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A comparison of N1 of the whole nerve action potential and wave i of the brain-stem auditory evoked response in Mongolian gerbil.

The present study seeks to provide empirical support for the assumption that wave i of the gerbil brain-stem auditory evoked response (BAER) corresponds to N1 of the whole nerve action potential (WNAP) by comparing the latency and amplitude of BAER wave i and WNAP N1. Fourteen 3-month old gerbils were anesthetized with Nembutal and Urethane-Dial. Normothermia was maintained by a homeothermic blanket system. BAERs were recorded with Grass needle electrodes placed subdermally. The WNAP was recorded with a silver wire placed in the round window niche. WNAP and BAER were simultaneously recorded with a passband of 100-10,000 Hz. Responses consisted of 500 sweeps, and two responses were obtained for each condition. Clicks were 25-microseconds electrical pulses. Tonebursts were shaped with a Hanning window, with 1-ms rise and fall times. Toneburst frequencies included 1, 2, 4, 8, and 16 kHz. For each stimulus, responses were obtained at levels of 30, 50, 70, and 90 dB pSPL. SPL was measured near the entrance to the ear canal with an Etymotic ER-7C probe microphone. Dependent variables were the latency and amplitude of N1 of the WNAP and wave i of the BAER. The latencies of wave i and N1 were very similar. Mean (across animal) latencies of N1 and wave i were within 70 microseconds for all six stimuli (clicks, tonebursts) and all four levels. Latency/intensity function slopes for N1 and wave i were also very similar, with both dependent variables showing an increasing latency/intensity function slope with decreasing toneburst frequency. The N1/wave i amplitude ratio was computed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

The role of antioxidants in protection from ototoxic drugs.

A number of studies have shown that cisplatin and gentamicin ototoxic effects may result from free radical-mediated damage due to the reduction of antioxidant substances and an increased lipid peroxidation. The authors summarize the results obtained evaluating the auditory and vestibular functions and the inner ear hair cell morphology and survival after administration of antioxidant agents against cisplatin and gentamicin. In the first experiment, albino guinea pigs were treated with gentamicin (100 mg/kg per day, i.m.) alone or gentamicin (100 mg/kg per day, i.m.) plus alpha-tocopherol (100 mg/kg per day, i.m.) for 2 weeks. In a second experiment, albino guinea pigs were injected with cisplatin (2.5 mg/kg per day) or cisplatin (2.5 mg/kg per day) plus tiopronin (300 mg/kg) for 6 days. Electrocochleographic recordings were made from an implanted round window electrode. In all experiments compound action potentials (CAPs) were measured at 2-16 kHz. Changes in cochlear function were characterized as CAP threshold shifts. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VOR). Frequency stimulation parameters ranged from 0.02 to 0.4 Hz and peak-to-peak amplitude was 20 degrees. Morphological changes were analysed by light microscopy and scanning electron microscopy. Both hearing loss and vestibular dysfunction induced by gentamicin were significantly attenuated by alpha-tocopherol. However, tiopronin co-therapy slowed the progression of hearing loss in cisplatin-treated animals and significantly attenuated the final threshold shifts. Cisplatin had little effect on the hair cells of cristae ampullares and maculae. Vestibular function was completely preserved in tiopronin co-treated animals. In conclusion, antioxidants such as alpha-tocopherol or tiopronin interfere with gentamicin and cisplatin damage and this suggests that they may be useful in preventing oto-vestibulotoxicity. Therefore, it is important to develop protective strategies that permit the avoidance of the toxic side effects of these drugs without interfering with their therapeutic effects.

Action Potentials↗

Residual mesenchyme persisting into adulthood.

