Ototoxicity of Povidone-Iodine applied to the middle ear cavity of guinea pigs.

OBJECTIVE: Povidone-Iodine preparation is used as a disinfectant in otological surgeries. The ototoxicity of Povidone-Iodine preparation was evaluated using infant, young and adult guinea pigs. The effects of different concentrations and of different exposure durations on compound action potentials were also studied. MATERIALS & METHODS: Povidone-Iodine was used to fill one middle ear cavity of the guinea pig, and the compound action potential (CAP) was measured from the round window membrane at 24h, 7 days, and 28 days. The contralateral side was filled with saline as control. Test sounds used were clicks and tone bursts of 2, 4, and 8 kHz. RESULTS: At 24h, Povidone-Iodine solution showed a significant toxic effect in the infant group. In the young animal group, no toxic effect was seen. In the adult group, a mild degree of deafness for 2 kHz was found. At 7 days, the young group showed significant hearing loss for all frequencies, but the adult group did not show any hearing loss. With a half strength solution, both young and adult group did not show hearing loss. At 28 days, with a full strength solution, hearing loss became prominent for all sound stimulation. With 1/8th dilution, the young group showed a moderate hearing loss, but the adult group did not. CONCLUSION: The thicker round window membrane in human is expected to provide more protection to the human cochlea than in the guinea pig model that we have studied. Mild hearing loss at 24h and 7 days using 10% solution, but no hearing loss with 5% solution at 7 days may indicate that rinsing of the middle ear cavity with saline during surgery should minimize the ototoxic effect of this product. The age of the animals does influence the outcome of the ototoxicity experiment. From this experiment, Povidone-Iodine preparations in the infant should be used with caution. Povidone scrub should not be used for otologic surgery.

Production of a human antibody fragment against the insulin-like growth factor І receptor as a fusion protein.

The aim of this study was to isolate single-chain variable fragments (scFvs) against human insulin-like growth factor I receptor (IGFIR) from a phage library displaying human scFvs. Isolated scFvs-displaying phages showed affinity for IGF-IR in comparison to the control. Expression of scFv proteins in Escherichia coli for further characterization, however, proved extremely difficult. Alternatively, the scFv protein was expressed as a fusion protein with a maltose-binding protein (MBP) that is a highly soluble E. coli protein. The MBPscFv fusion protein expressed in a soluble form in E. coli was purified to homogeneity by two-step affinity chromatography. The resulting MBP-scFv exhibited affinity for IGF-IR and structurally-related insulin receptor (IR). These results suggest both that MBPscFv fusion proteins are practical alternatives to isolating scFv proteins for further characterization and that successful isolation of human scFvs against a specific protein of interest requires vigorous screening in the early stages. Such screening is accomplished by using two independent screening methods such as measuring binding to IGF-IR but not to IR by ELISA or measuring competitive binding by IGF-I in addition to binding to IGF-IR alone.

Safety of ofloxacin (OFLX) and fosfomycin sodium (FOM) ear drops.

OBJECTIVE: The objective of this study is to evaluate the safety of two ear drops, Ofloxacin (OFLX: Taribid Otic Solution, Daiichi Seiyaku) and Fosfomycin sodium (FOM: Fosmicin S, Meiji Seiyaku). METHODS: Albino guinea pigs were used as experimental animals, and the ototoxicity was evaluated by means of threshold changes in the compound action potentials (CAP), when topically applied to the middle ear cavity of the guinea pig. The sound stimuli applied were; click sound, with tone bursts of 8 kHz, 4 kHz, and 2 kHz. In one group of animals, after one application of the ear drops in the right middle ear cavity, the change in CAP was compared with a contralateral saline control at 24h, one week, and four weeks. In other group of animals, the ear drops were applied into the middle ear cavity for seven consecutive days and the CAP was measured at 24h. RESULTS: At 24h the CAP threshold for click, 8 and 4 kHz elevated significantly for both the saline and ear drop treatment, but the threshold returned to normal when measured at 7 days and 28 days. Seven consecutive days of ear drops administration resulted in no reduction in the CAP for either ear drops. CONCLUSIONS: Based on the lack of changes in the CAP, these two ear drops studied did not show any significant ototoxicities.

