Michael J McKenna

Harvard Medical School, Boston, Massachusetts, United States

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Publications (104)195.92 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be more likely to increase in size. Clinicians should take into account tumor growth rate when counseling patients about treatment options.
    International journal of radiation oncology, biology, physics 05/2014; 89(1):113-9. · 4.59 Impact Factor
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    ABSTRACT: IMPORTANCE The etiology of superior canal dehiscence (SCD) involving the arcuate eminence is not completely understood, but genetic factors may play a role. One hypothesis is that patients are born with a defect of the superior canal, and an acute event (such as head trauma) or progressive loss of bone (eg, due to dural pulsations) may result in the onset of SCD symptoms. Familial SCD has only been briefly mentioned in the literature to date. OBSERVATIONS We report 3 families that each had 2 members with SCD syndrome. We found that first-degree relatives presented with similar complaints and that temporal bone computed tomography scans between relatives showed very similar skull base topography and anatomic SCD defects. CONCLUSIONS AND RELEVANCE The presence of symptomatic SCD among first-degree relatives and similar skull base topography suggests that genetics may play a role in the etiology of SCD.
    JAMA otolaryngology-- head & neck surgery. 02/2014;
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    ABSTRACT: Given the presence of a pathological immune response in sporadic vestibular schwannoma (sVS), this study aims to explore the roles of aspirin in minimizing sVS growth in vivo. Retrospective case review. Tertiary care hospital. People diagnosed with sVS and followed at a tertiary referral center by serial magnetic resonance imaging (MRI) for at least 4 months within the period of January 1980 through April 2012. Patient use of aspirin and sVS growth rate measured by changes in the largest tumor dimension as noted on serial MRIs Within a set of 689 cases, 347 were followed by serial MRI scans (50.3%); of the latter, 81 took aspirin, of which, 33 demonstrated sVS growth, and 48 did not. Of the 266 nonaspirin users, 154 demonstrated sVS growth, and 112 did not. A significant inverse association was found among aspirin users and sVS growth (odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.29-0.85), which was not confounded by age or sex. Our results suggest a potential therapeutic role of aspirin in inhibiting sVS growth.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 02/2014; 35(2):353-7. · 1.44 Impact Factor
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    ABSTRACT: Purpose Vestibular schwannomas (VS) are often followed without initial therapeutic intervention because many tumors do not grow and radiation therapy is associated with potential adverse effects. In an effort to determine whether maximizing initial surveillance predicts for later treatment response, the predictive value of preirradiation growth rate of VS on response to radiation therapy was assessed. Methods and Materials Sixty-four patients with 65 VS were treated with single-fraction stereotactic radiation surgery or fractionated stereotactic radiation therapy. Pre- and postirradiation linear expansion rates were estimated using volumetric measurements on sequential magnetic resonance images (MRIs). In addition, postirradiation tumor volume change was classified as demonstrating shrinkage (ratio of volume on last follow-up MRI to MRI immediately preceding irradiation <80%), stability (ratio 80%-120%), or expansion (ratio >120%). The median pre- and postirradiation follow-up was 20.0 and 27.5 months, respectively. Seven tumors from neurofibromatosis type 2 (NF2) patients were excluded from statistical analyses. Results In the 58 non-NF2 patients, there was a trend of correlation between pre- and postirradiation volume change rates (slope on linear regression, 0.29; P=.06). Tumors demonstrating postirradiation expansion had a median preirradiation growth rate of 89%/year, and those without postirradiation expansion had a median preirradiation growth rate of 41%/year (P=.02). As the preirradiation growth rate increased, the probability of postirradiation expansion also increased. Overall, 24.1% of tumors were stable, 53.4% experienced shrinkage, and 22.5% experienced expansion. Predictors of no postirradiation tumor expansion included no prior surgery (P=.01) and slower tumor growth rate (P=.02). The control of tumors in NF2 patients was only 43%. Conclusions Radiation therapy is an effective treatment for VS, but tumors that grow quickly preirradiation may be more likely to increase in size. Clinicians should take into account tumor growth rate when counseling patients about treatment options.
