Kyoshiro Yamakawa, MD, and temporal bone histopathology of Meniere's patient reported in 1938. Commemoration of the centennial of his birth.
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Biomedical subjects
Publications and source records attributed to T Morizono.
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Three-component analysis of caloric nystagmus, focusing on the horizontal, vertical, and torsional, using a computerized eye movement analysis system, was carried out in 10 normal human subjects. The caloric response was induced by cold stimulation to the right ear of the subjects in the supine and prone positions. In the supine position, the three components of nystagmus were toward the left (10 subjects), upward (eight subjects) or downward (two subjects), and clockwise (10 subjects). In the prone position, on the other hand, the three components were directed toward the right (10 subjects), downward (five subjects), upward (three subjects), and counterclockwise (10 subjects); there was no vertical direction in two subjects. These findings indicate that caloric stimulation activates the three semicircular canals simultaneously. Also the changes in the nystagmus direction in the supine and prone positions could be explained, at least partially, by the nonconvective component of caloric stimulation.
We have tested the hypothesis that the cause of cochlear dysfunction associated with perilymphatic fistula (PLF) is closely related to endolymphatic hydrops (ELH). Using guinea pigs, we studied the tone-burst elicited compound action potential (CAP) and its modulation as caused by a 50 Hz biasing tone in experimental PLF. We compared these results with those of experimental ELH. Following perilymph aspiration through the perforated round window membrane, mild but significant elevations of CAP thresholds at tested frequencies were found. A reduction in the amplitude of cochlear microphonics (CM) for a 50 Hz sine wave appeared to correlate with these CAP threshold changes. However, there were no significant changes in the modulation effect of the 50 Hz biasing tone on the CAP elicited by an 8 kHz tone burst. This finding differed from that in ears with experimental ELH, in which significant reductions of both 50 Hz CM and the degree of CAP modulation were consistently observed. We concluded that it is unlikely that the underlying mechanisms of a modification to the low frequency response of the base of the cochlea following perilymph aspiration is linked to that of experimental ELH.
By the use of computer-assisted morphometric analysis of the organ of Corti and/or measurements of action potential threshold changes, inner ear changes in chinchillas were evaluated 4 weeks after application on the round window membrane of a Pseudomonas aeruginosa exotoxin A solution. Severe inner ear damage was detected after application of 50 ng (5 microL at a concentration of 10 micrograms/mL) exotoxin A, whereas application of 5 ng exotoxin did not cause measurable inner ear damage. Perilymph concentrations of exotoxin A were measured with an enzyme-linked immunosorbent assay 1.5 to 19 hours after 50 ng, 0.5 micrograms, or 5 micrograms of exotoxin A was applied on the round window membrane. Only the highest concentration produced measurable levels of exotoxin in the inner ear fluids. It is concluded that exotoxin A present on the round window membrane of the chinchilla has the ability to penetrate into the inner ear and cause irreversible inner ear changes.
Pseudomonas aeruginosa exotoxin A was applied to the round window membrane of the chinchilla in concentrations ranging from 1 microgram/ml to 1 mg/ml. Haemophilus influenzae type b endotoxin (45,000 endotoxin units/ml) was applied in the same way. Five animals were also subjected to blocking of the Eustachian tube, 3 to 8 months earlier, resulting in serous otitis media and exotoxin A (1 mg/ml) was applied into the round window niche of these animals. Effects on the inner ear was recorded with quantitative morphology (hair cell counting) and electrophysiologically (action potential threshold measurements) 4 weeks after application of exotoxin A. Concentrations of exotoxin A in perilymph was measured with ELISA and concentration of endotoxin in perilymph was measured with Limulus Amoebocyte Lysate and Quantitative Chromogenic Limulus Amebocyte Lysate. Four weeks after application of exotoxin A at a concentration of 10 micrograms/ml severe inner ear damage could be demonstrated. No inner ear damage was demonstrated when lower concentrations were used. Passage into the inner ear could only be demonstrated after exposure of the round window membrane to an exotoxin A concentration of 1 mg/ml. Round window membranes affected by chronic inflammation were shown to be less permeable to exotoxin A, thus indicating that thickening of the round window membrane may have a protective effect on the inner ear. A low passage rate into the inner ear was demonstrated after endotoxin exposure. It may be concluded that small amounts of exotoxin A passing through the round window membrane may cause inner ear damage. The passage rates, however, for both exotoxin A and endotoxins are low.
