Recent advances in otitis media. Complications and sequelae.
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Biomedical subjects
Publications and source records attributed to T Morizono.
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The relationship between ABR on the one hand and acid-base balance, EEG findings and prognosis on the other was studied in 47 cases of DOA. As for the acid-base balance, the balance tipped to acidosis in almost all cases. The ABR showed wave I to wave V in 25 cases, wave I to wave III in 2 cases and only wave I or no response in 20 cases on the admission day. The EEG was isoelectric in 27 out of 35 cases. All the patients who showed some activity in EEG had ABR which showed waves I through V. However, 11 of the 27 patients who were isoelectric EEG showed wave I through V potentials in ABR. By the relationship between EEG and ABR, the cases could be classified into 4 types, namely, 1) there are EEG activities with ABR showing up to wave V and the other types EEG are isoelectric with ABR findings that 2) wave V appears, 3) wave V disappears to leave wave I-III and 4) only I wave or becomes no response. The acid-base balance of the cases was inclined to acidosis; therefore, the effect of acidosis on ABR, EEG and disturbance of the brain tissue due to anoxic state wave suspected. Prognosis of DOA cases was poor and 87.2% died. All the patients who exhibited no response in ABR and isoelectric EEG at anytime of their course, died eventually. These findings suggest that combination of EEG and ABR enables one to learn more exactly the central function in those with disturbance of consciousness.
The time courses of the endocochlear potential (EP) and the K+ concentrations in the inner ear fluid under permanent anoxia were observed in the chinchilla and guinea pig using K+-selective microelectrodes. The EP following 30 min of anoxia in the chinchilla (-10.9 +/- 2.2 mV) showed a significantly less negative value than that of the guinea pig (-25.7 +/- 2.6 mV). The K+ concentration in endolymph induced by anoxia decreased less in the chinchilla than in the guinea pig. The average K+ conductance of the cochlear partition 10-30 min after anoxia in the guinea pig (0.1703 +/- 0.0792 S) was approximately 7.9 times that of the chinchilla (0.0216 +/- 0.0042 S), which is thought to be responsible for the difference of the anoxic EP between the two species.
The effects of endotoxin, exotoxin, and otitis media on the permeability of the round window membrane (RWM) in chinchillas was investigated by detecting tetraethylammonium chloride, applied to the RWM, using a potassium-selective microelectrode in the scala tympani. The RWM, 48 hours following the application of endotoxin or exotoxin, became significantly more permeable to tetraethylammonium chloride than the normal RWM. Two weeks after the obstruction of the eustachian tube, the permeability of the RWM was decreased. These results suggest that bacterial toxins and the consequential migration of chemical inflammatory mediators act as promotive factors of RWM permeability, and that a pathologic thickness of the RWM and the presence of effusion induced by the obstruction of the eustachian tube acts as an inhibitory factor. In the clinical role of RWM permeability in human otitis media, these two factors must be taken into consideration.
The free Mg++ concentration in endolymph was measured with Mg++-selective microelectrodes based on the neutral ligand ETH 1117. The property of Mg++ microelectrodes was obtained from calibration solutions, containing various Mg++ concentrations with the background electrolytes resembling endolymph. The range between 10 and 0.1 mM Mg++ concentrations changed the potentials of Mg++ microelectrodes by 14.4 +/- 3.0 mV. The endocochlear potential and the Mg++ concentration in the endolymph were 82.0 +/- 5.0 mV and 0.77 +/- 0.29 mM in the guinea pig, and 84.4 +/- 4.9 mV and 1.12 +/- 0.24 mM in the chinchilla, respectively. These results are discussed in the light of the dependence of Na+, K+-ATPase and its interaction with Ca++.
The Ca2+ transport mechanism between endolymph and perilymph was evaluated by the effects of vanadate and amiloride on the endocochlear potential (EP) and the Ca2+ concentration in endolymph using Ca2+-selective microelectrodes. Under normal conditions, the EP was 81.8 +/- 0.9 mV, and the Ca2+ concentrations in endolymph and perilymph were 16.6 +/- 1.3 microM and 1.85 +/- 0.11 mM (N = 12), respectively. Therefore, the uphill electrochemical potential gradient for Ca2+ from perilymph to endolymph, 20.2 +/- 2.0 mV, indicates the existence of an active uptake of Ca2+ into endolymph. Vanadate, the inhibitor of Ca2+-ATPase, topically applied to the round window membrane caused biphasic changes of the EP and the endolymph Ca2+ concentration; the former in a transient increase followed by a consistent decrease and the latter in a slow decrease followed by a slow increase. Amiloride induced a slight EP depression and a concomitantly slight elevation of the Ca2+ concentration in endolymph. The electrochemical potential gradient for Ca2+ between endolymph and perilymph vanished with the use of vanadate but was not affected by amiloride. These results suggest that Ca2+-ATPase, sensitive to vanadate, maintained the bulk of active Ca2+ transport in the cochlea and that the participation of Na+-Ca2+ exchange is negligible.
