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Ototoxicity assessment of a gentamicin sulfate otic preparation in dogs.
1995
Strain G.M. | Merchant S.R. | Neer T.M. | Tedford B.L.
Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations.
Show more [+] Less [-]Evaluation of otoacoustic emissions in clinically normal alert puppies
2011
Schemera, Bettina | Blumsack, Judith T. | Cellino, Alice F. | Quiller, Travis D. | Hess, Bradley A. | Rynders, Patricia E.
Objective—To evaluate distortion product otoacoustic emission (DPOAE) measurements in puppies with normal hearing. Animals—23 clinically normal 7.5-to 10.5-week-old puppies. Procedures—A cross-sectional study was performed. The DPOAE measurements were obtained with a commercially available distortion product otoacoustic measurement system and were performed in a quiet, non-sound-attenuated room. All measurements were obtained from alert puppies and were repeated 1 or 2 times to ensure that the measurements were replicable. Results that were a minimum of 8 dB higher than the noise floor were accepted. Values from the first trial in which emissions were obtained at all test frequencies were used for analysis. Results—Otoacoustic emission measurements were easily obtained, robust, reliable, and consistent with auditory brainstem response and behavioral results. Conclusions and Clinical Relevance—Hearing screening in alert puppies can be accomplished reliably and rapidly with otoacoustic emissions testing. Results supported the possibility of the use of DPOAE measurement in hearing screening of dogs.
Show more [+] Less [-]Effects of an enrofloxacin–silver sulfadiazine emulsion in the ears of rabbits with perforated tympanic membranes
2019
Bateman, Fiona L. | Kirejczyk, Shannon G. M. | Stewart, Georgina V. | Cutler, Daniel C. | Quilling, Laura L. | Howerth, Elizabeth W. | Mayer, Joerg
OBJECTIVE To determine whether an enrofloxacin–silver sulfadiazine emulsion (ESS) labeled for treatment of otitis externa in dogs has ototoxic effects in rabbits following myringotomy. ANIMALS 6 healthy adult New Zealand White rabbits. PROCEDURES Rabbits were anesthetized for brainstem auditory-evoked response (BAER) tests on day 0. Myringotomy was performed, and BAER testing was repeated. Saline (0.9% NaCl) solution and ESS were then instilled in the left and right middle ears, respectively, and BAER testing was repeated prior to recovery of rabbits from anesthesia. Application of assigned treatments was continued every 12 hours for 7 days, and rabbits were anesthetized for BAER testing on day 8. Rabbits were euthanized, and samples were collected for histologic (6 ears/treatment) and scanning electron microscopic (1 ear/treatment) examination. RESULTS Most hearing thresholds (11/12 ears) were subjectively increased after myringotomy, with BAER measurements ranging from 30 to 85 dB in both ears. All day 8 hearing thresholds exceeded baseline (premyringotomy) values; results ranged from 30 to 85 dB and 80 to > 95 dB (the upper test limit) in saline solution–treated and ESS-treated ears, respectively. All ESS-treated ears had heterophilic otitis externa, epithelial hyperplasia of the external ear canal, various degrees of mucoperiosteal edema, and periosteal new bone formation on histologic examination. Scanning electron microscopy revealed that most outer hair cells in the ESS-treated ear lacked stereocilia or were absent. CONCLUSIONS AND CLINICAL RELEVANCE Results supported that ESS has ototoxic effects in the middle ear of rabbits. Further research is needed to confirm these findings. Myringotomized laboratory rabbits may be useful to study ototoxicity of drugs used in human medicine.
Show more [+] Less [-]Ototoxicity assessment of a gentamicin sulfate otic preparation in dogs
1995
Strain, G.M. | Merchant, S.R. | Neer, T.M. | Tedford, B.L.
Vestibulotoxic and ototoxic effects often are seen after long-term, high-dose systemic treatment with gentamicin, but toxic effects after topical use have not been reported in animals, to the authors' knowledge. Vestibular and auditory effects of twice daily otic gentamicin treatment for 21 days were evaluated in 10 dogs with intact tympanic membranes and in the same 10 dogs after experimental bilateral myringotomy. Each dog served as its own control; 7 drops of gentamicin sulfate (3 mg/ml in a buffered aqueous vehicle) were placed in 1 ear, and 7 drops of vehicle were placed in the opposite ear. Treatment and control ears were reversed after myringotomy. Vestibular function was evaluated daily by neurologic examination and behavioral assessment Auditory function was evaluated twice weekly by determination of brain stem auditory evoked potentials. Gentamicin sulfate placed in the ear of clinically normal dogs with intact or ruptured tympanic membranes, in the quantities used in this study, did not induce detectable alteration of cochlear or vestibular function. Serum gentamicin concentration after 21 days of treatment was detectable in only 2 dogs and was an order of magnitude below documented toxic concentrations.
