The patch-clamp methods were developed to investigate the ionic channels of cellular membrane. The methods and modes of patch-clamp study and the physiological role of voltage-dependent channels were briefly described in the text. The voltage-dependent channels of outer hair cells isolated guinea pig cochlea were investigated using patch-clamp technique in a whole-cell recording mode. Depolarizing voltage steps to potentials more positive than -30mV elicited a slowly inactivating outward K+ current (IKca), which is dependent on intracellular Ca2+. Hyperpolarizing voltage steps to more negative than -90mV rapidly inactivated an inward K+ current (IK, n), which is already activated at resting membrane potential. When both K+ current were suppressed by replacing K+ with other cation of large molecule, depolarizing voltage steps elicited a slowly-inactivating inward current. The relations between this current and external Ca2+ concentration indicated that outer hair cell possesses L-type Ca2+ channel. The electrical model of outer hair cell in guinea pig cochlea was discussed in accordance to these results and the previous report by Housley and Ashmore.
Sensory hair cells transduce mechanical information into electrical signals through mechanically gated ionic channels which is called as the mechano-electrical transduction (MET) channels. The mechanical displacement of the hair bundle towards the taller stereocilia generates inward-going MET currents. This currents generate depolarizing transduction potential which are transmitted to the central nervous system for further information processing. The angular displacement of the hair bundle is the primary factor in the gating of MET channel. The wide variety of monovalent cations including small organic cations and divalent cations were permeable through the MET channel (non-selective cation channel). Ca2+ permeability was about four times by monovalent cations. The single channel conductance of the MET determined by the step-like single channel currents was 50-100 pS. There are two hypothesis about the site of the MET channels; one is the base of the hair bundle and the other is the top of the hair bundle. The adaptation of the MET current was observed when steady displacement was applied to the hair bundle. Adaptation was dependent on the membrane potential and only observed in inward-going MET currents. Ca2+ influx through the MET channel is associated to the adaptation.
Extracellular signals such as neurotransmitters, hormones and growth factors are transduced to intracellular signaling via receptors. Chemoreceptors are classified into two categories, receptor-channel complexes and G protein-coupled receptors. Activated receptor-channel complexes open intrinsic ionic channel and change an ionic permeability of the membrane. G protein-coupled receptors couple various intracellular signaling pathways such as cAMP, inositol 1, 4, 5-trisphosphate (IP3), diacylglycerol and Ca2+. This review describes the recent studies of chemo-receptors in dissociated outer hair cells (OHCs) of guinea-pig cochlea using the whole-cell patch-clamp technique. Recent studies reveal that ATP, activating receptor-channel complexes in the apical portion of OHCs, opens a non-selective cation channel and that acetylcholine, acting on a novel cholinergic receptor, stimulates IP3 pathway via pertussis toxin sensitive G-protein, resulting in opening K channels in an intracellular Ca2+ dependent manner.
The accuracy of acoustic otoscope with a 201 recorder in detecting the presence or absence of middle ear effusion was examined. The angle formed by the tracing was calculated using the leastsquares method. 100 normal ears and 100 abnormal ears confirmed the presence of middle ear effusion were tested. Using a reflectivity of 5 as the cutpoint, the sensitivity was 85% and the specificity was 92%. Utilizing a cutpoint of 90 degrees resulted in the sensitivity of 94% and the specificity of 91%. The best strategy was seen with a criterion of low reflectivity (0-4) pass, high reflectivity (6-9) fail, and judging by the angle in cases with moderate reflectivity (4-6). The present study suggested that using the angle improved the accuracy in detecting middle ear effusion by acoustic otoscope.
