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Biomedical subjects

C G Wright

Publications and source records attributed to C G Wright.

At least 55 records · Page 3Linked to original sources
PubMed1988

Ototoxicity of Vasocidin drops applied to the chinchilla middle ear.

Some widely used ototopical preparations are potentially toxic to the middle and inner ear. Vasocidin Ophthalmic Solution (sulfacetamide sodium and prednisolone sodium phosphate) has been advocated as an alternative agent that may have fewer toxic side effects in the treatment of otorrhea. Vasocidin was introduced into the bullae of nine chinchillas to investigate the effects on the middle and inner ear. The organ of Corti and stria vascularis were found to be entirely normal in 17 of the 18 temporal bones studied. Changes observed in the middle ears at one week included inflammation, hemorrhage, and effusion. Examination of specimens at four weeks revealed resolution of most of the inflammatory changes. The results of this experimental study indicate that Vasocidin causes reversible middle ear inflammation with little or no toxic effect on inner ear structures.

Animals↗
PubMed1988

Effects of otic drops on chinchilla tympanic membrane.

Experimental studies have shown that if antibiotic otic drops reach the middle ear cavity they produce severe inflammation. However, the effects of these preparations on the tympanic membrane have not been thoroughly investigated. This study was designed to assess morphological changes in the chinchilla tympanic membrane two to 21 days after a single 0.2-mL application of an antibiotic otic preparation (Cortisporin Otic Suspension) to the middle ear cavity. At two days, the epidermal and the mucosal layers were destroyed. By four days, reepithelialization had occurred and all layers of the tympanic membrane subsequently became markedly hyperplastic. Disruption of the fibrous layer, invasion of keratinizing epidermis to the medial surface, and perforation were observed at three weeks. These findings indicate that tympanic membrane damage is a potentially significant aspect of the ototoxic properties of topical otic preparations.

Animals↗
PubMed1987

The role of insulin resistance in the pathogenesis of myotonic muscular dystrophy.

A study of glucose, insulin, lipids and lipoproteins in myotonic dystrophy (MyD) has shown elevation of fasting plasma insulin, triglycerides and very low density lipoproteins (VLDL) but no significant difference from normal in the fasting plasma glucose, total cholesterol or low and high density lipoproteins. Elevation of the total triglyceride and VLDL levels showed a direct relationship to hyperinsulinaemia. Insulin binding to cultured MyD fibroblasts under optimal conditions was significantly reduced but there was no difference in receptor affinity between MyD and control cells. In contrast to insulin binding, LDL binding to MyD fibroblasts was normal although there was a tendency to reduced LDL binding at 37 degrees C that may reflect mildly reduced lipid metabolism. The alterations in lipids and insulin in MyD are compatible with insulin resistance. Laboratory and clinical findings in MyD were compared with other inherited insulin-resistant diseases. MyD showed marked similarity to a group of disorders that have mild insulin resistance and mildly elevated plasma insulin in contrast to others with severe hyperinsulinaemia and insulin resistance. It is suggested that at least some clinical features of MyD may be due to diminished overall effect of insulin or other trophic factors on cell metabolism.

Adolescent↗
PubMed1987

Ototoxicity of neomycin and polymyxin B following middle ear application in the chinchilla and baboon.

Previous experimental studies have demonstrated structural damage of the organ of Corti and stria vascularis following application of combination antibiotic otic drops to the middle ear. In this investigation the ototoxic effects of neomycin and polymyxin B (two antibiotics often used together in ototopical preparations) were separately evaluated after administration of each agent to the middle ear cavities of chinchillas and baboons. The antibiotics were administered in saline solution at the same concentrations used in Cortisporin Otic Suspension (3.5 mg/ml neomycin base, 10,000 units/ml polymyxin B). In both the rodent and primate, polymyxin B consistently produced greater cochlear damage than did neomycin. In fact, the extent of hair cell loss and strial injury produced by polymyxin B alone was, in many cases, comparable to that previously observed after application of Cortisporin Otic Suspension itself. Hair cell loss in the baboon was markedly less severe than in the chinchilla. It is believed that differences in position and structure of the round window membrane are important factors in the differing levels of ototoxicity observed in the rodent and primate.

