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Biomedical subjects

J M Miller

Publications and source records attributed to J M Miller.

At least 109 records · Page 6Linked to original sources
PubMed2000

Treatment of Chlamydia trachomatis infections in pregnant women.

The intent of this article is to provide an overview of the epidemiology and pharmacotherapy, including cost analyses, of Chlamydia trachomatis infections in pregnant women. Chlamydia is a common sexually transmitted infection. For pregnant women, there are concerns both for the mother (post-partum endometritis, horizontal transmission) and the newborn (conjunctivitis, delayed pneumonia). Therapeutic options are restricted because of the fetus and include multi-day treatment with erythromycin, amoxicillin, clindamycin or single dose azithromycin. Clinical cure rates with these options are 86, 92, 93 and 95%, respectively. Pharmacoeconomic analyses have been conducted to determine if the initial increase in acquisition cost of azithromycin (approximately 3-fold higher than erythromycin or amoxicillin) is offset by improvement in compliance and drug efficacy. Clindamycin has received little attention because of its expense (4-fold more than azithromycin). Analyses have been retrospective. As models incorporate more complications of failure to cure, azithromycin increasingly becomes more cost effective and is our recommended treatment.

Adult↗
PubMed2000

Malaria, intestinal parasites, and schistosomiasis among Barawan Somali refugees resettling to the United States: a strategy to reduce morbidity and decrease the risk of imported infections.

In 1997, enhanced health assessments were performed for 390 (10%) of approximately 4,000 Barawan refugees resettling to the United States. Of the refugees who received enhanced assessments, 26 (7%) had malaria parasitemia and 128 (38%) had intestinal parasites, while only 2 (2%) had Schistosoma haematobium eggs in the urine. Mass therapy for malaria (a single oral dose of 25 mg/kg of sulfadoxine-pyrimethamine) was given to all Barawan refugees 1-2 days before resettlement. Refugees >2 years of age and nonpregnant women received a single oral dose of 600 mg albendazole for intestinal parasite therapy. If mass therapy had not been provided, upon arrival in the United States an estimated 280 (7%) refugees would have had malaria infections and 1,500 (38%) would have had intestinal parasites. We conclude that enhanced health assessments provided rapid on-site assessment of parasite prevalence and helped decrease morbidity among Barawan refugees, as well as, the risk of imported infections.

Adolescent↗
PubMed2000

Astigmatism and Amblyopia among Native American Children (AANAC): design and methods.

The overall goal of the AANAC study is to improve detection of astigmatism and prevention of amblyopia in populations with a high prevalence of astigmatism. To meet this goal, the study will evaluate four methods of screening for astigmatism in preschool children and will assess both the short-term and long-term benefits of early correction of astigmatism in improving acuity and preventing amblyopia. This paper presents an overview of the design and methodology of the AANAC study. Subjects are members of the Tohono O'Odham Nation, a Native American tribe with a high prevalence of astigmatism. Preschool-age children who attend Head Start are screened with four tools: the Marco Nidek KM-500 autokeratometer, the MTI photoscreener, the Nikon Retinomax K-Plus autorefractor, and the Lea Symbols acuity chart. Sensitivity and specificity for detection of significant astigmatism, as measured by a technique that uses both cycloplegic retinoscopy and cycloplegic autorefraction, is determined for each of the four screening tools. Presence of amblyopia is evaluated by measurement of best-corrected recognition acuity and acuity for orthogonal gratings. Spectacles are provided to all 3-year-old children with > or =2.00 diopters (D) of astigmatism and all 4- and 5-year-old children with > or =1.50 D of astigmatism. Persistence of amblyopia after glasses wearing is evaluated by follow-up measurement of best-corrected recognition acuity and acuity for orthogonal gratings, conducted 2-5 months after glasses are prescribed. Long-term effectiveness of early screening and glasses prescription is evaluated through measurement of recognition acuity in two groups of first-grade children: one group who participated in the Head Start program before the intensive vision screening program was initiated, and a second group who participated in the study's Head Start vision screening program.

