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At least 847 records · Page 47Linked to original sources
PubMed2004

Direct round window application of gentamicin with varying delivery vehicles: a comparison of ototoxicity.

OBJECTIVE: To evaluate patterns of ototoxic damage sustained from gentamicin applied directly to the round window in varying delivery vehicles. SETTING: The search for a reliable method of drug delivery to the inner ear continues. Vehicles such as Gelfoam, hyaluronic acid, and fibrin may allow for a more reproducible pattern of ototoxic damage. STUDY DESIGN: Histological evaluation of vestibular and cochlear damage was performed on Mongolian gerbils after a known dosage of gentamicin in different delivery vehicles. RESULTS: Variable ototoxic damage was caused by Gelfoam and fibrin-based vehicles. No ototoxic damage was found in the Healon vehicle. The vehicle of fibrin and Gelfoam combined resulted in severe damage. There was no evidence of selective cochlear or vestibular ototoxicity in any of the vehicles tested. CONCLUSIONS AND SIGNIFICANCE: The fibrin/Gelfoam vehicle was the only delivery system to produce reliable damage. Ototoxic damage depended on the vehicle. We found no evidence for selective vestibular ototoxicity with gentamicin.

Administration, Topical↗
PubMed2003

Protective effect of brain-derived neurotrophic factor against the ototoxicity of Pseudomonas aeruginosa exotoxin A.

OBJECTIVE: The protective effect of brain-derived neurotrophic factor (BDNF) against the ototoxicity resulting from exposure of Pseudomonas aeruginosa exotoxin A (PaExoA) to the middle ear was analyzed. The combined effect of BDNF and N(G)-nitro-L-arginine methyl ester (L-NAME) was also investigated. MATERIAL AND METHODS: Six groups of albino rats were instilled through the tympanic membrane into the round window niche with the following solutions: saline; PaExoA; BDNF; L-NAME; PaExoA + BDNF; and PaExoA + BDNF + L-NAME. Frequency-specific (2-31.5 kHz) auditory brainstem responses were used to obtain the hearing thresholds before and 2, 5 and 15 days after instillation. RESULTS: PaExoA penetrated from the middle ear into the cochlea, causing initially mixed hearing loss, followed by persistent sensorineural hearing loss. This impairment was blocked by BDNF at 6, 8 and 10 kHz on Day 2 and at 8 kHz on Day 5. L-NAME given in combination with BDNF did not show any additional protective effect. There were no significant differences in the thickness of the round window membrane between control ears and those in each instillation group. CONCLUSION: Our results suggest that BDNF may protect against cochlear damage caused by PaExoA in the middle turns of the ear.

ADP Ribose Transferases↗
PubMedDate not supplied

Healing of experimentally produced round window membrane rupture.

The healing mechanism of experimentally produced ruptures of the round window was histologically studied in guinea pigs. Surgically created rupture of the round window resulted in spontaneous closure within 2 weeks. Light microscopical examination indicated that the rupture closed with proliferation of connective tissue which usually appeared to protrude into the middle ear cavity, each case showing a unique shape. In one case, the wound was covered with granulation tissue at the site of closure on the middle ear surface. Although the rupture was closed by connective tissue, the elastic fibres of the middle layer remained disrupted at the early stage of healing.

Animals↗
PubMed2004

[Introduction of middle ear surgery "aimed at hearing improvement" by Jan Miodoński--tympanoplasty at the centenary of his birthday].

The author recalls the introduction of the functional surgery of the Middle Ear--tympanoplasty by Miodoński and reminds of Miodoński's types of surgical reconstruction of the sound conducting mechanism: 1. "Ecranisatio" of the Round Window--the formation of the Small Middle Ear--Myringoplatinopexy (1949); 2. "Columellisatio" of the "Small Middle Ear--the formation of the Middle Ear with one ossicle--the Columella Effect--Myringostepedopexy" (1949); 3. "Columellisatio I-III"--the connection of the malleus with the stapes--Ossiculoplasty--Malleostapedopexy (1955). A comparison of Miodoński's solution in the range of functional surgery of the Middle Ear with present reconstructive Middle Ear techniques leads us to the conclusion that most of the tympanoplasty are only various modifications of Miodoński's principles.

History, 20th Century↗
PubMed1987

Ototoxicity of an ototopical preparation in a primate.