In this study we compared hearing improvement in cases of chronic otitis media between a myringoplasty group and a group of myringoplasty with anterior spinotomy. The results indicated that in patients under 40 years old at 250 and 500Hz, the hearing level of the group of myringoplasty with anterior spinotomy improved significantly more than that of the myringoplasty group. For patients in their 40's and 50's at 250, 500, and 1000Hz, and for those above 60 at 1000Hz, in the group of myringoplasty with anterior spinotomy, the hearing level improved more significantly than that of myringoplasty group. These results showed that anterior spinotomy is the best procedure for chronic otitis media in middle-age persons showing an incomplete positive on a patch test.
Fifty-six patients with chronic otitis media, who presented with continuous otorrhea against conservative therapy for more than one month until admission, were reviewed. The patients were devided into the two groups; Group A: The otorrhea was ceased by intensive antibiotic therapy during admission before operation. Group B: The otorrhea continued until surgery. The total success rate for operation was 86.4% in group A and 89.5% in group B. The average period for complete epithelization after operation was 19.6 days in group A and 27.9 days in group B. The success rate for hearing improvement was 85.0% in group A and 85.7% in group B. Also, there was no significant difference in success rates between the patients with and without mastoidectomy. These results suggested that neither active otorrhea at surgery nor mastoidectomy could be an important factor to affect the success rate for tympanoplasty.
Case 1: A 34-year-old female complained of hearing difficulty and a sensation of fullness in the left ear since 1989. Otoscopic examination revealed swelling of the upper posterior wall of the left external auditory canal without tenderness. The ear drum was intact. A CT scan of the temporal bone showed a soft tissue mass in the mastoid cavity with a bone defect, extending from the upper posterior external auditory canal to the middle cranial fossa. The ossicular chain appeared normal. MRI demonstrated increased signal intensity in the same area on both T1 and T2 weighted images. Mastoidectomy revealed a brown colored cyst in the mastoid cavity and obstruction of the aditus ad antrum with cholesterol granuloma. Case 2: A 33-year-old male complained of recurrent ear discharge since 1989. He had gradually lost hearing acuity in the right ear since 1990. Rotatory vertigo accompanied by nausea developed on September 19th, 1990. The ear drum was extensively adherent to the promontorium. Purulent ear discharge was running form a small perforation in the flaccid portion of the right ear drum. A CT scan demonstrated maldevelopment of mastoid air cells and a soft tissue mass extending from the epitympanum to the mastoid cavity. Tympanoplasty was performed after removing the entire cyst wall which obstructed the aditus ad antrum. Chronic inflammation is considered a major factor in the formation of cholesterol cyst. We concluded that growth of a cholesterol cyst is promoted not only when ventilation and drainage of the middle ear cavity is markedly reduced by inflammation in the middle ear, but also when secretion of serous fluid is markedly increased by unknown factors.
Five cases of otogenic intracranial complications were hospitalized for emergency treatment from 1982 to 1991. Among them, 3 patients who received surgical procedures were presented. The most frequent causative disease was chronic otitis media with cholesteatoma. There was only one case who showed intracranial complication due to acute mastoiditis. MRI and CT scan were useful for diagnosis of the disease and selection of modalities of treatment.
A 63-year old male presented with 2 year history of dysarthria and gait disturbance. Right deafness, IX, X, XI and XIIth cranial nerve palsies were observed. MRI revealed a large mass lesion with high intensity in the right middle and posterior cranial fossa extending through enlarged jugular foramen to the temporal bone. Cerebral angiography demonstrated a large mass with blood supply from not only the right external and internal carotid but vertibral arteries. The tumor was removed subtotally by staged operation after radiotherapy. The procedure consisted of a ligation of the external carotid artery, temporal bone ressection and petrosal approach toward the intracranial region. After those strategies, the compressed brainstem and cerebellar hemisphere were almost restored.