Amblyopia↗
PubMed2000

Three-dimensional location of human rectus pulleys by path inflections in secondary gaze positions.

PURPOSE: Connective tissue pulleys serve as the functional mechanical origins of the extraocular muscles (EOMs). Anterior to these pulleys, EOM paths shift with gaze to follow the scleral insertions, whereas posterior EOM paths are stable in the orbit. Inflections in EOM paths produced by gaze shifts can be used to define the functional location of pulleys in three dimensions (3-D). METHODS: Contiguous magnetic resonance images in planes perpendicular to the orbital axis spanned the anteroposterior extents of 22 orbits of 11 normal adults with the eyes in central gaze, elevation, depression, abduction, and adduction. Mean EOM cross-sectional area centroids represented in a normalized, oculocentric coordinate system were plotted over the length of each EOM to determine paths. Path inflections were identified to define pulley locations in 3-D. RESULTS: All rectus EOM paths exhibited in secondary gaze positions distinct inflections 3 to 9 mm posterior to globe center, which were consistent across subjects. The globe center and the lateral rectus pulley translated systematically in the orbit with lateral gaze, whereas other pulleys remained stable relative to the orbit. CONCLUSIONS: Distinct inflections in rectus EOM paths in secondary gaze positions confirm the existence of pulleys and define their locations in 3-D. The globe and lateral rectus pulley translate systematically with gaze position. The EOM pulleys may simplify neural control of eye movements by implementing a commutative ocular motor plant in which commands for 3-D eye velocity are effectively independent of eye position.

Adult↗
PubMed1999

Rescue and regrowth of sensory nerves following deafferentation by neurotrophic factors.

Trauma and loss of cochlear inner hair cells causes a series of events that result first in the retraction of the peripheral processes of the auditory nerve, scar formation in the organ of Corti, and over the course of weeks to months (depending on the species) the loss of auditory nerve cell bodies (spiral ganglion cells). Neurotrophic factors play an important role in the mature nervous system as survival factors for maintenance and protection and also can play a role in regrowth. Studies in the cochlea now show that application of exogenous neurotrophic factors can enhance survival of spiral ganglion cells after deafness and induce regrowth of peripheral processes, perhaps by replacing lost endogenous factors. Combinations of factors may be most effective for achieving greatest survival and regrowth. Our studies find that brain-derived neurotrophic factor (BDNF) and glial-line-derived neurotrophic factor (GDNF) are very effective at enhancing spiral ganglion cell survival following deafness from ototoxic drugs or noise. It has also been found that BDNF plus fibroblast growth factor (FGF) is very effective at inducing process regrowth. Electrical stimulation also acts to enhance spiral ganglion cell survival, and the combination of electrical stimulation and neurotrophic factors could prove a most effective intervention.

Aminoglycosides↗
PubMed1999

Comparison of a novel rectilinear biphasic waveform with a damped sine wave monophasic waveform for transthoracic ventricular defibrillation. ZOLL Investigators.

OBJECTIVES: We compared the efficacy of a novel rectilinear biphasic waveform, consisting of a constant current first phase, with a damped sine wave monophasic waveform during transthoracic defibrillation. BACKGROUND: Multiple studies have shown that for endocardial defibrillation, biphasic waveforms have a greater efficacy than monophasic waveforms. More recently, a 130-J truncated exponential biphasic waveform was shown to have equivalent efficacy to a 200-J damped sine wave monophasic waveform for transthoracic ventricular defibrillation. However, the optimal type of biphasic waveform is unknown. METHODS: In this prospective, randomized, multicenter trial, 184 patients who underwent ventricular defibrillation were randomized to receive a 200-J damped sine wave monophasic or 120-J rectilinear biphasic shock. RESULTS: First-shock efficacy of the biphasic waveform was significantly greater than that of the monophasic waveform (99% vs. 93%, p = 0.05) and was achieved with nearly 60% less delivered current (14 +/- 1 vs. 33 +/- 7 A, p < 0.0001). Although the efficacy of the biphasic and monophasic waveforms was comparable in patients with an impedance < 70 ohms (100% [biphasic] vs. 95% [monophasic], p = NS), the biphasic waveform was significantly more effective in patients with an impedance > or = 70 ohms (99% [biphasic] vs. 86% [monophasic], p = 0.02). CONCLUSIONS: This study demonstrates a superior efficacy of rectilinear biphasic shocks as compared with monophasic shocks for transthoracic ventricular defibrillation, particularly in patients with a high transthoracic impedance. More important, biphasic shocks defibrillated with nearly 60% less current. The combination of increased efficacy and decreased current requirements suggests that biphasic shocks as compared with monophasic shocks are advantageous for transthoracic ventricular defibrillation.

