The relationship between the internal carotid artery (IC) and the eustachian tube (E) was examined under an operating microscope using forty human temporal bones. In one case, the bony wall above the IC was missing, so that the artery directly projected into the protympanum. In another case, bulging of the bony wall of the IC into the antero-inferior mesotympanum was found. The temporal bones were cut at several points so as to make sectional planes vertical to the long axis of the E. The distances from the sectional planes to the cochleariform process were determined to be 8, 10, 12, 14, 16, 18 and 20millimeters. We identified the plane nearest to the cochleariform process where the tubal cartilage was found and the degree of pneumatization of the interposing bone between the IC and the E. In addition, the following distances were measured: the shortest distance between the IC and the cochleariform process (distance a), the shortest distance between the IC and the bony anulus (distance b), the shortest distance between the IC and the E at each sectional plane (distance c), the width of the tubal cartilage (distance d) and of the interposing bone (distance e) on the line where the distance c was measured. The plane nearest to the cochleariform process where the tubal cartilage was found was 12mm from the process in 4 cases, 14mm in 15 cases, 16mm in 14 cases, and 18mm in 7 cases. The bone interpoisng between the IC and the E was pneumatized in 23 cases, and acellular in 17 cases. The mean± S. D. of distance a was 8.2±1.9 mm, and that of distance b was 4.7±2.0 mm. Distance c had the tendency to be longer as the observed sectional plane was separated further from the cochleariform process: 0.3±0.2mm (at the plane 8mm apart from the cochleariform process), 0.4±0.2 mm (10mm), 0.6±0.4 mm (12mm), 0.9±0.7mm (14mm), 1.2±0.8mm (16mm), 1.5±0.8mm (18mm), and 1.8±0.9mm (20mm).The distance between the IC and the E was not affected by the anatomical correlation between the IC and the middle ear, but was affected by the degree of the extension of the tubal cartilage toward the tympanic cavity and by the pneumatization of the interposing bone between the IC and the E. The further the tubal cartilage extended toward the tympanic cavity and the more the interposing bone was pneumatized the longer was the distance between the IC and the E.
The relationship between chronic middle ear inflammation and pneumatization hasbeen studied using pigs, whose tympanic bullae closely resemble the human mastoid air cell system. Squamous metaplasia of the middle ear mucosa was observed in inflamed ears in this series of experiments. The charactor of the stratified squamous epithelium caused by the metaplasia was then analyzed. Chronic middle ear inflammation could be induced in 68 of 73 ears which were treated to produce inflammation, and stratified squamous epithelium was observed in five of the inflamed ears. Details of the five ears were as follows. No.1: glycerin was injected into the middleear cleft five weeks after birth, and the tympanic bulla was removed seven weeks after birth. No.2: glycerin was injected into the middle ear cleft seven days after birth and streptococcus pneumoniae was injected two days later. The tympanic bulla was removed twenty four days after birth. No.3: glycerin was injected twice, with an interval of two days, starting one week after birth, and the tympanic bulla was removed six months after birth. No.4: glycerin was injected twice, with an interval of two days, starting one month after birth, and the tympanic bulla was removed six months after birth. No.5: glycerin was injected twice, with an interval of two days, staring two months after birth, and the tympanic bulla was removed six months after birth. Ear drum perforation was observed in three ears, No.1, No.3, and No.5. Purulent secretion was stagnant and pneumatization of the middle ear air cell system was inhibited in all five ears. The histological findings of these five ears were fundamentally the same as those of the ears without squamous metaplasia, and revealed non-specific chronic inflammation. However, the degree of inflammation was much greater in the five ears with squamous metaplasia. Specifically, inflammatory cell infiltration, sequestrum of trabeculae which constitute air cell structure, and abscess and granulation formation were observed. The stratified squamous epithelium surrounded these severe inflammatory changes. Transition from mucous membrane to the squamous epithelium was noted in No.2. It was concluded that squamous metaplasia of mucous membranes can be induced even in the setting of simple chronic otitis media if the inflammation is severe enough, and that it can be induced at a relatively early stage from the occurrence of inflammation, as seen in No.1 and No.2. In contrast with the stratified squamous epithelium observed in the human aural cholesteatoma, in the metaplastic squamous epithelium of these cases, continuity to the ear drum was not recognized, there was very little keratinization of epithelium or bone destruction. Moreover, the metaplastic squamous epithelium surrounded the inflammatory lesion, and the inflammatory change was slight in the subepithelial area. Whereas, in the human aural cholesteatoma, the inflammatory change occurred mainly in the subepithelial area. From these findings, it was concluded that the formation and charactor of the metaplastic squamous epithelium in these cases is quite different from that in the human aural cholesteatoma.
