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Biomedical subjects

R A Chole

Publications and source records attributed to R A Chole.

At least 37 records · Page 2Linked to original sources

Unusual lesions of the internal auditory canal.

Tumor types other than acoustic neuromas are uncommonly encountered in the cerebellopontine angle, and unusual lesions limited to the internal auditory canal (IAC) are given more rare. We present five patients with unusual tumors of the IAC including two meningiomas, two arachnoid cysts, and a hemangioma. These unusual tumors, and lipomas, are discussed. Particular attention is paid to the pathophysiology of the lesions and treatment recommendations. The differential diagnosis of intracanalicular lesions using magnetic resonance imaging is also presented.

Adolescent↗

In vivo effects of surgical sympathectomy on intramembranous bone resorption.

Bone modeling and remodeling are highly regulated processes in the mammalian skeleton. The exact mechanism by which bone can be modeled at a local site with little or no effect at adjacent anatomic sites is unknown. Disruption of the control of modeling within the temporal bone may lead to various bone disease such as otosclerosis, osteogenesis imperfecta, Paget's disease of bone, fibrous dysplasia, or the erosion of bone associated with chronic otitis media. One possible mechanism for such delicate control may be related to the ubiquitous and rich sympathetic innervation of all periosteal surfaces. Previous studies have indicated that regional sympathectomy leads to qualitative alterations in localized bone modeling and remodeling. In this study, unilateral cervical sympathectomy resulted in significant increases in osteoclast surface and osteoclast number within the ipsilateral bulla of experimental animals. The mechanisms by which sympathectomy leads to increased local bone loss is unknown. Potential mechanisms include disinhibition of resorption, secondary to the elimination of periosteal sympathetics, as well as indirect vascular effects.

Animals↗

Antimicrobial activity of silastic tympanostomy tubes impregnated with silver oxide. A double-blind randomized multicenter trial.

OBJECTIVE: To test the null hypothesis that impregnation of tympanostomy tubes with silver oxide did not alter the rate of postintubation otorrhea. DESIGN: Multicenter, double-blind, randomized clinical trial. OUTCOME MEASURE: Rates of postoperative otorrhea during a 1-year study in ears implanted with Silastic tubes compared with contralateral, identical tubes impregnated with silver oxide. SETTING AND PARTICIPANTS: Eight sites in the United States, 125 children aged 1.5 months to 12 years who had bilateral otitis media with effusion or bilateral recurrent acute otitis media. RESULTS: The overall incidence of postoperative otorrhea was 9.78% in the control ears and 5.08% in the ears with silver oxide-impregnated tubes (P = .01), but no effect was seen during the immediate postoperative period. Granulation tissue was seen adjacent to the tube during two visits in the ears with standard tubes (0.54%) and during two visits in the ears with experimental tubes (0.53%); cholesteatomas did not occur in either group. CONCLUSION: Silastic tubes impregnated with silver oxide seem to diminish the incidence of postoperative otorrhea in ears requiring long-term ventilation.

Anti-Infective Agents↗

In vivo inhibition of localized bone resorption by human recombinant interleukin-1 receptor antagonist.

Interleukin-1 (IL-1) has been implicated as a primary mediator of bone remodeling; it is a powerful activator of bone resorption both in vivo and in vitro. However, there is no direct evidence that IL-1 plays a role in physiological bone modeling or remodeling. Interleukin-1 receptor antagonist (IL-1ra) is a member of the IL-1 family, which bind to IL-1 receptors and blocks the action of IL-1 alpha and IL-1 beta. We have previously shown that IL-1ra blocks IL-1-induced bone resorption in vitro. Evidence is reported here that human recombinant IL-1ra (hrIL-1ra) inhibits strain-induced modeling in the gerbil auditory bulla while having no significant effect on apposition rate. Pressurization of the auditory bulla to 10 mm Hg above atmospheric pressure increased osteoclast surface from 3.62 to 19.14%. Infusion of hrIL-1ra during pressurization resulted in significant inhibition of osteoclast surface on the pressurized side. These findings suggest that IL-1 is a physiological mediator of bone modeling and that hrIL-1ra inhibits resorption but not apposition in the auditory bulla model.

Animals↗

Reversible blindness secondary to acute sphenoid sinusitis.

