Hilary Brodie - Academia.edu (original) (raw)

Papers by Hilary Brodie

Research paper thumbnail of MR, CT, and Plain Film Imaging of the Developing Skull Base in Fetal Specimens

BACKGROUND AND PURPOSE:The developing fetal skull base has previously been studied via dissection... more BACKGROUND AND PURPOSE:The developing fetal skull base has previously been studied via dissection and low-resolution CT. Most of the central skull base develops from endochon- dral ossification through an intermediary chondrocranium. We traced the development of the normal fetal skull base by using plain radiography, MR imaging, and CT. METHODS: Twenty-nine formalin-fixed fetal specimens ranging from 9 to 24 weeks'

Research paper thumbnail of A Pilot Study on the Efficacy of Continuous Positive Airway Pressure (CPAP) on the Manifestations of Ménière's Disease in Patients with Concomitant Obstructive Sleep Apnea Syndrome (OSAS)

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 11, 2015

To evaluate the effect of CPAP therapy on Ménière's disease patients with concomitant OSAS, s... more To evaluate the effect of CPAP therapy on Ménière's disease patients with concomitant OSAS, since recent reports suggest OSAS may cause dysfunction of the vestibular system. Prospective study using CPAP administered to patients diagnosed with "Definite Ménière's disease" according to the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery and combined with OSAS. University hospital. Twenty consecutive patients, 14 male and 6 female with active, unilateral, cochleovestibular Ménière's disease refractory to medical management who also had concurrent OSAS as defined by International Classification of Sleep Disorders II were selected to undergo solitary CPAP therapy. Audiometric testing, caloric testing, and DHI survey were conducted before and after CPAP therapy and compared to assess effectiveness of CPAP therapy as utilized for treatment of Ménière's disease. Although caloric testing did not show significant difference, audiometric tes...

Research paper thumbnail of Role of Tumor Necrosis Factor-?? in Sensorineural Hearing Loss after Bacterial Meningitis

Otology & Neurotology, 2005

Research paper thumbnail of Imaging findings of the developing temporal bone in fetal specimens

AJNR. American journal of neuroradiology, 1996

To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and... more To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT. Eighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed. The membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth. The study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning tec...

Research paper thumbnail of Impaired quality of sleep in Ménière's disease patients

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 15, 2010

To evaluate the quality of sleep in Ménière's disease patients with the use of polysomnograph... more To evaluate the quality of sleep in Ménière's disease patients with the use of polysomnography. Prospective study using polysomnography administered in patients diagnosed as "Definite Meniere's disease cases" according to the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. Thirty-five patients, 17 male and 18 female, aged 31 to 71 (58 average) years with active, unilateral, cochleovestibular Ménière's disease refractory to medical management underwent polysomnography. The results were compared with 35 healthy controls matched for age and sex. All participants underwent full-night polysomnography, and a sleep medicine physician interpreted the results. Total sleeping time in Ménière's disease was significantly higher than in controls. Stage 2 sleep was significantly longer and stage 3+4 shorter in Ménière's disease than controls, while there was no difference of stage 1 and REM. Arousal index was significantly higher in Ménièr...

Research paper thumbnail of Inhibition of post-meningitic cochlear injury with cerebrospinal fluid irrigation

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2006

Labyrinthitis ossificans, the pathologic ossification of the otic capsule associated with profoun... more Labyrinthitis ossificans, the pathologic ossification of the otic capsule associated with profound deafness and loss of vestibular function occurs frequently as a sequella of bacterial meningitis and subsequent purulent labyrinthitis. Experimentally, in Streptococcus pneumoniae meningitis, it has been shown that a vigorous inflammatory response to teichoic acids in the bacterial cell wall contributes to cochlear damage and subsequent fibrosis and ossification. The hypothesis of this study is that a dilution of concentration of inflammatory mediators through cerebrospinal fluid (CSF) irrigation will lead to a reduction in both inner ear pathology and permanent hearing loss. Auditory brainstem response testing was used to determine baseline hearing thresholds in 20 Mongolian gerbils (12 irrigated, 8 sham irrigated animals) at 32 kHz, 16 kHz, 8 kHz, and 4 kHz frequencies. Their thresholds at 14 days and 120 days post-procedure were also obtained. Streptococcus pneumoniae meningitis was...