Show more [+] Less [-]Brain stem auditory evoked potentials from bone stimulation in dogs
1993
Strain, G.M. | Green, K.D. | Twedt, A.C. | Tedford, B.L.
Brain stem auditory evoked potential (BAEP) testing with air-conducted click stimuli can be used to diagnose sensorineural deafness in dogs if conductive deafness can be ruled out. Detection of conductive deafness can be performed by recording BAEP elicited by a vibratory stimulus transducer placed against the skull. Air- and bone-conducted BAEP were compared in dogs, varying bone stimulator placement, click polarity, and stimulus intensity. Optimal bone stimulator placement was determined to be over the mastoid process, followed by the mandible and the zygomatic arch. Condensation polarity clicks gave responses preferable to those elicited by rarefaction or alternating polarity. Bone-conducted BAEP peak latencies were significantly longer than air-conducted latencies after correction of the latencies for the air conduction time accompanying air-conducted stimuli. Significant differences between stimulus modalities were not seen for BAEP peak amplitudes or interpeak latencies. Latency-intensity and amplitude-intensity regressions had similar effects for both modalities: latencies decreased and amplitudes increased as stimulus intensity increased.
Show more [+] Less [-]Power spectral analysis and digital filtration of brain stem auditory evoked potentials in dogs
1993
Kawasaki, Y. | Inada, S.
Power spectral analysis and digital filtering of brain stem auditory evoked potentials (BAEP) were performed in dogs. The BAEP were recorded in 7 dogs, using alternating clicks at frequency of 20 Hz. The clicks were delivered monaurally at intensity of 90-dB normal hearing level. Power spectral analysis indicated that the frequency compositions of the averaged responses were divisible into 4 frequency bands: A (30 to 390 Hz), B (390 to 680 Hz), C (680 to 910 Hz) and D (910 to 1960 Hz). The frequency limits of digital high-pass (HP) and low-pass (LP) filters, at which neither peak-to-peak nor absolute amplitudes were reduced, were 1,170 and 1,270 Hz for P1, 290 and 1,170 Hz for P2, 290 and 980 Hz for P3, 290 and 980 Hz for P4, and 200 and 880 Hz for P5, respectively. The dual structure of BAEP was confirmed in dogs. Below 200 Hz for the HP filter, peak-to-peak and absolute amplitudes of afl waves were not significantly reduced. Therefore, this frequency may be a boundary frequency between low- and high-frequency components of BAEP in dogs. The main source for the high- frequency components that constituted each positive peak and the following trough was derived from frequency bands C and D. The frequency limits of 200 Hz for a digital HP filter and of 1,270 Hz for a digital Lp filter, at which amplitudes of aU waves were not reduced, support the analog filter settings recommended for dogs (ie, less than and qual to 53 and 3,000 Hz for analog HP and LP filters, respectively).
Show more [+] Less [-]Ototoxic potential of gentamicin in ponies
1991
Nostrandt, A.C. | Pedersoli, W.M. | Marshall, A.E. | Ravis, W.R. | Robertson, B.T.
Ototoxicosis was evaluated in 6 healthy ponies given 5 mg of gentamicin/kg of body weight, q 8 h, IM. Ponies 1, 2, and 3 were dosed for 7 days and ponies 4, 5, and 6 were dosed for 14 days. Serum peak and trough concentrations of gentamicin were measured by radioimmunoassay at regular intervals. Brain stem auditory-evoked responses were recorded every 5 days up to 60 days after the first dose to monitor auditory function. Although serum gentamicin concentrations were within or above the accepted clinical therapeutic range, loss of auditory function was not observed at the frequency range (1 to 4 kHz) tested. Serum chemical values remained within the accepted clinical range and no evidence of nephrotoxicosis was observed. Seemingly, gentamicin given IM to healthy ponies was safe and had minimal risk of side effects.
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