Endotoxin contents both in the middle ear effusion (MEE) of secretory otitis media (SOM) and in the cholesteatoma were determined by Limulus assay. In 35 cases out of 50 MEE samples obtained from both fresh and recurrent SOM cases of children. the assay gave positive reactions ranging between 10^-9 and 10^-6g/ml. On the other hand, only 2 out of 17 samples produced positive reactions in MEE from adult SOM patients. All samples of cholesteatoma from 12 cases gave positive reactions in Limulus assay, the concentration of endotoxin ranging between 10^-9 and 10^-5g per one gram wet weight of the cholesteatoma contents. Bone resorbing activity, assesed by measuring the calcium release from cultured mouse calvarial bone, was stimulated by endotoxin in a dose dependent manner with maximal effect at the concentration of 10^-5g/ml. As bacterial endotoxin has been implicated in various immunological and biological activities, it may play an important role both in the pathogenesis in SOM, especially in that of children, and in bone resorption by cholesteatoma.

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The aim of this work was to prepare specific antibodies against various collagens for the study of immunohistological localization of collagen under normal and pathologic conditions. Human type I, III and V collagens were extracted from human dura mater and placenta using limited pepsin digestion followed by differential salt precipitation and chromatographic purification. The purity of collagens was assessed by SDS polyacrylamide gel electrophoresis. Antibodies against type I, III and V were prepared in rabbits, and showed a high reaction with the corresponding human collagens tested for activity using ELISA. However, antibodies to type I still showed some cross-reaction with type III as the same reaction as antibodies to type III with type I. By using these antibodies, tissue distribution of various types of collagen was examined in middle ear by peroxidase anti-peroxidase method. In granulation tissue it was revealed that type I and type III co-existed.

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The gas of the tympanic bulla was measured with gas chromatograph using 7 guinea pigs. The gas composition was 7.2±1.8%, 4, 8±1.0% and 8.5±3.4% in O₂, CO₂ and N₂, respectively. When the bulla was open, the gas composition became the same value as in the room air. The gas was taken 10, 30, 60 and 90 min. after the closure of the bulla wall. The result in the present study revealed that the CO₂ composition already started to recover in 10 min. and returned to the pie-open value in 30 to 60 min. The O₂, however, recovered much slower and it took more than 90 min. to reach the normal value. The recovery curve of these gases exhibited an exponential changes and the time constants of CO₂ and O₂ were 15 min. and 97 min., respectively.

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Forty-two specimens of human middle ear muscles, tenser tympani muscle and stapedius muscle, were examined histologically with regard to their functions and the effeet of aging. The average of narrow short diameters of their muscle fibers were 11.6μm in tenser tympani muscle and 9.4μm in stapedius muscle. With advancing age, they were prone to atrophy and the fibrotic change in stroma was increased. Three muscle fiber types, red, white and intermediate were identified, in which the white fiber was the predominant type in both tensor tympani and stapedius muscles. Our observations suggest that the middle ear muscles will have a phasic and kinetic muscle activity according to the property of white fiber and their functions will deteriorate with advancing age.

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The tympanic plexus of the small ganglions we studied with microscope. Serial sections of human temporal bones were used in this study. The course of tympanic plexus were roughly reconstructed, then the ganglion cells were plotted in the schema. 3 branches of the tympanic nerve were observed. They were tubal, anterior, and posterior branches. The ganglion cells were found mainly in the anterior branch, while less in the posterior branch. But the ganglion cells were presented in the tubal branch in limited cases. The ganglion cells were found to concentrate at the level of the umbo and of the stapes footplate. As these ganglion cells existed in the branch close to the lesser petrosal nerve, they were speculated to be parasympathetic.

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There has ever been a many experiment studing the anatomical structure of the tympanic isthmus, but most of which were carried out inspecting the tympanic isthmus, a small opening which permit aeration between the attic above, and the mesotympanum below, from superior portion of the attic after removing the tegmen tympani. Our aims to this experiment was to study the tympanic isthmus, a view from the anterior tympanum direct posterior, and to evaluate a air-pathway in the tympanum with reference to mucosal fold in the middle ear.
Tympanic isthmus were significantly seen anterior-posteriorly far behind the drum, located in between tensor tympani fold anterior and incudal fossa posterior, and in front of the facial canal. One of the constituent of the anterior tympanic isthmus, tensor tympani fold, was thought playing a important role for the direction of the air flow into the tympanum, as the dye, insuffrated from the ostium of the eustachian canal into the tympanic cavity similar to physiological state inspirated air bringing into the tympanic cavity on swallowing, was deposited significantly both in the oval, and round window niche.