Research paper thumbnail of Head and neck malignant metastasis to the cerebellopontine angle

Objectives: To present 3 patients with isolated metastatic lesions to the cerebellopontine angle ... more Objectives: To present 3 patients with isolated metastatic lesions to the cerebellopontine angle (CPA). The patient’s histories and clinical courses are reviewed.Methods: Clinical chart reviews of 3 patients with head and neck malignant lesions metastatic to the CPA was conducted.Results: The first patient had a temporal squamous skin cancer involving the temporal bone requiring a lateral temporal bone resection. The

Research paper thumbnail of Developmental assembly of transduction apparatus in chick basilar papilla

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 26, 2003

Hair cells, the sensory receptors of auditory and vestibular systems, use a transducer apparatus ... more Hair cells, the sensory receptors of auditory and vestibular systems, use a transducer apparatus that renders them remarkably sensitive to mechanical displacement as minute as 1 nm. To study the embryonic development of the transducer apparatus in hair cells of the chick auditory papilla, we examined hair cells that have been labeled with N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridiniumdibromide, which has been shown to permeate the transducer channels. In addition, mechanotransduction currents were recorded directly using whole-cell patch-clamp techniques. The structure of the hair bundle was examined using scanning electron microscopy, and immunofluorescence labeling for myosin 1c, myosin 7a, and plasma membrane Ca2+ ATPase 2 was studied to determine the developmental expression of these proteins in embryonic chick papillas. We demonstrate that the transducer apparatus is assembled jointly at embryonic day 11 (E11) of the developing chick basilar papilla. The res...

Research paper thumbnail of The editors and editorial board of the ARCHIVES would like to thank all of the dedicated peer reviewers who provide their expertise, insight, and judgment when reviewing manuscripts for publication. We extend a special appreciation to the reviewers listed below for their service in 2002

Research paper thumbnail of Chronology of labyrinthitis ossificans induced by streptococcus pneumoniae meningitis

The Laryngoscope, 1999

Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear a... more Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. A prospective randomized double-blind study. By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in six groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S. pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans.

Research paper thumbnail of Location and Timing of Initial Osteoid Deposition in Postmeningitic Labyrinthitis Ossificans Determined by Multiple Fluorescent Labels

The Laryngoscope, 2004

Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis... more Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis. The purpose of the study was to delineate the timing and location of initial ossification following pneumococcal meningitis, as well as subsequent remodeling and resorption, over the 3-month period after infection. Randomized, double-blind study. Fluorochromes are compounds that specifically incorporate into ossifying bone. Sequential addition of different colored fluorochromes during osteoneogenesis define the timing and location of osteoid deposition and mineralization. Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3, and control gerbils received saline. Both groups were injected with calcein on postoperative day 3, followed by xylenol orange, oxytetracycline, and alizarin red on days 7, 14, and 28 respectively. Ten experimental gerbils were killed 24 hours after each label, and an additional group at 84 days after infection. Two groups of 10 control gerbils were killed at 29 and 84 days after treatment. The temporal bones and tibias were harvested, embedded in plastic, and sliced with a diamond saw. Wafers at a thickness of 200 microm were mounted in sequence and examined. Sixteen of 49 experimental animals (33%) were positive for at least one of the fluorescent labels. Fluorescent labeled osteoid was present at all sampling times. Label extended from the endosteal wall into the lumen of the scala tympani between the vestibule and the round window membrane. Discrete sites of fluorescence varied among specimens and were associated with the opening of the cochlear aqueduct, the scala tympani, organ of Corti, and the stria vascularis and spiral ligament in all turns from base to apex. The results indicate that osteoid is deposited and begins mineralization by day 3 after infection, at least, and continues, at least, through the first 28 days after infection. There was no apparent resorption of new bone and remodeling by 84 days after infection.

Research paper thumbnail of Choristoma of the Middle Ear: A Component of a New Syndrome?

Otology & Neurotology, 2001

Salivary choristoma of the middle ear is a rare entity. The authors report the 26th known case, w... more Salivary choristoma of the middle ear is a rare entity. The authors report the 26th known case, which is unique in several respects: the patient had abnormalities of the first and second branchial arches, as well as the otic capsule and facial nerve in ways not yet reported. Our patient presented with bilateral preauricular pits, conchal bands, an ipsilateral facial palsy, and bilateral Mondini-type deformities. A review of the literature revealed salivary choristomas of the middle ear to be frequently associated with branchial arch abnormalities, most commonly the second, as well as abnormalities of the facial nerve. All 25 cases were reviewed and the results reported with respect to clinical presentation, associated abnormalities, operative findings, and hearing results. It has been proposed that choristoma of the middle ear may represent a component of a syndrome along with unilateral hearing loss, abnormalities of the incus and/or stapes, and anomalies of the facial nerve. Eighty-six percent of the reported patients with choristoma have three or four of the four criteria listed to designate middle ear salivary choristoma as part of a syndrome. In the remaining four patients, all of the structures were not assessed.