Severe ototoxicity has been observed in laboratory rodents after middle ear application of ototopical preparations or their constituents. Owing to their relatively high susceptibility, these animals may not be ideal experimental models. In the present study the ototoxicity of Cortisporin Otic Suspension (neomycin, polymyxin B, hydrocortisone) was studied using the baboon as a primate model. Middle and inner ear pathologic changes were assessed after a single application of the suspension to the tympanic cavity. Inner and outer hair cell loss occurred in all the experimental animals; it was, however, confined to the basal turn of the organ of Corti. Relative to previously studied rodents, the thicker, more densely structured round window membrane of the primate appears to provide better protection against penetration of ototoxic agents. Nonetheless, the results of this study indicate that ototopical preparations must be used with caution in clinical situations in which they may reach the middle ear.

Animals↗
PubMed1993

Fluorescein use in the detection of perilymphatic fistula: a study in cats.

A stained or colored perilymph would be a valuable tool to otologists for the detection of a perilymph fistula. We studied the effect of intravenously injected fluorescein on the inner ear in seven cats. Still and video photography was used to clearly document our findings. Intravenously injected fluorescein appeared within the soft tissue in less than 1 minute and stayed there for at least 3 1/2 hours. Fluorescence around the round window niche resulted from soft tissue (mucosal) fluorescence and extravasation of interstitial fluid (transudate). No fluorescence of perilymph was detected. Because of this, we do not believe intravenously injected fluorescein is useful in the detection of perilymph fistula. Intrathecal injection caused quick and intense staining of labyrinthine fluid.

Animals↗
PubMed2001

Targeted topical steroid therapy in sudden sensorineural hearing loss.

OBJECTIVE: To treat patients with sudden sensorineural hearing loss (SSNL) who failed oral prednisone therapy by using a round window membrane (RWM) microcatheter. This topical delivery strategy sought to improve effectiveness of steroid treatment to the inner ear by targeting drug delivery to the RWM. STUDY DESIGN: Nonrandomized prospective design. SETTING: Tertiary care facility. PATIENTS: Six patients with severe unilateral SSHL, five of whom were refractory to a course of oral steroid therapy treated within 6 weeks of SSHL and three additional patients treated more than 6 weeks after SSHL. INTERVENTION: Therapeutic use of RWM catheter. MAIN OUTCOME MEASURES: Pure-tone averages (PTAs) and word identification scores (WIS). RESULTS: Five of the six patients treated within 6 weeks of SSHL improved their WIS. Of the six, four returned to baseline hearing, one recovered hearing that could benefit by hearing amplification, and one regained moderate improvement in PTA but not WIS. CONCLUSION: Targeted topical steroid administration avoids the significant systemic side effects of oral steroids and may offer more effective dosing than simple transtympanic injection of medicine. Although these findings are preliminary, it is possible that after further study, targeted drug delivery may be a useful technique to consider in patients with severe to profound hearing loss that have failed all other management options.

Administration, Topical↗
PubMed2001

Clinical aspects of round window membrane permeability under normal and pathological conditions.

Current research and an overall review of 25 years of round window membrane studies are presented. The approach, rationale and concepts that have evolved from these studies are described. Ultrastructural studies of the round window membrane of humans, monkeys, felines and rodents have disclosed three basic layers: an outer epithelium, a middle core of connective tissue and an inner epithelium. Interspecies variations are mainly in terms of thickness, being thinnest in rodents and thickest in humans. Morphologic evidence suggests that the layers of the round window participate in resorption and secretion of substances to and from the inner ear, and that the membrane could play a role in the defense system of the ear. Different substances, including antibiotics and tracers, when placed in the middle ear side traverse the membrane. Tracers placed in perilymph become incorporated into the membrane by the inner epithelial cells. Permeability is selective and factors affecting permeability include size, concentration, electrical charge, thickness of the membrane and tacilitating agents. Passage of substances through the membrane is by different pathways, the nature of which is seemingly decided at the outer epithelium of the membrane. Round window membrane studies have provided increased knowledge of the anatomy and function of this structure, as well as new insights into pathology and pathogenesis. The concepts that have evolved from these studies are potentially useful for understanding middle and inner ear interactions, and for eventual drug delivery (based on permeability) to the inner ear.

