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Biomedical subjects

J M Aran

Publications and source records attributed to J M Aran.

At least 145 records · Page 8Linked to original sources

Summating potential and water balance in Meniere's disease.

The summating potentials (SP) to free-field 1-, 2-, 4-, and 8-kHz, 90-dB HL tone bursts were recorded by means of transtympanic electrocochleography in 45 patients divided into three groups: those with Meniere's disease, those whose diagnosis was uncertain, and control subjects. The similarities across frequencies between the human SP (promontory) and the experimental SP (DIF component from basal turn) suggest that the SP recorded in electrocochleography originates mostly from the base of the cochlea; negative values were observed at low frequencies (1 to 2 kHz), positive values at high frequencies (8 kHz). Patients with Meniere's disease showed significantly larger SP values than control subjects. The effect of orally administered glycerol on the SP and action potential amplitudes was evaluated by means of automated recordings repeated every 5 minutes. Summating potential values were remarkably constant in the control group. A decrease in SP absolute amplitude was observed in most patients with Meniere's disease and some subjects with uncertain diagnoses, specifically at low frequencies. These changes were frequently associated with action potential amplitude and auditory threshold improvements at low frequencies. It is assumed that the glycerol-induced SP changes at low frequencies are related to modifications in the low frequency mechanical response of the basilar membrane at the basal turn.

Adult↗

Observation of click-evoked compound VIII nerve responses before, during, and over seven months after kanamycin treatment in the guinea pig.

Compound VIII nerve action potential responses to clicks and filtered-clicks were recorded regularly over a period of 7 months following Kanamycin treatment (8 days, 400 mg/kg), in 3 awake guinea pigs each with an implanted electrode on the round window (left ear). From the end of the treatment the responses to the click became dissociated in various degrees within three major phases: (1) a rapid phase (8 to 10 days) where the responses were dramatically altered, (2) a recovery phase which lasted about 2 months, (3) a slow phase over the subsequent 5 months where the responses to the click decreased slowly but gradually while the N 1 component, as well as the responses to the 8 000 Hz filtered-click (which became recruiting at the end of the treatment), disappeared progressively. Responses to the low frequency filtered-clicks were less affected. Cochlear cytograms showed almost complete degeneration of the inner and outer hair cells of the first turn only.

Acoustic Stimulation↗

Normal and pathological adaptation of compound viii nerve responses in the guinea pig.

Adaptation of VIII nerve compound action potentials in response to trains of broad frequency spectrum clicks and high frequency filtered clicks is studied at various intensities in normal guinea pig under normal conditions, while masking with white noise and under pathological conditions after ototoxic antibiotic treatment. The results are discussed with respect to the clinical electro-cochleographic adaptation studies in man and the so-called two populations of receptors and nerve fibres in the cochlea.

Acoustic Stimulation↗

Evolution of CM, SP and AP during etacrynic acid intoxication in the guinea pig.

During etacrynic acid intoxication in the guinea pig, patterns of click-evoked compound electrocochleographic responses are similar to those observed in Menière and retro-cochlear human pathologies. Using high frequency tone bursts, SP, CM and AP were studied after intracardiac injection of etacrynic acid. The evolution of SP precedes that of CM and AP. Its change in polarity could be related to that reported for EP by Bosher et al. (1973). While during the recovery period SP overshoots (after 90 min), CM and AP increase more slowly (up to about 7 days) and in most cases AP amplitudes do not exceed 70-80% of their original value (25 days). N1, when present, keeps its classical pattern durint the entire evolution, whatever its amplitude and latency variations are. The early positive peak or negative shift observed in click-evoked human pathological electrocochleography can therefore be identified as SP. Thus this response is the indication of the presence of hair cells and of the impairment of the nerve fibre stimulation or response.

Acoustic Stimulation↗

Temporary tinnitus suppression in man through electrical stimulation of the cochlea.

While investigating the possibilities of electrically induced hearing in cases of profound deafness, we observed that very often an appropriate stimulation of the cochlea could result in tinnitus cancellation. We present here a progress report on that phenomenon, including 15 subjects. Such a cancellation was restricted to tinnitus subjectively localized in the ear under test, we observed no effect on noises localized in the other ear, or centrally. This suppression occurred so long as the cochlea was stimulated and stopped when the stimulation ceased. This phenomenon was very reproducible and did not seem to affect simultaneous normal acoustic hearing. It is hypothesized that this phenomenon acts through an inhibition of abnormal activity of sensorineural elements of the electrically stimulated cochlea.