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In order to determine development of each part of human middle ear, the development processes of various parts from the middle tympanum to the antrum were observed and compared relatively based on the epithelial invasion the auditory tube at each stage of fetal development using fetal temple from 17th to 26th weeks of gestation. The middle ear cavity is considered to be formed through combined effects of various processes such as epithelial invasion of the auditory tube, resorption of the fetal connective tissue, thinning of the bone wall of the otic capsule, outward proliferation of the temporal bone due to cartilaginous and fibrous bone formations, and active bone metabolism at the mastoid cavity, with formation of a series of pneumatic space. It was found that the resorption process of the fetal connective tissue did not occur uniformly, with a persisting tendency for the area from the superior tympanum to the periovular window for a prolonged period. These findings are interesting embryologically in terms of the causal relation in development from the posterosuperior area of the steatoma to the superior tympanum of the middle ear.

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The purpose of this study was to obtain a more natural tubal insufficiency than those induced by ligation, obstruction and cauterization etc. which had been often used by many authors based on the theory of Hydrops ex Vacuo. For this purpose, the pharyngeal orifice of the auditory tube in guinea pigs was irradiated with electron beam with a dose of 2000 rads. Histopathological changes in the middle ear and the auditory tube were observed in a series of single specimen with H-E staining 1, 2, 3, 6, 12 months after irradiation. In this study, middle ear with effusion without severe infection were used to elucidate the histopathological changes in the middle ear structure related to the auditory tube dysfunction. Middle ear effusion was classified into two categories, that is, effusion without infection (serous) and effusion with infection (purulent or mucoid). It was our conclusion that the infection based on the epithelial damage of the auditory tube was a important promoting factor to change the serous type effusion to the purulent or mucoid type effusion.

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Since the middle ear lining is an extension and a modification of the respiratory epithelium, it is conceivable that it has a mucociliary system and plays an important role in the clearance of the middle ear cavity. In the present work, the ciliary activity of the middle ear lining in the normal and some pathological conditions was studied by the photo-electric method of Ohashi & Nakai. In addition, the morphology of the middle ear lining in the above conditions was studied by the scanning and transmission electron microscopy. In sum, the following conclusion have been derived from the present work: 1) The activity is strengthened as the location becomes more distal to the eustachian tube. 2) The activity is declined by staphylococcus aureus as the location becomes more distal to the eustachian tube.

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In our previous paper we described that IgG antibody and its complement are present in the endolymphatic fluid and that there is a possibility that type III allergic reaction occurs even in the endolymphatic fluid. Moreover, we succeded in inducing endolymphatic hydrops experimentally in guinea pigs sensitized with rabbit's stria vascularis and complete adjuvant (Freund).
In the present study pretreatment for sensitization was made 5 times in spite of 4 times as used previously. In order to determine whether there is no difference in incidence and morphology of endolymphatic hydrops as compared to those observed in the previous study and to make clear the activation system for the complement involved in endolymphatic hydrops, the present study was conducted using C4 defficient guinea pigs (C4D guinea pigs). Endolymphatic hydrops was induced in 4 out of 10 cases (40%), with similar incidences as obtained in the previous study. However, in this study bilateral endolymphatic hydrops, which had not been observed in previous study, developed in 2 cases. Since endolymphatic hydrops was not induced in C4D guinea pigs, the main activation system of the complement in volved in endolymphatic hydrops was considered to be the classical pathway.

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Perfusion of Gentamicin through the perilymphatic space showed specific fluorescence distributed in the cochlea, especially in the outer hair cells, basement membrane and basilar crest. Although no fluorescence was seen in the cochlea treated with high dose of Gentamicin administered intraperitoneally, only type I hair cells in the vestibule were selectively stained with FITC. Futhermore some of the vestibular ganglion cells were also stained. We suppose that the difference of toxic effect between each aminoglycoside antibiotics is due to the selectiveness of receptor of each type of hair cells.

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Phoshatidylinositol bisphosphate (PhIP₂), which is suggested as an aminoglycosides receptor as well as regulator of ion transport, was localized in the gunea pig cochlea by protein A-gold technique. The used antibody was raised in rabbits and was very specific to PhIP₂. In the organ of Corti, PhIP₂ was localized mainly on the plasma membrane, mitochondria, stereocillia, microvilli, cuticular plate and synaptic membranes of the component cells. In the vascular stria PhIP₂ was found mainly on the plasma membrane and mitochondria of the basal infolding of the marginal cell. In these areas PhIP₂ is likely to regulate ion transport physiologycally and to exist as an aminoglycosides receptor.

