This investigation was designed to evaluate the effects of the antimetabolite 5-fluorouracil (5-FU) on cholesteatoma formation in a chinchilla model. The animals received middle ear applications of propylene glycol according to a procedure previously shown to produce cholesteatomas in 60% to 70% of animals. A 5% solution of 5-FU was then applied to the lateral surface of the tympanic membrane (TM) and, after 1 month, temporal bones were taken for histologic study. No macroscopically visible cholesteatomas were present in any of the 16 temporal bones included in the study. However, microscopic invasion of epidermis to the medial side of the TM was observed in four specimens; perforations were present in three of these. Although there was considerable variability in the response to 5-FU application, the majority of specimens showed little or no proliferation of connective tissue in the lamina propria of the TM. In the four specimens in which epidermis reached the medial side of the TM, it did so either by migration through microscopic breaks in the fibrous layer or via TM perforations. Thus, 5-FU did not completely inhibit migration of epidermis into the middle ear. However, the results of this study indicate that it does tend to reduce the proliferation of TM epidermis and connective tissue, thereby reducing the likelihood of cholesteatoma formation in the experimental model.

Animals↗

PubMedDate not supplied

Effect of topical hyaluronic acid on experimental cholesteatoma.

PURPOSE: Inflammation and connective tissue hyperplasia are believed to be important etiological factors in cholesteatoma pathogenesis. Previous work has shown that topically applied hyaluronic acid can reduce connective tissue proliferation in healing wounds and accelerate healing of tympanic membrane perforations. This study was undertaken to determine whether the antiproliferative effect of hyaluronic acid may inhibit propylene glycol-induced cholesteatoma in an animal model. MATERIALS AND METHODS: A 60% propylene glycol solution was injected bilaterally into the middle ear cavities of 20 adult chinchillas. The control group (N = 10) received propylene glycol alone. In addition to propylene glycol injections, the experimental group (N = 10) received repeated bilateral topical applications of 1.5% hyaluronic acid onto the tympanic membranes. Animals were killed at 4 weeks for gross and light microscopic examination. RESULTS: Seven control and 10 experimental animals survived the full 1-month study period. At the end of that time, cholesteatoma was found in 71% (10/14) of control ears and 70% (14/20) of experimental ears. Tympanic membrane structure did not differ significantly between groups by light microscopy and, in all animals, cholesteatomas originated by migration of hyperplastic epidermis through the tympanic membrane, as has been observed in previous studies using this animal model. CONCLUSION: Under the conditions of this study, topical hyaluronic acid had no significant effect on cholesteatoma formation.

Administration, Topical↗

PubMedDate not supplied

Pathology of neuroepithelial suprastructures of the human inner ear.

Neuroepithelial suprastructures in abnormal human inner ears were studied by light microscopy, scanning electron microscopy, and x-ray diffraction. The most common abnormality was calcification, which selectively affected the gelatinous membranes (otoconial, cupular, and tectorial) and the secretory tissues (stria vascularis and utricular dark cells). The structures most frequently affected were the otoconial membranes. The minerals involved were apatite, octacalcium phosphate, and vaterite, replacing the normal layer of calcium carbonate in the form of calcite crystals. The first two of these substances were sometimes mixed with calcite. In the saccule such abnormal otoconial deposits were usually associated with a collapsed saccular wall. Formation of abnormal otoconia is characterized as primary (no pre-existing normal calcite otoconia) or secondary (formed after the destruction of normal otoconia). Such deposits probably depend upon an abnormal composition of the endolymph, especially upon an elevated concentration of phosphate ions. It is inferred that a normal endolymphatic microhomeostasis is necessary to maintain the functional state of the neuroepithelial suprastructures.

Aged↗

PubMedDate not supplied

A calcareous concretion in the posterior semicircular duct of a human labyrinth.

Temporal bones were acquired four hours post mortem from a 67-year-old cancer patient. During dissection of the left vestibular labyrinth, a glistening white, spherical concretion was found in the posterior semicircular duct near the ampulla. The object was subsequently studied by light and scanning electron microscopy, x-ray diffraction, and x-ray energy dispersive elemental analysis. It was composed of four concentric layers: an outer zone of tabular vaterite crystals, a colorless intermediate zone of spherulitic octacalcium phosphate (OCP), and a cloudy core with inner and outer zones both composed of OCP. Examination of the vestibular receptor organs revealed severe loss of hair cells on all three cristae. Very few otoconia were present in the utricle, although the gelatinous layer of the otoconial membrane was intact on the macular surface. During the year preceding his death, the patient had received 800 mg of the potentially ototoxic drug cis-platinum. The concretion described in this report was, however, probably connected with age-related degeneration rather than with any effect of the drug.