Among cholesteatomas and chronic otitis medias, there are those of recurrent and intractable types, and as a result of repeating biopsy, we have found that there are the symptoms diagnosed as malignant tumor (e. g. squamous cell carcinoma, verrucous carcinoma, etc.). We Izave experienced a case which was suspected of a cholesteatoma of recurrent and intractable type initialy but diagnosed as a keratoacanthoma finally. The patient was a male aged 77 and visited our hospital with his chief complaints of the right otalgia and otorrhea July, 1983. The symptoms were diagnosed as the right cholesteatoma and otitis interna. Subsequently, radical operation was performed on the middle ear 4 times till September 1985, but the symptoms ocurred repeatedly, and the right facial palsy developed in October, 1985. Consecutively, headache became remarkable, and the Garcin syndrome occurred in Janualy 1986. He died due to the central respiratory disorder on Feb. 5. The lesion was considered to be a type of cholesteatomas, but ultimately as a result of making assessment repeatedly afterwards, keratoacanthoma was dagnosed. Keratoacanthoma is a releatively rare disease and seen frequently in the dermatological field. It is known that keratoacantoma most frequently arises from an area of sunexposed skin, particularly the facial surface. It resembles squamous cell carcinoma very closely histologically and clinically but is found to be the so-called pseudocarcinoma as it disapears naturally. However, there have been reports recently on the cases of keratoacanthoma which followed a malignant course, which caused metastasis to other sites and which was diagnosed as squamous cell carcinoma finally, though it was diagnosed as keratoacanthoma initially. Accordingly, recently in the literature keratoacanthoma has been emphasized a carefully histological diagnosis due to an excisional biopsy and surgical resection. Though we are not so familiar with this disease as otorhinolaryngologist, there are the large possibility that we confront this lesion in the otorhinolaryngological field from the fact that the incidence is high in the legion of the head and neck and that its occurrence appers from the epidermis histologically, for which we think that this is a disease we must diagnose and manage carelully.
The pathogenesis of sensorineural hearing loss which accompanies various forms of otitis media is attracting increasing interest. Endotoxin frequently found in middle ear effusion is considered to be one of the substances which might penetrate the round window membrane from the middle ear and exhibit ototoxicity in the inner ear. In this paper, the possible pathogenesis of the sensorineural hearing loss by a similar process was investigated by using endotoxin-like substance (lipoteichoic acid from Staphylococcus aureus). In Group A, the middle ear bulla of 31 guinea pigs was opened and 5 mg of lipoteichoic acid was placed on the round window membrane. In 12 guinea pigs of Group B, a very small amount of lipoteichoic acid solution (10 mg/ml) was injected into the scala tympani through the round window membrane. After various time intervals, the animals were sacrificed, the temporal bones removed, and histologic sections prepared. The cochlea was examined under a light microscope for possible pathology. No definite pathology was observed either in Group A or in the control group. In 5 out of 12 guinea pigs of Group B, severe cochlear pathology was observed. The pathology consisted of various combinations of fibrosis in the scala tympani and the scala vestibuli, atrophy and cystic degeneration of the stria vascularis, cyst-like formation of Reissner's membrane, degeneration of the organ of Corti with loss of hair cells, disappearance of the tectorial membrane, and inflammatory cell infiltration of the endolymphatic space. The results of the study did not prove that an endotoxin-like substance in the middle ear could cause cochlear damage, but they suggest the possibility that, once introduced into the inner ear, it could potentially cause cochlear pathology.