Consecutive CAP threshold shifts were studied in chinchillas following round window application of Cortisporin Otic Suspension for 10 minutes. A marked deterioration in CAP threshold was observed at 24 hours following otic application but these threshold shifts were reversible at lower frequencies. The shifts were progressive at higher frequencies at the 4 week measurement. The progressive high frequency loss with recruitment and with normal EP levels implies some hair cell dysfunction due directly to Cortisporin Otic Suspension ototoxicity and/or secondarily to middle ear inflammatory reactions to the otic. Short-term studies of ototopical drugs may result in misleading assessments as to the pattern and degree of ototoxicity. Long-term (i.e., one month or longer) studies are recommended for accurate ototoxicity assessment.
Ionic activities (K+, Na+, and Cl-) of the perilymph and endolymph of the basal turn were measured using ion-selective microelectrodes in experimentally induced endolymphatic hydrops of the guinea pig. Three months following the obstruction of the endolymphatic duct and sac, the endocochlear potential (EP) of hydroptic ears was measured at 59.7 +/- 9.6 mV (N = 12) which was significantly lower than the EP of the contralateral control ears (84.4 +/- 2.8 mV, N = 12). A paired t-test (P greater than 0.05) showed no significant differences of ion concentrations of the inner ear fluid between the hydroptic and contralateral ears. Ion permeabilities of the cochlear duct following anoxia were calculated according to the Nernst-Planck equation. Comparing hydroptic and normal ears following anoxia, a statistically significant decrease was observed in the permeability coefficients for K+. Similarly, K+ conductance was significantly lower in the hydroptic ears than in the normal ears. Total conductance of the cochlear duct, defined as the sum of each ion conductance, was 0.560 siemens in the normal ears and 0.217 siemens in the hydroptic ears. On the basis of the Goldman-Hodgkin-Katz equation, preexisting negative EP in the normal state was calculated to be -24.5 mV in normal ears and -21.4 mV in hydroptic ears. Therefore, the positive component of the EP was 108.9 mV in normal ears and 81.1 mV in hydroptic ears. These findings suggest that the pathophysiology of hydrops involves changes in K+ permeability and the inhibition of the electrogenic transport processes.
The ionic composition of the endolymph in the endolymphatic sac (ES) of the chinchilla was measured using double-barreled ion-selective micro-electrodes. The DC potential of the ES was 9.3 +/- 1.8 mV (N = 18). The K+, Na+, and Cl- concentrations of the ES were 13.3 +/- 4.7 mM (N = 6), 129.0 +/- 8.8 mM (N = 6), and 124.3 +/- 16.6 mM (N = 6), respectively. In light of the chemical potentials of the cochlear endolymph previously reported [Ikeda and Morizono (1989), Hear. Res., 39, 279-286] the pressure gradient of the endolymph between the cochlea and ES was calculated to be 71.5 mmHg at 38 degrees C. The contribution of the osmotic and hydrostatic pressure gradients of the endolymph to the longitudinal flow is discussed.
The effects of topical otic preparations (Cortisporin, Coly-Mycin, Aristocort, and Bestron) upon the permeability of the round window membrane (RWM) in chinchillas were investigated. Using K(+)-selective microelectrodes, the concentration of tetraethylammonium (TEA) ions was measured. Changes in the thickness of the RWM were measured using light microscopy. The RWM permeability was reduced significantly in Cortisporin- and Coly-Mycin-treated ears. Moreover, these two drugs resulted in a marked thickening of the RWM. In contrast, Aristocort or Bestron resulted in no alteration of the RWM permeability.
Maintenance of homeostasis of inner ear fluids and biochemical integrity of inner ear tissue are essential for proper functioning of the auditory and vestibular end organs. Although various regulatory mechanisms exist in a different portion of the labyrinth, the inner ear is known to respond to systemic challenges. The association of Meniere's syndrome with an imbalance of inner ear fluid homeostasis has been hypothesized for the past century. Among many factors, the effects of hormonal imbalance on inner ear fluid composition and inner ear function have however scarcely been studied. The purpose of this study was to explore the relationship between the autonomic nervous system and inner ear function and possible mechanisms of functional disturbances in an experimental condition. An infusion of supraphysiologic amounts of epinephrine, a stress related hormone, resulted in an elevation of osmolality in serum and perilymph. Furthermore, the infusion of epinephrine resulted in elevation of threshold, prolongation of latency, and depression of amplitude in the compound action potential of the auditory nerve. These findings were most marked at high frequencies. We hypothesized that the epinephrine-induced hearing loss was brought about by an increase in perilymphatic osmolality, as well as by the ionic imbalance caused by the osmotic gradient. Since emotional stress has been implicated as a mechanism of inducing a Meniere's attack, evaluation of the relationship between the autonomic system and cochlear function may contribute to the understanding of possible mechanisms of inner ear dysfunction caused by hormonal imbalances.