Sphenoid sinusitis is an elusive diagnosis with significant morbidity if not diagnosed and treated promptly. We have reported an unusual case of acute sphenoiditis mimicking Gradenigo's syndrome. This resulted in virtual bilateral blindness that entirely resolved with aggressive surgical and medical treatment. It is recommended that sphenoid sinusitis be strongly considered in patients with acute headache and fever. A detailed cranial nerve examination should be performed, and CT scans of the skull base and paranasal sinuses should be obtained. Immediate surgery is strongly recommended for acute sphenoid sinusitis at the first suggestion of a complication and in those patients not promptly responding to medical therapy. It is apparent that irreversible damage to the optic nerve can occur before the development of gross intraorbital pathology. Therefore we believe that delaying surgery until the visual acuity is worse than 20/60, as advocated by some authors, may not be in the patient's best interest. Surgery should be directed at removing the purulent material, obtaining cultures, removing irreversibly diseased mucosa, and maintaining drainage of the sphenoid sinus.

Acute Disease↗

Tinnitus, vertigo, and temporomandibular disorders.

Although tinnitus and vertigo have been reported as associated with temporomandibular disorders (TMD) for many years, no control studies have been reported. This study was designed to include two large control populations, as well as a large TMD sample. The null hypothesis was tested. The results revealed that tinnitus and vertigo were significantly more prevalent in the TMD group than in either control group. Reasons for the association of TMD and these otologic symptoms have been proposed and they are discussed. Presently the cause is unknown.

Adolescent↗

A mechanism for sympathectomy-induced bone resorption in the middle ear.

BACKGROUND: Recent investigations have demonstrated a link between sympathectomy and osteoclast-mediated bone resorption. The exact nature of this link, however, is unknown. We hypothesize that substance P, a potent vasoconstrictive neuropeptide found in peripheral sensory fibers, including those innervating bone, is the mediator of this phenomenon. To test this theory, the effects of substance P on in vitro calcium release from cultured neonatal mouse calvaria were assessed. In addition, an in vivo study was conducted whereby gerbils were injected with capsaicin to eliminate substance P-containing fibers before sympathectomy with 6-hydroxydopamine. If the effects of 6-hydroxydopamine were eliminated by prior administration of capsaicin, the role of sensory nerves in sympathectomy-induced resorption would be strongly implicated. IN VITRO STUDY: Substance P at 10(-8) mol/L was incubated with eight newborn Swiss-Webster mouse hemicalvarial explants and compared with explants incubated in control media alone. The neonatal mice were euthanized at day 3, and their hemicalvaria were preincubated in 2 ml of stock media without treatment for 24 hours at 36.5 degrees C as a stabilization period. After the stabilization period, the stock media were replaced with 2 ml of fresh control media or media containing substance P at 10(-8) mol/L. A similar experiment was performed with the addition of indomethacin at 5 x 10(-7). The explants were then incubated for 72 hours with gassing every 12 hours with a mixture of O2, N2, and CO2. At the end of the 72-hour period, the media were analyzed for calcium content by atomic absorption spectrophotometry and compared by one-way analysis of variance with Bonferroni-corrected post hoc tests. IN VIVO STUDY: Forty-eight Mongolian gerbils were placed into four groups: group 1 received intraperitoneal injections of 6-hydroxydopamine at 75 micrograms/gm body weight on days 1, 2, 6, 7, and 8; group 2 received identical injections of hydroxydopamine, but 12 hours after receiving subdermal injections of capsaicin at 50 micrograms/gm body weight; group 3 received only subdermal injections of capsaicin; and group 4 received only saline injections to serve as controls. Seven days after treatment, the animals were euthanized, and the ventral wall of each animal's right bulla was resected and quantified for osteoclast number and surface with a computer-based histomorphometry system. Analysis was then made by one-way analysis of variance with Bonferroni-corrected post hoc tests. RESULTS: The results of the in vitro study revealed that substance P at 10(-8) mol/L (11.05 +/- 3.37 micrograms/ml) induced significant calcium release from cultured neonatal mouse calvaria when compared with control bone incubated in base media alone (0.92 +/- 2.85 micrograms/ml, p < 0.01). The process was completely inhibited by 5.0 x 10(-7) indomethacin. The results of the in vivo study showed 6-hydroxydopamine treatment significantly increased both the osteoclast number (NOc/TL = 3.14 +/- 1.33/mm) and the osteoclast surface (OcS/BS = 16.04% +/- 6.95%) of bone when compared with bone from saline-treated controls (NOc/TL = 1.77 +/- 0.79/mm, p < 0.01; OcS/BS = 8.88% +/- 4.15%, p < 0.01). These 6-hydroxydopamine-induced increases were eliminated, however, in animals pretreated with capsaicin before sympathectomy (NOc/TL = 1.86 +/- 0.68/mm, p > 0.05; OcS/BS = 9.92 +/- 3.73, p > 0.05), whereas treatment with capsaicin alone had no effect when compared with bone from saline-treated controls (NOc/TL = 2.02 +/- 0.50/mm, p > 0.05; OcS/BS = 10.28% +/- 2.62%, p > 0.05). Substance P has thus been shown to induce calcium release from membranous bone in vitro, whereas capsaicin, a substance P-specific sensory neurolytic chemical, eliminates the in vivo osteoclast-inductive effects of 6-hydroxydopamine when given 12 hours before treatment. The results indicate that substance P is capable of inducing resorption and that substance P-containing sensory ne

Animals↗

Safety of silver oxide-impregnated silastic tympanostomy tubes.