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The mammalian inner ear is located deep within the temporal bone. The organ of Corti, the delicate sensory system for sound, is surrounded by two fluid systems; the potassium-rich endolymph and the sodium-rich perilymph. The pathogenesis of inner ear deafness is thought to be largely due to an imbalance of potassium and sodium ions in the inner ear fluids. Dynamic changes in K+ in the endolymph and perilymph were studied in the guinea-pig following cetrimide (cetrimonium bromide, a powerful cationic detergent which shows ototoxicity) applications on the round window membrane, intramuscular injection of potassium bromate (bread whitener, known to cause renal damage and permanent deafness in animals and man). Maximum fall in K+ concentration in the endolymoh (mM/min) and maximum K+ conductance (mM/min/mV) were 3.54 +/- 1.65 and 0.036 +/- 0.02 in cetrimide, and 1.85 +/- 0.35 and 0.021 +/- 0.009 in potassium bromate, respectively. In view of these findings, the influence of the active transport mechanism to K+ concentrations are discussed in comparison with dynamic changes in endolymph K+ induced by asphyxia and ethacrynic acid.
The primary histologic correlate of Menière's disease is endolymphatic hydrops. From this, many investigators have postulated the existence of endolymphatic hypertension, although there have been no measurements published to substantiate this concept. Seventy guinea pigs, surgically treated with right endolymphatic duct obstruction, were later assessed by use of a micro-electrode technique that measured their endolabyrinthine hydrostatic pressures. For 21 of these animals, the pressures of both scala tympani (Pst) and scala media (Psm) of both ears of each animal were successfully measured. Similar measurements were made in a control group of 25 guinea pigs that had not undergone any previous surgery. For normal ears--as well as those with hydrops-pressure differences between perilymph and endolymph (Psm - Pst) varied around 0 +/- 2.0 mm Hg. When only the right (obstructed) ears were considered, there appeared to be a slight, relative pressure elevation (p less than 0.05) in scala media during the first 7 days after endolymphatic duct obstruction-and in those ears with EP, less than 70 mV. The magnitude of this pressure difference that can be attributed to the state of endolymphatic hydrops-and not to natural variability-is calculated (within 95% confidence limits) to be less than 0.5 mm Hg.
Sensorineural hearing loss (SNHL) has been described clinically following chronic otitis media with effusion, but to the best of our knowledge, no studies have demonstrated SNHL in an animal model of otitis media. Using the chinchilla model of pneumococcal otitis media, significant SNHL was demonstrated after purulent otitis media, especially at higher frequencies. Animals with otitis media received penicillin G procaine treatment for five days after otitis media with effusion (OME) was first documented; resolution of middle ear infection was confirmed by middle ear effusion culture in all animals. Both the inoculated and uninoculated ears were examined by tone burst-elicited compound action potential at threshold. The inoculated ear showed a marked hearing loss of 13 to 36 dB three to four days after OME was first documented; a hearing loss up to 24 dB persisted two to five weeks after inoculation. The change in the compound action potential was highly significant at all frequencies studied. Conductive losses were largely ruled out because there was no middle ear effusion at death and the tympanogram was normal. Purulent labyrinthitis was ruled out by histopathological study. These results indicate that purulent pneumococcal otitis media in the chinchilla model causes significant SNHL and suggest that the pathogenesis of SNHL associated with chronic OME in humans may be studied in this model.
The use of glycerol continues to be a popular clinical test for diagnosing reversible hearing loss in patients with Meniere's disease, although its mechanism of action remains obscure. The purpose of this investigation was to study experimentally the alterations in the ionic composition and function of the cochlea which occur following glycerol administration. Immediate decreases in inner ear pressure and increases in AP threshold were seen. Delayed decreases in the endocochlear potential with increases in inner ear electrolytes occurred. However, we were unable to find any substantial changes in inner ear oxygen concentrations. Our findings support the concept that the principal action of glycerol is in osmotic reduction of inner ear pressure.
