Biomedical subjects

K C Horner

Publications and source records attributed to K C Horner.

At least 37 records · Page 2Linked to original sources

PubMed1991

[Experimental endolymphatic hydrops. Biochemical data in the guinea pig].

The electrochemical and osmotic composition of the inner ear fluids has been studied during experimental endolymphatic hydrops in guinea pig. The data showed that the modifications of the electrochemical composition of endolymph has been detected only after more than 2 weeks after the hydrops induction. The endocochlear potential, the K and Cl concentrations, and the osmolality progressively decreased between 6 and 9 weeks of hydrops. The longitudinal gradients disappeared. After 24 weeks of hydrops, the endocochlear potential was 50% of the initial value whereas the K and Cl concentrations and the osmolality were higher than that measured at 9 weeks but remained lower than contralateral, normal values. These results suggest that the alterations of the electrochemical and osmotic composition of endolymph that were observed during the evolution of experimental endolymphatic hydrops in guinea pig are related to an alteration of the permeabilities of the Reissner's membrane induced by an increase of hydrostatic pressure.

Animals↗

PubMed1991

The vestibular epithelia in experimental hydrops.

Morpho-pathological features, observed by scanning electron microscopy, in guinea pigs with endolymphatic hydrops of 4-14 months included shortening of the hair cell tufts, loss of tufts, retraction of sensory hair cells away from the surrounding tissue and hair cell loss. After 22 months of hydrops, there was complete loss of hair cells with indifferentiation of the epithelium. The loss of ciliary tufts involved loss of both stereocilia and kinocilia identified as short stubs and holes respectively. Control macular epithelia showed no hair tuft loss although ampullae in control ears could show some loss.

Animals↗

PubMed1991

[Experimental model of endolymphatic hydrops].

We have investigated by electrophysiology, morphology and pharmacology, the consequences of the surgical blocking of the endolymphatic duct in the guinea pig. We have demonstrated an immediate fluctuant CAP sensitivity loss on the low frequencies. Some weeks later a very high frequency loss can also be detected and finally after several months the mid frequencies are also affected and audiogram becomes relatively flat. This type of evolution of sensitivity loss corresponds remarkably well to the type of evolution of hearing loss observed in Ménière's patients. We have demonstrated that the early low frequency fluctuant losses are almost certainly a result of the selective atrophy of the short and middle stereocilia on the outer hair cells in the upper three cochlear turns, corresponding to a new hait cell pathology. Since ion channels are likely to be localised close to inter-stereocilia, row tip links this type of stereocilia atrophy could account for the low frequency fluctuant CAP sensitivity losses in hydropic cochleas. In addition this type of atrophy recalls a retrograde step in the ontogenesis of hair cells. Application of hydrostatic pressure directly to the endolymph via the endolymphatic duct provoked a high frequency sensitivity loss suggesting that endolymphatic pressure might be implicated in the late phase in the evolution of the hearing loss. Long-terme treatment by the diuretic chlorthalidone appeared to slow down the evolution of early low frequency CAP sensitivity loss and could reduce the volume of the hydrops. However in the long-term the CAP sensitivity loss was not arrested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Hypersensitivity of hydropic ears, at frequencies with normal thresholds, to temporary threshold shifts.

We have shown that experimentally-induced hydrops in the guinea pig systematically provokes an early low frequency (6.4 kHz and below) fluctuant hearing loss. The present study was aimed at investigating one aspect of the functioning of that part of the audiogram with normal CAP thresholds (mid and high frequencies) in early hydrops. Temporary threshold shifts (TTS) as a function of pure tone stimulation level (8 kHz, 1 min 75-95 dB SPL), were investigated. The TTS was measured as a function of pure-tone exposure level. The different points on the input/output curve were determined on sequential days in order to allow full recuperation from the previous stimulation. The group of hydropic ears (N = 5) proved to be more sensitive by about 6 dB than the group of control ears (N = 10). The data indicate that whilst short-term endolymphatic hydrops can be characterised by a selective low frequency loss other auditory deficits exist throughout the cochlea and become manifest at supraliminal stimulus levels.

Acoustic Stimulation↗

PubMed1990

Alterations of CAP audiogram by increased endolymphatic pressure and its relation to hydrops.

