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Bacterial cytolysin perturbs round window membrane permeability barrier in vivo: possible cause of sensorineural hearing loss in acute otitis media.

The passage of radioiodinated streptolysin-O (SLO) and albumin through the round window membrane (RWM) was studied in vivo. When applied to the middle ear, SLO became quantitatively entrapped in this compartment and no passage to the cochlea occurred. However, flux of radioiodinated albumin through the toxin-damaged RWM was observed. We propose that the passage of noxious macromolecules, such as proteases, from a purulent middle-ear effusion may be facilitated by pore-forming toxins, resulting in cochlear damage and sensorineural hearing loss.

Albumins↗

[Chronic mucous effusions of the middle ear and the influence on inner ear function (author's transl)].

Audiometric recordings of children suffering from chronic mucous effusion of the middle ear have revealed a statistically significant and permanent sensorineural hearing loss of high frequences. Attemps for mechanical or physical factors as explanation are not convincing. We believe that inner ear disturbances in chronic mucous effusion rise by direct intoxication of the basal turns of the cochlea caused by pathologic alterations of mucous membrane tissue. Certain substances like lysozymes or histamine are supposed to diffuse via round window membrane to the inner ear. On the other hand mucous effusion which fills the middle cavity prevents oxygen to diffuse from the middle ear to the inner ear. Maass et al. (1976) and Morgenstern (1977) clearly have shown that under physiological conditions oxygen tension in the perilymph of the basal cochlear turn partly depends on diffusion from the middle ear. The results of our clinical observations indicate that early diagnosis and prompt treatment is necessary to prevent permanent sensorineural hearing loss of high frequencies, especially in infants and children.

Audiometry↗

The normal chinchilla round window membrane.

The chinchilla round window membrane consists of three layers: (1) an outer epithelial layer facing the middle ear cavity with tight junctions and numerous desmosomes, (2) a middle connective-tissue layer consisting of fibroblasts, fibrocytes, collagen, elastin, capillaries, and myelinated and unmyelinated nerves, and (3) an inner cellular layer with thin cytoplasmic processes containing numerous micropinocytotic vesicles and dark granules similar in form to alpha-type glycogen. Studies of the fine structure of the normal round window membrane in animals are prerequisites to understanding the role of the round window membrane in both normal function and in diseased states such as otitis media.

Animals↗

Comparative ototoxicity of furosemide and piretanide.

The purpose of these studies was to compare the ototoxicity of piretanide to that of furosemide in the chinchilla. Chinchillas weighing 400 to 700 g were anesthetized with ketamine plus pentobarbital. Endocochlear potential (EP) was measured continuously by the round window approach using glass microelectrodes. Piretanide or furosemide injected through a jugular vein catheter in adults range from 10-100 mg/kg. Little or no change in EP was noted with doses below 15 mg/kg of either diuretic. The overall pattern of decline of EP was rather similar in piretanide-treated and furosemide-injected animals, and it was interesting to find that the dose-ototoxicity response curve for piretanide was similar to that for furosemide. The diuretic effect of equal ototoxic doses of either diuretic was equivalent. Both diuretics cause a decrease of endocochlear potential when applied locally to the round window membrane of the chinchilla as well as by systemic administration. These findings suggest that piretanide and furosemide have approximately the same propensity for ototoxicity.

Administration, Topical↗

Recurrent meningitis due to round-window fistula in Klippel-Feil syndrome. A case report.

Hearing is impaired in 30% of patients with Klippel-Feil syndrome, owing to a variety of anatomical deformities of the inner and middle ear cavities. Recurrent meningitis due to a stapedial footplate fistula associated with this syndrome is rare. A case of Klippel-Feil syndrome, deafness and recurrent meningitis due to a round-window fistula is described. Surgical sealing of the defect prevented further meningeal infections.

Cochlea↗

Intratympanic ciprofloxacin and the human labyrinthine sampling model.

OBJECTIVE: The aim of the study was to investigate the potential absorption of intratympanic ciprofloxacin through the human round window membrane. STUDY DESIGN: A prospective study. METHODS: Ciprofloxacin was instilled into the middle ear of 10 patients undergoing acoustic tumor removal. The lateral semicircular canal and vestibule were subsequently opened and, using a microsyringe, labyrinthine fluid was aspirated. A sample each of serum and cerebrospinal fluid was also drawn. RESULTS: Into each middle ear, 0.5 mL ciprofloxacin (0.3%) was instilled. The time interval between the ciprofloxacin application to the round window membrane and sampling of labyrinthine fluid and plasma ranged from 9 to 120 minutes. There was no measurable ciprofloxacin in the labyrinthine fluid, cerebrospinal fluid, or serum of 10 patients. CONCLUSION: The lack of measurable absorption of intratympanic ciprofloxacin into the inner ear indicates that the chance of ototoxicity when ciprofloxacin is used clinically, even in the presence of a tympanic membrane perforation, is low.