PURPOSE: (1) To detect the presence of residual mesenchyme in temporal bones of adults and children above 5 years of age; (2) to evaluate its regression with increasing age, and; (3) to detect pathologic conditions associated with the presence of unresolved mesenchyme. MATERIALS AND METHODS: We examined 1,404 human temporal bones of donors from 5 to 94 years of age for histopathologic evidence of mesenchyme. The presence of stellate (star-shaped) cells with interdigitating processes and large nuclei embedded in a structureless ground substance was labeled as "pure mesenchyme." Temporal bones showing these features and focal areas of fibrosis, fibroblasts, and capillaries were classified as showing "transitional mesenchyme." Selected sections were stained with Gomori's trichrome. Pathological features indicating otitis media and congenital anomalies of the ear were also documented. Case histories were reviewed, and any otologic complaints were noted. Statistical analysis was performed with the Chi-square test, analysis of variance, regression analysis, and confidence interval. RESULTS: Mesenchyme was found in 2.07% of temporal bones of patients from 5 to 81 years of age. Of these, 92.1% had transitional mesenchyme, whereas 7.9% had pure mesenchyme. Seventy-six percent of the bones showed mesenchyme in the mastoid air cells. In all 3 bones with pure mesenchyme, it was present in the round window niche. Otitis media was associated with residual mesenchyme in 84.2% of the temporal bones. No pattern of regression of mesenchyme with increasing age was observed in temporal bones from patients over the age of 5 years. CONCLUSIONS: Residual mesenchyme can be present in patients older than 5 years of age and can persist into adulthood, especially in the mastoid air cells. Persistence of mesenchyme is closely associated with evidence of otitis media.

Adolescent↗

Persistence of auditory nerve response and absence of brain-stem response in severe cerebral ischaemia.

Cerebral ischaemia, in which the brain-stem components of the ABP were isoelectric, was accompanied by the paradoxical persistence of the compound action potential of the auditory nerve (wave 1). This ischaemia was induced in cats by reducing mean arterial blood pressure and elevating intracranial pressure, resulting in decreased cerebral perfusion pressure (CPP). This is unexpected since the inner ear is supplied by a branch of an intracranial artery. To study this phenomenon, CPP was manipulated and when average CPP was 13.5 mm Hg, only wave 1 remained. In 7 of 9 experiments, clamping of both common carotid arteries did not abolish wave 1. Experiments with radioactive tracers demonstrated a remaining residual blood flow through the inner ear. This remaining auditory nerve response is probably not due to a very low metabolism of the inner ear or to the cochlea being supplied by anastomoses from the middle ear, supplied by the external carotid artery. The residual cochlear blood flow and the persistent wave 1 can probably be explained in the following way: at low CPPs the smaller intracranial blood vessels collapse so that the brain tissue is not perfused, leading to loss of the brain-stem components of the ABP. However, flow still persists in the larger intracranial arteries. This blood preferentially flows to the cochlea since the intracochlear pressure is slightly below the intracranial pressure due to the presence of the oval and round windows. Thus a sufficient blood flow to the cochlea is maintained, with sparing of wave 1.

Animals↗

Morphometry of the human cochlear wall and implications for cochlear surgery.

OBJECTIVE: To study the lateral wall of the cochlea in human temporal bones (TBs), in order to evaluate the feasibility of performing micro-dissection of the spiral ligament and an endosteal electrode implantation. MATERIAL AND METHODS: We reviewed the database of the TB bank of The House Ear Institute in search of bones that did not distort the otic capsule or spiral ligament, and selected 36 horizontally sectioned TBs. All bones had been removed using the en bloc technique, fixed in formalin, decalcified in EDTA, embedded in celloidin and cut into 20-pm serial sections. We evaluated sections stained with hematoxylin-eosin under a microscope, and made several measurements of the lateral wall of the cochlea using optical appliances. A total of 20 measurements were made at 3 levels: midmodiolar sections; sections at the round window niche; and sections containing the anterior border of the stapes footplate. RESULTS: The selected sections provide useful data when applied during surgery. All the numerical data were analyzed statistically and, although individual variability occurred, most of the measurements seemed to be quite homogeneous. CONCLUSIONS: A greater understanding of the microscopic anatomy and dimensions of the human TB will help to understand the surgical relationships at the lateral wall of the cochlea. Our study provides some numerical references for the dimensions of the cochlea that may help in cochlear surgery. These dimensions would be of particular interest in cochlear implantation, especially in the design of endosteal electrodes.

Adult↗

[Differential perilymph fistula diagnosis].