Animals↗
PubMed1991

Singular neurectomy update. II. Review of 102 cases.

During the past 18 years, 102 singular neurectomies (SN) were performed on 95 patients with chronic cupulolithiasis of the posterior canal sense organ. Bilateral sequential singular neurectomies were performed in 7 patients and unilateral singular neurectomies in 88 patients. Ninety-nine (97%) of the 102 singular neurectomies completely eliminated the positional nystagmus and vertigo produced by the involved (undermost) ear in the Hallpike maneuver. Following three singular neurectomies (3%), there was improvement but incomplete relief from the positional nystagmus. A sensorineural hearing loss caused by the singular neurectomies occurred in four patients (4%). A thorough knowledge of the surgical and histologic anatomy of the round window niche and singular canal, together with the use of local anesthesia to allow monitoring of a vestibular response to singular neurectomy are essential for effectiveness and safety.

Adult↗
PubMed2002

Conductive hearing loss: investigation of possible inner ear origin in three cases studies.

This is a report of three cases of mixed hearing loss that resulted from inner ear disorders. Two cases were unilateral and the third was bilateral. The diagnosis was based on the findings of normal middle and external ears in association with the absence of round window reflexes. The contralateral stapedial reflex was present in the two unilateral cases. This is the first documentation of conductive deafness due to inner ear abnormality. This diagnosis should be considered in cases of conductive hearing loss if the middle and external ears are normal. More studies are needed to establish the pathophysiology of this entity.

Acoustic Impedance Tests↗
PubMed1991

Round window versus promontory stimulation: assessment for cochlear implant candidacy.

Electrical stimulation of the cochlea is a part of the preliminary evaluation protocol for cochlear implant candidacy at many centers. Typically, a transtympanic needle electrode is placed on the promontory of the ear under consideration and electrical current is presented to measure auditory percepts and psychophysical-electrophysiologic measures. Since 1984, we have used a ball electrode placed directly on the round window (via a tympanotomy) for stimulation, with 27 subjects being so tested to date. Nine additional subjects have had stimulating electrodes placed on both the round window and the promontory. Seven of these subjects yielded complete data. For measurements of threshold, maximum acceptable loudness level, and dynamic range, promontory testing mean values were higher than round window measurements. However, the differences were not significant.

Adult↗
PubMedDate not supplied

Ototoxicity of neomycin and its penetration through the round window membrane into the perilymph.

The ototoxicity of neomycin and its concentration in the perilymph after direct application on the round window membrane were studied. After placing 5 mg of neomycin on the round window membrane of guinea pigs for various time intervals, concentration of the drug in the perilymph was determined by high performance liquid chromatography, and the cochlea was examined by light microscopy. Neomycin penetrated the round window membrane quite easily, and its concentration in the perilymph became extremely high in a short time and then decreased gradually. This indicates that high concentration of neomycin in the perilymph can be attained by application of a small amount of the drug on the round window membrane. Ototoxicity of neomycin was observed after application for 4 hours. Cochlear damage increased as neomycin application time became longer, but no consistent relationship was noted between the concentration of neomycin and the amount of damage. This result is discussed from the point of concentration and persistence of the drug in the inner ear fluids.

Animals↗
PubMed1996

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Aging↗
PubMed1996

Age-related decreases in endocochlear potential are associated with vascular abnormalities in the stria vascularis.

The density and diameter of strial capillaries were assessed in whole-mount preparations of the cochlear lateral wall from 18 gerbils aged in quiet for at least 36 months. Following morphometric analysis, histopathologic changes in selected regions of the lateral wall were examined by light and transmission electron microscopy. Alterations in strial vasculature were compared with the endocochlear potential (EP) measurements from the same ear. Vascular degeneration occurred in a segmental fashion in that regions of atrophic capillaries were found throughout the cochlea but primarily in the apical and lower basal turns and in the hook. The amount of stria with normal capillaries varied greatly among the aged ears, ranging from 19 to 87%. The resting EP also varied markedly, ranging from 23 to 83 mV. Little correlation was found between vascular alterations and the corresponding EP value from individual cochlear turns. However, significant correlations were found between the total strial area with normal vasculature and both the mean EP value and that recorded at either the round window or first turn in that ear.