Aged↗
PubMed1999

Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial). Global Use of Strategies To Open occluded coronary arteries.

We evaluated the effects of abciximab treatment during early angioplasty after clinically failed thrombolysis for acute myocardial infarction. In the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial of reteplase versus alteplase for acute infarction (n = 15,059), 392 patients underwent angioplasty a median of 3.5 hours after thrombolysis and had complete procedural data. We compared 30-day mortality and in-hospital outcomes between patients who received abciximab (n = 83) and those who did not (n = 309), and (among patients given abciximab) between those randomized to alteplase versus reteplase. Patients given abciximab had anterior infarction less often, but were more often in Killip classes III or IV. The 30-day mortality rate tended to be lower with abciximab (3.6% vs 9.7%, p = 0.076), more so after adjustment for baseline differences (p = 0.042). The composite of death, stroke, or reinfarction did not differ significantly with abciximab treatment (12% vs 14%, p = 0.7), but it occurred less often among abciximab-treated patients who had been randomized to reteplase (n = 55) versus alteplase (n = 28) (7% vs 21%, p = 0.08). Severe bleeding was increased among abciximab-treated patients (3.6% vs 1.0%, p = 0.08), despite less heparin use. No intracranial hemorrhages occurred with abciximab. The use of abciximab for early angioplasty after clinically failed thrombolysis resulted in trends toward lower 30-day mortality and increased bleeding.

Abciximab↗
PubMed1999

Use of capillary electrophoresis and fluorescent labeled peptides to detect the abnormal prion protein in the blood of animals that are infected with a transmissible spongiform encephalopathy.

Transmissible spongiform encephalopathies in humans and in animals are fatal neuro-degenerative diseases with long incubation times. The putative cause of these diseases is a normal host protein, the prion protein, that becomes altered. This abnormal prion protein is found mostly in the brains of infected individuals in later stages of the disease, but also can be found in lymphoid and other tissues in lower amounts. In order to eradicate this disease in animals, it is important to develop a system that can concentrate the abnormal prion protein and an assay that is very sensitive. The sensitivity that can be achieved with capillary electrophoresis makes it possible to detect the abnormal protein in blood. A peptide from the carboxyl terminal region, amino acid positions 218-232, was labeled with fluorescein during the synthesis of the peptide at the amino terminus. Antibodies that have been produced to this peptide were affinity purified and used in a capillary electrophoresis immunoassay. The amount of fluorescein labeled peptide in the capillary was 50 amol. Blood was obtained from normal sheep and elk, from sheep infected with scrapie and elk infected with chronic wasting disease. Buffy coats and plasma were prepared by a conventional method. After treatment with proteinase K, which destroys the normal protein but not the altered one, the blood fractions were extracted and tested in the capillary electrophoresis immunoassay for the abnormal prion protein. The abnormal prion protein was detected in fractions from blood from infected animals but not from normal animals. This assay makes a pre-clinical assay possible for these diseases and could be adapted to test for the abnormal prion protein in process materials that are used for manufacture of pharmaceuticals and products for human consumption.

Amino Acid Sequence↗
PubMed1999

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

Acute Disease↗
PubMed1999

Inner ear transgene expression after adenoviral vector inoculation in the endolymphatic sac.

