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Biomedical subjects

M V Goycoolea

Publications and source records attributed to M V Goycoolea.

At least 19 recordsLinked to original sources

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.

Acute Disease

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.

Acepromazine

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.

Animals

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.

Adolescent

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.

Animals

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 therapeutically releasable amount of ampicillin is presented. This device is in an insertable shape that allows placement into the middle ear via a myringotomy 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.

Administration, Topical

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.

Adult

Otitis media. 16 years of pathogenesis approach.

The authors describe 16 years of their approach to research in otitis media, their rationale, and the concepts that have evolved from their experiments and clinical work. The authors suggest that interest is the key to progress and not laboratory facilities. They extend an invitation to individuals with different backgrounds but common interest in otitis media to work together from the standpoint of pathogenesis.

Animals

Anatomical perspective, approach, and experience with multichannel intracochlear implantation.

An overall review of the authors' anatomical perspective, approach, and experience with multichannel intracochlear implantation is presented. This report includes pertinent anatomical observations and experimental surgical procedures on fresh temporal bones. Although the scala tympani in the basal turn of the cochlea has an adequate space laterally for the insertion of electrodes, in the upper turns the adequate space is located medially. This is, in practice, the single-most limiting factor for an electrode, inserted via the round window, to reach the apical turns without damaging the basilar membrane. An experimental surgical procedure is described in which a second electrode is inserted in the middle turn via a mastoidotomy-tympanotomy approach and reaches a point near the apex. Studies of horizontal sections of human temporal bones include a review of potential structures that could be stimulated by the electrical currents generated by electrodes. The wall of the carotid artery, located at 750 microns from the basal turn at the level of the round window niche, is considered a potential structure to be affected by long-term stimulation. Anatomical principles and surgical considerations for the mastoidotomy-tympanotomy approach are described as an alternative to the facial recess approach. In the authors' experience, this procedure is technically easier, eliminates the possibility of postauricular flap complications, provides a better angle for insertion of electrodes, requires shorter hospitalization, and permits faster recovery than the facial recess approach. The authors' clinical approach, results, and observations are reviewed. Of note is a successful home-based rehabilitation program.

Adult

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 microns, and a diameter of 0.5 microns. 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.

Animals

Ultrastructural studies of the human round window membrane.

An ultrastructural study of 14 round window membranes of seven human ears 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 these layers participate in absorption and secretion of substances to and from the inner ear. A comparison of morphological features of round window membranes suggests that the average thickness of 70 microns does not change with advancing age. However, in the elderly, the connective tissue has a looser arrangement; there is an increase in ground substance; and elastic fibers thicken. Fibroblast nuclei become larger, rounder, and less uniform and have extensions. The ultrastructure of the "false round window membranes," with epithelial cells of the same type bounding both sides, suggests that these membranes consist of juxtaposed epithelial folds of the overlying promontory.

Aging

Racial and familial factors in otitis media. A point prevalence study on Easter Island.

Of the 249 children aged 5 to 9 years who live on Easter Island, 220 underwent complete otolaryngological evaluation. Twenty children were found to have otitis media (acute, chronic, or both). Three of these children were genetically impure natives, nine were of mixed parentage, and eight were "continentals" (with a birth origin other than the island). None of the genetically pure natives had otitis media. Our data show that, in a population with all factors in common except for familial and racial background, the point prevalence of otitis media is higher in children of mixed or continental origin than in genetically pure native children. The high prevalence of otitis media in children of mixed parentage and in one particular family of European ancestry suggests the presence of intrinsic or pronicity factors that are seemingly transmissible.

Acute Disease

Permeability of the human round-window membrane to cationic ferritin.

An ultrastructural study was done in three sequential steps to determine if the human round-window membrane was permeable to macromolecules. Cationic ferritin was first placed for one hour in the round-window niche of two live rhesus monkeys. The same tracer was then placed in the same manner in two rhesus monkeys that had been dead for one hour. In both groups, cationic ferritin was observed to traverse the round-window membrane through pinocytotic vesicles into the scala tympani. After establishing that the transport capabilities of the round-window membrane of the monkey remained present one hour after death, cationic ferritin was placed for one hour in the round-window niche of two humans who had been dead for 30 minutes and one hour. The tracer was observed to traverse the round-window membrane through pinocytotic vesicles into the scala tympani in both humans. This report may be the first to document morphologically the permeability of human round-window membranes to macromolecules.

Animals

Perilymphatic hypertension.

A syndrome termed perilymphatic hypertension is described as being seen in a small subset of patients with sudden sensorineural hearing loss. A patent or semipatent cochlear aqueduct or modiolus are considered precursors to this condition. Perilymphatic hypertension is believed to predispose to perilymphatic fistula, which may be part of the process of resolution. The pathogenesis for perilymphatic hypertension and fistula are hypothesized and discussed. Treatment for this subset of patients consisted of paracentesis of the round window membrane followed by grafting, with improvement of hearing in certain patients. In no instance did hearing subsequently decrease.

Auditory Threshold

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-micron 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-micron 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 author's viewpoint are discussed.

Animals