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.

Gland formation in otitis media. An ultrastructural study in humans.

In an effort to evaluate mechanisms of new gland formation in otitis media, 14 human middle ear mucoperiostial tissue samples were obtained from 7 patients with a history of this disease. In areas of inflammatory reaction, especially in the promontory and anterior wall, the mucoperiosteum acquires polyploidal characteristics, with occasional epithelial breaks. The epithelium becomes thicker and the cells develop increased secretory activity. The invaginated portion of these polyploidal formations can be observed as pits lined by secretory epithelium. The cells in these invaginated areas: (i) fuse in areas of epithelial ruptures, leaving spaces into which cells secrete; (ii) develop dense cellular nests that bud off the epithelium, leaving empty spaces into which cells secrete. It is proposed that new gland formation can occur by means of fusion and formation of cellular nests that bud off the epithelium.

Mastoid and tympanomastoid procedures in otitis media: classic mastoidectomy (simple, modified, and radical) and current adaptations; open-cavity, closed-cavity, and intact-bridge tympanomastoidectomy.

Otitis media is a multifactorial, multifaceted disease that manifests itself in the middle ear, mastoid, and eustachian tube. To select a rational therapy, physicians must have an understanding of the anatomy, function, and pathology of the organs involved and of the mechanisms of disease. The purpose of this article is to provide surgical principles in tympanomastoidectomy and an overall concept of the procedures available. Simple mastoidectomy is described in detail as a general approach.

The theory of the trigger, the bridge and the transmigration in the pathogenesis of acquired cholesteatoma.

The purpose of the study was to evaluate factors in the otitis media process that could play a role in the pathogenesis of acquired cholesteatoma. The study was divided in two parts: firstly the temporal bones of 75 cats and 15 chinchillas with induced otitis media, and 78 human bones with otitis media were evaluated. Special emphasis was placed on epithelial breaks. These breaks were commonly observed, leaving areas of connective tissue of the mucoperiostium in direct contact with the middle ear effusion. As these changes progressed, the effusion became organized, serving as a bridge for granulation tissue. In later stages these areas became totally or partially covered with epithelium. Areas of epithelial breaks became connected to each other through the organized effusion. Cholesteatomas in humans seem to spread using the connective tissue as scaffolding. Secondly, we reviewed 15 chinchillas in which a chemically modified membrane was placed leading from the external auditory canal to the promontory, through a tympanic membrane perforation. Squamous epithelial migration with cholesteatoma formation occurred through the tympanic membrane perforation, collagen membrane, organized effusion and granulation tissue in 53.5% of the experimental animals. The authors propose the theory that for transmigration of squamous epithelium to occur, a trigger (inflammatory process) and a bridge (granulation tissue and organized effusion) are needed in a predisposed subject.

Round window membrane. Structure function and permeability: a review.

The ultrastructure of the round window membrane of humans, monkeys, felines, and rodents discloses 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 thicker in humans. Morphologic evidence suggests that the layers of the round window participate in absorption and secretion of substances to and from the inner ear, and that the entire membrane could play a role in the defense system of the ear. Different substances, including antibiotics, local anesthetics, and tracers such as cationic ferritin, horseradish peroxidase, and 1 mu latex microspheres, are placed in the middle ear side traverse the membrane. Cationic ferritin and 1 micron microspheres placed in perilymph become incorporated by the inner epithelial cells of the membrane. Permeability is selective; factors include size, concentration, liposolubility, electrical charge, and thickness of the membrane. Passage of substances through the round window membrane is by different pathways, the nature of which is seemingly decided at the outer epithelium of the round window membrane.

Oval and round window membrane changes in otitis media in the human. An ultrastructural study.

An ultrastructural study of oval and round window changes in otitis media in humans was done. Ten cases were evaluated. In this first ultrastructural study of oval and round windows in otitis media, done at different stages of the disease, the round window membrane changes were similar to those of the mucoperiostium. Morphologic evidence suggests that the round window membrane layers participate in absorption and secretion of substances to and from the inner ear, such that the entire membrane could play a role in a middle and inner ear "defense system." Although the middle ear side of the footplate of the stapes had histopathological changes, the vestibular side remained essentially unchanged.