Aged↗

Persistent inner ear injury after diving.

OBJECTIVE: The purpose of this multiple case report was to discuss the occurrence and cause of sudden sensorineural hearing loss after diving. STUDY DESIGN: The study design was a retrospective case review. SETTING: The study was conducted at an academic tertiary referral center. PATIENTS: In this multiple case report, two teenagers with unilateral sudden sensorineural hearing loss after diving, one from a starting block and one from a 1-m board, while performing school swimsports were included. INTERVENTION: The patients underwent diagnostic tympanotomy with sealing of the round and oval window membranes and a vasoactive rheologic therapy combined with corticosteroid treatment. MAIN OUTCOME MEASURES: The average pure-tone bone-conduction thresholds were calculated. The appearance of nystagmus, vertigo, and tinnitus was analyzed. RESULTS: Both patients experienced unilateral sudden deafness after performing a headfirst pike-type dive into a swimming pool. None of the patients contacted with the bottom of the pool. In one patient, a rupture of the round window was found intraoperatively. In the other patient, no rupture of the round or oval window was seen intraoperatively. In spite of sealing of the round window and application of vasoactive rheologic therapy, hearing did not improve significantly in either of the patients. CONCLUSION: Rupture of the round window may occur after diving even if the dive is performed from a low height into the water and the bottom of the pool is not contacted. Besides direct contusion to the external ear and barotrauma, other causes such as whiplash mechanism have to be considered.

Adolescent↗

[Experimental study of extracochlear electric stimulation].

The efficiency and feasibility of chronic extracochlear implantation and electric stimulation were studied in two adult cats and four 2-month kittens. The first electrode was placed on the round window by fixing the lead wire on the bridge of aditus between the middle ear and bulla cavity; the second electrode was placed on the surface of the tympanic promontory; the third was inserted into the temporal muscle out of the bulla and the forth fixed in transverse sinus with dental cement. ABRs and EABRs were recorded pre- and postoperatively and during electric stimulation. The results indicated that: (1) The chronic electric stimulation could be carried on with round window electrode; the fixation of round window electrode is satisfactory without the influence of postnatal skull growth. (2) EABRs evoked by electrically stimulating round window electrode were mainly generated by the auditory system, but its short response was partly generated by the vestibular system. (3) EABRs evoked by electric stimulation of round window electrode were contaminated by facial nerve response which could be inhibited by 2% xylocaine injection of foramen stylomastoid. (4) The EABRs evoked by stimulating tympanic promontory electrode is uncertain.

Animals↗

Rupture of the round window membrane.

Considerable interest has been displayed in sudden sensori-neural deafness in recent years, and especially since Blair Simmons postulated that this could be caused by mechanical disruption of the membranes in the inner ear. The literature concerning such reports is reviewed briefly and two cases of rupture of the round window membrane resulting from inner ear barotrauma are reported in detail. Both these cases were experienced divers who had had little difficulty in auto-inflation whilst diving. The first case had progressive sensori-neural deafness with mild vertigo, and tympanotomy revealed rupture of the round window membrane in both ears. These ruptures were repaired with plugs of fat, following which his hearing was restored. The second case developed marked vertigo following a dive and was thought to be suffering from decompression sickness. When the appropriate treatment did not help him, tympanotomy was performed and a rupture of the round membrane was found. This was plugged with fat with a most satisfactory result. Both of these cases had difficulty with autoinflation, and had been aware of such difficulties for some time. Nasal problems were responsible for this, and it is strongly recommended that all divers should have normal nasal function and that they should be educated in the technique of autoinflation, and, in particular, in the importance of avoiding forceful autoinflation at all times. A third case of rupture of the round membrane following an injury to the head is also reported.

Adult↗

Vestibular effects of chronic perilymph fistula in the cat.

Chronic, unilateral perilymph fistulae were created in cats by removal of the round window membrane and placement of a tympanostomy tube into the round window. Rotary chair, fistula, caloric, and vestibulospinal tests were performed before and after fistulization, and periodically for 2 weeks. At 2 weeks, patency of the fistula was documented by fluorescein injection into the spinal fluid and visualization of leakage into the middle ear bulla via the fistula. All the cats had a patent fistula at 2 weeks, but one of the three cats had a greater perilymph leak than the others. The cat with the more active leak had a spontaneous nystagmus toward the side of the fistula on the first postoperative day; this changed to nystagmus toward the opposite side by the third postoperative day. The other cats had a spontaneous nystagmus toward the opposite side from the first postoperative day. Most abnormal test results returned to normal in the first week after fistulization. Histologic study of the temporal bones revealed that the cat with the greater leak had a wider cochlear aqueduct than the other cats.