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To investigate the influence of the cervical input to the equilibrium, the effect of neck vibratory stimulation on body sway was analyzed in 49 normal human subjects. Body perturbations during standing posture were recorded by a force platform with or without vibratory stimulus on the upper cervical region, and analyzed by computer. During the neck vibratory stimulation, the center of gravity was shifted to the forward, and the amplitude of the body sway was increased especially along the front-rear axis. These results indicate that the proprioceptive inputs from the cervical receptors largely modifies the body equilibrium in normal subjects.
Bestron, a new otic preparation containing cefmenoxime, was applied to the round window membrane of the chinchilla and the long-term cochleotoxicity was evaluated by means of electrocochleography. The thresholds of the compound action potential (CAP) in all frequency areas tested ranged within normal values. The input-output and -latency relationships of the CAP resulted in no significant deterioration of hearing. However, identical treatment with Cortisporin resulted in elevated CAP threshold in the high frequency area and deterioration of the input-output and -latency of the CAP. These findings indicate that Bestron is noncochleotoxic as compared with Cortisporin and therefore may be used safely in the treatment of infected ears.
Sensorineural hearing loss (SNHL) has been documented in patients with otitis media. Despite a number of clinical and pathologic works dealing with this common problem, animal studies searching for possible relationships between the middle ear inflammation and cochlear function remain insufficient. Bacterial inoculation and ototoxins and inflammatory products in the middle ear cavity cause SNHL in rodents. Human serum albumin placed in the middle ear cavity in chinchillas also produces SNHL, owing to the effects of nonspecific inflammation in the middle ear cavity. Most of the middle ear inflammatory mediators enter the inner ear through the round window route, and alteration of the permeability of the round window membrane plays an important role in causing cochlear dysfunction. Although an immunologic response in the middle ear plays an important role in otitis media, the immunologic response in the inner ear as it relates to middle ear inflammatory mediators requires further study.
The effect of pneumococcal otitis media on the permeability of the round window membrane was evaluated using tetraethylammonium ions as a tracer. Round window membrane permeability is reduced significantly at resolved stages of purulent otitis media. In contrast, measurements of round window membrane permeability indicate that acute purulent otitis media has a tendency to facilitate such permeability. Moreover, histologic observations of the round window membrane following bacterial inoculation further support the evidence of functional changes in round window membrane permeability. These findings indicate that the round window membrane in resolved stages of purulent otitis media plays a protective role in preventing the penetration of harmful substances into the inner ear.
A new technique for an eye movement analysis system utilizing infrared video recording and a computerized image recognition method is presented. The system consists of an infrared lighting apparatus, a very small infrared video charge-coupled device camera, a video tape recorder, an analogue-digital converter, and microcomputers. This system makes it possible to simultaneously analyze the slow-phase velocity quantitatively not only of the horizontal and vertical but also of the rotatory components of the energy-induced nystagmus. The maximum slow-phase velocity of the rotatory component of energy-induced nystagmus was found to be 4.1 degrees per second on an average in this study.
The compound action potential (CAP) of the eighth nerve and the endocochlear potential (EP) were examined in the chinchilla as an animal model when Escherichia coli endotoxin (100 micrograms) was applied to the middle ear cavity. A significant elevation of the CAP threshold at 2, 3, and 4 kHz was observed 48 h after the instillation of endotoxin, but this hearing loss was thought to be caused by a conductive component. No significant change in the CAP threshold was recognized 30 days after instillation. The EP in either period showed no significant difference. These findings indicate that the application of endotoxin at the concentration used in the present study does not cause a cochlear disturbance.
The dc potential and ion composition (K+, Na+, and Ca++) in the hair cells of the cochlea were examined using ion-selective microelectrodes. The K+, Na+, and Ca++ concentrations were 124.0 +/- 29.8 mM, 6.9 +/- 4.1 mM, and 1.7 +/- 1.4 microM in the hair cells, respectively. The electrochemical potential gradients for K+, Na+, and Ca++ across the apical membranes of the hair cells were calculated to be 160.0 +/- 29.8 mV, 87.6 +/- 27.0 mV, and 194.4 +/- 35.2 mV, respectively. Those for K+, Na+, and Ca++ across the basolateral membranes of the hair cells were -12.6 +/- 33.3 mV, 126.8 +/- 28.3 mV, and 170.8 +/- 30.1 mV, respectively. These findings were discussed in light of the transport mechanism necessary to maintain the ionic composition of hair cells.