Research paper thumbnail of Long-Term Hearing Loss in Gerbils With Bacterial Meningitis Treated With Superoxide Dismutase

Otology & Neurotology, 2008

The treatment of superoxide dismutase (SOD) in gerbils with bacterial meningitis will not only pr... more The treatment of superoxide dismutase (SOD) in gerbils with bacterial meningitis will not only prevent cochlear fibrosis and neo-ossification but also reduce hearing loss. SOD an O2-scavenger, has been shown to prevent cochlear fibrosis and neo-ossification in gerbils infected with bacterial meningitis when injected intrathecally. The objective of this study is to investigate the effects of SOD on long-term hearing loss in gerbils infected with bacterial meningitis and to assess the relationship between hearing results and the amount of fibrosis. The effectiveness of middle ear infusion of SOD will also be examined. Meningitis was induced in 3 groups of 10 gerbils with injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received intrathecal SOD, group 2 received a middle ear infusion of SOD, and group 3, the control group, received no SOD. Histologic data and auditory brainstem responses were obtained from each gerbil. In the intrathecal SOD group, the average deterioration in pure tone thresholds between the preoperative baseline and 15 weeks after induction of meningitis at 4, 8, 16, and 32 kHz was significantly less than that of the middle ear SOD and the control group (p = 0.001). There was no significant difference between the middle ear SOD and the control group. There was no fibrosis in the intrathecal SOD group, 15% of the gerbils developed an average of 11% fibrosis in the middle ear SOD group, and 20% of the gerbils developed an average of 15% in the control group. Intrathecal infusion of SOD not only prevented cochlear fibrosis and neo-ossification after bacterial meningitis but also decreased subsequent hearing loss.

Research paper thumbnail of Assessing Stapes Piston Position Using Computed Tomography

Otology & Neurotology, 2009

Temporal bone computed tomographic (CT) scanning in the postoperative stapedotomy patient is inac... more Temporal bone computed tomographic (CT) scanning in the postoperative stapedotomy patient is inaccurate in assessing stapes piston position within the vestibule. Poststapedotomy patients that have persistent vertigo may undergo CT scanning to assess the position of the stapes piston within the vestibule to rule out overly deep insertion. Vertigo is a recognized complication of the deep piston, and CT evaluation is often recommended. The accuracy of CT scan in this setting is unestablished. Stapedotomy was performed on 12 cadaver ears, and stainless steel McGee pistons were placed. The cadaver heads were then scanned using a fine-cut temporal bone protocol. Temporal bone dissection was performed with microscopic measurement of the piston depth in the vestibule. These values were compared with depth of intravestibular penetration measured on CT scan by 4 independent measurements. The intravestibular penetration as assessed by computed tomography was consistently greater than the value found on cadaveric anatomic dissection. The radiographic bias was greater when piston location within the vestibule was shallower. The axial CT scan measurement was 0.53 mm greater, on average, than the anatomic measurement. On average, the coronal CT measurement was 0.68 mm greater than the anatomic measurement. The degree of overestimation of penetration, however, was highly inconsistent. Standard temporal bone CT scan is neither an accurate nor precise examination of stapes piston depth within the vestibule. We found that CT measurement consistently overstated intravestibular piston depth. Computed tomography is not a useful study in the evaluation of piston depth for poststapedectomy vertigo and is of limited value in this setting.

Research paper thumbnail of The effects of superoxide dismutase in gerbils with bacterial meningitis

Otolaryngology - Head and Neck Surgery, 2004

Inflammatory products, such as oxygen radicals generated during the course of bacterial meningiti... more Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea. Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments. To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis. Meningitis was induced in three groups of 10 gerbils by intrathecal (IT) injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received IT SOD, group 2 received intramuscular (IM) SOD, and group 3, the control group, received IM normal saline. Histologic data and auditory brainstem responses (ABR) were obtained from each gerbil. Fibrosis and/or neo-ossification were near absent in the IT SOD group and significantly less fibrosis occurred in the IM group (IT vs. IM: P = 0.010; IT vs. control group: P = 0.001). The amount of surviving spiral ganglion cells correlated inversely with the extent of fibrosis (r = -0.753, P < 0.00001). IT injection of SOD significantly reduced cochlear fibrosis and neo-ossification, reduced the spiral ganglion cell loss, and decreased damage of the cochlear components following bacterial meningitis.