    International journal of radiation oncology, biology, physics 01/2014; 89(1):113–119. · 4.59 Impact Factor
  • Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 10/2013; 34(8):1546-1547. · 1.44 Impact Factor
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    ABSTRACT: HYPOTHESIS: We hypothesize that the severity of hearing loss (HL) associated with sporadic vestibular schwannomas (VS) is correlated with tumor secretion of proteins with ototoxic or otoprotective potential. BACKGROUND: Because the recognition that HL associated with VS is not solely due to compression of the auditory nerve, elucidating the mechanism by which VS cause HL has been an important task. We previously showed that VS stratified by hearing have differential gene expression. We now focus on identifying differentially expressed proteins in tumor secretions. METHODS: Fresh surgical specimens of VS were incubated in sterile PBS at 37°C to collect secretions. The specimens were divided into a group associated with good hearing (GH, word recognition ≥70% and pure-tone average ≤30 dB, n = 11) or poor hearing (PH, n = 10). The groups were compared using a customized cytokine array. Statistically significant results were verified with an enzyme-linked immunosorbent assay on a different set of secretions (n = 8 for GH and n = 10 for PH group). RESULTS: Of the 37 molecules we studied, 9 were significantly expressed in secretions from VS compared with secretions from control nerves. Secretion of fibroblast growth factor 2 (FGF2) was 3.5-fold higher in VS associated with GH versus PH based on cytokine array analysis (p = 0.02), which was validated with enzyme-linked immunosorbent assay. CONCLUSION: This study highlights FGF2, a mitogen known to protect the auditory nerve, as a potential tumor-secreted mediator of hearing protection in VS. If FGF2's significant role in hearing protection in patients with VS is validated, then FGF2 could be used as a biomarker for HL in VS, and therapeutic targeting of the FGF2 signaling pathway may reduce HL due to VS.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 03/2013; · 1.44 Impact Factor
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    ABSTRACT: Until now, the use of computed tomography (CT) in the diagnosis and evaluation of otosclerosis has been based on correlation of radiologic findings to patient histories, intraoperative examinations, and audiologic data. The purpose of this study was to compare CT findings in otosclerosis to histopathology. Prospective blinded. Radiology department in a tertiary referral hospital and otopathology laboratory. Temporal bones from patients with otosclerosis and other otologic diseases (used as controls). Blinded review of specimen CT scans by radiologists and comparison of CT findings to histopathology of the same bones. Ability of CT to diagnose otosclerosis, identify otosclerotic foci in defined zones of the otic capsule, determine endosteal layer involvement, oval window (OW) obliteration, and round window (RW) obliteration. In a randomized blinded evaluation, radiologists identified 8 of 10 bones with otosclerosis and made 3 false-positive diagnoses from the 36 control bones. Radiologic examination correctly identified otosclerosis anterior to the oval window, in the pericochlear area, and in the round window niche in 17 of 17, 9 of 11, and 3 of 6 bones, respectively. CT correctly determined involvement of the endosteal layer, OW obliteration, and RW obliteration in 5 of 8, 2 of 2, and 2 of 2 temporal bones. High-resolution CT is highly sensitive and specific for the diagnosis of otosclerosis when compared with histopathology. Very small and subtle otosclerotic foci seen on pathology may be missed on CT. Although CT was able to positively identify cochlear endosteal margin involvement, the false-negative rate on CT was significant.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 01/2013; 34(1):22-8. · 1.44 Impact Factor
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    ABSTRACT: OBJECTIVES/HYPOTHESIS: To determine the utility of cervical vestibular evoked myogenic potential (cVEMP) thresholds in the surgical management of bilateral superior canal dehiscence syndrome (SCDS). STUDY DESIGN: Retrospective review. METHODS: We identified patients who underwent surgical treatment for SCDS from our database of 147 patients diagnosed with superior canal dehiscence (SCD) between 2000 and 2011 at our institution. The diagnosis of SCDS was based on clinical signs and symptoms, audiometric and cVEMP testing, and high-resolution computed tomography. RESULTS: We identified 38 patients who underwent SCD surgery in 40 ears (2 bilateral). In seven patients with bilateral SCD, the more symptomatic ear had lower cVEMP thresholds, a larger air bone gap and a lateralizing tuning fork. In 13 patients with perioperative cVEMP testing, thresholds increased in 12 patients following primary repair, and no threshold shift was seen in one patient with persistence of symptoms after revision surgery. Audiometric data showed a significant mean decrease of the low-frequency air-bone gap and a mild (high-frequency) bone conduction loss after surgical repair. CONCLUSIONS: We found that, 1) preoperative cVEMP thresholds, the magnitude of the air-bone gap and tuning-fork testing are important to confirm the worse ear in patients with bilateral SCD, 2) elevation of cVEMP thresholds following surgery correlates with improvement of symptoms and underscores the importance of postoperative testing in patients with bilateral disease or recurrence of symptoms and, 3) SCD plugging is associated with a partial closure of the air-bone gap and a mild (high-frequency) sensorineural hearing loss.