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Autoimmunity to type II collagen has been found in human diseases such as relapsing polychondritis, otosclerosis and Meniere's disease. Several animals sensitized with type II collagen developed the pathological lesions in the ear, similar to those seen in the above disease. We examined anatomical distribution of type II collagen in the ear immunohistochemically by using monoclonal antibody to type II collagen. Type II collagen was located in the following areas. In the External and Middle ear; auricular and external auditory canal cartilage, tympanic membrane (lamina propria), tympanic annulus, interossicular joints, stapes footplate, fissure ante fenestram, eustachian tubal cartilage. In the Inner ear, Cochlea; globuli interossei in otic capsule, Rosenthal canal in modiolus, osseous spiral lamina, spiral ligament, limbs, tectorial membrane. Vestibule; subepithelial layer of utricular and saccular maculae, semicircular canal membrane, ampullary cristae and endolymphatic duct and proximal part of the sac.

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Localization of inositol phospholipids synthesis and metabolism in the cochlea was studied by means of autoradiography with ³H-myo-inositol . The most heavily labeled tissue was the stria vascularis. The nerve fibers of osseous spiral lamina and the synapses of outer hair cells also had many silver grains. The distribution of inositol phospholipids in any cells of cochlea was diffuse, but so far as cell membranes were concerned, the silver grains were most accumulated in that of outer hair cells. About the distribution of silver grains any differences among the each turns of cochlea were not found.

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In order to analyze the cell kinetics of the component cells of the cochlea, we have carried out the Feulgen-DNA cytofluorometry on these cells of human by “serial section method” as reported previously.
The result obtained from 16 cases (0 to 87y. o.) revealed all the hair cells and pillar cells gave diploid G1 pattern in DNA distribution. But Hensen's cells in 7 cases (9 to 87y. o.) and Deiters' cells in 2 cases (58 and 79y. o.) included tetraploid cells and Hensen's cells in one case (33y. o.) included a octaploid cell. Interestingly, polyploidization of Hensen's cells was observed almost allways in the neighborhood of the damaged hair cells and the polyploid cells seemed to occupy the empty space.
These results indicate that some of the supporting cells in organ of Corti can synthesize the nuclear DNA. This polyploidization may be involved in the compensatory mechanism of damaged organ of Corti.

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The histochemical localization of CAH in the inner ear of guinea pig was studied with Hansson's method and Yokota's method. All cells possessing the cell membrane infoldings are proved to have the enzymatic activity. The cochlear hair cells show strong enzymatic activity while the vestibular hair cells show no appreciable activity. Both cochlear and vestibular supporting cells show enzymatic activity. The stria vascularis, dark cells and endolymphatic sac, which are generally acknowledged to be involved in production and absorption of inner ear fluid, are proved to have enzymatic activity. The cells, which are already proved to have Na⁺-K⁺-ATPase activity, show the enzymatic activity in the present study. The histochemical reaction products showing the enzymatic activity are observed in the cytoplasm, nucleus and cell membrane with both light microscope and electron microscope. The regulation of the fluid and ion in the inner ear is probably a complex mechanism involving not only various cells but also several enzymes such as CAH, Na⁺-K⁺-ATPase and adenylate cyclase.

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GABAergic system in the cochlear nuclei was investigated in the rat by means of immunohistochemical method using glutamate decarboxylase (GAD) as a marker. In the dorsal cochlear nucleus (DCN), GAD-like immunoreactive (GADI) fibers were distributed diffusely, while in the ventral cochlear nucleus (VCN) although a number of GADI fibers were also seen, most of them were found to be localized near the cell soma as if forming axo-somatic contact. In the DCN a group of GADI cells were found in its deep region, but no GADI cells in the VCN. Present experimental immunohistochemical demonstrated that most of GADI fibers are supplied by intrinsic GADI cells presumably located in the DCN, while those in the VCN by extrinsic origins, because deafferentation of the cochlear nucleus resulted in a disappearance of GADI fibers in the VCN but remained to be intact in the DCN. These regional morphological difference were supported by the present immunoelectron microscopic analysis; GADI fibers in the DCN formed mostly axo-dendritic synapse, while those seen in the VCN make axo=somatic synapse.

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Cochlear endolymph, scala tympani perilymph and scala vestibuli perilymph were collected from fetal, neonatal and matured guinea pigs. The concentrations of Na and K in these fluids were assessed using a microflame photometer. By the 49th gestation day, electrolytes composition in the endolymph was already characterized by a high level of K and low level of Na.