Research paper thumbnail of Venous channels of the petrous apex: Their presence and clinical

Otolaryngology - Head and Neck Surgery, 1997

A methyl methacrylate casting technique was used to make detailed casts of the intracerebral veno... more A methyl methacrylate casting technique was used to make detailed casts of the intracerebral venous system of four human cadaver specimens. Seven of the eight petrous apices studied were diploeic (n = 5), or pneumatic (n = 2) and had venules coursing in the anterior petrous apex. These venules form conduits connecting the cavernous to the inferior petrosal sinus or the jugular bulb and have not been previously described. In addition to the air cell system of the petrous apex, these venules may represent pathways for the spread of infection and the development of petrous apicitis, Gradenigo's syndrome, and the rare otogenic cavernous sinus thrombophlebitis. Their presence also may help explain the location of cholesterol granulomas, which afflict this area of the skull base.

Research paper thumbnail of Induction of labyrinthitis ossificans after pneumococcal meningitis: An animal model

Otolaryngology - Head and Neck Surgery, 1998

Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologi... more Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of labyrinthitis ossificans.

Research paper thumbnail of Role of cochlear implantation in susac?s syndrome

Otolaryngology - Head and Neck Surgery, 2004

Objectives: Susac’s syndrome is characterized by the triad of branched retinal artery occlusions,... more Objectives: Susac’s syndrome is characterized by the triad of branched retinal artery occlusions, cochlear microangiopathy, and encephalopathy. The underlying process is thought to be a small vessel vasculitis causing microinfarcts in the retina, cochlea, and brain. The purpose of this report is to present the applicability of cochlear implantation in Susac’s syndrome with associated auditory neuropathy and encephalopathy.Methods: A clinical

Research paper thumbnail of Neurotologic Emergencies: What the General Otolaryngologist Needs to Know

Otolaryngology -- Head and Neck Surgery, 2013

ABSTRACT Program Description: This miniseminar, presented on behalf of the American Neurotology S... more ABSTRACT Program Description: This miniseminar, presented on behalf of the American Neurotology Society, is designed to provide the practicing general otolaryngologist with immediately useful clinical pearls in the evaluation and management of patients presenting with neurotologic emergencies. Five expert neurotologists will present the current state of the art in the following areas: temporal bone fracture, acute mastoiditis, meningitis, idiopathic facial nerve palsy, and sudden hearing loss. These patients often present the clinician with challenges, including how to assess, when and what to test, and what treatment options to offer, as well as what the expected outcomes are. ARQ and Q&A will be emphasized.

Research paper thumbnail of History of Aromatase: Saga of an Important Biological Mediator and Therapeutic Target

Endocrine Reviews, 2009

Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens. Initial studies ... more Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens. Initial studies of its enzymatic activity and function took place in an environment focused on estrogen as a component of the birth control pill. At an early stage, investigators recognized that inhibition of this enzyme could have major practical applications for treatment of hormone-dependent breast cancer, alterations of ovarian and endometrial function, and treatment of benign disorders such as gynecomastia. Two general approaches ultimately led to the development of potent and selective aromatase inhibitors. One targeted the enzyme using analogs of natural steroidal substrates to work out the relationships between structure and function. The other approach initially sought to block adrenal function as a treatment for breast cancer but led to the serendipitous finding that a nonsteroidal P450 steroidogenesis inhibitor, aminoglutethimide, served as a potent but nonselective aromatase inhibitor. Proof of the therapeutic concept of aromatase inhibition involved a variety of studies with aminoglutethimide and the selective steroidal inhibitor, formestane. The requirement for even more potent and selective inhibitors led to intensive molecular studies to identify the structure of aromatase, to development of high-sensitivity estrogen assays, and to "mega" clinical trials of the third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, which are now in clinical use in breast cancer. During these studies, unexpected findings led investigators to appreciate the important role of estrogens in males as well as in females and in multiple organs, particularly the bone and brain. These studies identified the important regulatory properties of aromatase acting in an autocrine, paracrine, intracrine, neurocrine, and juxtacrine fashion and the organ-specific enhancers and promoters controlling its transcription. The saga of these studies of aromatase and the ultimate utilization of inhibitors as highly effective treatments of breast cancer and for use in reproductive disorders serves as the basis for this first Endocrine Reviews history manuscript.