    The Laryngoscope 09/2012; · 1.98 Impact Factor
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    ABSTRACT: To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL). Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. In recent years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis. Retrospective review. Tertiary referral center, ambulatory care. Risedronate or zoledronate administration. Bone conduction pure tone threshold averages (PTAs) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4% and 18% in WR based on binomial variance. All 10 patients had audiometric progression of SNHL in the pretreatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e., stabilization) at an average follow-up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications. Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third-generation bisphosphonate treatments is warranted.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 08/2012; 33(8):1308-14. · 1.44 Impact Factor
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    ABSTRACT: Early studies suggest that bevacizumab treatment can result in tumor shrinkage and hearing improvement for some patients with neurofibromatosis type 2 (NF2). The aim of this study was to report extended follow-up in a larger cohort of similarly treated patients. Retrospective study. Tertiary referral center Thirty-one consecutive NF2 patients who received bevacizumab for progressive vestibular schwannomas. Hearing improvement, defined as an improvement in word recognition score above the 95% critical difference compared with baseline, and radiographic response, defined as a 20% or greater decrease in tumor volume compared with baseline. The median age was 26 years (range, 12-73 yr). The median volumetric tumor growth rate before treatment was 64% per year. At the time of analysis, the median duration of treatment was 14 months (range, 6-41 mo) with a total of 47 patient-years of follow-up. A hearing response occurred in 57% (13/23) of evaluable patients and a radiographic response in 55% (17/31) of target vestibular schwannomas. The median time to response was 3 months for both end points. The only clinical or radiographic feature at baseline that correlated with change in tumor volume at 3 months was the mean apparent diffusion coefficient value, a radiologic marker of edema (p = 0.036). Ninety percent of patients had stable or improved hearing after 1 year of treatment and 61% at 3 years; 88% of patients had stable or decreased tumor size after 1 year of treatment and 54% at 3 years. Overall, treatment was well tolerated. Bevacizumab treatment was followed by hearing improvement and tumor shrinkage in more than 50% of progressive vestibular schwannomas in NF2 patients. Stable or improved hearing was retained in the majority of patients.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 08/2012; 33(6):1046-52. · 1.44 Impact Factor
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    ABSTRACT: To identify clinical factors associated with prolonged recovery after superior canal dehiscence surgery. Retrospective review. Tertiary care academic medical center. Thirty-three patients that underwent surgery for SCDS were identified from a database of 140 patients diagnosed with SCD (2000-2010) at the Massachusetts Eye and Ear Infirmary (U.S.A.). The diagnosis of SCDS was based on clinical signs and symptoms, audiometric and vestibular testing and high-resolution temporal bone computed tomography. For the primary repair, the superior canal was plugged in 31 patients through a middle fossa craniotomy approach and in 1 patient through a transmastoid approach. In 1 patient, the SCD was resurfaced through a middle fossa craniotomy approach. Postoperative clinical signs and symptoms and factors that may influence duration of disequilibrium after surgery. Thirty-three patients (15-71 yr; mean, 43 yr) underwent surgery for SCDS on 35 ears (2 bilateral). Mean follow-up was 28.7 months (range, 3 mo to 10 yr); 33 of 33 (100%) patients experienced initial improvement of the chief complaint. Three patients required revision surgery, improving symptoms in 2 patients. Six patients had dizziness lasting more than 4 months postoperatively, and all had bilateral SCD, migraines, and a dehiscence of 3 mm or greater. Surgical plugging of SCD is an effective management option to provide long-term improvement of the chief complaint in SCDS patients. Patients with bilateral SCD, a history of migraines, and larger defects may be at risk of prolonged recovery and should be appropriately counseled.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 06/2012; 33(5):824-31. · 1.44 Impact Factor
  • Alicia M Quesnel, Michael J McKenna