Gene transfer has been performed in a variety of organs. In the mammalian inner ear, viral vectors have been used to introduce exogenous reporter genes via the scala tympani into the cochlea. While scala tympani inoculation is clinically feasible, it is not without risks. Moreover, transgene expression has so far been restricted to the cochlear tissues in the perilymphatic spaces that are contiguous with the scala tympani. To achieve gene transfer of vestibular organs and cells surrounding the endolymphatic space, and to extend the clinical utility of inner ear gene therapy, we developed a new surgical approach for vector inoculation. A replication-deficient adenoviral vector, Ad.RSVntlacZ, was injected into the guinea pig endolymphatic sac. A large number of blue (LacZ-positive) cells was observed in the endolymphatic sac and duct, the vestibule, and the ampulla. Blue cells were also detected in the cochlea, mainly in cells bordering the endolymphatic space: marginal cells in the stria vascularis and supporting cells in the organ of Corti. These findings indicate that inoculation of viral vectors into the endolymphatic sac can provide efficient gene transfer into a variety of cell types that are not accessible via scala tympani inoculation.

Adenoviridae↗
PubMed1999

Catheter ablation of accessory pathways, atrioventricular nodal reentrant tachycardia, and the atrioventricular junction: final results of a prospective, multicenter clinical trial. The Atakr Multicenter Investigators Group.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of a temperature-controlled radiofrequency catheter ablation system. METHODS AND RESULTS: The patient population included 1050 patients who had undergone ablation of atrioventricular nodal reentrant tachycardia (AVNRT), an accessory pathway (AP), or the atrioventricular junction (AVJ). Ablation was successful in 996 patients. The probability of success was highest among patients who had undergone ablation of the AVJ, lowest in patients who had undergone ablation of an AP, and in between for patients who had undergone ablation of AVNRT. A major complication occurred in 32 patients. Four variables predicted ablation success (AVJ, AVNRT, or left free wall AP ablation and an experienced center). Four factors predicted arrhythmia recurrence (right free wall, posteroseptal, septal, and multiple APs). Two variables predicted development of a complication (structural heart disease and the presence of multiple targets), and 3 variables predicted an increased risk of death (heart disease, lower ejection fraction, and AVJ ablation). CONCLUSIONS: These findings may serve as a guide to clinicians considering therapeutic options in patients who are candidates for ablation.

Adolescent↗
PubMed1999

Attenuation of cochlear damage from noise trauma by an iron chelator, a free radical scavenger and glial cell line-derived neurotrophic factor in vivo.

Tissue injury by reactive oxygen species (ROS) may play a role in noise-induced hearing loss (NIHL). Since iron is involved in ROS generation, we studied if an iron chelator, deferoxamine mesylate (DFO), alone or in combination with mannitol, a hydroxyl scavenger and weak iron chelator, attenuates NIHL. Further, we investigated if glial cell line-derived neurotrophic factor (GDNF) provides additive or synergistic protection of the cochlea from acoustic trauma when given together with DFO and mannitol. Pigmented female guinea pigs were exposed to noise (4 kHz octave band, 115 dB SPL, 5 h). One hour before, immediately after, and 5 h after noise exposure, subjects received an injection of 5 ml saline/kg (control, group I), 100 mg DFO/kg (group II), 15 mg mannitol/kg (group III), or both DFO and mannitol (group IV and V). Animals in group V underwent implantation of an osmotic pump filled with GDNF (100 ng/ml) in the left ear 4 days before noise. Each treatment afforded some protection from noise damage. Group I showed significantly greater outer hair cell loss and threshold shifts at two or more frequencies compared to groups II through V. GDNF provided an additive functional, but not morphological, protection with DFO and mannitol. These findings indicate that iron chelators can attenuate NIHL, as do ROS scavengers, supporting the notion that ROS generation plays a role in NIHL. Additional functional protection provided with GDNF suggests that GDNF may attenuate noise-induced cochlear damage through a mechanism that is additive with antioxidants.

Animals↗
PubMed1999

A study of antenatal cocaine use-chaos in action.