Otorrhea occurs after the insertion of tympanostomy tubes in as many as 50% of ears. Although topical antibiotic solutions minimize otorrhea in the immediate postoperative period, recurrent otorrhea is sometimes a clinical problem. The antimicrobial effects of silver oxide when impregnated into a tympanostomy tube may decrease the incidence of recurrent otorrhea. This study demonstrates that silver oxide-impregnated silicone elastomer is well tolerated within the middle ear of gerbils when implanted for 1 year, and the tissue reaction is no more than silicon elastomer without silver oxide. When applied directly to the round window of guinea pigs, there was no evidence of ototoxicity of silver oxide as measured by electrocochleography (N-1 thresholds) and cytocochleography (hair cell counts). These animal studies indicate that silver oxide-impregnated silicone elastomeric tympanostomy tubes may be used safely in clinical trials to determine efficacy.

Animals↗

Human recombinant interleukin-1 receptor antagonist blocks bone resorption induced by interleukin-1 beta but not interleukin-1 alpha.

Both interleukin-1 alpha (IL-1 alpha) and interleukin-1 beta (IL-1 beta) are powerful stimulators of bone resorption in vivo and in vitro. Interleukin-1 receptor antagonist (IL-1ra) binds to many interleukin-1 receptors. It does not activate the receptor and effectively blocks the action of IL-1 alpha and IL-1 beta. In this study, human recombinant IL-1ra, at 100-fold excess, was found to block bone resorption in cultured mouse calvaria due to IL-1 beta but not IL-1 alpha. These observations may be explained by differential affinities of receptors for IL-1 alpha, IL-1 beta and rhIL-1ra on target bone cells.

Analysis of Variance↗

Bone lining cells of the mammalian cochlea.

It is generally believed that all bone surfaces are covered by a nearly continuous layer of cells known as bone lining cells (BLC) which separate the general extracellular fluid (GECF) from bone and its fluid compartment. Within the cochlea of some mammals regions of bone matrix are exposed to extracellular fluid. Within the scalae of the cochlea, perilymph is in contact with bone matrix; there is no evidence of a lining endothelium. Within the modiolus and subjacent to the spiral ligament, bone matrix is in contact with GECF. These findings may have importance in understanding calcium homeostasis within the scalae and may relate to the pathophysiology of labyrinthitis ossificans. Additionally, since BLCs probably represent a specific phenotype, the presence of a pure population of BLCs within the scalae may provide a source for the development of a pure culture of this cell.

Animals↗

Apical cochlear nerve exposed to perilymph in the gerbil and rat.

There is considerable controversy regarding the origin and composition of perilymph in the scala vestibuli and scala tympani and the barriers and transport mechanisms between them. To elucidate the anatomical separation between perilymph and the extracellular fluid which surrounds the cochlear nerve in Mongolian gerbils (Meriones unguiculatus) and Sprague Dawley rats (Rattus rattus) we examined the modiolus, osseous spiral lamina and the bone of the perilymphatic scalae using light and electron microscopy. Although the cochlear nerve, spiral ganglion and their extracellular fluid are separated from perilymph by the bone of the modiolus in the middle and basal turns, no bone separates these neural structures from perilymph in the apical turn in the two species examined. Instead, the spiral ganglion and axonal elements of the apical turn were covered by a continuation of the bone lining cell layer of the scala tympani. Gaps between lining cells appeared to provide direct communication between the perilymphatic fluid and the extracellular fluid investing the cochlear nerve. Various authors have described openings in modiolar bone in both the scala vestibuli and the scala tympani. While the bone and cellular covering of the modiolus in the basal middle turns of the cochlea is not presumed to be a complete barrier to fluid exchange between the two scalae and the modiolar canal it can be expected to impose some limitation on the rate of passive diffusion. Therefore our data indicates that in the apical turn of the Mongolian gerbil and Sprague-Dawley rat there may be a more significant communication between perilymph and the extracellular fluid and neural elements of the apical modiolar canal than previously reported.

Animals↗

Ossiculoplasty with presculpted banked cartilage.

The use of self-stabilizing, presculpted cartilage homografts for middle ear reconstruction has an established track record with long-term results equivalent to reconstruction methods using alloplastic material. This method affords several advantages over other techniques, which will be discussed in detail.