Prevalence of microfissures in the human temporal bone: a report of 1000 temporal bones.

A total of 1000 human temporal bones were studied to determine the prevalence of two microfissures: 1. the one between the facial canal and the vestibule, 2. the microfissure between the round window niche (RWN) and the posterior semicircular canal (PSC). Additionally, this study compares the prevalence according to temporal bone age and sex. The microfissure between the facial canal and the vestibule was observed in 470 (47%) temporal bones, with a bilateral presence of 77.2%. The prevalence of this microfissure increases linearly with age. It was not found in any bone within the 0 to 2 age group. It was present in 3 (7.3%) bones from the 2 to 9 age group, as opposed to 374 (54.8%) bones from the 40 and over group. The microfissure between the RWN and the PSC was detected in 915 (91.5%) temporal bones. This second microfissure was found to be an overwhelmingly bilateral entity. The prevalence of this other microfissure also increases with age. This microfissure was also not present in any temporal bone within the 0 to 2 age group. It was found in 28 (68.3%) bones from the 2 to 9 age group, in contrast to 678 (99.4%) temporal bones from the 40+ group.

Sustained release of antimicrobials in the middle ear using a biodegradable support.

The ototoxicity of a poly-L-lactic acid biodegradable support incorporating a therapeutically releasable amount of ampicillin was studied. This device has a shape that allows placement in the middle ear via a myringotomy incision. Once in the middle ear, it expands without mechanical interference and provides extended release of ampicillin. In vitro studies documented sustained release of ampicillin, and in vivo efficacy was demonstrated in otitis media induced in chinchillas and cats. Previous histopathologic studies showed a lack of inflammatory reaction from the device itself and documented its biodegradable characteristics. There was no evidence of ototoxicity on morphometry of the organ of Corti (hair cell counts) in chinchillas exposed to these devices for 3 weeks with and without ampicillin.

Prevalence of carotid canal dehiscence in the human middle ear: a report of 1000 temporal bones.

A total of 1000 human temporal bones were used to study the prevalence of carotid canal dehiscence, microdehiscence, and thin bony coverage. Additionally, this study compares the prevalence according to sex and temporal bone age. A carotid canal dehiscence was detected in 77 (7.7%) bones. It was present bilaterally in 23.2% of the paired temporal bones. The prevalence of carotid canal dehiscence decreases with increasing temporal bone age. It was found in 10 (15.9%) bones in the younger than 2 age group, as opposed to 43 (6.3%) bones from the 40 and older group. The concept of microdehiscence of the carotid canal is introduced. A carotid canal microdehiscence was found in 74 (7.4%) bones. Microdehiscences were noted to occur bilaterally in 12.3% of the paired bones. The prevalence of carotid canal microdehiscence also decreases with increasing temporal bone age. It was detected in 7 (11.1%) bones in the younger than 2 age group, in contrast to 51 (7.5%) bones in the 40 and older group. A total of 134 (15.5%) temporal bones were found to have a thin bony coverage, without the presence of a dehiscence or microdehiscence. The prevalence of thin coverage was noted to increase linearly with age. A thin carotid canal was found in 2 (8.3%) bones from the younger than 2 age group, whereas 113 (17.3%) temporal bones from the 40 and older group exhibited this entity. To the best of our knowledge, this is the first systematic study of histologic sections of a large number of temporal bones that looks at these entities.

Overall view and rationale for surgical alternatives for incapacitating peripheral vertigo.

This article describes an overall view and the rationale for the different surgical alternatives available for treating incapacitating peripheral vertigo. The authors emphasize that the number of patients requiring surgery is very small, and that the surgical procedures available do not provide 100% relief nor are they free of risks. A need for individualized attention to patients and a careful selection of the most appropriate surgical procedure for each particular case are strongly stressed.

Prevalence of facial canal dehiscence and of persistent stapedial artery in the human middle ear: a report of 1000 temporal bones.