Research paper thumbnail of MR, CT, and Plain Film Imaging of the Developing Skull Base in Fetal Specimens

BACKGROUND AND PURPOSE:The developing fetal skull base has previously been studied via dissection... more BACKGROUND AND PURPOSE:The developing fetal skull base has previously been studied via dissection and low-resolution CT. Most of the central skull base develops from endochon- dral ossification through an intermediary chondrocranium. We traced the development of the normal fetal skull base by using plain radiography, MR imaging, and CT. METHODS: Twenty-nine formalin-fixed fetal specimens ranging from 9 to 24 weeks'

Research paper thumbnail of A Pilot Study on the Efficacy of Continuous Positive Airway Pressure (CPAP) on the Manifestations of Ménière's Disease in Patients with Concomitant Obstructive Sleep Apnea Syndrome (OSAS)

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 11, 2015

To evaluate the effect of CPAP therapy on Ménière's disease patients with concomitant OSAS, s... more To evaluate the effect of CPAP therapy on Ménière's disease patients with concomitant OSAS, since recent reports suggest OSAS may cause dysfunction of the vestibular system. Prospective study using CPAP administered to patients diagnosed with "Definite Ménière's disease" according to the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery and combined with OSAS. University hospital. Twenty consecutive patients, 14 male and 6 female with active, unilateral, cochleovestibular Ménière's disease refractory to medical management who also had concurrent OSAS as defined by International Classification of Sleep Disorders II were selected to undergo solitary CPAP therapy. Audiometric testing, caloric testing, and DHI survey were conducted before and after CPAP therapy and compared to assess effectiveness of CPAP therapy as utilized for treatment of Ménière's disease. Although caloric testing did not show significant difference, audiometric tes...

Research paper thumbnail of Role of Tumor Necrosis Factor-?? in Sensorineural Hearing Loss after Bacterial Meningitis

Otology & Neurotology, 2005

Research paper thumbnail of Imaging findings of the developing temporal bone in fetal specimens

AJNR. American journal of neuroradiology, 1996

To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and... more To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT. Eighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed. The membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth. The study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning tec...

Research paper thumbnail of Impaired quality of sleep in Ménière's disease patients

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 15, 2010

To evaluate the quality of sleep in Ménière's disease patients with the use of polysomnograph... more To evaluate the quality of sleep in Ménière's disease patients with the use of polysomnography. Prospective study using polysomnography administered in patients diagnosed as "Definite Meniere's disease cases" according to the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. Thirty-five patients, 17 male and 18 female, aged 31 to 71 (58 average) years with active, unilateral, cochleovestibular Ménière's disease refractory to medical management underwent polysomnography. The results were compared with 35 healthy controls matched for age and sex. All participants underwent full-night polysomnography, and a sleep medicine physician interpreted the results. Total sleeping time in Ménière's disease was significantly higher than in controls. Stage 2 sleep was significantly longer and stage 3+4 shorter in Ménière's disease than controls, while there was no difference of stage 1 and REM. Arousal index was significantly higher in Ménièr...

Research paper thumbnail of Inhibition of post-meningitic cochlear injury with cerebrospinal fluid irrigation

Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery, 2006

Labyrinthitis ossificans, the pathologic ossification of the otic capsule associated with profoun... more Labyrinthitis ossificans, the pathologic ossification of the otic capsule associated with profound deafness and loss of vestibular function occurs frequently as a sequella of bacterial meningitis and subsequent purulent labyrinthitis. Experimentally, in Streptococcus pneumoniae meningitis, it has been shown that a vigorous inflammatory response to teichoic acids in the bacterial cell wall contributes to cochlear damage and subsequent fibrosis and ossification. The hypothesis of this study is that a dilution of concentration of inflammatory mediators through cerebrospinal fluid (CSF) irrigation will lead to a reduction in both inner ear pathology and permanent hearing loss. Auditory brainstem response testing was used to determine baseline hearing thresholds in 20 Mongolian gerbils (12 irrigated, 8 sham irrigated animals) at 32 kHz, 16 kHz, 8 kHz, and 4 kHz frequencies. Their thresholds at 14 days and 120 days post-procedure were also obtained. Streptococcus pneumoniae meningitis was...