Role of dorsal neck proprioceptive inputs to vestibular compensation in humans.

To investigate the role of cervical proprioceptive inputs in the process of vestibular compensation, we performed static posturography in patients with acute and compensated unilateral vestibular dysfunction, by applying vibratory stimulation to the dorsal neck muscles. Neck vibration induced disequilibrium in both groups of patients, but was more pronounced in the compensated patients. These results indicate that manipulation of the neck afferents causes discompensation in subjects whose vestibular dysfunction has already been compensated by multisensory inputs including neck afferents.

A 'neural' response with 3-ms latency evoked by loud sound in profoundly deaf patients.

A large negative deflection with a latency of 3 ms was observed in the auditory brainstem response (ABR) waveforms of some patients with peripheral profound deafness. This deflection was termed the N3 potential. In this paper, we review patients with the N3 potential and discuss the characteristics of abnormal ABR waveforms. The origin of the N3 potential was also discussed, especially with respect to vestibular evoked potentials. In most of the patients, audiograms showed no response to the maximum output of an audiometer in the high-frequency range and a residual response in the low-frequency range. The N3 potentials were noted at intensities of 80 dB nHL or greater. As the stimulus intensity increased, the amplitude of the potential increased and the latency decreased. A high repetition rate (83.3/s) of the click stimulus influenced the latency and amplitude of the N3 potential. The potential was replicated on retest within less than a month, and had a consistent latency and amplitude over the scalp. The results indicate that the N3 potential is not an electrical artifact but a physiological neural response evoked by a loud sound. The N3 potential is most likely not an auditory evoked response from cochlear or a response from a semicircular canal, because it has a 3-ms latency, a sharp waveform, and is unassociated with vertigo. The results suggest that the N3 potential may be a saccular acoustic response.

Developmental anatomy of the supratubal recess in temporal bones from fetuses and children.

The supratubal recess (STR), located superior to the bony eustachian tube and anterior to the attic and often the site of disease, is clearly separated from the attic by the presence of a bony partition. Its anatomic development in childhood, however, remains nuclear. We reviewed serial horizontal sections of fetal and children's temporal bones from the collection of the Otopathology Laboratory, University of Minnesota. Apparently, upward expansion of the bony eustachian tube begins at a late fetal stage and continues throughout childhood, thus forming the STR. Our finding that the STR had already developed in temporal bones without pneumatization of petrous bone suggests that its formation is independent of the air-cell system. Absorption of mesenchymal tissue in the STR tends to be slower than elsewhere in the temporal bone. Surrounded solely by petrous bone, the STR seems, both developmentally and anatomically, a distinctive compartment of the middle ear.

Three-component analysis of benign paroxysmal positional nystagmus.

Three-component analysis of Benign Paroxysmal Positional Nystagmus (BPPN), focusing on the horizontal, vertical, and torsional, using a computerized eye movement analysis system, was carried out in 10 patients. Using a pendular rotation stimulus, we also measured three components of eye movement elicited from the vertical semicircular canals in normal subjects. We compared two components (vertical and torsional) of BPPN with that of eye movements elicited from the vertical semicircular canals. In BPPN, the torsional component of eye movements was larger than that of the vertical component. Conversely, the vertical component from the vertical semicircular canals was larger than that of the torsional component. From these results, by analysing the vestibulo-ocular reflex of the vertical semicircular canals, it is difficult to support the idea that the pathology of the BPPV is localized in the posterior semi-circular canal alone.

Low-frequency biasing of round window responses in guinea pigs and chinchillas.