The purpose of this study was to determine the effects of an intravenous injection of a hyperosmotic agent (mannitol) on the volume density (Vv) of the primary components of the stria vascularis (SV). Chinchillas received either a 2.0 g/kg injection of mannitol or an equal volume of saline as a control. At 1, 10 and 60 min after the injection, the right cochleas were fixed with osmium tetroxide and prepared for transmission electron microscopy. At a distance of 70% from the cochlear apex, the complete radial area of the SV was photographed and stereologically analyzed. Additional animals received mannitol or bumetanide for the purpose of measuring serum osmolality and the endocochlear potential (EP). The present results showed elevation of serum osmolality after mannitol but not after bumetanide and depression of the +EP after bumetanide but not after mannitol. Vv alterations of SV components after mannitol were similar to those Vv changes observed in a previous study, after bumetanide. After treatment with either diuretic, the Vv of the marginal cells decreased and the Vv of the intermediate cells and intercellular spaces increased. We conclude that since the Vv alterations of the SV components are so similar after both diuretics, none of these alterations is a morphological correlate of a depressed +EP which was observed after bumetanide. A model of the action of mannitol on the SV is proposed.
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Previous investigation has suggested that the ototoxicity of furosemide is related to penetration of the drug into the inner ear and that active drug transport out of the inner ear may be responsible for maintaining the serum-perilymph drug concentration gradient. We further tested this hypothesis by investigating the endocochlear potential (ototoxicity) and furosemide perilymph concentrations after furosemide administration to chinchillas pretreated with the organic anion transport inhibitor, probenecid. Probenecid pretreatment attenuated the fall in endocochlear potential seen after furosemide (25 mg/kg i.v.): untreated, 58.6 +/- 27.0 mV; probenecid pretreatment, 14.1 +/- 11.9 mV (P less than .01). Furosemide concentrations in perilymph were correspondingly lower after probenecid (P less than .003), although serum furosemide concentrations were not affected by probenecid pretreatment. Diuresis, measured over an 8-hr period after furosemide, was also uneffected by probenecid. These results confirm the proposed relationship between inner ear furosemide concentrations and the occurrence of ototoxicity due to this drug. However, the determinants of penetration of this drug into the inner ear are unclear. The observation that probenecid pretreatment attenuates the ototoxic effect of furosemide while the diuretic effect is preserved suggests this drug combination warrants further investigation.
The ototoxic effect of povidone-iodine antiseptics topically applied to the chinchilla round window was examined with particular emphasis on the action potential (AP) input-output function at 2 and 4 kHz. A group of chinchillas exhibited a marked elevation of AP threshold at 8 and 12 kHz, with only a slight threshold elevation at 2 and 4 kHz. A distinct decruitment (less than normal growth of response with increasing sound intensity) of the AP input-output function was, however, found at the lower frequencies. There are implications of an ototoxically induced high-frequency hearing loss on speech frequencies.
The latency of the N1 component of tone burst evoked compound action potentials was examined in chinchilla following acute pure-tone trauma. At and below the trauma frequency (4 kHz) the N1 latency at threshold generally increased, while above the trauma frequency it decreased; tonotopically paralleling pitch shifts observed in humans following pure-tone trauma. When N1 latency at threshold is considered across animals as a linear function of dB SPL at threshold, after trauma a high degree of linear correlation was found at 6 and 8 kHz, while a low degree of linear correlation was found at 4 kHz. An interpretation and the significance of the data are discussed.
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Otic drops have been proposed as a form of prophylaxis against the otitis media which follows middle ear contamination by water in patients with tympanostomy tubes. The potential adverse effects of this form of therapy were studied in chinchillas with tympanostomy tubes; 31 chinchillas underwent bilateral tympanostomy tube insertion. Seven animals had a mixture of green dye and Cortisporin otic suspension placed in both external auditory canals 24 hours following the placement of tympanostomy tubes and were sacrificed 30 minutes later for gross examination; 3 of these animals had previous eustachian tube obstruction with Silastic sponge. Twenty-one animals had Cortisporin otic suspension placed in the right external auditory canal on postoperative days 3, 4, 5, 6 and 7. No otic drops were placed in the left ear. Ten of these 20 animals had VIIIth nerve action potentials measured on postoperative day 17 and the other 11 animals had VIIIth nerve action potentials measured on postoperative day 42 followed by immediate sacrifice for histological examination and scanning electronmicroscopy. The remaining 3 animals had VIIIth nerve action potentials measured 21 days following tympanostomy tube insertion and served as electrophysiological controls. The 8 ears receiving Cortisporin otic drops mixed with green dye from animals with normal eustachian tubes showed staining of the round window membrane at sacrifice, while the 6 ears receiving Cortisporin otic suspension and green dye from animals with eustachian tube obstruction demonstrated no dye in the middle ear. All animals receiving Cortisporin otic drops in the right ear showed an intra-aural difference in action potentials with the right ear being attenuated by an average of 10.3 dB at 2,000 Hz, 12 dB at 4,000 Hz, 21 dB and 8,000 Hz, and 26 dB at 12,000 Hz. Morphological study revealed hair cell loss in the hook portion of the cochlea in those animals receiving Cortisporin otic drops. It was concluded from this study that, in patients with patent tympanostomy tubes in place, potentially ototoxic topical agents should be used with caution.