A total of 1000 temporal bones were used to study the prevalence of facial canal dehiscence and of persistent stapedial artery in detail. Of the temporal bones studied, 560 (56%) contained at least one facial canal dehiscence. There was a 76.3% prevalence of bilaterality of this canal wall gap. The most common site of dehiscence was the oval window area. The concept of microdehiscence of the facial canal is introduced. One third of the temporal bones observed had a microdehiscence of the facial canal, usually located at the oval window area (74.9%) and found bilaterally 40% of the time. The authors found a 0.48% prevalence (5 out of 1045) of persistent stapedial artery. This is the first histological study of temporal bones to report a prevalence of this vascular anomaly.

In search of missing links in otology. III. Development of a new animal model for cholesteatoma.

An experimental study was conducted in chinchillas regarding the pathogenesis of acquired cholesteatoma (keratoma). The placement of a chemically modified gelatin membrane from the external auditory canal to the promontory through a tympanic membrane perforation stimulated squamous epithelial cell migration. Cholesteatoma formation with the presence of keratin debris and inflammatory reactions was observed in the middle ear and anterior bulla in 53.5% of the experimental animals. These experimental findings show for the first time the presence of epithelial migration and true cholesteatoma formation in the middle ear of chinchillas in an experimental model with deliberate perforation of the tympanic membrane. Erosion of the cochlear walls was observed in areas with granulation tissue and cholesteatoma. The importance and significance of the migration of squamous epithelium and of the middle ear inflammatory reaction in the genesis of acquired cholesteatomas are discussed.

Middle ear susceptibility to Pseudomonas infection during acute otitis media.

Pneumococcal otitis media was induced bilaterally, and Pseudomonas was inoculated unilaterally into the middle ears of 36 chinchillas to study the pathogenesis of chronic suppurative otitis media. Half of the animals were treated with penicillin prior to Pseudomonas inoculation (day 7, late Pseudomonas), and half were inoculated with Pseudomonas before penicillin treatment (day 3, early Pseudomonas). A third group of 18 chinchillas received unilateral Pseudomonas inoculation without pneumococcus or penicillin (control). Animals with early Pseudomonas were significantly less susceptible to Pseudomonas infection in the Pseudomonas-inoculated ear than animals with late Pseudomonas and controls. Susceptibility to Pseudomonas infection in the contralateral ears, which were not inoculated with Pseudomonas, was significantly lower in early Pseudomonas and control animals than in late Pseudomonas animals. Increased susceptibility in the late Pseudomonas group might have been due to altered nasopharyngeal microflora or persisting eustachian tube dysfunction--factors that may be important in the pathogenesis of chronic suppurative otitis media in humans.

Pseudomonas otitis media after eustachian tube obstruction.

Previous experiments have shown that Pseudomonas aeruginosa may infect the middle ears of chinchillas by way of the eustachian tube and that chinchillas with acute otitis media (AOM) are more susceptible to pseudomonas infection than animals without AOM. The purpose of this experiment was to examine the effects of otitis media with effusion (OME), induced by means of eustachian tube obstruction, on middle ear susceptibility to nasal inoculation of P. aeruginosa. Chinchilla eustachian tubes were obstructed with silicone rubber sponge bilaterally; OME developed in eight animals (11 ears)--three bilaterally and five unilaterally--and persisted for 6 months. Ten chinchillas with normal eustachian tube function served as controls. All animals were nasally inoculated with 5 x 10(6) colony-forming units of P. aeruginosa. Pseudomonas otitis media developed in eight of 11 OME ears with effusion, none of five ears without OME, and four of 20 control ears (chi 2 = 11.782, p = 0.003). Therefore, P. aeruginosa can infect the middle ear by way of the eustachian tube. Tubal dysfunction may lead to the development of chronic suppurative otitis media by increasing tubotympanic susceptibility to opportunistic pathogens.

Extended middle ear drug delivery. A new concept; a new device.