Most current theories regarding the inner ear pathology of Menières disease assume that there is an augmentation of the endolymphatic pressure due to the presence of hydrops. In this study normal hearing pigmented guinea pigs were employed to investigate the effect of increased endolymphatic pressure on the compound action potential (CAP) audiogram. All animals were implanted with an electrode on the round window and the CAP audiogram was determined prior to further surgery. The endolymphatic canal was then visualised by a posterior fossa intra-dural surgical approach. A hole was pierced in the canal and a cannula inserted. The CAP audiogram was again determined before, and at frequent intervals after, the application of hydrostatic pressure (0.5-1 cm Hg). A similar sequence of CAP sensitivity losses was observed within 2 h for 0.5 cm Hg or 15 min for 1 cm Hg. There was at first a very high frequency loss, followed by a very low frequency loss and finally a mid frequency sensitivity loss rendered the audiogram flat and lying around 50 dB sound pressure level. Given that the first characteristic index for experimental hydrops is a low frequency loss the present data suggest that an increase in endolymphatic pressure, as in these experiments, is likely to be a rather late pathological feature of hydrops. Indeed we have shown that a high frequency loss develops at a second phase during the evolution of hydrops.

Action Potentials↗

PubMed1990

Morphological changes of hair cell stereocilia and tectorial membrane in guinea pigs with experimentally induced hydrops.

Endolymphatic hydrops was surgically induced in guinea pigs. Atrophy of middle and short stereocilia on the outer hair cells in the upper 13 mm of the cochlea was systematically observed by scanning electron microscopy in guinea pigs with hydrops between 5-22 months. Light microscope and scanning electron microscope observations indicated that the tectorial membrane in the apical three turns was often abnormally elevated, and could be vertically positioned in longstanding hydrops. The atrophy of outer hair cell middle and short stereocilia and the elevation of the tectorial membrane certainly contribute to the pathophysiology of experimental hydrops and might be implicated in Menière's disease.

Animals↗

PubMed1989

Asymmetry of evoked rotatory nystagmus in the guinea pig after experimental induction of endolymphatic hydrops.

We have previously shown by chronic implantation of round window electrodes, that after the experimental induction of endolymphatic hydrops by surgical blockade of the endolymphatic canal, in the guinea pig, there is a low/mid-frequency fluctuant hearing loss, followed by a very high frequency loss and after a few months the audiogram is flat. This evolution reproduces exactly that observed in Meniere's patients. The aim of this study was to investigate the evolution of one aspect of vestibular function in parallel with audiogram changes. The nystagmic responses in the dark were tested every month during the 4 months which followed hydrops induction. There was considerable variation in the number of evoked saccades for different control animals and even between different recordings for the same control animal. However, in general, the number of saccades to right and left rotation was symmetrical for control animals, whereas for hydropic animals there was a period, within the first 2 months post-operation, when there was a reduction of saccades to the left (operated side) with sometimes an increase to the right. This asymmetry which occurred in the period of fluctuant hearing losses did not however appear synchronized with audiogram fluctuations. The nystagmic responses tended to become symmetrical over the 4 months post-operation. Oral administration of glycerol to animals whose nystagmus was asymmetric brought the vestibular response towards symmetry in 50% of the cases. Although episodes of vertigo, as known in Meniere's disease, were never observed in operated guinea pigs, these data indicate that they have some functional vestibular disturbance.

Animals↗

PubMed1988

Evolution of recruitment at different frequencies during the development of endolymphatic hydrops in the guinea pig.

The study of human temporal bones has identified endolymphatic hydrops as a common feature of several diseases. In particular it is systematically found in those bones removed from patients with premortem Menière's disease. Menière's disease is known to induce sensorineural pathology with recruitment, which changes with the evolution of the hearing loss, and is suspected to induce a cochlear conductive loss by a possible increase in static pressure of endolymph. Amplitude/intensity functions of sensorineural responses can reflect recruitment and/or conduction loss. Experimentally induced hydrops in animals provokes cochlear physiological alterations, some of which closely resemble certain features of Menière's disease. In the present study using a guinea-pig animal model, we have examined amplitude/intensity functions at the round window for cochlear microphonics (RWCM), summating potentials (RWSP) and action potentials (CAP) at different stages of hearing loss in experimentally induced hydrops. During the period of fluctuating thresholds there was reduction of maximal RWCM amplitude, no change in RWSP and recruitment on the CAP. At a later stage when the audiogram was flat and fluctuations were no longer seen, RWCM remained unchanged. At this time RWSP could show recruitment while CAP amplitudes at all intensities were reduced, indicating either a cochlear conductive loss and/or a general depression of neural activity.

Animals↗

PubMed1988

Atrophy of middle and short stereocilia on outer hair cells of guinea pig cochleas with experimentally induced hydrops.