OBJECTIVE: This study identified behaviors or conditions associated with cocaine use among prenatal patients and evaluated pregnancy outcomes. STUDY DESIGN: A case-control study of patients attending a neighborhood-based prenatal program was conducted. For each patient who used cocaine, the next prenatal registrant with both a negative history of cocaine use and a negative urine screen for cocaine served as the control. RESULTS: Cocaine use was associated with older, multiparous women who had a history of prior low birth weight infants. Prenatal care was obtained later and less frequently. Other substances, including tobacco, alcohol, and marijuana, were more commonly used. A history of physical abuse and violence, as well as incarceration, was identified more often. The prevalence of syphilis was higher. Women who used cocaine were delivered of their infants earlier; prematurity occurred more often. Their infants were smaller. Regression analysis identified factors other than cocaine as important in either low birth weight or preterm delivery. Attainment of a greater number of prenatal care visits was associated with improved outcome. CONCLUSION: Women who use cocaine have numerous significant life disturbances, which may collectively influence pregnancy outcome. Cocaine use itself is a marker and did not appear to influence the prevalence of low birth weight or preterm delivery.

Alcohol Drinking↗
PubMed1999

Once-daily valacyclovir hydrochloride for suppression of recurrent genital herpes.

OBJECTIVE: To document the frequency of genital herpes recurrences in men and women with histories of recurrent genital herpes during 1 year of continuous, suppressive therapy with valacyclovir hydrochloride (HCl). METHODS: In an open-label clinical trial conducted at 11 centers, 127 subjects (46 women and 81 men) with histories of recurrent genital herpes (at least 6 recurrences per year) were treated with valacyclovir HCl (500 mg once daily), and their clinical status was followed up for 1 year. Genital herpes recurrences were documented in diaries, and quarterly clinic visits were made for evaluating lesion recurrences and drug safety. In cases of recurrence, subjects self-treated with valacyclovir HCl 500 mg twice daily for 5 days, then resumed once-daily treatment. RESULTS: After the first 3 months of suppressive therapy, 81% of subjects were free of recurrence. Recurrence-free rates remained undiminished during the second, third, and fourth quarters (84%, 84%, and 91%, respectively) and were similar for men and women. Thirty of 46 women (65%) and 56 of 81 men (69%) remained recurrence free during the study and therapy was well tolerated. Adverse events were mild, infrequent, and not considered related to the study drug. CONCLUSION: Valacyclovir HCl was highly effective and well tolerated as continuous suppressive therapy in men and women with recurrent genital herpes. Potential benefits of the once-daily regimen of valacyclovir HCl include improved patient compliance.

Acyclovir↗
PubMed1999

Different motor systems use similar damped extraretinal eye position information.

Extraretinal eye position information (EEPI) shifts the directional significance of retinal loci by an angle roughly equal to that of an associated saccade, with the shift reported to begin 0-250 ms before the saccade and to continue apace with the saccade, or sluggishly, over a period as much as an order of magnitude longer. These different estimates of remapping initiation and duration could be due to various factors, including different localizing responses, retinal loci of probe flashes, and saccade target predictability. We compared manual and gaze pointing to probe flashes at controlled retinal loci under identical stimulus conditions and in the same subjects, and found that EEPI was similar: both hand and gaze pointing EEPI shifted over about 140 ms, beginning about 50 ms before the saccade. For both pointing responses, remapping appeared to be initiated later for parafoveal loci than for loci 10 degrees to either side. We found no effect of saccade target predictability. We show that variability in EEPI and sensory processing only slightly (approximately 5%) inflates estimates of EEPI shift duration. Based on our results, and comparisons with recent studies, we argue that similar EEPI parameters apply to hand pointing, eye pointing and visual comparisons, and that remaining differences across studies can reasonably be attributed to differences in stimulus conditions.

Fixation, Ocular↗
PubMed1999

Fos-like immunoreactivity in the auditory brainstem evoked by bipolar intracochlear electrical stimulation: effects of current level and pulse duration.