Cartilage↗

Incomplete coverage of mammalian bone matrix by lining cells.

A functional "membrane" is thought to exist that separates the general extracellular fluid from the bone extracellular fluid. Many investigators have concluded that bone lining cells form this barrier. It is posited that alterations in this barrier may lead to the recruitment of osteoclasts and contribute to the control of extracellular calcium homeostasis. The present ultrastructural studies, however, demonstrated that significant portions of the resting bone are in contact with the general extracellular fluid. In certain regions of the cochlea, up to 88% of the bone surface is in contact with extracellular fluid. These anatomic observations require a critical reevaluation of current theories of the physiologic roles of bone lining cells in osteoclast recruitment and calcium homeostasis.

Animals↗

Differential osteoclast activation in endochondral and intramembranous bone.

Osteoclast activation within the temporal bone leads to hearing loss in a variety of pathologic conditions, including otosclerosis, osteogenesis imperfecta, Paget's disease of bone, and chronic otitis media. Although endochondral (EC) bone is remodeled in these diseases, it is relatively more resistant to remodeling when compared to intramembranous (IM) bone. In this study, localized bone resorption and remodeling were induced on the inner surface of the middle ear by pressurization with air to 10 mm Hg above atmospheric. Osteoclast surface increased in IM bone, but not in EC bone. This study supports the concept that there may be fundamental differences between EC and IM bone and that EC is more resistant to pressure-induced localized resorption than IM bone.

Animals↗

Dexamethasone inhibition of the development of dysplastic bony lesions in LP/J mice.

Inbred LP/J mice have been observed to spontaneously develop abnormal bony lesions of the ossicles and otic capsule that progress throughout the life of the animals. This genetically inherited murine disorder produces bony lesions that share some gross and histologic features with bony lesions seen in human tympanosclerosis. Previous studies on LP/J mice have demonstrated evidence of immunologically mediated injury in the progression of the newly forming bony lesions. This study was designed to examine the effects of dexamethasone on the development of the bony lesions in LP/J mice. The purpose was to attempt to elucidate the relationship of the immunologic injury observed in earlier studies and the progression of the dysplastic bony lesions. The results show that LP/J mice treated with dexamethasone developed significantly fewer dysplastic bony lesions compared to the age-matched, saline-treated controls. There was also a statistically significant difference in the quantity and cellularity of the middle ear effusions between the experimental and control animals.

Animals↗

Risedronate activity in the fetal and neonatal mouse.

Otosclerosis, chronic otitis media with and without cholesteatoma, and Paget's disease of bone are just a few of the many diseases of the ear that exhibit abnormalities of bone modeling and remodeling. These diseases result in chronic infection, vestibular dysfunction, and hearing loss. Bisphosphonates are a promising new class of drugs potentially useful in the treatment of these disorders. Currently used in diseases with high rates of bone turnover (Paget's disease of bone, hypercalcemia of malignancy, and osteoporosis), they have been found to be strong inhibitors of bone resorption. A third generation bisphosphonate, 2-(3-pyrindyl)-hydroxyethylidene bisphosphonate (risedronate) is being investigated for toxicity, increased efficacy, and oral administration. In this study the in vitro and in vivo anti-resorptive activity of risedronate was quantified by measuring calcium release in a neonatal mouse calvarial culture system. This model was used to test direct in vitro effects, in vivo exposure in neonatal mice, and the possible effects of in utero and lacteal exposure. Calcium release activated by parathyroid hormone (PTH) was significantly inhibited when risedronate was only present in the pre-incubation media. When risedronate was administered subcutaneously to neonatal mice it resulted in a significant decrease in PTH-activated calcium release in explanted calvaria in vitro. Transplacental and lactational transfer of biologically effective risedronate was not demonstrated in this study; however, a paradoxic increase in PTH-stimulated calcium release in vitro from calvaria theoretically exposed transplacentally and lacteally was noted. This effect was unexplained by the data.

Analysis of Variance↗

Tinnitus and vertigo in patients with temporomandibular disorder.

The association of tinnitus and vertigo with temporomandibular disorder (TMD) has been debated for many years. The observation that patients with TMD have otologic symptoms is confounded because tinnitus and vertigo are common symptoms in the normal population. The present study was conducted to determine if tinnitus and vertigo are actually more prevalent in patients with TMD than in appropriate age-matched controls. One control group was recruited from patients seeking care for health maintenance and the other from patients seeking routine dental care. We surveyed 1032 patients: 338 had TMD and 694 served as two age-matched control groups. Tinnitus and vertigo symptoms were significantly more prevalent in the TMD group than in either of the control groups. The mechanism of the association of TMD and otologic symptoms is unknown.

Adolescent↗