Research paper thumbnail of Head and neck malignant metastasis to the cerebellopontine angle

Objectives: To present 3 patients with isolated metastatic lesions to the cerebellopontine angle ... more Objectives: To present 3 patients with isolated metastatic lesions to the cerebellopontine angle (CPA). The patient’s histories and clinical courses are reviewed.Methods: Clinical chart reviews of 3 patients with head and neck malignant lesions metastatic to the CPA was conducted.Results: The first patient had a temporal squamous skin cancer involving the temporal bone requiring a lateral temporal bone resection. The

Research paper thumbnail of Developmental assembly of transduction apparatus in chick basilar papilla

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 26, 2003

Hair cells, the sensory receptors of auditory and vestibular systems, use a transducer apparatus ... more Hair cells, the sensory receptors of auditory and vestibular systems, use a transducer apparatus that renders them remarkably sensitive to mechanical displacement as minute as 1 nm. To study the embryonic development of the transducer apparatus in hair cells of the chick auditory papilla, we examined hair cells that have been labeled with N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl) pyridiniumdibromide, which has been shown to permeate the transducer channels. In addition, mechanotransduction currents were recorded directly using whole-cell patch-clamp techniques. The structure of the hair bundle was examined using scanning electron microscopy, and immunofluorescence labeling for myosin 1c, myosin 7a, and plasma membrane Ca2+ ATPase 2 was studied to determine the developmental expression of these proteins in embryonic chick papillas. We demonstrate that the transducer apparatus is assembled jointly at embryonic day 11 (E11) of the developing chick basilar papilla. The res...

Research paper thumbnail of The editors and editorial board of the ARCHIVES would like to thank all of the dedicated peer reviewers who provide their expertise, insight, and judgment when reviewing manuscripts for publication. We extend a special appreciation to the reviewers listed below for their service in 2002

Research paper thumbnail of Chronology of labyrinthitis ossificans induced by streptococcus pneumoniae meningitis

The Laryngoscope, 1999

Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear a... more Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. A prospective randomized double-blind study. By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in six groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S. pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans.

Research paper thumbnail of Location and Timing of Initial Osteoid Deposition in Postmeningitic Labyrinthitis Ossificans Determined by Multiple Fluorescent Labels

The Laryngoscope, 2004

Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis... more Variable amounts of fibrosis and neo-ossification fill the cochlea following bacterial meningitis. The purpose of the study was to delineate the timing and location of initial ossification following pneumococcal meningitis, as well as subsequent remodeling and resorption, over the 3-month period after infection. Randomized, double-blind study. Fluorochromes are compounds that specifically incorporate into ossifying bone. Sequential addition of different colored fluorochromes during osteoneogenesis define the timing and location of osteoid deposition and mineralization. Mongolian gerbils were infected by intrathecal injection of Streptococcus pneumoniae type 3, and control gerbils received saline. Both groups were injected with calcein on postoperative day 3, followed by xylenol orange, oxytetracycline, and alizarin red on days 7, 14, and 28 respectively. Ten experimental gerbils were killed 24 hours after each label, and an additional group at 84 days after infection. Two groups of 10 control gerbils were killed at 29 and 84 days after treatment. The temporal bones and tibias were harvested, embedded in plastic, and sliced with a diamond saw. Wafers at a thickness of 200 microm were mounted in sequence and examined. Sixteen of 49 experimental animals (33%) were positive for at least one of the fluorescent labels. Fluorescent labeled osteoid was present at all sampling times. Label extended from the endosteal wall into the lumen of the scala tympani between the vestibule and the round window membrane. Discrete sites of fluorescence varied among specimens and were associated with the opening of the cochlear aqueduct, the scala tympani, organ of Corti, and the stria vascularis and spiral ligament in all turns from base to apex. The results indicate that osteoid is deposited and begins mineralization by day 3 after infection, at least, and continues, at least, through the first 28 days after infection. There was no apparent resorption of new bone and remodeling by 84 days after infection.

Research paper thumbnail of Choristoma of the Middle Ear: A Component of a New Syndrome?

Otology & Neurotology, 2001

Salivary choristoma of the middle ear is a rare entity. The authors report the 26th known case, w... more Salivary choristoma of the middle ear is a rare entity. The authors report the 26th known case, which is unique in several respects: the patient had abnormalities of the first and second branchial arches, as well as the otic capsule and facial nerve in ways not yet reported. Our patient presented with bilateral preauricular pits, conchal bands, an ipsilateral facial palsy, and bilateral Mondini-type deformities. A review of the literature revealed salivary choristomas of the middle ear to be frequently associated with branchial arch abnormalities, most commonly the second, as well as abnormalities of the facial nerve. All 25 cases were reviewed and the results reported with respect to clinical presentation, associated abnormalities, operative findings, and hearing results. It has been proposed that choristoma of the middle ear may represent a component of a syndrome along with unilateral hearing loss, abnormalities of the incus and/or stapes, and anomalies of the facial nerve. Eighty-six percent of the reported patients with choristoma have three or four of the four criteria listed to designate middle ear salivary choristoma as part of a syndrome. In the remaining four patients, all of the structures were not assessed.