The exact mechanism of salicylate ototoxicity, reversible sensorineural hearing loss and tinnitus, is still unknown and the studies on the transport mechanism into the cochlea seems to shed light on its generation mechanism. In our previous studies, it has been concluded that the transport mechanism of furosemide andpenicillin G (organic anions) from the blood vessels into the perilymph is pronouncedly different between the scala tympani (ST) and the scala vestibuli (SV) of the guinea pig, i.e. active transport in ST and passive transport in SV. Aspirin (acetylsalicylic acid; ASA) and sodium salicylate (SA) are also organic anions. The goal of the present study is to examine the transport mechanism of ASA and SA in the cochlea of the guinea pigs and to determine whether the different transport system in two scalae is also present in case of ASA and SA. In the present study, the sequential samples of ST and SV perilymph, cerebrospinal fluid (CSF) and serum were taken after intravenous administration of 100mg/kg of ASA or SA and the concentrations of ASA and SA were determined using high-performance liquid chromatography. Because of the rapid hydrolysis of ASA to SA, with a elimination constant of 3.8×10-3h-1, there was no difference of the concentration or kinetic of SA in these body fluids between ASA and SA administration. In the serum, SA was relatively slowly eliminated with mean concentrations of 302 μg/ml and 155μg/ml at 5 minutes and 180 minutes after injection of SA (or ASA), respectively. The concentration of SA in CSF rapidly increased after administration of SA and reached the maximum value of 17.4μg/ml at 30 minutes. It was gradually declined thereafter (6.74μg/ml at 180 minutes). These kinetics of SA in the serum and CSF were analogous to those of furosemide and penicillin G. In the ST perilymph, SA was slowly accumulated (2.92μg/ml at 5 minutes) and was not eliminated for following 3 hours after injection of ASA or SA (36.4μg/ml at 180 minutes). In contrast to the different kinetics of furosemide or penicillin G in ST from SV, the concentration of SA in the SV perilymph exhibited very similar time course to that in the ST perilymph. The different transport mechanism of SA from furosemide or penicillin G in ST is suggested by the following view points; 1) No elimination of SA was found in ST at least for three hours, though there was a rapid elimination of furosemide after the early peak (at 15 minutes). 2) The kinetic of SA in ST was very similar to that in SV, while the concentrations of furosemide were very different between ST and SV perilymph. 3) The ST perilymph/serum gradient of SA was relatively low (1: 4.2, at 180minutes), compaired with furosemide (higher than 1: 65, at any time).
We studied the effect of elevation of inner ear pressure on cochlear blood flow using laser Doppler flowmeter and non-radioactive microspheres in guinea pigs. The animals were anesthetized with either intraperitoneal ethyl carbamate (Urethane; 1.5-2.0g/kg) or pentobarbital sodium (Nembutal; 30-40mg/kg). Tracheostomy was performed, and the animals were paralyzed with succinylcholine chloride. Their pulmonary ventilation was maintained with an artificial respirator. The bony wall of the scala tympani of the basal was drilled, and a glass capillary tube was inserted into the perilymph and fixed to the bone with dental cement to prevent leakage. The glass capillary tube was connected by a catheter and three-way tap to a pressure transducer, with the third outlet of the tap communicating with a saline reservoir. The perilymphatic pressure could be altered by raising or lowering the reservoir. When the perilymphatic pressure was altered, we measured cochlear blood flow by laser Doppler flowmeter (Advance ALF 2100). The laser Doppler flowmeter has a needle probe (o.d. 1.0mm) and the tip of the probe was placed on the bony wall of the cochlea after removing the middle ear mucosa. Non-radioactive microspheres, suspended in 1.0-2.0 ml saline, were injected into the left ventricle after thoracotomy was performed. After the microspheres were injected, the animals were sacrificed by intracardial injection of KC1, the temporal bones were removed, fixed with 2% glutaraldehyde, and decalcified in 10% EDTA. Using the surface preparation technique and phase contrast microscopy, we counted the number of microspheres trapped in the blood vessels of the cochlea dividing the cochlea into lateral, spiral and central portions. The lateral portion included radiating arteioles in the roof of scala tympani, the vessels in the spiral ligament and the vessels in the stria vascularis. The spiral portion included the vessels of the basilar membrane, the vessels of the tympanic lip and the vessels of spiral lamina. The central portion included the vessels of modiolus. In some animals, endolymphatic pressure and endocochlear potential (EP) were measured simultaneously with a single glass microelectrode (WPI model 900) when the perilymphatic pressure was altered. The endolymphatic pressure and the perilymphatic pressure varied coincidentally. When the inner ear pressure was raised to relatively high levels, EP decreased to a negative value in a similar way as in response to anoxia. The laser Doppler flowmeter showed reduction of cochlear blood flow when the inner ear pressure was raised. Immediately after the inner ear pressure was raised, the cochlear blood flow measured by the laser Doppler flowmeter decreased. This decrease was reversible upon applications of pressure for brief periods of time. The degree of the reduction of cochlear blood flow depended on the degree of the elevation of the inner ear pressure. The required inner ear pressure for the reduction of cochlear blood flow was low in hypotensive animals. The inner ear pressure necessary to lower the cochlear blood flow was related to the blood pressure of the animals. When the distribution of microspheres was evaluated, blood flow decreased significantly in the lateral portion and in the spiral portion. Though the blood flow in the central portion decreased after the elevation of the inner ear pressure, the degree of the reduction was small compared to that in the lateral and spiral portions. It is considered that the inner ear pressure is not transmitted directly to the blood vessels of the modiolus. Because venous pressure in the cochlea is considered to be identical to the inner ear pressure, it is considered that cochlear perfusion can be calculated as the difference between the mean arterial blood pressure and the inner ear pressure.