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The unbalance between production and absorption of endolymph brings endolymphatic hydrops. The influx and efflux of water of endolymph is thought to be a function of static pressure gradient and osmotic pressure gradient. We planned to observe the movement of endolymph by changing of endolymphatic pressure via a glass capillary inserted into ductus cochlearis through spiral ligament. Thirteen guinea pigs weighted 350-600g were used for this experiment. The permeability of the tissue surrounding endolymphatic space is calculated as resistance that was 5×10¹⁴ m^-4·kg·s^-1 sa mean value. (It ranged 8×10¹³ to 1.7×10¹⁵ m^-4·kg·s^-1)

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Regarding the causes of endolymphatic hydrops in Meniere's disease, vascular dysfunction is considered to be one of them. As the endolymphatic hydrops existed in scala media, it is important to know the blood flow in scala media in order to reveal the connection between vascular disorder and the hydrops. However, up until now, there was no report to measure it by using current method due to the anatomical restrictions. Therefore, the blood flow in the scala media was measured by using hydrogen clearance method, which was considered to be suitable to measure it, in normal guinea pigs and guinea pigs with hydrops. Guinea pigs with hydrops were produced experimentally by cauterizing the endolymphatic sac with 10% silver nitrate solution. In normal guinea pigs, the blood flow inscala media was 6.7±0.9ml/min/100g (n=14). In guinea pigs with hydrops, the blood flow in scala media was 5.5±0.7 ml/min/100g (n=10). It was suspected that the decrease of blood flow in scala media of guinea pigs with hydrops would be caused by atrophy with stria vascularis, from the histopathological findings.

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In order to investigate the inner ear changes induced by barotrauma, various degrees of the atmospheric pressures were given to guinea pigs in a chamber and cochlear action potentials were recorded after compression and decompression. In the group of slow compression and decompression normal AP responses were obtained in most animals. In the group of rapid compression and decompression the threshold of AP was risen in most animals and the latency of AP was a little prolonged. The rise of the threshold of AP was more frequently noted in the group of rapid compression than in that of rapid decompression. It is assumed from present experiments that the inner ear barotrauma was more easily arisen from compression than decompression and no difference was noted between once load and twice or three times loads.

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In order to investigate the inner ear changes induced by barotrauma, various degrees of the atmospheric pressures were given to guinea pigs in a chamber and morphological changes in the cochlear sensory hairs were mainly studied by means of scanning electron microscope. The main morphological changes of sensory hairs were disarrangement, degeneration, break-off and disappearance. In the group of rapid compression and decompression the severe damage of sensory hairs was noted, and the group of rapid compression and slow decompression was more easily damaged than that of slow compression and rapid decompression. The damage of sensory hairs was noted mainly in the cochlear basal turn. Both inner hairs and outer hairs were damaged, but inner hairs and the first row of outer hairs were more easily damaged than the second and third rows of outer hairs. Round window membrane rupture was not noted in all experimented animals.

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Rabbits were exposed to the pure tone (2 KHz, 100 dB for 2 hours) and the change of the nerve endings of the outer hair cells with the lapse of time during one month was studied by the electron microscope. In the afferent nerve endings mitochondriae dilated and small vesicles decreased in number immediately after acouctic exposure. These changes in the afferent nerve ending after acoustic exposure recovered during the period of one month. In the efferent nerve endings mitochondria dilated and were distributed in the whole nerve endings and small vesicles decreased in number immediately after acoustic exposure. The efferent nerve endings after acoustic exposure recovered slower than afferent nerve endings. Furthermore the changes of the agglomerations of the synaptic vesicles along the synaptic membrane and the gapstructures in the synaptic cleft in the efferent nerve ending after acoustic exposure are briefly discussed.

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Thirty seven guinea pigs were used to investigate the influence of rotatostimulation on the lateral crista ampullaris. After repeating the turning stimuli of ctpulometric mode (maximum turning velocity 450°/sec) for 48, 72 or 144 hours, the morphological change of crista ampullaris of the ampullopetal side was compared with that of the microscope. The first degenerative changes of sensory epithelium were observed in the central part of the crista ampullaris of the ampullopetal side. Type I cells, and showed degeneration of mitochondria and extension of endoplasmic reticulum. In a more advanced state of degeneration, the cytoplasm filled with vacuoles was observed. These findings were more remarkable in the ampullopetal side than in the ampullofugal side.