Cochlea↗

Conflicting electrophysiological and anatomical data from drug-impaired guinea pig cochleas.

In guinea pigs that had been treated with very large doses of the aminoglycoside amikacin (14 x 450 mg/kg/day, i.m.) clear, short-latency responses to various click stimuli could be recorded at the round window. When the same cochleas were examined histologically, no outer or inner hair cells could be found along the entire length of the basilar membrane, save for a very few outer hair cells remaining at the apex. The response patterns resembled that of the compound action potential, and various characteristics suggest that they were of neural origin. Vestibular function, investigated by electronystagmography during rotation, appeared normal, as did most of the saccular and utricular hair cells. Transmission electron microscopy revealed a significant number of cochlear nerve fibres still innervating the remnants of Corti's organ. In other cochleas with similarly extensive destruction induced by another aminoglycoside (sisomycin, 14 x 125 mg/kg/day, 15 days as well as 3 months post-Rx), no responses could be recorded from the round window. Cochleas that were less affected, with the upper turns preserved, gave only small, long-latency responses. These preliminary observations are confirmed by further experiments now in progress. They suggest that unless a considerable number of inner hair cells remained undetected in the lower basal turn, a possibility that appears highly unlikely, there was either a direct mechanical excitation of cochlear nerve fibres, or an acoustical stimulation of vestibular sense organs.

Acoustic Stimulation↗

Transtympanic and surface recordings in the diagnosis of retrocochlear disorders.

A series of patients presenting with subsequently surgically confirmed central tumour involving the auditory pathways were investigated using both transtympanic electrocochleography (TT ECochG) and surface recordings of brainstem evoked responses (BER). While ECochG allows a detailed study of peripheral function, BER allow the investigation of neural conduction up to the level of the inferior colliculus. Valuable information can be obtained from: (1) comparison of the amplitudes of the sensory and neural components of the ECochG; (2) comparison of ECochG, BER and auditory thresholds; (3) time interval measurements between the auditory nerve response (N1 on the ECochG) and the inferior colliculus (wave P4-5 on BER); (4) contralateral comparisons. Similar measurements performed in pure cochlear pathologies, mainly in Meniere's disease, yielded very significant differences.

Audiometry↗

Electrophysiological monitoring of the cochlea during and after total destruction of the organ of corti.

A series of acoustically evoked potentials can be recorded from the cochlea up to the auditory cortex in guinea pigs where the organ of Corti has been totally destroyed after extensive treatment with amikacin, but where some of the spiral ganglion neurons always remain and where the vestibular receptors are only slightly affected. The cochlear responses have been monitored in guinea pigs permanently implanted with a round window electrode and receiving such treatment. The normal auditory nerve compound action potential disappears within a few days, while the very typical response (diphasic, short latency (0.3 ms) small amplitude) appears. This response then remains remarkably constant in time as far as we could observe (up to almost one year). This response might be a component of the normal response, undiscernible under normal conditions but revealed by the selective impairment of the labyrinth by amikacin, in contrast to the global effect of every other known otodestructive agent. Some basic questions still remain: which fibres are effectively stimulated (cochlear or vestibular), what are their central projections, and what kind of sensation is conceivably associated with these responses?

Amikacin↗

Spiral ganglion changes after massive aminoglycoside treatment in the guinea pig. Counts and ultrastructure.

Morphological changes of the eighth nerve were observed in the guinea pig between 1 month and 1 year after treatment with large doses of the antibiotic amikacin which resulted in complete cochlear hair cell destruction. The neural retrograde degeneration was found to be relatively fast, with a considerable loss (30 to 55%) of ganglion cells one month after treatment, continuously increasing (up to 85) after one year. Gross changes in the habenula perforata and in the spiral ganglion are described, together with ultrastructural alterations of organelles important for the cell metabolism and axonal transport. The rapid degeneration and the morphological findings suggest a direct influence of toxic substances on the ganglion cells.

Amikacin↗

Vestibular acoustic reception in the guinea pig: a saccular function?