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    ABSTRACT: The current practitioner is more often managing intracanalicular vestibular schwannomas than in the past, as improved imaging and heightened awareness leads to earlier diagnosis of these tumors. The role of observation, microsurgery, and radiation treatment in the management of intracanalicular tumors continues to evolve. The goal of this article is to evaluate and summarize recent literature pertaining to the management of intracanalicular vestibular schwannomas. Watchful waiting is an important management option for patients with minimal symptoms. The literature on the natural history of small vestibular schwannomas continues to expand, with particular emphasis on the expected hearing outcomes. Microsurgical techniques also focus on hearing preservation. Presence of fundal fluid and good or normal hearing preoperatively are positive predictors of hearing preservation after surgery. Long-term follow-up after radiation therapy for vestibular schwannomas continues to demonstrate excellent tumor control rates, although hearing preservation rates are modest. Multiple factors, including status of hearing, presence of vestibular symptoms, patient age, medical comorbidities, institutional outcomes, and patient preferences, help determine the management strategy for patients with an intracanalicular vestibular schwannoma.
    Current opinion in otolaryngology & head and neck surgery 10/2011; 19(5):335-40.
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    ABSTRACT: To determine whether pediatric and adult patients with superior canal dehiscence (SCD) at the superior petrosal sinus (SPS) develop superior canal dehiscence syndrome (SCDS). Retrospective review. Tertiary care academic medical center. Pediatric and adult patients with SPS-associated SCD were identified from a database of 131 patients with SCD based on high-resolution temporal bone computed tomography. One pediatric patient experienced incapacitating exercise-induced vertigo, and this patient's superior semicircular canal defect was plugged via a transmastoid approach. The 11 remaining patients were managed by observation. Clinical symptoms and signs, audiologic testing, vestibular evoked myogenic potentials, and radiologic data. Twelve patients, aged 15 to 84 years, with SCD caused by the SPS contacting the superior semicircular canal were identified. The most characteristic clinical feature in this population (5/12) was dizziness related to exercise and exertion. Bilateral SCD was observed in 3 patients. Eleven patients did not have severe symptoms and were managed conservatively. One patient, aged 15, required surgical intervention for incapacitating vertigo and experienced relief of symptoms with reversal of diagnostic indicators postoperatively. This is the first reported surgical repair of SCDS in a pediatric patient. This is the first series of patients who have SCDS due to contact of the SPS with the superior semicircular canal. Exercise and exertion-related symptoms are common in patients who have SCD owing to this cause. Transmastoid superior canal plugging is feasible and successful in treating SCDS in the pediatric patient.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 10/2011; 32(8):1312-9. · 1.44 Impact Factor
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    ABSTRACT: Progress in the synthesis of novel fluorescent conjugates of N-heterocyclic bisphosphonate drugs and related analogues, together with some recent applications of these compounds as imaging probes, are briefly discussed.
    Phosphorus Sulfur and Silicon and the Related Elements 04/2011; 186(4):970-971. · 0.60 Impact Factor
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    ABSTRACT: Reciprocating drug delivery is a means of delivering soluble drugs directly to closed fluid spaces in the body via a single cannula without an accompanying fluid volume change. It is ideally suited for drug delivery into small, sensitive and unique fluid spaces such as the cochlea. We characterized the pharmacokinetics of reciprocating drug delivery to the scala tympani within the cochlea by measuring the effects of changes in flow parameters on the distribution of drug throughout the length of the cochlea. Distribution was assessed by monitoring the effects of DNQX, a reversible glutamate receptor blocker, delivered directly to the inner ear of guinea pigs using reciprocating flow profiles. We then modeled the effects of those parameters on distribution using both an iterative curve-fitting approach and a computational fluid dynamic model. Our findings are consistent with the hypothesis that reciprocating delivery distributes the drug into a volume in the base of the cochlea, and suggest that the primary determinant of distribution throughout more distal regions of the cochlea is diffusion. Increases in flow rate distributed the drug into a larger volume that extended more apically. Over short time courses (less than 2h), the apical extension, though small, significantly enhanced apically directed delivery of drug. Over longer time courses (>5h) or greater distances (>3mm), maintenance of drug concentration in the basal scala tympani may prove more advantageous for extending apical delivery than increases in flow rate. These observations demonstrate that this reciprocating technology is capable of providing controlled delivery kinetics to the closed fluid space in the cochlea, and may be suitable for other applications such as localized brain and retinal delivery.