Electrocochleography by the transtympanic electrode technique was performed in patiemts with sudden sensorineural deafness in a week after onset, and evoked otoacoustic emissions were recorded by Rion and Cortitone N-1 probe. Fast component was detected when a pure tone audiogram at 1 kHz showed hearing level less than 40-45dB, and then a slow component was detected. In an 18-year-old man with postoperative cerebellar astrocytoma, the detection threshold of CM at 1 kHz was 40dBnHL, while pure tone audiogram showed a total deafness. In this case the detection threshold of fast component was 10dBnHL and a slow component was 0dBnHL. We assumed that evoked otoacoustic emissions are detected when the threshold of CM at 1kHz becomes less than 40-50dBnHL, and that they might have reflected the function of the hair cells.
In general, onset of sudden deafness is abrupt and after the initial examination, their hearing levels are improved or stable. But in a few cases, progression of hearing loss occurs after the initial examination. We analyzed 60 patients with sudden deafness including 8 patients showing progression of hearing loss over 10dB occured after the initial examination. 1) Ten percents of all cases showed progression of hearing loss over 10dB after the initial examination. 2) At progression of hearing loss, their audiograms showed near total or profound hearing loss of same degree in all frequencies. 3) Between the two groups, there are no significant statical difference in ages, sex and prognosis and it was suggested that the progression of hearing loss occured after the initial examination was one of the natural course of sudden deafness. 4) In the cases of the progression of hearing loss after the initial examination, it is necessary to determine which is better to use hearing level of the initial examination or progression of hearing loss for study of sudden deafness.
A 54-year-old man complained of acute bilateral hearing loss and tinnitus. An audiogram demonstrated a symmetrical sensorineural hearing loss of about 60dB. Gaze nystagmus was observed. He suddenly developed a disturbance of articulation, vertigo and nausea during otological examinations. CT scan and MRI revealed a focal infarction of the bilateral middle cerebellar peduncles. Angiogram showed an occlusion of the left vertebral artery and left anterior inferior cerebellar artery (AICA) and a stenosis of the right AICA. After conservative treatment, hearing loss was rapidly improved, but cerebellar symptoms were improved slowly. Otological symptoms were due to circulatory insufficiency of the labyrinthine artery. The presumed diagnosis was anterior cerebellar artery syndrome caused by occlusion or insufficiency of the bilateral AICA.
Internal auditory canal demonstrated on conventional roentgenograms (Stenver's projection, magnification 1.4X) was studied in 200 clinical cases, 30 cases with bilateral enlargement of the internal auditory canal, and 30 cases with unilateral acoustic neuroma. In clinical cases, vertical diameter ranged from 4mm to 10mm with an average of 6.2±1.2mm, and bilateral difference was 3mm or less. The shape of the canal was straight in 90.5% and identical bilaterally in 90.5%. In cases with bilateral enlargement, maximal vertical diameter was 16mm, and bilateral difference was 3mm or less. The shape of the canal was oval in 68.3% and identical bilaterally in 90%. In cases with unilateral acoustic neuroma, vertical diameter ranged from 6mm to 20mm and, in 66.7%, bilateral difference was 3mm or more, up to 12mm. The shape of the canal was narrowed laterally in 40%. Most of the cases with bilateral enlargement of the canal, especially symmetrical and oval one, were considered to be a normal variant.
The localization and expression of the EGFR were retrospectively analyzed in 44 cases with middle ear cholesteatoma by the immunohistochemical technique using monoclonal antibodies from formalin-fixed, paraffin-embedded tissue obtained during surgery. The correlation between the EGFR immunoreactivity and clinical features of cholesteatoma was studied to evaluate the significance of the EGFR in cholesteatoma. The results were as follows; 1. The EGFR was positive in 39 out of 44 cases (88.6%) by the immunohistochemical technique using anti-EGFR monoclonal antibody. 2. The expression of the EGFR was strong on the upper part of the prickle cell layer and faint on the horny, granular and basal cell layer of the squamous epithelium of the cholesteatoma matrix. 3. The cases with active cholesteatoma expressed stronger EGFR immunoreactivity than those with inactive cholesteatoma. These findings suggest that the EGFR plays an important role in acceleration of proliferation and keratinization of the epithelial matrix in cholesteatoma.