Animals↗

Round window membrane permeability. An in vitro model.

The round window membrane is regarded to be the main route for passage of potentially ototoxic substances from the middle ear cavity into the inner ear. This is of clinical importance in acute otitis media and chronic otitis media, where sensorineural hearing impairments sometimes develop. The accuracy and reliability of an in vitro round window membrane permeability model was studied. The round window membrane of the mongolian gerbil was resected, together with its bone niche. The preparation was mounted between two glass chambers, representing the middle ear cavity and the perilymphatic space respectively. Passage through the round window membrane did not occur within 3 h for low-density lipoprotein with a molecular weight of 2,300 kD and high-density lipoprotein with a molecular weight of 115-350 kD. Horseradish peroxidase, with a molecular weight of 40 kD, passed the round window membrane at a mean rate of 6 micrograms/h when the concentration of the protein was 10 g/l in the middle ear chamber. The present in vitro model is considered to be free of leakage artifacts between the chambers. Passage rates for different substances through the round window membrane can be calculated under controlled conditions using this type of in vitro model.

Animals↗

Estimation of perilymph concentration of agents applied to the round window membrane by microdialysis.

OBJECTIVE: The round window membrane (RWM) is known to be permeable to various biological substances. Application of biological substances to the RWM has been shown to affect inner ear fluid composition and damage hair cells, resulting in functional changes RWM instillation of gentamicin, a preferentially vestibulotoxic aminoglycoside, is used as a therapeutic treatment for patients with intractable vertigo and is gaining acceptance as a chemical vestibular ablation agent, despite considerable variations in the incidence and severity of hearing loss associated with gentamicin. Clearly, the susceptibility of vestibular and auditory hair cells to the ototoxic effects of gentamicin is not well understood. The aim of this study was to understand the kinetics of urea and methylene blue instilled into the inner ear space through the RWM and to establish a method for determining the optimal dosage for the treatment of inner ear disorders. MATERIAL AND METHODS: We used inner ear microdialysis to quantify changes in perilymph concentration of low molecular weight agents applied to the RWM in a chinchilla model. RESULTS: Preliminary results after placement of a microdialysis probe and application of a low molecular weight marker (urea) to the RWM were extrapolated from a time versus concentration plot from dialysates sampled over a 3-min interval using modifications of standard microdialysis equations for estimation of in vivo recovery. Our data suggest that inner ear microdialysis can be used to measure the pharmacokinetics of a low molecular weight agent within the perilymphatic space without the need for repeated direct sampling. CONCLUSION: Inner ear microdialysis may be a useful method for establishing a therapeutic dosage for ototoxic agents used in the treatment of inner ear disorders.

Animals↗

Acoustic-structural coupled finite element analysis for sound transmission in human ear--pressure distributions.

A three-dimensional (3D) finite element (FE) model of human ear with accurate structural geometry of the external ear canal, tympanic membrane (TM), ossicles, middle ear suspensory ligaments, and middle ear cavity has been recently reported by our group. In present study, this 3D FE model was modified to include acoustic-structural interfaces for coupled analysis from the ear canal through the TM to middle ear cavity. Pressure distributions in the canal and middle ear cavity at different frequencies were computed under input sound pressure applied at different locations in the canal. The spectral distributions of middle ear pressure at the oval window, round window, and medial site of the umbo were calculated and the results demonstrated that there was no significant difference of pressures between those locations at frequency below 3.5 kHz. Finally, the influence of TM perforation on pressure distributions in the canal and middle ear cavity was investigated for perforations in the inferior-posterior and inferior sites of the TM in the FE model and human temporal bones. The results show that variation of middle ear pressure is related to the perforation type and location, and is sensitive to frequency.

Acoustic Stimulation↗

A comparative study of intratympanic steroid and NO synthase inhibitor for treatment of cochlear lateral wall damage due to acute otitis media.