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The purpose of this study is to investigate inner ear changes due to aging in rabbits aged 1-5 years. The outer and inner hair cells of the left ears were examined by surface preparation technique under a phase contrast microscopy. At 1 year of age, the hair cell loss was slight. At 2 and 3 years, the outer hair cell loss was pronounced in the upper half part of the basal turn. At 5 years the outer hair cell loss was greatest in the apical turn. In all animals inner hair cell loss was slight. No precise relationship between the outer hair cell loss and aging was observed in this study. Horizontal sections of the right ears with H-E staining were examined under light microscopy. The spiral ganglion cells were not decreased in almost all animals. The stria vascularis showed slight atrophy in the animal aged 5 years.

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Intra cysterna and thalamus injection of mumps vaccine had been performed in ten monkeys, after three weeks latter, these monkeys were saccrified under Ketaral anesthesia. Histopathological studies were performed these ten monkeys, three were affected chorionmeningitis, the other four had lymphoid cells infiltration in cortex, two were lymphoid cells infiltration in mid brain. The inner ear of these ten monkeys were studied under microscope, in some monkeys had hydrops of scala media and saccular wall, and the other had an abnormal ovoidal vacuolen near Hensen cells, and displacement of tectorial membrane.
As the results, there were no remarkable pathological findings in tectorial membranes, hair cells, stria vascularis, and spiral ganglion cells.

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Mumps is thought to be the most common cause of unilateral acquired sensorineural deafness in children. Mumps deafness is usually sudden in onset, profound or complete, and may be associated with vestibular symptoms. The author's clinical survey of 52 patients with unilateral deafness which could be reasonably ascribed to mumps indicates that the hearing loss is exclusively unilateral, severe or total, and permanent; and that approximately 44% of the patients experienced dysequilibrium of vestibular origin. An analysis of the present series of mumps deafness also suggests that the primary route of invasion is hematogenous, and thus the term “viral endolymphatic labyrinthitis” is proposed as the possible pathogenesis of the deafness, since both tympanogenic and meningogenic routes of viral invasion to the labyrinth can be excluded on the basis of the clinical and CSF findings. This view of the pathogenesis, particularly that mumps meningitis is not associated with deafness is supported by several authors (Vuori et al. 1962, Azimi et al. 1969, Lindsay 1973, Nadol 1978 etc.). The incidence of deafness following mumps appears to be very low (about 1:20, 000).

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Pathogenesis of viral labyrinthitis is still poorly understood. In this study, the cochleas of 8 adult guinea pigs with intralabyrinthine inoculation of HVJ (Sendai Virus) and of 3 adult guinea pigs with intravascular injection of HVJ were investigated by histopathological and immunohistochemical technique (immunofluorescence and Avidin-Biotin-Peroxidase Complex method). In intralabyrinthine inoculated animals, viral antigens were immunohistochemically found in the stria vascularis, Reissner's membrane, supporting cells of the Organ of Corti of several inoculated cochleas examined. In intravascular injected animals, viral antigens were immunohistochemically found in the stria vascularis, supportig cells of the Organ of Corti. This findings suggests endolymphatic labyrinthitis. In all cochleas examined, there were no evidence of IgG, IgM, C3, C4 precipitation.

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Pathogenesis of the mumps deafness is still poorly understood. In this study, mumps virus was propagated in the line of Vero cells, inoculated in the cochleas of 10 guinea pigs (130-250 gm) and subsequent changes were examined by electron microscopy. Of these, mumps infection was confirmed in 4 ears, 3 of which demonstrating distinct viral lesions. The infection of the cells were indicated by intracytoplasmic occurance of the fibrous viral protein, i. e., nucleocapsids, and by budding processes at the endolymphatic surface. The cells bearing nucleocapsids were predominant in the marginal cells of stria vascularis, in two layers of Reissner's membrane and, on rare occasions, in Claudius cells. The organ of Corti was severely damaged in the basal turn; The outer hair cells had mostly disappeared. Distortion or proliferation of the supporting cells ensued but many of the inner hair cells remoined intact in that area.

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Herpes simplex virus was inoculated into the cisterna magna of the guinea pigs, and morphological changes of the meninges, the cochlear aqueduct and the organ of Corti were observed by means of a scanning electron microscope and a light microscope with HE staining and immunofluorescent antibody staining. The viral antigen were seen in the meninges by immunofluorecent antibody staining. Light microscopic studies revealed the infiltration of the inflammatory cells to the meninges and the cochlear aqueduct. The same finding of the cochlear aqueduct was observed by means of a scanning electron microscope. However, there were no morphological changes in the organ of Corti in spite of these changes in meninges and the cochlear aqueduct.