Acoustic Stimulation↗
PubMed2003

High variability of perilymphatic entry of neutral molecules through the round window.

OBJECTIVE: To improve the efficacy of intratympanic therapy using perilymphatic entry through the round window membrane. MATERIAL AND METHODS: The perilymphatic entry characteristics of 2 neutral molecules, mannitol (182.2 Da) and inulin (7,000 Da), were studied. A polyethylene catheter was placed in contact with the guinea pig round window membrane and sealed with cyanoacrylate glue. This catheter was linked to an osmotic minipump that delivered 100 microl portions of 3H-mannitol or 3H-inulin solutions over a 7-day period at a constant rate (0.5 microl/h). Perilymph in the scala vestibuli and scala tympani, cerebrospinal fluid (CSF) and plasma were sampled after 4-7 days of delivery. RESULTS: Despite the constant rate of infusion, perilymphatic radioactivity varied widely from one animal to the other, probably as a function of the position of the microcatheter within the round window niche and/or the permeability of the round window. Even a large molecule such as inulin entered the perilymphatic space. Seven days after the beginning of 3H-mannitol administration, the radioactivity was higher in the perilymph of the scala tympani than in that of the scala vestibuli. The perilymphatic radioactivity on Day 7 was approximately 50% lower than that measured on Day 4 (p = NS). Finally, round window membrane delivery did not preclude distant spread of the molecules into the blood and CSF. CONCLUSIONS: Using round window membrane delivery, the perilymphatic entry of mannitol and inulin depended on their molecular weight. Intratympanic delivery induced a high inter-individual heterogeneity of the drug concentration within the inner ear, with subsequent variability of the therapeutic effects.

Administration, Topical↗
PubMed1983

[Differential diagnostic reflections on sudden deafness: rupture of the round window membrane].

The rupture of the round window membrane has been the origin of sudden deafness in two cases that are described in this presentation. We are able to verify the rupture of the round window membrane before surgery by using differential diagnostic criteria, though there existed only relative slight hearing losses of about 40 dB. After surgery we found normal hearing in one case and a decreased hearing loss in the other. Vestibular symptoms have been leading to the diagnosis in both cases and the middle ear effusion in one case.

Adult↗
PubMed1994

Absent round window reflex: possible relation to step-wise hearing loss.

The diagnosis of perilymphatic fistula can be confusing and prone to error. The signs and symptoms can be extremely varied, and currently there is no clinical or laboratory test that accurately predicts the presence of this entity. The only reliable method of diagnosis, namely surgical exploration, is often frustrating as, commonly, no evidence of an active fistula is found. Four children initially believed to have a perilymphatic fistula were found on exploration instead to have an absent round window reflex with normal mobility of the ossicular chain. These children presented with a history of abrupt, step-wise decreases in their hearing thresholds that frequently progressed from a mixed to a purely sensorineural loss. No anatomic abnormalities were found on high-resolution computed tomography. The authors theorize that this finding may represent altered fluid dynamics within the inner ear. Whether it signifies a prior fistula that has spontaneously healed remains to be confirmed. A review of the literature along with possible pathophysiologic mechanisms is presented.

Adolescent↗
PubMedDate not supplied

Subepithelial fiber components of the round window membrane of the guinea pig: an ultrastructural and immunohistochemical study.

Subepithelial fiber components of the round window membrane (RWM) of the guinea pig were studied by the following methods: transmission electron microscopy (TEM), scanning electron microscopy (SEM) with NaOH treatment, high-voltage electron microscopy (HVEM) and immunohistochemical staining. SEM observation revealed intersecting collagen fibers and a vascular network in the middle layer. TEM observation showed that at the attachment region to the bone fibroblasts, collagen fibers and elastic fibers were intermingled with each other, and mesenchymal cells (bone-lining cells) were scattered on the surface of the bone. The cytoplasmic processes of fibroblasts and bone-lining cells were connected by interdigitations. HVEM demonstrated that collagen fibers of the RWM were directly linked to the fibers of the bone matrix. Immunohistochemically, the middle layer was positive for antibody to type I collagen. Immunoreaction for fibronectin was also positive at the middle layer and most intense in the region attached to the bone. Thus, the RWM is securely attached to the bone by type I collagen fibers together with the bone-lining cells and fibroblasts.

Animals↗