We studied the damage to the cochlear lateral wall induced by otitis media and the therapeutic effects of intratympanic administration of steroid and nitric oxide (NO) synthase inhibitor. In Sprague-Dawley rats, right middle ear cavities were inoculated with lipopolysaccharide, followed after 30 min by intratympanic administration of dexamethasone, NOS-inhibitor or PBS. Twenty-four hours after lipopolysaccharide inoculation, cochlear blood flow was measured by laser-Doppler flowmetry. Prostaglandin E(1) was topically applied to the round window membrane of the right ear and changes in cochlear blood flow were calculated. Changes of cochlear blood flow were significantly different among the three groups. Increases in cochlear blood flow following PGE(1) application were higher in the group that received NOS-inhibitor. Electron microscopic examination revealed that changes in the stria vascularis were less severe in rats treated with dexamethasone or NOS-inhibitor. Our results show the effectiveness of intratympanic dexamethasone or NOS-inhibitor in treating cochlear lateral wall damage caused by otitis media.

Amidines↗

Inner ear disturbances following inoculation of endotoxin into the middle ear.

Inner ear function was assessed by a frequency-specific (+/-100 Hz) auditory brainstem response (ABR) technique after a single instillation of a suspension of purified E. coli lipopolysaccharide in sterile water into the round window (RW) niche in rats. Instillation of endotoxin caused a transient concentration and tonotopically dependent dysfunction of the inner ear. The largest threshold impairment occurred in the high-frequency region anatomically located close to the RW. At 31.5 kHz the threshold impairment persisted throughout the study. Morphologic damage to the inner ear was not detected at the light microscopic level when using serial sections from decalcified specimens. Our study supports the clinical hypothesis that remnants of non-viable bacteria such as endotoxins, when trapped in the middle ear, can promote middle ear effusion and dysfunction of the inner ear.

Animals↗

Electrocochleographic recordings in chronic and healed perilymphatic fistula.

This study examined electrocochleographic recordings in 15 guinea pigs with perilymphatic fistulas. A chronic round window fistula was induced in each animal by insertion of a sigmoid stainless steel needle with the lumen intact. In the contralateral control ear, a similar needle was inserted with the lumen crushed. In this way the model compared acute (control group) versus chronic (experimental group) perilymphatic fisulae. Electrocochleographic recordings were obtained before, immediately after needle insertion, in a subset at two to three weeks after needle insertion, and again at 17-22 weeks when the fistulas had healed with the needles still in place. Minimal threshold changes were noted from the pre- to the acute post-condition. More marked elevation of threshold was noted for the 17-22 weeks condition. Threshold elevation was greater in the experimental ears but was present in the control ears. The SP/AP amplitude ratio was generally stable for the pre- to post-conditions in both ears. For the 17-22 week epoch the SP/AP amplitude ratio was still fairly stable for the click stimulus but the ratio diminished for the toneburst stimuli. For the subset analyzed at 7-21 days the SP/AP amplitude ratio tended to increase for both groups for all stimuli although AP thresholds were normal.

Animals↗

Round window application of D-methionine provides complete cisplatin otoprotection.

OBJECTIVE: Cisplatin is a widely used, very effective chemotherapeutic agent that can cause severe ototoxicity. In this study, D-methionine was tested as an otoprotectant via round window membrane (RWM) application in the chinchilla. METHODS: A minute amount of cisplatin alone, or D-methionine followed by cisplatin, was applied topically directly to the intact RWM of anesthetized adult chinchillas. Auditory brainstem responses were measured before and 1 week after topical round window application. Animals were killed, and the cochleas were examined. RESULTS: The ears pretreated with D-methionine were completely protected from hearing loss and hair cell loss in the organ of Corti compared with controls. The ears receiving cisplatin without D-methionine protection sustained nearly complete hearing loss with threshold shifts of >60 dB, with extensive outer hair cell loss throughout the organ of Corti but particularly in the basal turn. CONCLUSION: These results demonstrate that topical D-methionine provides excellent otoprotection against cisplatin-induced ototoxicity both electrophysiologically and structurally.

Administration, Topical↗

The histologic characteristics of the core of the fissula ante fenestram.

In earlier studies of perilymphatic fistulae, we described their histologic criteria and the clinical criteria for the identification and prediction of patencies of the labyrinth capsule related to disorders of hearing and balance. These patencies were either of the fissula ante fenestram or of the round window niche-posterior canal ampulla fissure. The permeability of the fibrous core of a patent fissula ante fenestram has been questioned, authors of some earlier articles arguing that the tissue is loose, others that it is dense. This study demonstrates loose fibrous and cellular structure in the fissula's tract, dense collagen at the circumference. The loose arrangement of tissue suggests that fluid can pass through this patency, and it appears similar to that of the spiral ligament which has been shown to contain perilymph by way of intercellular communications with the perilymphatic space.

Ear, Middle↗