The authors present the development of a new device that consists of a biodegradable support matrix incorporating a therapeutically releasable amount of ampicillin. This device is in an insertable shape that allows easy placement into the middle ear. Once in the middle ear cavity it expands, contacts the walls, and provides extended sustained release of ampicillin. In vitro studies over three months documented the consistent release of therapeutically effective levels of ampicillin. In vivo efficacy was demonstrated in the cat otitis media induced by eustachian tube obstruction. Cultures of normal cat middle ear cavities prior to obstruction revealed no microflora. Cultures after obstruction of the middle ears of animals treated with this device had no growth of bacteria as early as one week after obstruction (10 out of 12 cats). The contralateral untreated ears became culture negative at two weeks post obstruction, suggesting that the effect of the device is not limited to the treated ear. Histopathological studies showed the effect of the device as early as one week post obstruction in treated ears and after two weeks in the contralateral ear. Both ears became normal at three months, while obstructed untreated animals (controls) developed chronic irreversible otitis media changes. In addition, histopathological findings documented a lack of inflammatory reaction from the device itself, and its capacity of being biodegradable. Topical extended middle ear drug delivery can become a significant form of treatment for middle ear disease and has the potential of being useful as a source for inner ear drug delivery.

The round window membrane under normal and pathological conditions.

Current research and an overall review of round window membrane studies is presented and the concepts that have evolved from these studies are described. Ultrastructural studies of the round window membrane of rodents, felines, and primates disclosed three basic layers: an outer epithelium lining the middle ear, a middle core of connective tissue, and an inner epithelium bordering the inner ear. Morphological evidence suggests that the membrane participates in: (a) the release of mechanical energy supplied by the ossicular chain to the labyrinthine fluids; (b) an alternative route for sound energy to enter the cochlea; (c) secretion into and absorption from perilymph; and (d) the defense system of the middle and inner ears. Permeability of the round window is considered an accident and not a function of the membrane. The complications of permeability (potential ototoxicity) and its potential usefulness (drug delivery) are discussed.

Otosclerosis: the University of Minnesota temporal bone collection.

A study of 1452 human temporal bones revealed a previously unpublished material of 144 bones with otosclerosis. After exclusion of infants and individuals of races other than white, the incidence of otosclerosis was 12.75%. Of the bones with otosclerosis, 56.1% belonged to men and 43.9% to women. The incidence of clinical and histologic otosclerosis was practically the same for men (44.7% to 55.3%) as for women (47% to 53%). However, the incidence of bilateral otosclerosis was higher in women (88.9%) than in men (65.2%). Bilateral otosclerosis was present in 75.6%, whereas it was unilateral in 24.4%. Sixty-six (66) ears (45.8%) had clinical otosclerosis, whereas 78 (54.2%) had histologic otosclerosis--frequently unifocal lesions. The most common site was anterior to the oval window (117 ears, 81.25%), followed by round window niche (52 ears, 36.11%), apical and medial cochlear wall (31 ears, 21.52%), and anterior wall of the internal auditory canal (27 ears, 18.75%). The activity of lesions was directly related to their size. Smaller lesions were predominantly inactive, whereas medium and larger lesions were predominantly active. There was a positive correlation when the size of the lesions, activity, and degree of cochlear endosteal involvement were compared with bone conduction thresholds (37 cases). Correlations between size and activity, and between activity and associated sensorineural hearing loss did not necessarily follow the sequence of an initial active stage (spongiotic) to a final inactive one (sclerotic). Comparison of cases of otosclerosis with equivalent age groups of the normal population yielded worse bone conduction thresholds for the otosclerosis cases only in the age group 60 to 69 years and older. Comparison of average bone conduction thresholds between bones with one site of endosteal involvement (28.26 dB HL) revealed no significant differences. Bones with two or more sites of endosteal involvement had significant differences. Bones with two or more sites of endosteal involvement had significantly worse bone conduction thresholds (62 dB HL). The overall results are not suggestive of an association of sensorineural hearing loss with otosclerosis without stapedial fixation.

The significance of experimental animal studies in otitis media.

Animal models have been instrumental in investigating otitis media. Experimental models have allowed for focused research on how such factors as eustachian tube dysfunction and microbial infection contribute to the pathogenesis of otitis media. Antibacterial therapy and immunologic prophylaxis have been developed using these models. Current research is aimed at generating an objective index of middle ear inflammation for guiding patient management.

Otitis media: the pathogenesis approach. General surgical approach based on pathogenesis. An overall approach.

The authors present an overall approach and fundamental concepts based on pathogenesis. They advocate an open-minded approach, tailoring the treatment to each individual patient rather than fitting patients into preestablished classifications.