Scanning electron microscopy was employed to investigate hair cell morphology at different stages in the development of experimentally induced hydrops in the guinea pig. A particular form of morpho-pathology, never before described, was identified as characteristic of hydropic cochleas. The pathology was characteristically identified as atrophy of the short and middle stereocilia on the outer hair cells while the inner hair cell stereocilia did not have such a pathology. The atrophy was restricted to the upper cochlear turns in remarkable correspondence with the low/middle frequency sensitivity loss and was detected only at the end of the period of fluctuating thresholds. These stereocilia perturbations appear therefore to be linked with the threshold fluctuations and represent the first evidence for a clear correlation between hair cell morphology and physiology in the experimental model of endolymphatic hydrops. Such a morphopathology might also be expected to occur in cochleas of Menière's patients but may have been overlooked in the past because of the discrete nature of the pathology.

Animals↗

PubMed1988

Independent fluctuations of the round-window summating potential and compound action potential following the surgical induction of endolymphatic hydrops in the guinea pig.

The diagnosis of Menière's disease is classically based on the triad of symptoms including fluctuating hearing loss, tinnitus and vertigo. Modifications to the electrocochleographic response have been searched as a possible help in the diagnosis. Various authors have reported a tendency for an increased ratio of the summating potential (SP) to action potential (AP) which is generally thought to be due to an enhanced SP. However, the large variability between patients has precluded any clear-cut conclusion. This dispersion of data might represent real individual differences or might be attributed to unavoidable technical variations, such as electrode placement and/or precise control of stimulus levels. As an attempt to answer this issue, we employed an animal model of experimental hydrops in which these difficulties can be overcome by chronic implantation of round-window electrodes and carefully controlling the stimulus level. In the present study, the SP and AP were monitored over several months for different frequencies and different intensities. In the early period of fluctuating thresholds at low and mid frequencies, AP amplitude varied in loose correspondence with the fluctuating audiogram. The SP amplitude also varied apparently not associated with AP or threshold changes and no consistent increase in SP was observed. At a later stage when all thresholds were elevated both SP and AP diminished. In normal ears increases in the stimulus intensity induce an augmentation of SP/AP. In hydropic ears, at the period of fluctuating thresholds, the SP/AP growth curve was at first similar to that of controls but later became very variable for different animals, but in general much larger than normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1987

Glycerol-induced changes in the cochlear responses of the guinea pig hydropic ear.

Pigmented guinea pigs were chronically implanted with bilateral round-window electrodes. Endolymphatic hydrops was induced by obstruction of the endolymphatic duct on one side. At 1-5 months post-surgery, glycerol was orally administered to each animal and the acute effect on cochlear and eighth nerve responses was investigated. Doses from half to four times the clinical dose of glycerol failed to improve the CAP audiogram in operated ears and were often found to raise the thresholds. Glycerol was found to diminish the amplitude of the summating potential as well as that of the compound action potential. Similar effects were observed for the higher doses in the control ears, although no effect was seen when doses used were equal to or less than the clinical dose. Our data suggest that the cochlear conditions in the guinea pig model of hydrops differ notably from those seen in patients with Ménière's disease.

Animals↗

PubMed1987

Rapidly fluctuating thresholds at the onset of experimentally-induced hydrops in the guinea pig.

Pigmented guinea pigs were chronically implanted bilaterally with a platinum electrode on each round window. After recovery the endolymphatic sac was destroyed and the duct blocked on one side only; the other side was employed as a control. The round window response thresholds on both sides were recorded several times per week over a three month period. There were three main results. A sensitivity loss of up to 20 dB was observed for frequencies between 250 Hz and 6.4 kHz within two weeks post-op. At the end of three months the threshold elevation for these frequencies was as much as 50 dB. On the other hand the thresholds for frequencies between 8 and 16 kHz remained within 10 dB of their pre-operative value for at least two months. The thresholds fluctuated with a shift of as much as 25 dB within 24 h. The threshold elevation was associated with a decrease in the latency, at threshold, of the round window AP response which at frequencies between 250 Hz and 6.4 kHz was as short as that for 8 kHz. This observation suggested that it was the base, only, of the cochlea which responded. The present study has indicated that experimentally induced endolymphatic hydrops in the guinea pig mimics well the progressive and fluctuating hearing loss characteristic of Ménière's disease.

Animals↗

PubMed1987

Deoxyglucose demonstration of in-utero hearing in the guinea pig foetus.

2-Deoxyglucose (2-[14C]DG) autoradiography was used to demonstrate central auditory function in the foetal guinea pig in-utero. The major advantage of this approach is that the experiment is carried out with the foetuses within the intact amniotic sac. Using pure tone stimuli at around 100 dB SPL, isofrequency bands of elevated metabolic activity were observed in the inferior colliculus of the majority of foetuses within the last 10 days of gestation.

Acoustic Stimulation↗

PubMed1986

The tensor tympani muscle reflex in the mouse.