Animals↗
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↗
PubMed1986

A balanced translocation in mice with a neurological defect.

A semisterile male translocation heterozygote [t(2; 14) 1Gso] that exhibited neurological symptoms and an inability to swim (diver) was found among the offspring of male mice treated with triethylenemelamine. All breeding and cytogenetic data showed a complete concordance between translocation heterozygosity and the neurological disorders. Homozygosity for the translocation seemed to be lethal at an early embryonic stage. Despite the distinctive neurologic symptoms, no anatomic or histological defects in either the ear or in the central nervous system were observed. Thus, a balanced chromosomal translocation can produce disease with an inheritance pattern that mimics a single dominant gene defect.

Animals↗
PubMed1985

Ototoxicity of low- and moderate-dose cisplatin.

Twenty-four patients with head and neck neoplasms were prospectively evaluated for cisplatin (DDP)-induced ototoxicity. Patients were selected from a larger population based on the uniformity of their chemotherapy regimen, renal status, lack of prior or concurrent exposure to ototoxic agents, and availability for repetitive audiometric testing in the same setting. Scanning electron microscopy of the inner ear was performed on four temporal bones. Hearing impairment was found to be dose-related, irreversible within the confines of the study period, and primarily in the higher frequencies. Vestibular toxicity was rare and well-documented by our testing methods in only one patient. Based on the results of this study, and a review of animal and human data on DDP ototoxicity, the authors concluded that ototoxic screening should be reserved for patients defined as "at risk" and those patients receiving more than 400 mg of DDP under the conditions stated in this report.

Aged↗
PubMed1985

A morphometric technique for analysis of cochlear vessels.

A computer based system was developed for morphometric analysis of the cochlear lateral wall vasculature. Variables measured were vascular density, RBC density, vessel width, aggregation density, lumen compression count, WBC count and pigment density. Vessels were divided into three systems based on the lateral wall structures that they supplied. The results indicated that these three vessel systems were morphologically distinct in terms of their vascular density, RBC density, and vessel width. How these differences relate to functional needs of the lateral wall is discussed.

Animals↗
PubMed1985

A morphometric study of microvascular pathology following experimental rupture of Reissner's membrane.

In a previous paper (this volume) we described a method for evaluating the cochlear microvasculature. This method was applied to the analysis of lateral wall tissue from chinchillas sacrificed 1 h, 24 h, 1 week and 3 weeks after surgical rupture of Reissner's membrane. The degree, direction, and time course of pathological changes seen in the microvessels were different for the system of stria vascularis vessels, the system of spiral ligament vessels, and the system of spiral prominence vessels. These results indicate that it is important to evaluate all of the lateral wall vessels rather than just the stria vascularis, and emphasize the importance of dividing the microvasculature into three independent systems, in order to obtain a clearer perspective on microvascular changes which occur following cochlear trauma.

Animals↗
PubMed1984

A "new" lethal multiple congenital anomaly syndrome: joint contractures, cerebellar hypoplasia, renal hypoplasia, urogenital anomalies, tongue cysts, shortness of limbs, eye abnormalities, defects of the heart, gallbladder agenesis, and ear malformations.

Three cases of a lethal malformation syndrome with severe visceral anomalies were seen in two families and include one pair of sibs. The predominating external manifestations are mesomelic dwarfism, micrognathia, V-shaped upper lip, microglossia, thick alveolar ridges, ambiguous genitalia, webbed neck, highly arched palate, clubfeet, fused fontanelles, inclusion cysts of the tongue, four-finger creases, digital anomalies, apparently low-set ears, widely spaced nipples, and dislocated thighs and forearms. The internal findings include oligopapillary renal hypoplasia, severe congenital heart defect, cerebellar hypoplasia, pulmonary hypoplasia, hypoplastic larynx, and hypoplastic gallbladder. Other findings from the two autopsies and one clinical investigation not documented in all three patients include unilobar lungs, hydrocephalus, cataracts, microphthalmia, polydactyly, islet cell hyperplasia, suprapubic skin crease, urethral anomalies, and a decreased number of turns of the cochlea. The hypoplasia seen in the several affected organs is similar to the disordered development seen in experimental models of branching epithelial morphogenesis in which mesenchymal-epithelial interaction has been disrupted.

