compared with Békésy fixed-frequency audiometry in the sensitive region for ototoxicity (SRO). DESIGN: Twenty-nine normal-hearing subjects (20 females, 9 males) performed 2 different automated audiometry tests at least 4 times over a period of no less than 3 weeks. Ages ranged from 23 to 35 years (average = 28 years). Subjects completed testing under Sennheiser HDA-200 headsets. Initial fixed-frequency audiometry thresholds were obtained at frequencies ranging from 0.5 to 20 kHz to identify each subject's highest audible frequency, which was used to determine the SRO. The SRO was defined as the seven frequencies at and below the highest audible frequency in 1/6-octave steps. These frequencies were monitored with fixed-frequency audiometry. At each session, the FLFT test was administered at 80 dB SPL. Subjects used a Békésy-style tracking method to determine the frequency threshold. All testing was completed in a sound booth (single wall, Industrial Acoustics Company) using a computerized, laptop-based, system. FLFT repeatability was calculated as the root mean square difference from the first test session. FLFT accuracy was calculated as the difference from the highest audible frequency determined from fixed-frequency audiometry interpolated to 80 dB SPL level. RESULTS: The FLFT average RMSD for intersession variability was 0.05 ± 0.05 octaves. The test showed no learning effect [F(3,78) = 0.7; p = 0.6]. The overall intersession variability for SRO fixed-frequency audiometry thresholds at all frequencies was within clinically acceptable test-retest variability (10 dB) at 5.8 dB (range 2.7 to 9.9 dB). The SRO fixed-frequency audiometry therefore served as a repeatable basis of comparison for accuracy of the FLFT test. The mean absolute difference between the fixed-frequency audiometry and FLFT-determined highest audible frequency was 0.03 octaves. The FLFT and the highest audible frequency via fixed-frequency audiometry at 80 dB SPL were not different statistically (p = 0.12). The FLFT took approximately 30 seconds to complete, compared with approximately 4.5 min for fixed-frequency audiometry SRO and 20 to 25 min for a traditional ototoxic audiometric assessment. CONCLUSIONS: The Békésy-style FLFT was repeatable within 1/12 octave (1 step size in the testing procedure). The FLFT agreed well with the highest audible frequency determined via fixed-frequency audiometry at 80 dB SPL. The FLFT test is amenable to automatic and self-administration and may enable quick, accurate, noise-tolerant ototoxicity, and high-frequency hearing monitoring.

DPOAE level mapping for detecting noise-induced cochlear damage from short-duration music exposures.

Distortion product otoacoustic emission (DPOAE) level mapping provides a comprehensive picture of cochlear responses over a range of DP frequencies and f2/f1ratios. We hypothesized that individuals exposed to high-level sound would show changes detectable by DPOAE mapping, but not apparent on a standard DP-gram. Thirteen normal hearing subjects were studied before and after attending music concerts. Pure-tone audiometry (500-8,000 Hz), DP-grams (0.3-10 kHz) at 1.22 ratio, and DPOAE level maps were collected prior to, as soon as possible after, and the day after the concerts. All maps covered the range of 2,000-6,000 Hz in DP frequency and from 1.3 to -1.3 in ratio using equi-level primary tone stimuli. Changes in the pure-tone audiogram were significant (P ≤ 0.01) immediately after the concert at 1,000 Hz, 4,000 Hz, and 6,000 Hz. The DP-gram showed significant differences only at f2= 4,066 (P = 0.01) and f2= 4,348 (P = 0.04). The postconcert changes were readily apparent both visually and statistically (P ≤ 0.01) on the mean DP level maps, and remained statistically significantly different from baseline the day after noise exposure although no significant changes from baseline were seen on the DP-gram or audiogram the day after exposure. Although both the DP-gram and audiogram showed recovery by the next day, the average DPOAE level maps remained significantly different from baseline. The mapping data showed changes in the cochlea that were not detected from the DP-gram obtained at a single ratio. DPOAE level mapping provides comprehensive information on subtle cochlear responses, which may offer advantages for studying and tracking noise-induced hearing loss (NIHL).

Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals.

PURPOSE: Green tea and green tea polyphenols have been shown to possess cancer preventive activities in preclinical model systems. In preparation for future green tea intervention trials, we have conducted a clinical study to determine the safety and pharmacokinetics of green tea polyphenols after 4 weeks of daily p.o. administration of epigallocatechin gallate (EGCG) or Polyphenon E (a defined, decaffeinated green tea polyphenol mixture). In an exploratory fashion, we have also determined the effect of chronic green tea polyphenol administration on UV-induced erythema response. EXPERIMENTAL DESIGN: Healthy participants with Fitzpatric skin type II or III underwent a 2-week run-in period and were randomly assigned to receive one of the five treatments for 4 weeks: 800 mg EGCG once/day, 400 mg EGCG twice/day, 800 mg EGCG as Polyphenon E once/day, 400 mg EGCG as Polyphenon E twice/day, or a placebo once/day (8 subjects/group). Samples were collected and measurements performed before and after the 4-week treatment period for determination of safety, pharmacokinetics, and biological activity of green tea polyphenol treatment. RESULTS: Adverse events reported during the 4-week treatment period include excess gas, upset stomach, nausea, heartburn, stomach ache, abdominal pain, dizziness, headache, and muscle pain. All of the reported events were rated as mild events. For most events, the incidence reported in the polyphenol-treated groups was not more than that reported in the placebo group. No significant changes were observed in blood counts and blood chemistry profiles after repeated administration of green tea polyphenol products. There was a >60% increase in the area under the plasma EGCG concentration-time curve after 4 weeks of green tea polyphenol treatment at a dosing schedule of 800 mg once daily. No significant changes were observed in the pharmacokinetics of EGCG after repeated green tea polyphenol treatment at a regimen of 400 mg twice daily. The pharmacokinetics of the conjugated metabolites of epigallocatechin and epicatechin were not affected by repeated green tea polyphenol treatment. Four weeks of green tea polyphenol treatment at the selected dose and dosing schedule did not provide protection against UV-induced erythema. CONCLUSIONS: We conclude that it is safe for healthy individuals to take green tea polyphenol products in amounts equivalent to the EGCG content in 8-16 cups of green tea once a day or in divided doses twice a day for 4 weeks. There is a >60% increase in the systemic availability of free EGCG after chronic green tea polyphenol administration at a high daily bolus dose (800 mg EGCG or Polyphenon E once daily).