After complete destruction of cochlear but preservation of vestibular hair cells in the guinea pig acoustically evoked responses can still be recorded from the round window up to the auditory cortex. At all levels these responses differ from those observed in normal animals but their frequency sensitivity and selectivity make them akin to responses from auditory organs. In a series of experiments a complete cochlear destruction was combined with a total or partial destruction of the vestibule. After complete cochlear and vestibular hair cell destruction no acoustic response could be recorded. But in cases of total cochlear and drastic ampullar and utricular destruction together with an almost undamaged saccular sensory epithelium the same peculiar acoustic responses could be observed. These results support the hypothesis of a functional acoustic reception by the saccule in a mammal.

Aminoglycosides↗

Electrocochleographic measures of cochlear frequency selectivity in hearing loss of cochlear origin.

One of the basic functions of the cochlea is to separate out the frequency components which are present in complex sounds. This frequency selectivity can be measured objectively in the clinic from the compound action potential (AP) during transtympanic electrocochleography, using a two-tone masking paradigm. An AP is evoked by a test tone near to threshold, and a measure is made of the frequency bandwidth over which this AP can be suppressed by a continuous pure tone masker. In normal-hearing subjects, this frequency range is 0.17-0.39 octaves (test tone pip at 4 or 8 kHz). In patients with cochlear deafness, this bandwidth is greatly enlarged, ranging from 0.42-2.2 octaves. Some observations suggest that a deterioration in frequency selectivity can occur before any important threshold elevation. The early detection of this could be a warning sign of potential cochlear susceptibility. In the clinic the measure is already of use: a deterioration is a positive indication of cochlear involvement in a hearing loss.

Audiometry↗

Functional and morphological changes in experimental endolymphatic hydrops.

Electrocochleograms (ECochG) in response to tone bursts and electronystagmograms (ENG) during sinusoidal rotational stimulation were monitored in guinea pigs equipped with chronically implanted round-window and periocular electrodes before and for as long as 90 days after uni- or bilateral surgical obliteration of the endolymphatic duct. The presence of cochlear and saccular endolymphatic hydrops was verified during microdissection of the inner ear, and cochlear hair cell counts were performed in some of the animals. The results indicate that in surgically-induced endolymphatic hydrops, cochlear and vestibular changes occur similar to those observed clinically in Menière's disease: fluctuant threshold shifts, threshold elevation at low frequencies, sensorineural loss at all frequencies with recruitment, increase in the ratio of summating potential to compound action potential (SP/CAP), asymmetry and recruitment in the ENG, and increased vestibular excitability, with occasional post-rotational and spontaneous nystagmus. Functional changes could not be clearly correlated with those seen by light microscopy, since hair cell loss was confined mainly to the apical coil. The observations indicate that the guinea pig with surgically-induced endolymphatic hydrops can be a useful model of Menière's disease, not only on morphological grounds, but also on the basis of functional changes, which over the relatively short term of observation represent a dysfunction rather than a loss of sensorineural structures.

Animals↗

Audiometric and electrophysiological correlations in sudden deafness.

Electrophysiological measures were collected over 3 years in 61 cases of sudden deafness. Electrocochleography (ECochG) and Auditory Brainstem Responses (ABR) using click stimuli were recorded down to threshold and compared with pure-tone and speech audiometry data. This study was intended to precise 1) localization of the disorder, 2) prognosis, 3) analysis of the contribution of different frequencies in click-evoked responses. The following results are: 1) In most cases the observations indicated that the inner ear was affected. 2) However, in 19 cases electrophysiological measures revealed a retrocochlear involvement. Four acoustic neuromas were evidenced by CT scan. In 3 of these, audiometric and electrophysiological thresholds returned merely to normal levels after medical treatment, while brainstem responses remained delayed. Thus in these cases recovery would seem to be related to release of vascular compression in the auditory internal meatus. 3) When the latencies of the VII nerve potential (N1) and wave V (PV) were short, and the therapy undertaken early, a good recovery was often obtained. 4) When recovery occurred on low frequencies only, the electrophysiological responses to the click showed slight latency increases.

Adolescent↗

Progressive degeneration in the cochlear nucleus after chemical destruction of the cochlea.

In the guinea pig, the organ of Corti and the spiral ganglion cells were destroyed by administering gentamicin into the inner ear. The antero-ventral cochlear nucleus (AVCN) was studied with electron microscopy 15 and 30 days after treatment. There does not seem to be a specific type of degeneration induced by the drug. For nerve terminals, a progressive degeneration occurred: after 15 days, clear and swollen boutons appeared and after 30 days an electron-dense type of degeneration was observed. The cell bodies of the AVCN did not seem altered infirming a rapid, direct or indirect, neurotoxic effect of the drug.