Research paper thumbnail of Long-Term Hearing Loss in Gerbils With Bacterial Meningitis Treated With Superoxide Dismutase

Otology & Neurotology, 2008

The treatment of superoxide dismutase (SOD) in gerbils with bacterial meningitis will not only pr... more The treatment of superoxide dismutase (SOD) in gerbils with bacterial meningitis will not only prevent cochlear fibrosis and neo-ossification but also reduce hearing loss. SOD an O2-scavenger, has been shown to prevent cochlear fibrosis and neo-ossification in gerbils infected with bacterial meningitis when injected intrathecally. The objective of this study is to investigate the effects of SOD on long-term hearing loss in gerbils infected with bacterial meningitis and to assess the relationship between hearing results and the amount of fibrosis. The effectiveness of middle ear infusion of SOD will also be examined. Meningitis was induced in 3 groups of 10 gerbils with injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received intrathecal SOD, group 2 received a middle ear infusion of SOD, and group 3, the control group, received no SOD. Histologic data and auditory brainstem responses were obtained from each gerbil. In the intrathecal SOD group, the average deterioration in pure tone thresholds between the preoperative baseline and 15 weeks after induction of meningitis at 4, 8, 16, and 32 kHz was significantly less than that of the middle ear SOD and the control group (p = 0.001). There was no significant difference between the middle ear SOD and the control group. There was no fibrosis in the intrathecal SOD group, 15% of the gerbils developed an average of 11% fibrosis in the middle ear SOD group, and 20% of the gerbils developed an average of 15% in the control group. Intrathecal infusion of SOD not only prevented cochlear fibrosis and neo-ossification after bacterial meningitis but also decreased subsequent hearing loss.

Research paper thumbnail of Assessing Stapes Piston Position Using Computed Tomography

Otology & Neurotology, 2009

Temporal bone computed tomographic (CT) scanning in the postoperative stapedotomy patient is inac... more Temporal bone computed tomographic (CT) scanning in the postoperative stapedotomy patient is inaccurate in assessing stapes piston position within the vestibule. Poststapedotomy patients that have persistent vertigo may undergo CT scanning to assess the position of the stapes piston within the vestibule to rule out overly deep insertion. Vertigo is a recognized complication of the deep piston, and CT evaluation is often recommended. The accuracy of CT scan in this setting is unestablished. Stapedotomy was performed on 12 cadaver ears, and stainless steel McGee pistons were placed. The cadaver heads were then scanned using a fine-cut temporal bone protocol. Temporal bone dissection was performed with microscopic measurement of the piston depth in the vestibule. These values were compared with depth of intravestibular penetration measured on CT scan by 4 independent measurements. The intravestibular penetration as assessed by computed tomography was consistently greater than the value found on cadaveric anatomic dissection. The radiographic bias was greater when piston location within the vestibule was shallower. The axial CT scan measurement was 0.53 mm greater, on average, than the anatomic measurement. On average, the coronal CT measurement was 0.68 mm greater than the anatomic measurement. The degree of overestimation of penetration, however, was highly inconsistent. Standard temporal bone CT scan is neither an accurate nor precise examination of stapes piston depth within the vestibule. We found that CT measurement consistently overstated intravestibular piston depth. Computed tomography is not a useful study in the evaluation of piston depth for poststapedectomy vertigo and is of limited value in this setting.

Research paper thumbnail of The effects of superoxide dismutase in gerbils with bacterial meningitis

Otolaryngology - Head and Neck Surgery, 2004

Inflammatory products, such as oxygen radicals generated during the course of bacterial meningiti... more Inflammatory products, such as oxygen radicals generated during the course of bacterial meningitis, can damage nerve endings, hair cells, and/or supporting cells in the cochlea. Superoxide dismutase (SOD), an O2-scavenger, has been shown to play an important role in the protection against radical toxicity in various animal experiments. To study the antioxidant effects of SOD on the inflammatory response of gerbils with bacterial meningitis. Meningitis was induced in three groups of 10 gerbils by intrathecal (IT) injection of Streptococcus pneumoniae into the cisterna magna. Group 1 received IT SOD, group 2 received intramuscular (IM) SOD, and group 3, the control group, received IM normal saline. Histologic data and auditory brainstem responses (ABR) were obtained from each gerbil. Fibrosis and/or neo-ossification were near absent in the IT SOD group and significantly less fibrosis occurred in the IM group (IT vs. IM: P = 0.010; IT vs. control group: P = 0.001). The amount of surviving spiral ganglion cells correlated inversely with the extent of fibrosis (r = -0.753, P < 0.00001). IT injection of SOD significantly reduced cochlear fibrosis and neo-ossification, reduced the spiral ganglion cell loss, and decreased damage of the cochlear components following bacterial meningitis.