If sudden unilateral deafness accompanied by vertigo and spontaneous nystagmus on the afflicted side occurs during birth, a perilymph fistula with rupture of the round window membrane caused by pressure has to be considered. A 35-year-old pregnant patient was presented with the aforementioned symptoms on the day she gave birth to triplets. During examination, surditas and a paranasal hyposensitivity were found on the right side. Furthermore, a spontaneous nystagmus on the affected side occurred which was not suppressed by fixation. The nystagmus was apparent as a direction-fixed gaze nystagmus. Saccades during smooth pursuit testing as well as a lack of the auriculofacial reflex during contralateral stimulation of the deaf ear could be observed. Magnetic resonance imaging (MRI) of the skull revealed a fresh hemorrhagic cavernoma of the cerebellar pedunculi. This rare lesion caused a nerve compression of the fifth and eighth cranial nerve due to perifocal edema. Neurosurgical intervention was not necessary because of subsequent spontaneous resorption of the lesions and abatement of the deafness within a few days.

Adult↗

Cochlear blood flow in response to dilating agents.

Reduced cochlear blood flow (CBF) has been implicated in various pathologies of the inner ear, including sudden deafness, noise-induced hearing loss and Meniere's disease. Thus the aim of some current therapeutic regimens to treat these conditions is to increase CBF and thereby improve oxygenation of the inner ear tissues. Most of the vasodilating agents in clinical use, however, do not have specific experimental evidence to support their effects on CBF. The hypotension which can follow systemic administration may limit their local effectiveness and general utility, just as it complicates the interpretation of the data in animal experiments. In the current study we investigated the effect of six agents, known for their systemic cardiovascular actions, on CBF: hydralazine, sodium nitroprusside, papaverine, nicotinic acid, verapamil and histamine. The effect of these drugs was studied after topical applications on the round window membrane (RWM) and systemic intravenous administrations. CBF was monitored with a laser Doppler flowmeter (LDF). Topical administration of sodium nitroprusside was the most effective in increasing CBF, followed, in order, by hydralazine and histamine. No change in CBF was observed for papaverine, verapamil or nicotinic acid. Systemic administrations of all the agents caused a marked decrease in blood pressure and variable effects on CBF. We discuss the CBF changes in relation to the different pharmacological mechanisms of action of each drug. The study demonstrates the effectiveness of topical application of vasodilating agents in increasing CBF.

Administration, Topical↗

Inner hair cell responses to the velocity of basilar membrane motion in the guinea pig.

Triangular wave acoustic stimulation at 200 Hz produced the expected square wave cochlear microphonic at the round window membrane and within the scala media. Intracellular recordings from inner hair cells (IHC) of the first cochlear turn showed a combination waveform having both spike impulse and square wave features. The IHC response suggests a sensitivity of these cells to both the displacement and to the velocity of basilar membrane motion.

Acoustic Stimulation↗

Delivery of neurotrophin-3 to the cochlea using alginate beads.

OBJECTIVE: The aim of this study was to design a novel cochlear neurotrophin (NT) delivery system for the rescue of auditory neurons after ototoxicity-induced deafening. BACKGROUND: NT-3 is a trophic growth factor that promotes the survival of the auditory nerve and may have a potential therapeutic role in slowing neuron loss in progressive deafness, especially as an adjunct to the current cochlear implant. Beads made from alginate are biodegradable, slow release substances that can be placed at the round window or inside the cochlea. This study investigated the loading properties, release kinetics, and implantation potential of alginate beads loaded with NT-3. METHODS: Alginate beads were prepared using an ionic gelation technique and postloaded with NT-3. Release of NT-3 was measured using enzyme-linked immunosorbent assay over 5 days. Alginate beads were implanted into deafened guinea pigs for 28 days, after which survival of auditory neurons was assessed. RESULTS: Enzyme-linked immunosorbent assay studies demonstrated a 98% to 99% loading of NT-3 with a slow, partial release over 5 days in Ringer's solution. Furthermore, the addition of heparin to the delivery system modulated NT-3 release to a steadier pattern. Implantation of alginate-heparin beads in guinea pig cochleae produced minimal local tissue reaction. NT-3 loaded beads implanted at both the round window and within the scala tympani of the basal turn provided auditory neurons significant protection from degradation and apoptosis compared with unloaded beads or untreated cochleae. CONCLUSIONS: This study demonstrates alginate beads to be a safe, biodegradable and effective delivery system for NT-3 to the cochlea.