Fos-like immunoreactivity was used to compare the auditory brain stem excitation elicited by bipolar electrical stimulation of the cochlea at various current levels relative to the electrically evoked auditory brain stem response threshold for a 50-micros/phase monophasic pulse. Fos-like immunoreactive cells were labeled in primary auditory brain stem regions. The distribution of labeled cells was restricted to regions known to be cochleotopically related to the stimulated region of the scala tympani. Some labeled cells were observed at 2x electrically evoked auditory brain stem response threshold. The number, density and spatial distribution of labeled cells were quantified in the dorsal cochlear nucleus and inferior colliculus, and found to increase with increasing level of stimulation. For 50-micros pulses, the location of labeled neurons remained reasonably restricted to narrow bands within each region until the 1Ox level of stimulation (20 dB above electrically evoked auditory brain stem response threshold) was reached. While a monotonic increase in Fos-like immunoreactivity with increasing stimulus level was observed in most nuclei, for cells of the superficial layer of the dorsal cochlear nucleus, a non-monotonic change with increasing stimulus level was seen. This dorsal cochlear nucleus non-monotonicity may indicate that, at higher levels of stimulation, a secondary indirect inhibitory input, probably associated with activation of deep layer dorsal cochlear nucleus cells, reduces excitatory responses at the superficial layer of the dorsal cochlear nucleus. Electrically evoked auditory brain stem response and Fos expression showed parallel changes as a function of stimulus level and pulse duration. The data indicate that discrete activation of cell populations within the central auditory pathways can occur with bipolar electrical stimulation to the highest levels of stimulation typically useful in humans. The data also indicate a close, but not identical, quantitative relationship between Fos-like immunoreactivity and electrophysiological response amplitude. These findings support the view that a study of Fos-like immunoreactivity can provide a powerful and quantitative tool for study of the dynamic response characteristics of cells of the central auditory system to electrical stimulation at suprathreshold levels. The data suggest that there is a monotonic increase in the number of neurons responsive to intracochlear electrical stimulation as a function of stimulus level, at least through the upper half of the dynamic range, but that this increase does not result in a complete loss of spatial selectivity. Coupled with previous psychophysical studies, these results suggest that the increase in the number of activated neurons is functionally beneficial, resulting in improved discrimination of changes in the electrical signals.

Animals↗
PubMed1999

Acquired resistance to acoustic trauma by sound conditioning is primarily mediated by changes restricted to the cochlea, not by systemic responses.

Hearing loss caused by intense sound exposure can be significantly reduced by pre-exposing subjects to moderate-level acoustic stimuli. This phenomenon occurs in a variety of mammals. We investigated whether sound conditioning provides acquired resistance to acoustic trauma through local mechanisms selectively in the conditioned ears or if systemic mechanisms are involved that would yield contralateral protection in unconditioned ears. Guinea pigs (group I) in which one external ear canal was occluded were exposed to conditioning sound (2-20 kHz, 85 dB SPL, 5 h/day, 10 days). After removing the occlusion, the animals were then subjected bilaterally to intense noise (2-20 kHz, 110 dB SPL, 5 h) 5 days after the last conditioning exposure. Animals without ear canal occlusion were also exposed to the intense sound without conditioning (group II) or following the same conditioning exposure (group III). Intense sound exposure caused significantly greater permanent ABR threshold shifts at all frequencies tested (4, 8, 12, 16 and 20 kHz) in group II than in group III. In group I, the occluded ears showed significantly greater threshold shifts at all frequencies compared to the unoccluded ears. The threshold shifts in the occluded ears in group I were identical to those observed in group II; and the shifts in unoccluded ears in group I were identical to those in group III. Protective effects provided by sound conditioning were almost the same in group III and in the unoccluded ears in group I. The extent of hair cell damage supported the physiological findings. These results indicate that acquired resistance to acoustic trauma provided by sound conditioning is restricted to the cochlea exposed to conditioning sound, suggesting that conditioning protection is mediated primarily by the changes that occur locally within the conditioned cochlea. This animal model, with unilateral external ear canal occlusion during sound conditioning, is useful for studies of the mechanisms of conditioning protection.

Acoustic Stimulation↗