In search of missing links in otology. iii. development of a new animal model for cholesteatoma

Hueb, Marcelo M.; Goycoolea, Marcos V.; Muchow, David C.; Duvall, Arndt J.; Paparella, Michael M.; Sheridan, Carolyn

doi:10.1288/00005537-199307000-00011

Cited by 20 publications

(17 citation statements)

References 26 publications

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“…13 Theses description have also been published by other authors. 3,14 The tympanic membrane alterations we found in 40 ears (control and experiment groups) included visible retro-tympanic cholesteatomas in four ears, of which two presented retraction, and tympanic membrane perforation in seven ears. We were able, therefore, to observe cholesteatoma formation in retracted, intact and perforated tympanic membranes; perforation might be secondary to necrosis, itself resulting from inflammation caused by the middle ear mucosa-irritating agent.…”

Section: Discussionmentioning

confidence: 90%

Efeito do ácido trans-retinóico na inibição de colesteatoma em cobaias

Antunes

Fukuda

Penido

et al. 2008

Rev. Bras. Otorrinolaringol.

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Middle ear cholesteatoma affected more than 5 million people until the 80`s. Many animal models were used, unsuccessfully, to study an alternative therapy to cholesteatoma. Aim: observe the effect of the trans-retinoic acid in the inhibition of middle ear cholesteatomas induced by propylene glycol. Study Design: Clinical and Experimental. Methods: 25 guinea pigs were submitted to the application of a 100% propylene glycol solution in their bulla bilaterally and a solution of trans-retinoic acid was applied locally in the external right ear, while in the left ear saline solution was applied (control ear). The guinea pigs were slaughtered and their temporal bones were prepared for macroscopic and histological analysis. Results: The macroscopic findings had evidenced the presence of cholesteatoma in 25% of the right ears and 85% of the left ears (P=0.0003 *). The histological study had evidenced the presence of cholesteatoma in 30% of right ears and 75% of the left ears (P=0.0104*). Conclusion: The local use of the trans-retinoic acid is effective in inhibiting the induced formation of cholesteatomas in guinea pigs.

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Section: Discussionmentioning

confidence: 90%

Efeito do ácido trans-retinóico na inibição de colesteatoma em cobaias

Antunes

Fukuda

Penido

et al. 2008

Rev. Bras. Otorrinolaringol.

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“…The animals were divided into groups of 5 and sacrificed at 8, 10 and 12 weeks after the initial procedure. This experiment and the temporal bone processing have been previously reported (3). Sections 18 vm thick were stained with hematoxylin and eosin and studied under light microscopy.…”

Section: Methodsmentioning

confidence: 99%

The Theory of the Trigger, the Bridge and the Transmigration in the Pathogenesis of Acquired Cholesteatoma

Goycoolea¹,

Hueb²,

Muchow³

et al. 1999

Acta Oto-Laryngologica

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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.

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“…Knochenabbau ist kein auf das Cholesteatom beschränktes Phänomen, sondern kommt auch bei chronischer Otitis media ohne Cholesteatom vor [5,26,35,39,80,81]. Cholesteatommatrix hat nie direkten Kontakt zum Knochen [1,2,60,80,81].…”

Section: Enzyme Der Wundheilungunclassified

“…Die Freilegung der Kollagenmatrix ist ein intensiver Abbaureiz für die Metalloproteinasen aus den Fibroblasten und Makrophagen des Granulationsgewebes [26]. In Zellkultur wird Knochenresorption, aber auch Knochenneubildung durch dieses Schlüsselzytokin der Wundheilung stimuliert [25,39]. In Zellkultur wird Knochenresorption, aber auch Knochenneubildung durch dieses Schlüsselzytokin der Wundheilung stimuliert [25,39].…”

Section: Enzyme Der Wundheilungunclassified

Die Rolle des Perimatrixfibroblasten bei der Entstehung des erworbenen Mittelohrcholesteatoms

Milewski

1998

HNO

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The epithelial pathogenesis of acquired cholesteatoma has been widely accepted, but clinical and experimental data have not been able to answer questions like: How does a cholesteatoma start or grow or how is bone resorption of conducted? From our own experiments and literature a new hypothesis of cholesteatoma origin and growth is drawn. Three prerequisites are necessary for development: (1) the unique anatomical situation at the ear-drum (two different epithelial layers close together); (2) chronic destruction of the submucosal tissue in the middle ear (infection, inflammation); (3) wound healing (proliferation phase). Destruction of the submucosal space by middle ear infection and cell necrosis starts the wound healing cascade. In wound healing generally the connective tissue fibroblasts and macrophages play a pivotal role. Cytokines of the wound healing thought to promote the re-epithelization of the mucosal defect and scar tissue development act upon the intact squamous cell layer of the outer surface of the ear-drum at the same time. Thereby a proliferation of the undamaged epithelial layer is induced. Cholesteatoma matrix is always surrounded by a layer of connective tissue, the perimatrix. Persistence of the inflammation causes permanent wound healing in the perimatrix, proliferation of the fibroblasts (granulation tissue) and proliferation of the epithelium (matrix). It is speculated that by virtue of wound healing cytokines of fibroblasts and macrophages are the driving forces of cholesteatoma origin, growth and bone destruction.

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In search of missing links in otology. iii. development of a new animal model for cholesteatoma

Cited by 20 publications

References 26 publications

Efeito do ácido trans-retinóico na inibição de colesteatoma em cobaias

Efeito do ácido trans-retinóico na inibição de colesteatoma em cobaias

The Theory of the Trigger, the Bridge and the Transmigration in the Pathogenesis of Acquired Cholesteatoma

Die Rolle des Perimatrixfibroblasten bei der Entstehung des erworbenen Mittelohrcholesteatoms

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