David Muchow

Experimental studies on round window structure: Function and permeability†

Current research and an overall review of 12 years of round window membrane studies is presented. The approach, rationale, and concepts that have evolved from the studies are described. An ultrastructural study of the round window membrane of rhesus monkeys disclosed three basic layers: an outer epithelium, a middle core of connective tissue, and an inner epithelium. Morphologic evidence in monkeys, cats, and chinchillas suggests that these 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. Cationic ferritin, horseradish peroxidase, 1‐μm latex spheres, and neomycin‐gold spheres placed in the middle ear of these experimental animals were observed to traverse the round window membrane through pinocytotic vesicles. Three‐micron latex spheres and anionic ferritin were not incorporated by the membrane. Cationic ferritin and 1‐μm latex spheres placed in perilymph were incorporated by the inner epithelial cells, suggesting absorptive capabilities of the round window membrane. Cationic ferritin was observed within the mesothelial cells underlying the scala tympani side of the basilar membrane, suggesting a role for these cells in the inner‐ear defense system. A review of the subject and a general perspective from the authors viewpoint are discussed.

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.

In search of missing links in otology. II. development of an implantable middle ear drug delivery system: Initial studies of sustained ampicillin release for the treatment of otitis media

The development of a new device that consists of a biodegradable support incorporating a thera‐peutically releasable amount of ampicillin is presented. This device is in an insertable shape that allows placement into the middle ear via a myringot‐omy incision. Once in the middle ear cavity, it expands, contacts the walls, and provides extended release of ampicillin. In vitro studies (3 months) documented the consistent release of therapeutic levels of ampicillin. In vivo efficacy was demonstrated in otitis‐induced chinchillas (bacterial inoculation). The device compared favorably with topical and systemic treatment and prophylaxis of otitis media. The device was also efficient in repeated bacterial challenges. 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.

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.

Ultrastructural studies of the peripheral extensions (dendrites) of type I ganglion cells in the cat.

An ultrastructural study of peripheral extensions (dendrites) of type I ganglion cells in seven healthy adult cats and one cat that underwent bilateral cochlear injection of neomycin was undertaken. Morphologic evidence revealed that the peripheral process (dendrite) consistently has a smaller diameter than the central process. As the dendrite reaches the cell body, there is a constricted segment with a length that ranges from 10 to 30 μm, and a diameter of 0.5 μm. This region is covered by a continuous myelin sheath that does not thin. The central process (axon) does not have a corresponding constriction, and consists of a myelin covered, smoothly tapered segment that extends to the first axonal node of Ranvier. In the deafened cat, some cell bodies of the surviving ganglion cells appeared to have a residual portion of dendrite. These morphologic characteristics might have physiologic implications both in the mechanisms of normal hearing and in cochlear implantation.

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.

In search of missing links in otology. I. development of a collagen‐based biomaterial

Experiments leading to the development and use of a biomaterial based on reconstituted collagen for use in tympanoplasty are presented. A stable, even membrane with optimal strength and an organized matrix of collagen protein strands has been obtained. Biocompatibility was documented by subcutaneous implantation, cytotoxicity with agar overlay, cell contact, and cell‐growth inhibition studies. Experimental grafting in chinchillas with perforated tympanic membranes demonstrated that the collagen membrane performed well in all cases. Histopathological studies in chinchillas showed that the collagen membrane compared favorably with fascia grafts. Of significance is that: 1. The membrane has a matrix of microperforations that enhance tissue ingrowth, allow stable anchoring, and permit aeration of the middle ear cavity. 2. The membranes obtained are not exposed to aldehyde cross‐linking; therefore, tissue reaction due to aldehydes is avoided.