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Irritative nystagmus directing toward affected side was produced by injection of several solutions such as Ca²⁺ decreasing ajents (Sodium citrate, Na₂-EDTA, NaHCO₃, Na₂C₂O₄) and KCl into the facial nerve through the stylomastoid foramen.
Time course of the nystagmus, the cochlear whole nerve action potential (AP) and cochlear microphonics (CM) were measured in guinea pigs. KCl induced short period of irritative nystagmus and followed to paralytic nystagmus. Ca²⁺ decreasing ajents induced long lasting irritative nystagmus and disappered without paralytic nystagmus. After 3.8% Sodium citrate injection AP and CM amplitudes were decreased and thresholds were elevated.

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Histopathological studies of inner ears on EAE in guinea pigs, rats and mice induced by various kinds of antigen were performed.
The following results were obtained.
1) Inner ear changes were rarely observed only in guinea pigs EAE induced by brainstem and acoustic nerve truncs.
2) No histopathological evidence was presented in othor antigen groups (cranial nerve of bull and myelin basic protein).
3) Inner ear changes were characterized by infiltration of plasma cells and leucocytes into spiral ganglions.
4) Thin precipitates were observed over the surface of stria vascularis.

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The effects of long-term hyperlipidemia on the hearing organ are not well known experimentally, because it is difficult to get the animals which have hyperlipidemia for a long time. So we studied the effects using Watanabe heritable hyperlipidemic rabbits (WHHL rabbit) which hereditarily have about ten times higher serum cholesterol and triglyceride from their birth without hyperlipid feed than normal rabbits. We physiologically evaluated the hearing by ABR. Morphological observation was done by light microscopy and transmission electron microscopy. Sensorineural hearing loss was observed in WHHL rabbits and pathological changes were observed in stria vascularis and outer hair cells. Based on these results, we think that hyperlipidemia can cause the sensorineural hearing impairment.

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The inner ears in a nontreated guinea pig with irregular pinna reflex loss (20, 15, 12, 6, 4, 3, 1, 0.5KHz) were investigated by surface preparation technique. Nitro blue tetrazolium reduction reaction was used for demonstration of alteration in formazan formation. Bilateral spiral organs showed such hair cell damages as decreased formation of formazan, swelling, desquamation and missing. The hair cell damages occurred in both outer and inner hair cells bilaterally but irregularly as Fig. 1. Outer hair cell loss was more extensive in the left cochlea than in the right. Peripheral nerve fibers occasionally indicated decrease in formazan formation. The hair cell damage involved also bilateral vestibular organs. These findings suggest that the irregular pinna reflex loss in the guinea pig most probably was attributed to spontaneous acute viral cochleo-vestibular labyrinthitis.

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The ototoxicity of various aminoglycoside antibiotics, tobramycin (TOB), gentamicin (GM), kanamycin (KM), amikacin (AMK), and dibekacin (DKB), was evaluated after a single injection into the facial nerve through the stylomastoid foramen. Sixty-nine albino rabbits weighing about 3kg were used. Each drug was dissolved 100mg/ml, and 0.04ml given. The concentration of these drugs in perilymph and tympanic cavity was concurrently measured. No hair cell damage was observable in any rabbit decapitated 24hours after the injection. But in all animals decapitated 10 days after the injection, outer hair cells were damaged. The outer hair cell damage caused by TOB and GM was far higher than that from KM, AMK or DKB. However, there were no differences in the perilymph concentration among these drugs. These results coincide with the ototoxic evaluation of these drugs when given by general administration. Mechanism of inner ear damage caused by an injection of aminoglycoside antibiotics into the facial nerve through the stylomastoid foramen is discussed.

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Guinea Pig were used in this study and were divided into three groups (normal animals, KM-intoxicated animals and SM-intoxicated animals). The alternation of endolymphatic potentials after asphyxic anoxia were recorded simultaneously at the two different places, namely in the cochlea (CEP) and the vestibuli (VEP). The histological damages of cochlea and vestibular sensory epithelium were investigated after the SDH staining. (1) The VEP felt down under negative value and the CEP stayed positive value after anxia in KM-intoxicated guinea pigs. The sensory cells in the vestibular organs in KM-treated animals were almost normal but the sensory cells in the corti were severely damaged. (2) The completely reverse phenomena occured in SM-intoxicated animals.
It was concluded that the changes of both CEP and VEP during asphyxic anoxia were closely related to hair cell damages of those organs.

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The magnitude of endocochlear dc potential (EP) is diminished transiently by the administration of Nitrogen Mustard or its derivative, Nitromin. Based on our experimental findings we speculated that the cells in the inner spiral tunnel may be important in thinking the mechanism of this phenomenon. To check the appropriateness of our speculation the minute comparative study of the histopathological changes of the cells on the basilar membrane, between the animals whoes EP was diminished and the animals whoes EP remained within normal ranges after the administration of Nitromin. Kanamycin sulfate administered guinea pigs were also examined. Double blind technique was adopted to exclude the individual propensity in evaluating the histopathological changes. The cells in the inner spiral tunnel showed some histological changes in the animals whoes EP was diminished. However they were mild changes and further experiment should be done to come to a conclusion.

