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Imiquimod, an immune response modifier, has been demonstrated to be safe and effective in the treatment of external genital and perianal warts caused by human papillomavirus (HPV). To identify the molecular mechanism(s) by which condylomata acuminata clear during topical treatment with imiquimod, wart skin biopsies were taken from patients before treatment, at treatment week 6, and at the end of treatment. Tissues were analyzed for HPV DNA and for mRNA of several cytokines and HPV gene products. Wart clearance was associated with evidence of tissue production of interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha. Regression of warts was strongly associated with a decrease in HPV DNA and in mRNA expression for both early and late viral proteins. Thus, topical imiquimod treatment of anogenital warts led to significant increases in local production of multiple interferon mRNAs and a significant reduction in virus load as measured by decreases in HPV DNA and mRNA for early HPV proteins.

Purpose This cross-sectional study had two goals: (1) Identify and quantify the effects of aging on the auditory brainstem response (ABR); (2) Describe how click rate and hearing impairment modify effects of aging. Research Design and Analysis ABR measures were obtained from 131 predominately male Veteran participants aged 26 to 71 yr. Metrics analyzed include amplitude and latency for waves I, III, and V, and the I–V interpeak latency interval (IPI) at three repetition rates (11, 51, and 71 clicks/sec) using both polarities. In order to avoid confounding from missing data due to hearing impairment, participants had hearing thresholds <40 dB HL at 2 kHz and 70 dB HL at 4 kHz in at least one ear. Additionally, the median 2, 3, and 4 kHz pure tone threshold average (PTA2,3,4) for the sample, ~17 dB HL, was used to delineate subgroups of better and worse hearing ears, and only the better hearing sample was modeled statistically. We modeled ABR responses using age, repetition rate, and PTA2,3,4 as covariates. Random effects were used to model correlation between the two ears of a subject and across repetition rates. Inferences regarding effects of aging on ABR measures at each rate were derived from the fitted model. Results were compared to data from subjects with poorer hearing. Results Aging substantially diminished amplitudes of all of the principal ABR peaks, largely independent of any threshold differences within the group. For waves I and III, age-related amplitude decrements were greatest at a low (11/sec) click rate. At the 11/sec rate, the model-based mean wave III amplitude was significantly smaller in older compared with younger subjects even after adjusting for wave I amplitude. Aging also increased ABR peak latencies, with significant shifts limited to early waves. The I–V IPI did not change with age. For both younger and older subjects, increasing click presentation rate significantly decreased amplitudes of early peaks and prolonged latencies of later peaks, resulting in increased IPIs. Advanced age did not enhance effects of rate. Instead, the rate effect on wave I and III amplitudes was attenuated for the older subjects due to reduced peak amplitudes at lower click rates. Compared with model predictions from the sample of better hearing subjects, mean ABR amplitudes were diminished in the group with poorer hearing, and wave V latencies were prolonged. Conclusions In a sample of veterans, aging substantially reduced amplitudes of all principal ABR peaks, with significant latency shifts limited to waves I and III. Aging did not influence the I–V IPI even at high click rates, suggesting that the observed absolute latency changes associated with aging can be attributed to changes in auditory nerve input. In contrast, ABR amplitude changes with age are not adequately explained by changes in wave I. Results suggest that aging reduces the numbers and/or synchrony of contributing auditory nerve units. Results also support the concept that aging reduces the numbers, though perhaps not the synchrony, ...

Abstract-Thirty-six blast-exposed patients and twenty-nine non-blast-exposed control subjects were tested on a battery of behavioral and electrophysiological tests that have been shown to be sensitive to central auditory processing deficits. Abnormal performance among the blast-exposed patients was assessed with reference to normative values established as the mean performance on each test by the control subjects plus or minus two standard deviations. Blast-exposed patients performed abnormally at rates significantly above that which would occur by chance on three of the behavioral tests of central auditory processing: the Gaps-In-Noise, Masking Level Difference, and Staggered Spondaic Words tests. The proportion of blast-exposed patients performing abnormally on a speech-in-noise test (Quick Speech-In-Noise) was also significantly above that expected by chance. These results suggest that, for some patients, blast exposure may lead to difficulties with hearing in complex auditory environments, even when peripheral hearing sensitivity is near normal limits.Key words: audiometric evaluation, auditory dysfunction, auditory processing disorder, blast, central auditory processing, evoked potential, hearing loss, rehabilitation, traumatic brain injury, Veterans. INTRODUCTION The recent conflicts in Afghanistan and

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Objectives/Hypothesis Determine the effects on hearing of diabetes mellitus (DM) severity. Study Design We conducted a cross-sectional study among Veterans to investigate the relationship of diabetes severity and hearing in randomly selected subjects with (165) and without (137) DM and who had no more than a moderate hearing loss. Methods Subjects were classified by three age tertiles (<50, 50–56, and 57+ years). Diabetes severity was classified as insulin-dependent (IDDM), noninsulin-dependent (NIDDM), or no DM. Other DM measures included concurrent serum glucose, serum HbA1c, duration of disease, and several measures of DM-related complications. Pure-tone thresholds were measured in both ears of each subject at frequencies from 250 Hz through 14,000 Hz. Outcome measures were adjusted for age and frequency and analyzed for differences between subject groups using analysis of variance. Contrasts of the mean NIDDM and IDDM thresholds at each frequency to the DM group, and controlled for the effects of frequency, age, and interactions were modeled. Results There was greater hearing loss in younger tertile DM subjects compared to those without DM. Significant hearing differences were at all frequencies for NIDDM subjects, but for IDDM subjects, differences were at 1,000 Hz and below, and 10,000 Hz and above. Over age 50 years, there were significant associations between hearing at low frequencies and IDDM only. Self-report of prior noise exposure did not explain observed differences. Conclusions Diabetes is associated with an increased risk of hearing loss, and this difference is manifest particularly in adults <50 years old.