Click evoked electromyographic (EMG) recordings were made from the contralateral tensor tympani muscle of anaesthetised mice. The mean threshold of the EMG response was around 50 dB SPL (peak equivalent) with a mean latency close to 4 ms. The mean amplitude of the response increased over a range of 70 dB to reach a level of around 150 microV with a mean latency around 3.5 ms. The tensor tympani muscle activity was investigated also in profoundly hearing-impaired mutant mice with either cochlear dysfunction (deafness) or brainstem dysfunction (quivering). No evoked EMG activity was detected in either group of hearing-impaired mutants. The data suggest that EMG activity in the mouse can provide a sensitive monitor of auditory function. The study of reflex activity in further mouse mutants is likely to provide information on the vulnerability of the reflex to different types of naturally occurring cochlear and brainstem pathology.

Animals↗

PubMed1986

Central auditory function in a hearing-impaired white mouse.

The dysfunction of the stria vascularis in the viable dominant spotting mutant mouse results in the reduction or the absence of the endocochlear potential. However, these mutants respond to an intense acoustic stimulus with a Preyer reflex (pinna twitch). This study used 14C autoradiography and electromyography to investigate central auditory responses in this mutant. There were three main findings: autoradiography demonstrated an increase in the metabolic rate within each of the central auditory nuclei during noise exposure compared with silence; electromyographic recordings indicated that there was no tensor tympani muscle reflex; the mutants were found to be susceptible to audiogenic seizures. It was concluded that the central auditory pathway of the viable dominant spotting mutant could be activated despite the abnormal strial function. Absence of the tensor tympani muscle reflex, together with auditory deprivation, might contribute to the susceptibility to audiogenic seizures.

Acoustic Stimulation↗

PubMed1986

[In utero demonstration of the functional activity of the auditory system of the fetus of guinea pigs by 14C 2-deoxyglucose autoradiography].

Pregnant guinea pigs injected with 2-DG between 10 to 2 days before birth, were exposed to loud free field pure tones (nine frequencies tested from 0.8 to 20 kHz). Specific bands of labeling were observed in the Inferior Colliculi of most of the fetuses whatever the frequency tested. The location of these isofrequency laminae shifted with stimulus frequency, their orientation were similar to those observed in the mothers. No such bands were found either in the control females or their fetuses. These results demonstrate that the auditory system of the fetus responds to frequencies up to 20 kHz, exhibits frequency selectivity and tonotopic organization in utero.

Animals↗

PubMed1985

Combined electrophysiological and autoradiographic delimitation of retrocochlear dysfunction in a mouse mutant.

The hereditary retrocochlear dysfunction in the quivering (qv) mouse was investigated with autoradiography and single unit recordings. Whilst the cochlea appears to function normally, earlier studies had indicated some single unit dysfunction detectable at the level of the cochlear nucleus (CN) and abnormality of auditory evoked potentials recorded at the inferior colliculus (IC). The present study investigated the possibility of progressive deterioration of function at successive higher levels in the auditory system. The 2-deoxyglucose technique illustrated auditory activity in the CN of quivering mice similar to that seen in normally-hearing control animals. There was only a slight increment in metabolic activity detectable at the level of the IC. Electrophysiology demonstrated that this minimal IC activity was the result of abnormally raised thresholds associated with all single units recorded, rather than of activity in a few normally responding cells. There was no evidence from autoradiography for any enhanced auditorily evoked metabolic activity in either the superior olivary complex or the lateral lemniscus. This study suggests that the retrocochlear dysfunction in quivering mice is due to a specific abnormality at a low stage in the auditory pathway rather than being non-specific and cumulative over stages.

Animals↗

PubMed1985

Distortion product otoacoustic emissions in hearing-impaired mutant mice.

The acoustic intermodulation distortion product (2f1-f2) was recorded in the ear canal of two different types of normally hearing mice and in four different types of hearing-impaired mutant mice. In the normally hearing animals, primary tones at levels of 60- to 100-dB SPL evoked distortion product emissions (DP's) at 20-50 dB below the primary levels. In the hearing-impaired mutants the level was dependent on the particular type of auditory dysfunction associated with the mutation. In both the deafness and the viable dominant spotting mutants, where either the whole organ of Corti or the stria vascularis is affected by the mutation, no DP's could be detected. The quivering mutant has a central auditory dysfunction associated with the nuclei of the superior olivary complex and the lateral lemniscus, with apparently normal cochlear function. DP's at levels and thresholds similar to those in normally hearing animals were recorded in quivering mice. The Bronx Waltzer mutant has a full complement of outer hair cells but only about of 20%-25% inner hair cells. DP's of small amplitude were recorded but the thresholds were raised by about 30 dB. The data suggest that the 2f1-f2 emission can be used as a noninvasive monitor of cochlear function.

Acoustic Stimulation↗