The acoustic biasing technique using low-frequency sound is of increasing interest to investigators, not only as a means of studying cochlear transduction but also as a promising tool for assessing cochlear pathology such as endolymphatic hydrops. We compared normal modulation patterns of round window responses in guinea pigs and chinchillas, whose low-frequency auditory characteristics are known to be different. A 50-Hz sine wave (90 dB SPL for guinea pigs and 80 dB SPL for chinchillas), which evoked an equivalent magnitude of cochlear microphonics (CM) in both species, was used to modulate the compound action potential (CAP) and the summating potential (SP) elicited by 8-kHz tone bursts. Overall patterns of CAP and SP modulation were almost identical between the two species except for a difference in the phase of 50 Hz CM. The phase of maximum SP enlargement was in accord with that of maximum CAP suppression, which led to inferred basilar membrane (BM) position at maximum scala tympani displacement by between 45 and 90 degrees. More complex or hysteresis effects seemed to be involved in the modulation of CAP and SP magnitude, in addition to the biasing effect owing solely to BM displacement.

A device for controlling odorant stimulation and olfactory evoked responses in humans.

We developed a device for odorous stimuli control to record olfactory evoked responses from the human scalp. The characteristics of the apparatus are as follows. Translating the subject's respiration into electric signals with a sensor attached to the nose. The period and timing of odorous stimuli could be adjusted, so that stimuli could be synchronous with respiration. The interstimulus interval could be arbitrarily selected once every 1 to 9 respiration(s) so that adaptation could be prevented. We obtained evoked responses to odorous stimuli using this apparatus from the human scalp, whose positive peak latencies were approximately 350 and 700 msec. Such responses were not recorded if oxygen stimuli were used instead of odorous stimuli or with click sounds produced by the switching electromagnetic valve. Three types of odorant evoked scalp potentials were obtained in normal human subjects. The first type consisted mainly of two positive peaks with a peak latency of about 350 msec (P350) and about 700 msec (P700). The second type and the third type consisted of only one positive peak with a peak latency of about 350 msec and 700 msec, respectively. Such a P350 or P700 peak as that observed in the normal subjects was not detected in anosmic patients.

Analysis of auditory brainstem response waveforms derived ipsilaterally and contralaterally to monaural stimulation.

The auditory brainstem responses (ABRs) obtained from 28 normal healthy adults were studied using the ipsilateral and contralateral recordings from the positions of vertex and each mastoid to monaural stimulation. Each wave of ABRs recorded by ipsilateral and contralateral derivations to stimulation site showed slightly significantly differences. Comparing the ipsilateral and contralateral data, the latencies of waves II and V showed a slightly small reduction in the ipsilateral recording, while these of waves III and IV showed a small increase. Next, the distributions of potentials and latencies of waves II to V were investigated from ABRs situating different electrodes in mid-coronal array of the scalp and non-cephalic reference electrode on the seventh cervical vertebra (CVII). The results of latencies showed the reverse relation to the data obtained from the ipsilateral and contralateral recordings using the reference electrodes on each mastoid. These facts suggest that the comparable differences of latencies in the bilaterally recorded ABRs are explained by the pseudo-phenomena of differential recordings, which the phase delayed or advanced potential propagated to each mastoid being reference electrode position.

Topography of binaural interaction in the auditory brainstem response.

The scalp topography of binaural interaction (BI) in the auditory brainstem response (ABR) was studied in fourteen normal individuals. BI was observed from all recording sites of the scalp, and the peak amplitude was noted mostly in the bilateral parietal and occipital regions. There was a significant difference in amplitude shown by significance probability mapping (SPM) when the waveform obtained by binaural stimulation was compared with the sum of the waves obtained by monaural stimulation. The topography of BI was different from that of the wave III and the wave IV/V complex. In contrast to previous reports by other workers, we found that BI mainly corresponded to the first half of the wave IV/V complex.

The temporal bone in multiple myeloma.

Multiple myeloma is a malignant disease of the skeleton. Anatomically, any bone may ultimately come to be involved in a given case. In a literature review, no published series of temporal bone findings have been reported. In this study, oto-histopathologic changes associated with multiple myeloma are analyzed and reported in 15 temporal bones from 8 patients. The bone marrow of 13 temporal bones was involved by the tumor. Osteolysis was evident in 11 temporal bones. Serous otitis media (SOM) or purulent otitis media (POM) was seen in 13 ears with 12 showing mastoid effusions. Eight ears exhibited pathological changes in inner ears, including degeneration of the organ of Corti, atrophy of stria vascularis, decreased ganglion cells, and labyrinthine hydrops. The inner ear changes were most severe in 2 patients who had otologic symptoms. Infiltration of myeloma cells was not apparent in the middle ear mucosa or the inner ears.