Alginates↗

Monitoring of cochlear function during cochlear implantation.

OBJECTIVE: To report the feasibility of monitoring cochlear function during cochlear implantation. STUDY DESIGN: Case report. SETTING: Tertiary care referral center. METHODS: A child with audiologic features typical of bilateral auditory neuropathy underwent cochlear implantation. The scala tympani was entered inferior and slightly anterior to the round window membrane margin and smooth electrode insertion was achieved. Using single polarity click stimuli, the cochlear microphonic was measured at several steps during surgery. RESULTS: Cochlear microphonics were present at all stages during the implantation process and were clearly distinguished from neural responses by stimulus polarity inversion and constant latencies, despite changes in stimulus level. With the electrode in situ, amplitudes were smaller but persisted until the final measurement at 10 minutes after insertion. At follow-up 2 weeks after surgery, behavioral audiometry results indicated profound hearing loss in the operated ear. CONCLUSIONS: This paper demonstrates the feasibility of monitoring cochlear function during cochlear implantation. The routine surgical approach did not appear to adversely affect the functional measurements. Standard size, full electrode insertion did diminish the amplitude of the cochlear microphonics, possibly as a result of intracochlear mechanical impairment. Ultimately, profound hearing loss was documented, indicating that factors other than immediate changes induced by electrode insertion were likely responsible for the loss of cochlear function.

Cochlear Implantation↗

Topical antibiotic ear drops: are they safe?

A discharging ear is a very common condition for the general practitioner and the ENT surgeon. Oral and intravenous antibiotics have potential complications, are costly, and exhibit increasing resistance. This study explores the advantages and disadvantages of all common otic preparations and compares effectiveness, safety, cost and complication rates. In chronic otitis media (chronic discharging ears), topical antibiotics seem to be the treatment of choice by comparison with oral or intravenous antibiotics. Cultures and antibiograms do not correspond directly to clinical efficacy, as laboratory determination of resistance does not take into account the high concentration of antibiotics in local preparations. It is safer to use quinolone drops as a first-line treatment, but it is still possible to use short courses of other drops if quinolones are either unavailable or contraindicated (e.g. allergy), or when bacteria are resistant to them. However, in such a situation, a round window membrane involved in an established inflammatory process and therefore less permeable to the passage of topical preparations is the preferred setting, as ototoxicity is a potential complication, especially in the case of gentamicin, in which case patients should be warned accordingly.

Administration, Topical↗

Cochlear and vestibular lesions in capsular otosclerosis as seen in microdissection.

In 24 temporal bones from patients with otosclerosis prepared by the method of microdissection and surface preparations, otosclerotic foci could be clearly seen during removal of the otic capsule. The state of activity of each focus was estimated on the basis of its consistency and vascularity. Small anterior foci constituted the most common form of involvement of the otic capsule. All were judged to be inactive, and none of them appeared to have caused obvious sensorineural degeneration. No cases of "pure cochlear otosclerosis" were seen. Sensorineural degeneration was associated with large anterior foci which reached the upper basal turn. One specimen displayed a circumscribed sensorineural degeneration in the upper basal turn, with an almost exact correspondence between the location and extent of the cochlear lesion and the site of invasion by the otosclerotic process in the bone and endosteum bordering on scala media and scala tympani. It is postulated that a toxic factor had diffused from the focus and acted directly on the organ of Corti. When multiple foci were present they were usually poorly defined. The otosclerotic process involved the round window, with new lamellar bone formation in the scala tympant of the lower half of the basal turn. The most extensive sensorineural degeneration in the entire material was seen in this group. One specimen also had severe cochlear hydrops. In three specimens large shunts were observed to connect the otosclerotic foci with the cochlear vasculature, which was severely dilated. Where otosclerosis involved the endosteum of the scala tympani, loss of vessels was observed. One specimum with extensive active capsular otosclerosis had severe sensorineural degeneration of the vestibular system. Vestibular pathology in fenestrated ears is also described. In a specimen from a patient with no caloric reaction, numerous hair cells were present in the macular organs.