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First step of aminoglycosides ototoxicity is considered to be electronic binding of basic aminoglycosides (AGs) to acidic phosphatidyl inositol diphosphate. Therefore, competitive binding ability of AGs against basic dyes to acidic glycosaminoglycans was investigated as a predictive method of ototoxicity. The totoluidine blue (TB) method was best among several methods examined so far. Neutral red and alcian blue were employed as new dyes at this experiment, but they were not so good as TB. Furthermore, ototoxicity of the new AGs such as fortimicin, netilmicin, sisomicin, micramicin and habekacin, was predicted by the TB method. However, their predicted ototoxicities were much higher than their results obtained from experimental animals. This indicates that ototoxicity is not produced only by their basicities.

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The ototoxicity of habekacin (HBK) was compared with that of amikacin (AMK) using white rabbits with electrodes permanently implanted in the round windows. The animals were given doses of 40 or 60mg/kg/day of the drugs intramuscularly or intravenously consecutively for six days, then a one day intermission for a period of five weeks. The daily changes of cochlear microphonics at intensities of 80, 90 and 100 dB at frequencies of 2, 8 and 15KHz were measured, and on the 12th day after the last injection all animals were prepared for histopathological studies of the inner ears. The electrophysiological and histopathological findings showed that the ototoxicity of HBK was much less than that of AMK.

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Poly-L-lysine, a polycationic hydrophilic molecule, showed a large expansion of polyphosphoinositide monolayer and produced a significant loss of cochlear microphonics when perilymphatic space of the guinea pig cochlea was perfused. In contrast, L-lysine, a monomer of poly-L-lysine, had only a little effect on polyphosphoinositide monolayer and no effect on cochlear microphonics even at the concentration of 10 mM.
These data support well our hypothesis that polyphosphoinositides might be receptors of aminoglycoside antibiotics. Moreover, expansions of polyphosphoinositide monomolecular films by aminoglycosides are correlated well with their ototoxicities in perilymphatic perfusions of guinea pig cochleas.

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Electrophysiologic and histopathologic changes in the cochlea following administration of cisplatin were studied in guinea pigs. Hearing function was tested by ABR and morphological studies were conducted by scanning electron microscope. The susceptibility to cochlea by cisplatin was dose-dependent. A recovery was observed in ABR in some animals which were given 9mg/kg cisplatin intramuscularly. The outer hair cells were mainly damaged in the basal and second turns. The first and the second rows of them tended to be more severely damaged. The inner hair cells were rarely damaged. There was a close correlation between loss of cochlear hair cells and suppression of ABR. However, mild cochlear damage was observed in some guinea pigs, which represented no hearing impairment.

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The protective effect of fosfomycin against cisplatin-induced ototoxicity was studied in rats. Rats were injected intravenously with daily doses of 1, 2, 5 and 10mg/kg of cisplatin with or without 300mg/kg of fosfomycin for a period varing from 1 to 10 days. The outer hair cell loss was most pronounced in the basal turn, and this loss spread from the basal turn towards the upper turns. The outer hair cell loss was apparently reduced histopathologically in animals receiving both cisplatin and fosfomycin more than in animals receiving cisplatin alone. Nephrotoxicity and cisplatin level in serum were also reduced in animals receiving both cisplatin and fosfomycin. Therefore, the mechanism of reduction in ototoxicity may be considered that the transferability of cisplatin into the inner ear is decreased, and finally ototoxicity is reduced.

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Nitrogen Mustard-N-Oxide was injected into the cardiac cavity of guinea pigs to produce experimental damage of inner ear. The influences of steroid treatment were observed with scanning electron microscopy. In previous study, the outer hair damage was so severe with the administration of Nitromin 10mg/kg, that the influences of steroid treatment were not observed clealy. However, when the dose of Nitromin was reduced to 5mg/kg to observe the influences of steroid, the following interesting findings were obtained;
In the simultaneous administration of Nitromin and steroid comparing to the single administration of Nitromin, the degree of outer hair damage was more severely and the extent of damage was more broadly than that of the latter.