Aged↗

PubMedDate not supplied

Ototoxicity of otic drops applied to the middle ear in the chinchilla.

Previous studies have shown that the application of topical otic drops to the external ear canals of animals with patent tympanostomy tubes may result in hearing impairment and cochlear hair cell loss. Otic drops are used in patients with tympanostomy tubes or tympanic membrane perforations and could have deleterious effects on the human membranous labyrinth. This report describes the inner ear damage that occurred after direct application of aminoglycoside-containing otic drops to the middle ears of experimental animals. The membranous labyrinths of 25 chinchillas were studied two days to five months after application of Cortisporin otic suspension (which contains neomycin, polymyxin B, hydrocortisone, and propylene glycol) to the middle ear cavity. Application of 0.5 ml of Cortisporin resulted in degeneration of all inner and outer hair cells throughout the cochlea, as well as severe damage to the stria vascularis. Moderate to severe degeneration of the vestibular receptor organs was also observed. The endolymphatic sacs showed dark-staining endolymph, cellular debris, and macrophages in the sac lumina, as well as increased activity of the epithelial lining.

Animals↗

PubMedDate not supplied

Middle ear cholesteatoma: an animal model.

Topical otic preparations now in clinical use contain a variety of antibiotics and solvents that may produce severe inflammation if they reach the middle ear cavity. This report describes the response of the chinchilla middle ear to direct application of one such preparation that appears to act as a nonspecific irritant. Cortisporin otic suspension (containing neomycin, polymyxin B, hydrocortisone, and propylene glycol) was introduced into the bullae of 32 chinchillas that were kept alive for four days to five months before histologic examination of their temporal bones. All the experimental animals had tissue damage and inflammation within the middle ear. The changes observed included proliferation of ciliated and secretory columnar cells, formation of granulation tissue, bone erosion, and osteoneogenesis. Some areas of the mucosa underwent metaplasia to stratified squamous epithelium; this metaplastic epithelium, however, did not produce keratin. In the majority of animals kept for two months or more, cholesteatoma was identified in the middle ear. The cholesteatomas appeared to develop as a result of penetration of external canal epidermis through intact tympanic membranes or as the result of migration of epidermis through perforations. The experimental cholesteatomas behaved like those seen clinically in humans, with extensive erosion of bony structures within the middle ear.

Animals↗

PubMedDate not supplied

Inner ear anomalies in two cases of trisomy 18.

Two cases of trisomy 18 in which temporal bone defects were limited to the inner ears are described. Several abnormalities were present that have not been described previously in this syndrome. The first case involved a 1-month-old female infant who died of congenital heart defects. Cochlear nerve fibers were absent on the left side, with near-normal innervation on the right. Although the organ of Corti was present bilaterally, some of the outer hair cells were deformed, having small rounded cell bodies unsupported by Deiters' cells. On the right, similar abnormal cells were found in the tunnel of Corti. Vestibular defects in this case included reduced nerve supply of the left saccular macula, cysts in the superior and posterior cristae, and absence of the utriculoendolymphatic valve. The second case involved a newborn male infant with multiple congenital anomalies. The major cochlear defect was a deformity of the stria vascularis. In the lower apical turn, the stria was adherent to Reissner's membrane and extended beneath it into scala media. Large capillaries, which ran freely suspended in scala vestibuli, entered the upper portion of the stria. Severe atresia of the lateral and posterior semicircular ducts was found in the vestibular apparatus.

Chromosomes, Human, 16-18↗

PubMedDate not supplied

Observations of human fetal otoconial membranes.

Intact otoconial membranes from 31 human fetuses ranging in gestational age from 14 to 36 weeks were studied. At all stages of development specimens from different individuals showed marked variations in overall shape. During the course of the second and third trimesters, both saccular and utricular otoconial membranes were found to increase three to fourfold in surface area and more than twofold in weight. Near the end of gestation the fetal specimens were about equal in area and weight to otoconial membranes from children up to 13 years of age. However, the crystal layers of the fetal membranes has less prominently developed surface contours than usually observed in children and adults, indicating that maturational changes continue after the time of birth.

Acoustic Maculae↗

PubMedDate not supplied

Absence of otoconia in a human infant.