Aged↗

Intraoperative assessment of perilymphatic fistulas with intrathecal administration of fluorescein.

OBJECTIVES: Assessment of perilymphatic fistulas remains a diagnostic problem. Because of a lack of reliable clinical tests, exploratory tympanotomy is necessary to detect membrane leaks in the middle ear. To improve objectivity in the intraoperative visualization of perilymphatic fistulas, we used intrathecal fluorescein for perilymph staining to increase the sensitivity and specificity of diagnosis of perilymphatic fistulas. STUDY DESIGN: Prospective study in the setting of a tertiary, referral, and academic center. METHODS: Twenty-eight patients with suspected traumatic, idiopathic, iatrogenic, or inflammatory perilymphatic fistulas were admitted for exploratory tympanoendoscopy for perilymphatic fistula detection. Twenty-five to 100 mg sodium fluorescein 10%, diluted with cerebrospinal fluid, was administered by lumbar puncture 2.5 to 23.5 hours before tympanoendoscopy. The oval and round window niches were microscopically and endoscopically observed with white and blue light, using specific filters. RESULTS: In two patients (7%), obvious fluorescence was detected behind the round window membrane with blue light. Direct observation of perilymph in stapedectomy and in semicircular canal fistula revealed no staining. Neurological complications of intrathecal fluorescein, as reported by other authors, were not observed. CONCLUSIONS: Probably because of a different patency of the cochlear aqueduct, intrathecal fluorescein for intraoperative detection of perilymphatic fistula resulted in a significant perilymph staining in only a few patients. Considering the possible complications of this method, we would not recommend it for routine evaluation of perilymphatic fistula.

Adult↗

Ionic and potential changes of the endolymphatic sac induced by endolymph volume changes.

The endolymphatic sac (ES) is believed to be the locus for endolymph volume regulation in the inner ear. It has recently been shown that induced endolymph volume changes in the cochlea result in anatomical changes in the ES, suggesting that function of the sac varies according to endolymph volume status. In the present study we have recorded luminal concentrations of K(+) and Na(+) from the ES and the endolymphatic sac potential (ESP) during cochlear endolymph volume changes. ES recordings were made by an extradural approach, thereby preserving normal cerebrospinal fluid resting pressure. Cochlear endolymph volume changes were generated by performing injections or withdrawals through a pipette inserted into endolymph by a round window approach. The pre-treatment concentrations of K(+) and Na(+) in the ES were found to be 8.4 mM (S.D. 3.3, n=8) and 128. 6 mM (S.D. 18.4, n=10) respectively, and the mean ESP was 14.4 mV (S. D. 5.2, n=18). Endolymphatic injections were found to produce a sustained increase in the K(+) content of the ES by an average of 19. 9 mM and to decrease Na(+) by 30.7 mM measured 50 min after the start of injection. The time for K(+) increase to occur was found to correlate with the injected volume, with larger injected volumes producing a more rapid increase. Endolymphatic withdrawals were found to induce a slow decline in endolymphatic K(+) by an average of 3.4 mM measured at 50 min after withdrawal, although no significant change of Na(+) was detected. Volume-induced ESP changes were highly variable. Injections produced a small increase in the mean ESP and withdrawals produced a small decrease but neither change was statistically significant and some animals showed potential changes in the opposite direction. These data show that a change in cochlear endolymph volume status results in a physiologic response of the ES which is sustained for a considerable period. If the ES plays a part in the restoration of normal endolymph volume, this process appears to proceed slowly, based on the prolonged time courses of ionic changes observed.

Animals↗

In vivo capillary diameters in the stria vascularis and spiral ligament of the guinea pig cochlea.