    Journal of Controlled Release 03/2011; 152(2):270-7. · 7.63 Impact Factor
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    ABSTRACT: In vitro treatment of Nf2-deficient cells with epidermal growth factor receptor (EGFR) inhibitors can reduce cellular proliferation. We sought to determine the activity of erlotinib for progressive vestibular schwannoma (VS) associated with neurofibromatosis 2 (NF2). Retrospective case review. Tertiary referral center. Eleven NF2 patients with progressive VS who were poor candidates for standard therapy. Erlotinib 150 mg daily. A radiographic response was defined as >or= 20% decrease in tumor volume compared with baseline. A hearing response was defined as a statistically significant increase in word recognition score (WRS) compared with baseline; a minor hearing response was defined as a 10 dB improvement in pure-tone average with stable WRS. : Before treatment, the median and mean annual volumetric growth rate for 11 index VS were 26% and 46%, respectively. Among 10 evaluable patients, the median time-to-tumor progression was 9.2 months. Three patients with stable disease experienced maximum tumor shrinkage of 4%, 13%, and 14%. Nine patients underwent audiologic evaluations. One experienced a transient hearing response, 2 experienced minor hearing responses, 3 remained stable, and 2 developed progressive hearing loss. The median time-to-progressive hearing loss was 9.2 months and to either tumor growth or progressive hearing loss was 7.1 months. Adverse treatment effects included mild-to-moderate rash, diarrhea, and hair thinning, with 2 episodes of grade 3 toxicity. Erlotinib treatment was not associated with radiographic or hearing responses in NF2 patients with progressive VS. Because a subset of patients experienced prolonged stable disease, time-to-progression may be more appropriate than radiographic or hearing response for anti-EGFR agents in NF2-associated VS.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 09/2010; 31(7):1135-43. · 1.44 Impact Factor
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    ABSTRACT: To describe a case and discuss the differential diagnosis of facial nerve paresis presenting years after resection of multiple recurrent parotid pleomorphic adenoma. Case report of a patient on immunosuppressive therapy with facial nerve weakness 3 years after last resection for multiple recurrent pleomorphic adenoma. Computed tomography and magnetic resonance imaging followed by surgical exploration, resection, and reconstruction. Histopathologic diagnosis and treatment outcome. Final diagnosis of recurrent pleomorphic adenoma causing compression of the facial nerve at the stylomastoid foramen. Facial nerve weakness caused by a benign salivary gland tumor is rare. Although alternate diagnoses must be considered, recurrent pleomorphic adenoma alone may impair facial function by impinging on the nerve in the stylomastoid foramen.
    Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology 09/2010; 31(7):1157-9. · 1.44 Impact Factor
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    ABSTRACT: Our long term goal is to understand the molecular pathology of otosclerosis and to develop better forms of therapy. Toward this goal, the current study focused on characterizing the molecular factors responsible for the unique biological features of the otic capsule: its minimal rate of remodeling, and lack of healing capacity when fractured. We compared expression levels of 62 genes involved in bone metabolism between the adult murine otic capsule and the tibia and parietal bones; the latter exemplify bones formed by endochondral and intramembranous ossification, respectively. Gene expression levels were measured using real-time quantitative RT-PCR and analyzed using tools of bioinformatics. Expression patterns of key genes were verified with in situ hybridization. The molecular profile of the otic capsule was distinctly different from that of the tibia and parietal bone. Genes found to be most characteristic of the otic capsule were: osteoprotegerin (opg), bone morphogenetic protein receptor 1b (bmpr1b) and bone morphogenetic protein 3 (bmp3). Expression levels were high for opg and bmpr1b, and minimal for bmp3 within the otic capsule. We concluded that opg and bmpr1b likely play important roles in inhibition of remodeling within the otic capsule.