Temporal bone specimens were obtained at autopsy from a six-week-old victim of sudden infant death syndrome. The inner ears were microdissected and studied by a combination of light and scanning electron microscopy. Otoconia were completely absent from the sensory organs of the saccule and utricle on both sides. However, the gelatinous otoconial membranes, neuroepithelia, and innervation were normal. In parallel with unusually light pigmentation of the skin in this Negro infant, relatively few melanocytes were found in the membranous walls of the saccule and utricle. No abnormalities were present in other inner ear structures. This anomaly, which we believe was congenital in nature, is strikingly similar to a genetically determined inner ear defect which has been extensively studied in experimental animals.

Acoustic Maculae↗

PubMedDate not supplied

Vaterite otoconia in two cases of otoconial membrane dysplasia.

Scanning electron microscopy, electron microprobe analysis, and x-ray powder diffraction were used to study temporal bone specimens obtained at autopsy from an infant with Potter syndrome and from a second trimester fetus, which was the product of an elective abortion. The mothers of both the infant and fetus were juvenile-onset rheumatoid arthritis patients who took prostaglandin inhibitors during pregnancy. The infant's external ears were low set and the left ear canal was stenotic. The vestibular maculae on the left were covered by aberrant otoconia composed of vaterite. In the right inner ear, otoconia were entirely absent, although the gelatinous otoconial membranes were intact. Only the left saccule and right utricle from the fetus were studied; both contained vaterite crystals similar to those in the infant. In addition, apatite was present in the fetal utricle, apparently lying on the macula beneath the vaterite otoconia.

Abnormalities, Multiple↗

PubMedDate not supplied

Auditory and temporal bone abnormalities in CHARGE association.

CHARGE association is a recently described cluster of congenital defects including ocular coloboma, heart disease, choanal atresia, retarded development and/or CNS abnormalities, genital hypoplasia, and ear anomalies. Although congenital hearing loss has been reported in CHARGE association, no information regarding the underlying temporal bone disease is available in the literature to date. The authors evaluated four patients with multiple anomalies consistent with CHARGE syndrome. Two surviving patients have bilateral severe hearing loss on auditory brain stem response testing. Two patients did not survive, and their temporal bones were obtained at autopsy for histologic examination. All four temporal bones showed severe middle ear defects including ossicular deformities, absence of the stapedius muscle, absence of the oval window, aberrant course of the facial nerve, and dehiscence of the facial nerve canal. In the more severely affected case, a Mondini-type malformation of the cochlea was present, together with multiple anomalies of the vestibular apparatus. Vestibular defects also occurred in the other case; however, the cochleae were found to be normally developed.

Abnormalities, Multiple↗

PubMedDate not supplied

Morphologic effects of glycerol and urea on cochlear tissues of the chinchilla.

Glycerol and urea are used as test agents in confirming the diagnosis of endolymphatic hydrops. Although both substances act as osmotic diuretics, recent evidence suggests that they may have differing physiologic effects on the inner ear. This study was designed to compare the morphologic effects of urea and glycerol on cochlear tissues, using the chinchilla as an experimental model. Animals were given subcutaneous injections of glycerol (2 g/kg) or urea (1.2 g/kg) over periods of 3 hours, 4 days, or 1 week. Both agents were found to produce ultrastructural changes, including spiral ligament vacuolization, intracellular alterations of the stria vascularis, and increased numbers of Hensen's bodies in outer hair cells. These alterations appeared indicative of metabolic stress, but not toxicity. The morphologic findings provided no evidence that glycerol and urea affect the inner ear by fundamentally different mechanisms of action.

Animals↗

PubMedDate not supplied

Anatomic considerations in the posterior approach to the internal auditory canal.

We dissected 30 human temporal bones in order to establish a reliable method for avoidance of the membranous labyrinth in acoustic neuroma surgery. We believe that the variability of the surgical landmarks is sufficient to make complete reliance on anatomic measurements quite treacherous. Fine-cut computed tomograms were evaluated, and it was determined that measurements taken from such scans can define the anatomy of individual temporal bones. We conclude that hearing conservation surgery for acoustic neuroma is a relatively difficult surgical exercise and that complete familiarity with the anatomy and use of all available landmarks is required for successful tumor removal and hearing conservation. Success can be improved further by using measurements taken from the individual patient's preoperative CT scan.

Dissection↗

PubMedDate not supplied

Pincoytosis in the pillar cells of the organ of Corti.

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Animals↗