Abnormalities, Multiple↗
PubMed1984

Surface morphology of the inner sulcus and related epithelial cells of the cochlea following acoustic trauma.

When the organ of Corti is severely traumatized by intense (160 dB) blast waves, such that as much as 7 mm of Corti's organ is torn loose from the basilar membrane, the cells of the inner sulcus respond to the altered biochemical milieu of the endolymph by a profile elaboration of surface membrane, zeiosis and the development of numerous pseudopodia and microvilli. On the basis of our longitudinal study, this surface reaction appears to peak at approximately 10 days after trauma and may indicate that the inner sulcus cells are extremely active in the endocytosis of cellular debris. Signs of active changes on the surface of the inner sulcus cells occur immediately following trauma, and activity continues for as long as 30 days after exposure. The cells of Claudius, as well as other epithelial cells on the basilar membrane, are also capable of extreme membrane proliferation and mobility. Possible mechanisms for the unusual behavior and the role of the inner sulcus cells in the normal functioning cochlea are discussed.

Animals↗
PubMed1984

Inflammatory effects of otic drops on the middle ear.

Combination topical otic preparations are used to treat many infections of the external and middle ears. Despite the presence of ototoxic drugs in a number of these drops and convincing evidence of sensorineural hearing loss in humans and animal studies (Meyerhoff et al., presented at Southern Section Triological Meeting, Jan. 1983) following use of these medications, otic drops remain the cornerstone of treatment for many infectious disorders of the ear. Twelve chinchillas underwent bilateral tympanostomy tube placement and daily instillation of Cortisporin Otic Suspension (polymyxin B, neomycin, hydrocortisone, propylene glycol) in the right external auditory canal for 7 consecutive days. The animals were sacrificed 3 days later, 10 days following initiation of the Cortisporin Otic Suspension treatment. Following routine preparation of the temporal bones for light microscopy, the tissue was evaluated for evidence of inflammatory changes. All 12 animals demonstrated granulation tissue, effusion and focal hemorrhage in the ears subjected to the Cortisporin Otic Suspension. All of the contralateral control ears were normal. The present data suggest that this inflammatory response is due to a topical irritant effect of the otic preparation.

Animals↗
PubMed1983

Tympanostomy tubes and otic drops.

Otic drops have been proposed as a form of prophylaxis against the otitis media which follows middle ear contamination by water in patients with tympanostomy tubes. The potential adverse effects of this form of therapy were studied in chinchillas with tympanostomy tubes; 31 chinchillas underwent bilateral tympanostomy tube insertion. Seven animals had a mixture of green dye and Cortisporin otic suspension placed in both external auditory canals 24 hours following the placement of tympanostomy tubes and were sacrificed 30 minutes later for gross examination; 3 of these animals had previous eustachian tube obstruction with Silastic sponge. Twenty-one animals had Cortisporin otic suspension placed in the right external auditory canal on postoperative days 3, 4, 5, 6 and 7. No otic drops were placed in the left ear. Ten of these 20 animals had VIIIth nerve action potentials measured on postoperative day 17 and the other 11 animals had VIIIth nerve action potentials measured on postoperative day 42 followed by immediate sacrifice for histological examination and scanning electronmicroscopy. The remaining 3 animals had VIIIth nerve action potentials measured 21 days following tympanostomy tube insertion and served as electrophysiological controls. The 8 ears receiving Cortisporin otic drops mixed with green dye from animals with normal eustachian tubes showed staining of the round window membrane at sacrifice, while the 6 ears receiving Cortisporin otic suspension and green dye from animals with eustachian tube obstruction demonstrated no dye in the middle ear. All animals receiving Cortisporin otic drops in the right ear showed an intra-aural difference in action potentials with the right ear being attenuated by an average of 10.3 dB at 2,000 Hz, 12 dB at 4,000 Hz, 21 dB and 8,000 Hz, and 26 dB at 12,000 Hz. Morphological study revealed hair cell loss in the hook portion of the cochlea in those animals receiving Cortisporin otic drops. It was concluded from this study that, in patients with patent tympanostomy tubes in place, potentially ototoxic topical agents should be used with caution.

Action Potentials↗