Pathogenesis of tympanosclerosis.

In spite of the wealth of information on the clinical, histologic, and pathologic aspects of tympanosclerosis, the pathogenesis of tympanosclerosis is still unclear. In an attempt to understand the pathogenesis, 319 human temporal bones from 196 individuals with otitis media were studied. The extent and nature of tympanosclerosis and the characteristics of the otitis media associated with it were studied. Forty-five temporal bones from 35 individuals with otitis media were found to have tympanosclerosis, giving an incidence of 14.1%. It was seen most commonly in individuals over 40 years of age (86.7%). The male-to-female ratio was 1.6:1. The most common site of occurrence was the tympanic membrane (88.9%). Tympanosclerosis was seen more often in the anterior and posterior inferior quadrants of the tympanic membrane and that, too, in a central position. Tympanosclerosis was seen more commonly in temporal bones with irreversible inflammatory changes, and in this group, late plaques were more commonly seen than early or intermediate plaques. Audiometric charts failed to show any direct relationship between extent of tympanosclerosis and the severity of hearing loss. The only audiometric finding of any consequence was a mixed hearing loss in the presence of middle ear tympanosclerosis.

Potter's syndrome: a temporal bone histopathological study.

Histopathological findings in seven temporal bones from four infants diagnosed as Potter's syndrome are described. The infants were labelled as Potter's syndrome after autopsy confirmed bilateral renal agenesis. Extrarenal manifestations included pulmonary hypoplasia and facial anomalies. The middle ear volume in infants with Potter's syndrome remained unchanged with age resulting in a significantly higher percentage of residual middle ear mesenchyme in these infants as compared to normal infants. Dehiscence of the facial nerve was seen in all the temporal bones studied. One ear showed the presence of eosinophilic effusion in the endolymphatic sac, an underdeveloped malleus and a wide facial nerve canal. The inner ear structures showed no significant anomalies except for the absence of the organ of Corti in the basal turn of the cochlea in one of the ears.

Three-component analysis of caloric nystagmus in humans.

Three-component analysis of caloric nystagmus, focusing on the horizontal, vertical, and torsional, using a computerized eye movement analysis system, was carried out in 10 normal human subjects. The caloric response was induced by cold stimulation to the right ear of the subjects in the supine and prone positions. In the supine position, the three components of nystagmus were toward the left (10 subjects), upward (eight subjects) or downward (two subjects), and clockwise (10 subjects). In the prone position, on the other hand, the three components were directed toward the right (10 subjects), downward (five subjects), upward (three subjects), and counterclockwise (10 subjects); there was no vertical direction in two subjects. These findings indicate that caloric stimulation activates the three semicircular canals simultaneously. Also the changes in the nystagmus direction in the supine and prone positions could be explained, at least partially, by the nonconvective component of caloric stimulation.

Low-frequency modulation of compound action potential in experimental perilymphatic fistula and endolymphatic hydrops.

We have tested the hypothesis that the cause of cochlear dysfunction associated with perilymphatic fistula (PLF) is closely related to endolymphatic hydrops (ELH). Using guinea pigs, we studied the tone-burst elicited compound action potential (CAP) and its modulation as caused by a 50 Hz biasing tone in experimental PLF. We compared these results with those of experimental ELH. Following perilymph aspiration through the perforated round window membrane, mild but significant elevations of CAP thresholds at tested frequencies were found. A reduction in the amplitude of cochlear microphonics (CM) for a 50 Hz sine wave appeared to correlate with these CAP threshold changes. However, there were no significant changes in the modulation effect of the 50 Hz biasing tone on the CAP elicited by an 8 kHz tone burst. This finding differed from that in ears with experimental ELH, in which significant reductions of both 50 Hz CM and the degree of CAP modulation were consistently observed. We concluded that it is unlikely that the underlying mechanisms of a modification to the low frequency response of the base of the cochlea following perilymph aspiration is linked to that of experimental ELH.