    Hearing research 02/2010; 265(1-2):83-9. · 2.18 Impact Factor
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    ABSTRACT: To reclassify facial nerve hemangiomas in the context of presently accepted vascular lesion nomenclature by examining histology and immunohistochemical markers. Cohort analysis of patients diagnosed with a facial nerve hemangioma between 1990 and 2008. Collaborative analysis at a specialty hospital and a major academic hospital. Seven subjects were identified on composite review of office charts, a pathology database spanning both institutions, and an encrypted patient registry. Clinical data were compiled, and hematoxylin-eosin-stained specimens were reviewed. For six patients, archived pathological tissue was available for immunohistochemical evaluation of markers specific for infantile hemangioma (glucose transporter protein isoform 1 [GLUT1] and Lewis Y antigen) and for lymphatic endothelial cells (podoplanin). All patients clinically presented with slowly progressive facial weakness at a mean age of 45 years without prior symptomatology. Hemotoxylin-eosin-stained histopathological slides showed irregularly shaped, dilated lesional vessels with flattened endothelial cells, scant smooth muscle, and no internal elastic lamina. Both podoplanin staining for lymphatic endothelial cells and GLUT1 and LewisY antigen staining for infantile hemangioma endothelial cells were negative in lesional vessels in all specimens for which immunohistochemical analysis was performed. Lesions of the geniculate ganglion historically referred to as "hemangiomas" do not demonstrate clinical, histopathological, or immunohistochemical features consistent with a benign vascular tumor, but instead are consistent with venous malformation. We propose that these lesions be classified as "venous vascular malformations of the facial nerve." This nomenclature should more accurately predict clinical behavior and guide therapeutic interventions.
    Otolaryngology Head and Neck Surgery 01/2010; 142(1):108-14. · 1.73 Impact Factor
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    ABSTRACT: Delivery of medications to the inner ear has been an area of considerable growth in both the research and clinical realms during the past several decades. Systemic delivery of medication destined for treatment of the inner ear is the foundation on which newer delivery techniques have been developed. Because of systemic side effects, investigators and clinicians have begun developing and using techniques to deliver therapeutic agents locally. Alongside the now commonplace use of intratympanic gentamicin for Meniere's disease and the emerging use of intratympanic steroids for sudden sensorineural hearing loss, novel technologies, such as hydrogels and nanoparticles, are being explored. At the horizon of inner ear drug-delivery techniques, intracochlear devices that leverage recent advances in microsystems technology are being developed to apply medications directly into the inner ear. Potential uses for such devices include neurotrophic factor and steroid delivery with cochlear implantation, RNA interference technologies, and stem-cell therapy. The historical, current, and future delivery techniques and uses of drug delivery for treatment of inner ear disease serve as the basis for this review.
    Ear and hearing 11/2009; 31(2):156-65. · 2.06 Impact Factor

Publication Stats

2k Citations
195.92 Total Impact Points

Institutions

  • 1992–2014
    • Harvard Medical School
      • Department of Otology and Laryngology
      Boston, Massachusetts, United States
  • 2013
    • Beth Israel Deaconess Medical Center
      • Department of Radiology
      Boston, MA, United States
  • 2012
    • University Medical Center Utrecht
      • Department of Otorhinolaryngology - Head and Neck Surgery
      Utrecht, Provincie Utrecht, Netherlands
  • 2003–2012
    • Massachusetts General Hospital
      • • Department of Neurology
      • • Department of Surgery
      Boston, Massachusetts, United States
  • 2011
    • Draper Laboratory
      Cambridge, Massachusetts, United States
  • 1995–2011
    • Massachusetts Eye and Ear Infirmary
      • Department of Otolaryngology
      Boston, MA, United States
  • 2008
    • Saint Louis University
      Saint Louis, Michigan, United States
  • 2007
    • University of Texas Medical Branch at Galveston
      Galveston, Texas, United States
  • 2005
    • Tripler Army Medical Center
      Honolulu, Hawaii, United States
  • 2004
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 1997
    • University of Massachusetts Medical School
      Worcester, Massachusetts, United States