Malleus fixation is said to cause an air-bone gap at low frequencies producing what is called stiffness-curve. At surgical operation we have found that many cases of chronic otitis media, which at low frequencies show an incomplete improvement of hearing following a patch test before operation, are accompanied with malleus neck fixation to the anterior tympanic wall. We experimentally fixed the malleus neck of cat and found it to cause CM amplitude decrease. CM inhibition rates versus frequencies before and after malleus neck fixation were measured and evaluated. Following malleus neck fixation inhibition rates were larger than 90% at frequencies lower than 600Hz. As frequency increased, inhibition rates tended to decrease in less than 40% at frequencies between 2kHz and 7kHz. Above 8 kHz inhibition rates increased as frequency increased. These changes in inhibition rates may correspond to the stiffness-curve in man.
In middle ear diseases including otitis media with effusion (OME), there are various lipids mediators such as leukotoriene C4, D4 (LTC4, LTD4) and prostaglandin E2 (PGE2) in the effusion of the tympanic cavity. Therefore, it is important to examine the effect of these mediators on middle ear clearance. We studied on the effect of LTC4, LTD4 and PGE2 on mucociliary transport of the eustachian tube both in vitro and in vivo. Healthy guinea pigs with normal Preyer's reflexes were used in vitro study. Normal ciliated epithelium was carefully obtained from the tubotympanium and incubated with RPMI solution in the from of tissue culture. The epithelial specimens were incubated with LTC4, LTD4 and PGE2 respectively, ranged at the concentrations of 10-8M and 10-6M. Ciliated cells of the specimens were observed under an inverted microscope. Ciliary activity of each ciliated cell was photo-electrically measured on a TV monitor. LTC4 and LTD4 inhibited ciliary activity at the concentrations of 10-8M and 10-6M in vitro. PGE2 promoted ciliary activity at the concentrations of 10-8M and 10-6M. Healthy chinchillas were used in vivo study. The animals were free of middle ear infection and hearing loss as determined by otomicroscopy, tympanometry and auditory brainstem response (ABR). One ml each of 10-5M LTC4, LTD4, PGE2 and the control solution (10-3 ethanol/saline) was directly injected into the tympanic bulla with a 27-gauge syringe under anesthetization. The middle ears were examined by otomicroscopy, tympanometry and ABR across time. LTC4 and LTD4 inhibited mucociliary transport of the eustachian tube. However, there was no significant difference between PGE2 and the control.
The endolymphatic sac blood flow (ESBF) and cochlear blood flow (CBF) in normal guinea pigs were measured by laser-Doppler flowmetry (Advance Laser Flowmeter, Model ALF 2100) following intravenous administration of 70% isosorbide (1.6ml/kg), 50% glycerol (2.4ml/kg) or diphenidol hydrochloride (10mg/kg) under general anesthesia with intraperitoneal injection of pentobarbital sodium. Respiration was controlled by a respirator after tracheotomy and blood pressure was monitored through the femoral artery (Gould Statham P23 ID Pressure Transducer). For ESBF measurements, a probe was placed on the right endolymphatic sac after entering the posterior fossa via the dorsal approach. For CBF measurements, a probe was placed on the basal turn of the right cochlea via the ventral approach. Isosorbide, glycerol or diphenidol hydrochloride was administered respectively through the jugular vein for 60 seconds. Both ESBF and CBF increased immediately after administration of isosorbide or glycerol, reached a peak within 2-5 minutes and decreased gradually to the initial baseline levels in 12-18 minutes. On the contrary, diphenidol hydrochloride induced a reduction of both ESBF and CBF. Blood flow changes were usually corresponded to systemic blood pressure changes. The magnitude of the CBF response in these 3 different drugs tended to be slightly greater than that of the ESBF response. This may be resulted from the anatomical difference of each blood supply i.e. CBF from the vertebrobasilar artery and ESBF from the external carotid artery.