Blood microvessels in the membraneous lateral wall of the cochlea were examined using intravital microscopic techniques. A video analysis system made serial diameter measurements at 1 micron intervals along the length of selected vessel segments during four experimental conditions. For each vessel segment, the serial measurements were statistically converted into a single diameter estimate, such that the flow resistance in a uniform vessel of this diameter would equal the resistance of the real non-uniform vessel. Nominal vessel diameters found (spiral ligament: 9-12 micron; stria vascularis: 12-16 micron) were nearly double those reported earlier in histological observations (Axelsson, 1968). During stimulation the largest diameter change seen was a 3.7% dilation (about 0.5 micron) in response to breathing 5% CO2 in oxygen. Theoretically, this change could reduce vascular fluid resistance by 16%, nearly enough to explain the observed flow increase of 20%. No diameter changes occurred for 5% CO2 in air despite a 50% flow increase, nor for air pressure pulses applied at the tympanic membrane. Round window electrical stimulation of 50 microA also produced dilation (less than 2.5%), but higher current levels were ineffective. In general, blood flow increases seen in this study could not adequately be attributed to the small lateral wall vessel diameter increases nor systemic causes, suggesting that lateral wall blood flow in these instances is dependent on control within the modiolus.

Animals↗

Prevention of cisplatin ototoxicity using transtympanic N-acetylcysteine and lactate.

HYPOTHESIS: Transtympanic administration of the antioxidant N-acetylcysteine or lactated Ringer's solution onto the round window membrane will prevent cisplatin ototoxicity in the guinea pig model. BACKGROUND: Cochlear ototoxicity is a well-known side effect of cisplatin administration, with the mechanism of injury thought to rest in oxidative damage to the outer hair cells. However, previous attempts at transtympanic antioxidant delivery have met with varied success. We present an effective method of counteracting cisplatin ototoxicity via the transtympanic application of lactated Ringer's solution or N-acetylcysteine. METHODS: Baseline distortion product otoacoustic emission measurements were obtained. Intraperitoneal cisplatin was administered to a cumulative dose of 20 mg/kg. The middle ears were either untreated (control) or filled with normal saline (negative control), 2%N-acetylcysteine diluted in normal saline (treatment), or lactated Ringer's solution (treatment) via anterosuperior quadrant myringotomies. Posttreatment distortion product otoacoustic emissions were obtained. RESULTS: Animals in the untreated control group and the negative control normal saline group demonstrated consistent obliteration of distortion product otoacoustic emissions. However, those receiving either lactated Ringer's solution or 2%N-acetylcysteine diluted in normal saline demonstrated significant preservation of distortion product otoacoustic emissions. The treatment regimen was well tolerated, with minimal animal loss. CONCLUSION: We have demonstrated the efficacy of transtympanic lactated Ringer's solution and N-acetylcysteine in the prevention of cisplatin ototoxicity using a guinea pig model. The possible mechanisms for the high efficacy of lactated Ringer's solution are discussed in detail.

Acetylcysteine↗

[Experimental studies on the effect of labyrinth anesthesia].

Injection of tetracaine into the tympanic cavity inhibits, independently of histologic lesions of the round window membrane, the active electrogenic pump in the stria vascularis cells. The DC potential in the endolymph is reduced with increasing doses of tetracaine, while the K+-Cl- activity is unchanged for 120 min. This drug does not alter the permeability of Reissner's membrane. Near the stria vascularis area, the oxygen pressure in the endolymph increases significantly after the effects of 4% tetracaine.

Anesthesia, Local↗

Catastrophic otologic injury from oral jet irrigation of the external auditory canal.

Jet irrigation is an accepted method for removal of cerumen from the external auditory canal. Even at a submaximal power setting, oral jet irrigators can generate enough force to rupture the tympanic membrane. Parameters for safe use of these irrigators have never been established. Three cases are reported in which, in addition to tympanic membrane rupture, oral jet irrigators caused ossicular disruption, round and oval window fistulae, and subluxation of the stapedial footplate. A prospective study performed on 25 fresh cadavers demonstrated a 6% incidence of tympanic membrane perforation when the power setting was one-third full power or greater. Recommendations are made for safe use of oral jet irrigators for removal of external auditory canal cerumen.

Aged↗