Animals↗

Glycine immunoreactivity in the brainstem auditory and vestibular nuclei of the guinea pig.

An immunohistochemical study was performed on the brainstem of the guinea pig, using a specific antibody against glycine. Glycine-like immunoreactivity was observed in stellate and multipolar neurons in the cochlear nucleus, in the medial and lateral nuclei of the trapezoid body and in the ventromedial periolivary cell group. No immunoreactive neurons were found in the vestibular nuclei. Positive fibre tracts were observed mainly in dorsal acoustic stria and lateral lemniscus. The results are consistent with electrophysiological and anatomical data from the literature concerning the response pattern in the fusiform layer of the dorsal cochlear nucleus and the phenomenon of binaural inhibition in the superior olivary complex.

Animals↗

Relationship between the nephrotoxicity and ototoxicity induced by gentamicin in the guinea pig.

Guinea pigs were treated with daily single subcutaneous injections of 60 mg gentamicin per kg for 3 weeks. Renal, cochlear and vestibular functions were monitored before, during and after treatment. The degree and onset of gentamicin oto- and nephrotoxocity differed during the treatment period. Alterations to the kidney functions were observed from the first week while the onset of ototoxicity occurred later, at the third and fourth week for the cochlear and vestibular functions respectively. Moreover, when treatment ended, renal function demonstrated signs of recovery, while auditory and vestibular function continued to worsen. Deficits in cochlear function and structural changes (missing outer hair cells) correlated with gentamicin serum concentrations, while vestibular alterations (loss in nystagmic reactions) did not. No distinct relationship could be established between auditory and vestibular loss and the renal parameters monitored. The results suggest that gentamicin-induced nephro- and oto-toxicity are dissociated phenomena and that cochleotoxicity was dependent on aminoglycoside serum level.

Animals↗

Frequency selectivity: reliability of electrocochleographic measures with iso-intensity masking.

In a group of 12 normal or hearing-impaired subjects, frequency selectivity was determined psychoacoustically and electrophysiologically with the fast ECochG iso-intensity masking procedure, using a 4 kHz test tone and simultaneous pure-tone masking. Psychoacoustic curves measured twice for each subject were reproducible and showed a broadening related to hearing loss. The curves determined with ECochG repeated two or three times for each subject varied greatly for half of the subjects and their widths were not related to hearing loss. ECochG measures were reproducible in the cases where the amplitude of the response was larger. The data set out the conditions and limits of this ECochG procedure for clinical use.

Audiometry, Evoked Response↗

Dynamic changes following combined treatment with gentamicin and ethacrynic acid with and without acoustic stimulation. Cellular uptake and functional correlates.

Regional selectivity of gentamicin (GM) ototoxicity was studied in guinea pigs (GPs) using electrophysiological, morphological, autoradiographic and immunohistological observations following combined treatment with GM (150 mg/kg i.m.) and ethacrynic acid (EA) (30 mg/kg i.c. or i.v., 1.5 h after GM injection). The GPs were either continuously stimulated every 5 min with a series of 256 clicks (70 dB peSPL, 10/s) during 3 h for monitoring fast changes in VIII nerve compound action potential (CAP) after the EA injection, and thereafter kept in the animal quarters (background noise of 60 dB SPL) (group I), or similarly monitored for only 10 min after the EA injection and thereafter kept in a soundproof room (around 0 dB SPL) (group II). Whenever GM labelling was observed it was localized only in the sensory hair cells. From 3 h after EA injection, the GPs in group I presented threshold elevations in the high-frequency region, which progressed to 60-80 dB at all frequencies at and after 48 h. Parallel to the threshold pattern, GM uptake in outer hair cells (OHCs) was seen with an increasing concentration from apex toward base from 3 to 24 h, while after 48 h almost all OHCs were destroyed and inner hair cells (IHCs) were marked by GM. In group II no changes in CAP thresholds were observed until more than 24 h, although GM was detected in the hair cells from 6 h on. At this early stage, the distribution of GM lacked a clear pattern, particularly without a clear apex-base gradient, and GM deposits were found only around the basal body. However in both groups, in late stage (greater than 24 h), the base-apex gradient was more pronounced and GM was found throughout the cell body, with a marked concentration below the cuticular plate. These results suggest that GM may penetrate hair cells around the basal body and that activating the cells by sound potentiates both GM uptake and its intracellular toxicity.

Acoustic Stimulation↗