Research paper thumbnail of Venous channels of the petrous apex: Their presence and clinical

Otolaryngology - Head and Neck Surgery, 1997

A methyl methacrylate casting technique was used to make detailed casts of the intracerebral veno... more A methyl methacrylate casting technique was used to make detailed casts of the intracerebral venous system of four human cadaver specimens. Seven of the eight petrous apices studied were diploeic (n = 5), or pneumatic (n = 2) and had venules coursing in the anterior petrous apex. These venules form conduits connecting the cavernous to the inferior petrosal sinus or the jugular bulb and have not been previously described. In addition to the air cell system of the petrous apex, these venules may represent pathways for the spread of infection and the development of petrous apicitis, Gradenigo's syndrome, and the rare otogenic cavernous sinus thrombophlebitis. Their presence also may help explain the location of cholesterol granulomas, which afflict this area of the skull base.

Research paper thumbnail of Induction of labyrinthitis ossificans after pneumococcal meningitis: An animal model

Otolaryngology - Head and Neck Surgery, 1998

Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologi... more Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of labyrinthitis ossificans.

Research paper thumbnail of Role of cochlear implantation in susac?s syndrome

Otolaryngology - Head and Neck Surgery, 2004

Objectives: Susac’s syndrome is characterized by the triad of branched retinal artery occlusions,... more Objectives: Susac’s syndrome is characterized by the triad of branched retinal artery occlusions, cochlear microangiopathy, and encephalopathy. The underlying process is thought to be a small vessel vasculitis causing microinfarcts in the retina, cochlea, and brain. The purpose of this report is to present the applicability of cochlear implantation in Susac’s syndrome with associated auditory neuropathy and encephalopathy.Methods: A clinical

Research paper thumbnail of Neurotologic Emergencies: What the General Otolaryngologist Needs to Know

Otolaryngology -- Head and Neck Surgery, 2013

ABSTRACT Program Description: This miniseminar, presented on behalf of the American Neurotology S... more ABSTRACT Program Description: This miniseminar, presented on behalf of the American Neurotology Society, is designed to provide the practicing general otolaryngologist with immediately useful clinical pearls in the evaluation and management of patients presenting with neurotologic emergencies. Five expert neurotologists will present the current state of the art in the following areas: temporal bone fracture, acute mastoiditis, meningitis, idiopathic facial nerve palsy, and sudden hearing loss. These patients often present the clinician with challenges, including how to assess, when and what to test, and what treatment options to offer, as well as what the expected outcomes are. ARQ and Q&A will be emphasized.

Research paper thumbnail of History of Aromatase: Saga of an Important Biological Mediator and Therapeutic Target

Endocrine Reviews, 2009

Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens. Initial studies ... more Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens. Initial studies of its enzymatic activity and function took place in an environment focused on estrogen as a component of the birth control pill. At an early stage, investigators recognized that inhibition of this enzyme could have major practical applications for treatment of hormone-dependent breast cancer, alterations of ovarian and endometrial function, and treatment of benign disorders such as gynecomastia. Two general approaches ultimately led to the development of potent and selective aromatase inhibitors. One targeted the enzyme using analogs of natural steroidal substrates to work out the relationships between structure and function. The other approach initially sought to block adrenal function as a treatment for breast cancer but led to the serendipitous finding that a nonsteroidal P450 steroidogenesis inhibitor, aminoglutethimide, served as a potent but nonselective aromatase inhibitor. Proof of the therapeutic concept of aromatase inhibition involved a variety of studies with aminoglutethimide and the selective steroidal inhibitor, formestane. The requirement for even more potent and selective inhibitors led to intensive molecular studies to identify the structure of aromatase, to development of high-sensitivity estrogen assays, and to "mega" clinical trials of the third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, which are now in clinical use in breast cancer. During these studies, unexpected findings led investigators to appreciate the important role of estrogens in males as well as in females and in multiple organs, particularly the bone and brain. These studies identified the important regulatory properties of aromatase acting in an autocrine, paracrine, intracrine, neurocrine, and juxtacrine fashion and the organ-specific enhancers and promoters controlling its transcription. The saga of these studies of aromatase and the ultimate utilization of inhibitors as highly effective treatments of breast cancer and for use in reproductive disorders serves as the basis for this first Endocrine Reviews history manuscript.