The incidence and features of spontaneous acoustic emission (s-OAE) in guinea pigs were studied. The incidence of s-OAE observed here was approximately 20% in 248 ears, which is unexpectedly high compared with recently reported data. Behavior of s-OAE, its electrical correlate and endocochlear DC potential (EP) were simultaneously observed in hypoxia and in furosemide administration. The changes of s-OAE and its electrical correlate were basically related to the movement of EP in both of the experiments. This result suggests that s-OAE is highly dependent on cochlear metabolism.
The electrocochleographic CM and AP were recorded by the transtympanic needle electrode technique in subjects with normal hearing. The CM and AP were recorded simultaneously, employing short tone bursts as the acoustic stimulation. Detection thresholds of CM were low at 1 kHz and 0.5 kHz of which frequencies were near to the value of psychoacoustic hearing threshold in the normal hearing, but the detection thresholds at both 4 and 8 kHz were 40 to 50 dB higher than those of the middle frequencies. The latency-intensity curves of CM were similar to those of AP (N1) except at high sound intensity level above 60 dB nHL. Two CM components of which one was obtained in response to the high sound intensity of stimulation and the other component in the level of low sound intensity, were recorded in near 40 dB nHL. There was the possibility that these two components were recorded primarily regardless of the sound intensity of stimulation. Pseudolatency in the records of detection threshold was about 7 ms at 1 kHz and 10 ms at 0.5 kHz. Latency-intensity relationship in AP (N1) has been subdivided into two parts, of which shallow part (L-part) was below 60 dB nHL and steep part (H-part) above 60 dB nHL. Latency of AP (N1) near the detection thresholds at 1 kHz and 0.5 kHz was almost same as the pseudolatency of CM. It was assumed that the marked elongation of this pseudolatency might relate to the time for boosting the sensitivity of basilar membrane motion.
Development of Endocochlear DC potential (EP) was examined corresponding to changes in electrical resistance in the cochlear duct, and a negative EP value caused by anoxia in guinea pig embryos and neonates. EP developed rapidly during the 59th to 64th gestational days (mean gestation days; 67). This rapid EP growth was simillar to that observed in the neonates of rats, rabbits and cats. During those gestation days, electrical resistance of the cochlear duct also grew. There was a high correlation between these two values. During the same gestation days, negative EP voltage caused by anoxia also grew. There was also a high negative correlation with the growth of EP voltage. Since electrolytes gradient between the endolymph and the perilymph was established before the 59th gestation day, an increase in electrical resistance of the cochlear duct might grow EP voltage and negative EP voltage caused by anoxia during these days.
A computerized recording-analysis system of auditory evoked responses for laboratory animals is developed. The stimulation system is controlled using a GPIB board and a digital interface board in the slots of the personal computer PC-9801 (NEC), and the signals generated by the animal are amplified and then digitalized by an A/D converter also mounted in the computer. The following parameters are controlled on the keyboard: averaging count; sampling time; timing to start rejecting data; and wave form, frequency, phase and attenuation of stimulus sound. Study of the auditory evoked responses of experimental perilymphatic fistula guinea pigs with this system demonstrated availability and userfriendliness of the system as well as residual hearing between 10 and 14kHz in over one-third of the animals.