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It became evident in our previous studies that glycerol and isosorbide, both hyperosmotic agents, potentiate the EP-decrease caused by furosemide because of their osmotic opening actions at the blood-cochlea barrier. Dextran which has a high colloidal osmotic pressure is considered to exert an effect on water migration across the blood vessel walls. The present study using dextran failed to reveal any potentiation of EP-decrease caused by furosemide. Thus it could be assumed that dextran does not possess any effect on the permeability of the blood-cochlea barrier as far as furosemide is concerned.

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Since the first description of temporal bone histopathological findings of trisomy E by Edwards in 1960, 8 cases have been reported until 1983. They varied widely ranging from a normal temporal bone to severe malformations of both the middle and inner ear structures. But the most general anomalous findings among these are; aberrant course of tensor tympani muscle, anomalous structure of the ossicles, obtuse angle of facial nerve genu with ganglion cells displaced into internal acoustic canal, and decreased spiral ganglion cells.
In our present series of 2 cases, one had general anomalies described above. The second case had, in addition to general anomalies, markedly underdeveloped osseous labyrinth which caused distortion of membranous labyrinth and spiral lamina. Furthermore some part of membranous labyrinth are collapsed because of high pressure of perilymph caused by intracranial hydrops.

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Temporal bone histopathology was presented in an five-month-old infant with 6p partial monosomy who demonstrated atresia auris congenita dextra with microtia. The right external auditory canal was completely occluded by a bony atresia plate. The temporal bone showed multiple anomalies of the middle ear, including hypoplastic epitympanum, absence of malleus and incus, columellar shaped stapes with footplate fixation posteriorly and abnormal courses of the branched facial nerve and the trigeminal nerve associated with ectopic ganglions. In addition, there was a wide communication between the saccular and utricular spaces. The vestibular aqueduct and the endolymphatic duct and sac ended blindly in the otic capsule without reaching the posterior cranial fossa. The bony and membranous cochlea appeared normal.

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A 57-year-old female experienced bilateral profound deafness 1 year prior to death during the clinical course of relapsing polychondritis. The left ear was examined by scanning electron microscope (SEM), and the right ear by light microscope after processing by the conventional celloidin method. Both inner ears showed changes similar to so-called endolabylinthitis. Comparison of findings gained by these two different morphological methods gives a better understanding than either method alone. For example, SEM examination showed that repair of the membranous cochlea was done by proliferating cells from Reissners' membrane.

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Primary malignant ear tumor is rather rare entity. Because of the rarity, it is often misdiagnosed as chronic otitis media and misses the beneficial timimg of surgery. Six relevant cases have been treated at our clinic during the last 5 years.
Temporal bones were obtained at autopsies from the two cases of primary squamous cell carcinoma and were studied histopathologically with regard to surgical procedures.
A case, of which polytomographies of the temporal bone had suggested invasion and destruction by the tumor at the posteroinferior wall of the ear canal and adjacent mastoid air cells, was proved retrospectively to be as a candidate for the piecemeal resection of Campbell. Histopathologic findings on the further extensively invaded case showed that en bloc partial resection of the temporal bone by Lewis and Page seems to be rather a gambling operation for the invasion into the pyramidal apex and the coexisting infection.

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After the closure of the round window membrane of guinea pig by various adhesive agents, the inner ear function were observed by cochlear microphonics (CM) and action pctential (AP). At the same time, the perilymphatic oxygen tension in scala tympani were measured by polarographic methods.
CM and AP were significantly dropped after three weeks of closure and the perilymphatic oxygen tension of closed side dropped about 50% compared with non-closed side.
In addition to these chronic experiment, dynamic changes of the perilymphatic oxygen tension were measured after flowing air, pure oxygen and nitrogen.
As a result, the perilymphatic oxygen tension significantly increased after flowing pure oxygen, but decreased after flowing nitrogen.
We assumed that these results were caused by some disturbance of oxygen transport from the middle ear cavity to perilymphatic space through the round window membrane.

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Dynamic changes in the oxygen tension in scala tympani was measured through a small hole drilled in the bony wall of the basal turn cochlea using the poralographic technique. The oxygen consumption of the inner ear was calculated by the following equation. V (dC/dt) =q₁+q₂-q₃, where V represents the volume of the tympanic perilymph, dC/dt the time differentiation of the oxygen tension, q₁ the oxygen supply through the round window membrane, q₂ the oxygen supply through theinner ear vessels, and q₃ the oxygen consumption of the inner ear tissue. The results to be drawn from the study are ; 1) The oxygen consumption rate is 1.73×10_-1mL/100g/min. 2) Autoregulation of the inner ear vessels is present. 3) Oxygen supply to the tympanic perilymph through the round window membrane is approximately 14% in the room air and can be elevated as high as 79% in pure oxygen compared with that of the inner ear vessels.

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