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1.
Laryngoscope ; 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38877834

ABSTRACT

OBJECTIVE: Although screening protocols for patients who present with asymmetric sensorineural hearing loss (ASNHL) exist, there are no clear guidelines to direct practitioners. In particular, various thresholds have been proposed for the degree of hearing loss that should prompt MRI studies, but the topic remains understudied. This project aims to compare protocols followed by practitioners to guide their imaging practices. STUDY DESIGN: Web-based survey. SETTING: Otolaryngology faculty at academic medical centers. METHODS: A list of 530 otolaryngologists (276 otology/neurotology specialists, 254 general otolaryngologists) was compiled. A survey consisting of three parts: demographics, general practice patterns, and simulated patient cases was distributed. RESULTS: A total of 468 surveys were successfully distributed, resulting in 88 (18.8%) responses. The majority of respondents (63.8%) self-reported their definition of ASNHL as ">30 dB hearing asymmetry at one frequency OR >20 dB hearing asymmetry at two continuous frequencies OR >10 dB hearing asymmetry at three contiguous frequencies." Overall, general otolaryngologists were more likely to observe asymmetric findings with serial audiogram alone, whereas otology/neurotology specialists were more likely to obtain imaging. CONCLUSION: There is significant variability between providers with regard to managing patients with ASNHL and evidence-based guidelines would be useful in guiding imaging practices. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.

2.
Front Neurosci ; 17: 1228506, 2023.
Article in English | MEDLINE | ID: mdl-37942141

ABSTRACT

Introduction: Processing the wealth of sensory information from the surrounding environment is a vital human function with the potential to develop learning, advance social interactions, and promote safety and well-being. Methods: To elucidate underlying processes governing these activities we measured neurophysiological responses to patterned stimulus sequences during a sound categorization task to evaluate attention effects on implicit learning, sound categorization, and speech perception. Using a unique experimental design, we uncoupled conceptual categorical effects from stimulus-specific effects by presenting categorical stimulus tokens that did not physically repeat. Results: We found effects of implicit learning, categorical habituation, and a speech perception bias when the sounds were attended, and the listeners performed a categorization task (task-relevant). In contrast, there was no evidence of a speech perception bias, implicit learning of the structured sound sequence, or repetition suppression to repeated within-category sounds (no categorical habituation) when participants passively listened to the sounds and watched a silent closed-captioned video (task-irrelevant). No indication of category perception was demonstrated in the scalp-recorded brain components when participants were watching a movie and had no task with the sounds. Discussion: These results demonstrate that attention is required to maintain category identification and expectations induced by a structured sequence when the conceptual information must be extracted from stimuli that are acoustically distinct. Taken together, these striking attention effects support the theoretical view that top-down control is required to initiate expectations for higher level cognitive processing.

3.
Otol Neurotol ; 44(10): 1100-1105, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37758317

ABSTRACT

OBJECTIVE: To evaluate long-term effects of COVID-19 on auditory and vestibular symptoms in a diverse cohort impacted by the initial 2020 COVID-19 infection in the pandemic's epicenter, before vaccine availability. STUDY DESIGN: Cohort study of individuals with confirmed COVID-19 infection, diagnosed in the March-May 2020 infection wave. A randomized, retrospective chart review of 1,352 individuals was performed to identify those with documented new or worsening auditory (aural fullness, tinnitus, hyperacusis, hearing loss) or vestibular (dizziness, vertigo) symptoms. Those with documented symptoms (613 of the 1,352 initial cohort) were contacted for a follow-up telephone survey in 2021-2022 to obtain self-report of aforementioned symptoms. SETTING: Academic tertiary hospital system in Bronx, NY. PATIENTS: Adults 18 to 99 years old with confirmed COVID-19 infection, alive at time of review. One hundred forty-eight charts were excluded for restricted access, incomplete data, no COVID-19 swab, or deceased at time of review. INTERVENTION: Confirmed COVID-19 infection, March to May 2020. MAIN OUTCOMES MEASURES: Auditory and vestibular symptoms documented in 2020 medical records and by self-report on 2021 to 2022 survey. RESULTS: Among the 74 individuals with documented symptoms during the first 2020 COVID-19 wave who participated in the 2021 to 2022 follow-up survey, 58% had documented vestibular symptoms initially in 2020, whereas 43% reported vestibular symptoms on the 2021 to 2022 survey ( p = 0.10). In contrast, 9% had documented auditory symptoms initially in 2020 and 55% reported auditory symptoms on the 2021 to 2022 survey ( p < 0.01). CONCLUSIONS: COVID-19 may impact vestibular symptoms early and persistently, whereas auditory effects may have more pronounced long-term impact, suggesting the importance of continually assessing COVID-19 patients.


Subject(s)
COVID-19 , Tinnitus , Adult , Humans , Adolescent , Young Adult , Middle Aged , Aged , Aged, 80 and over , Retrospective Studies , Cohort Studies , Vertigo/diagnosis , Tinnitus/epidemiology , Tinnitus/etiology , Tinnitus/diagnosis
4.
J Neurol Surg Rep ; 84(2): e51-e58, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37090942

ABSTRACT

Ectopic pituitary tumors are neoplasms with no connection to the pituitary gland and are commonly deposited in other areas of the anterior skull base. A 32-year-old woman presented with a 3-month history of right-sided facial weakness, sensorineural hearing loss, diplopia, and severe headaches. Physical examination revealed a mid-dilated sluggishly reactive right pupil with slight limitation in all gazes, as well as right-sided orbicularis weakness, lagophthalmos, and decreased facial sensation. A magnetic resonance imaging (MRI) of the head without contrast revealed a 3.7 × 1.8 × 2.6 cm mildly enhancing mass in the right internal acoustic meatus and along the petrous ridge. The case was brought before the institution's tumor board, where concern for higher grade pathology, such as hemangiopericytoma, was discussed. Per patient preference, surgical biopsy of the tumor was performed. Immunohistochemical staining revealed a World Health Organization (WHO) grade II neuroendocrine tumor, with cells staining positive for synaptophysin, chromogranin, and CD56, with a K i -67 index of 8%. In addition to the ectopic location, this pituitary tumor was noted to be aggressive in nature based on its high K i -67 index. Surgical excision and radiologic therapy of tumors involving the CPA are appropriate treatments in most cases.

6.
J Neurol Surg B Skull Base ; 83(3): 237-247, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35769796

ABSTRACT

Objectives Antibiotic use in lateral skull base surgery (LSBS) has not been thoroughly investigated in the literature. There is wide variability in antibiotic use and insufficient data to guide management. This study aims to describe the factors and patterns influencing antibiotic use in LSBS among the membership of the North American Skull Base Society (NASBS). Design An online-based survey was designed and distributed to the membership of the NASBS. Data was analyzed using bivariate analysis and logistic regression modeling. Setting Online-based questionnaire. Participants NASBS membership. Main Outcome Measures Use of intraoperative antibiotics and use of postoperative antibiotics. Results The survey response rate was 26% (208 respondents). Of the 208 total respondents, 143 (69%) respondents performed LSBS. Most respondents are neurosurgeons (69%) with the remaining being otolaryngologists (31%). The majority of respondents (79%) are fellowship-trained in skull base surgery. Academic or government physicians make up 69% of respondents and 31% are in private practice with or without academic affiliations. Bivariate analysis showed that practice setting significantly influenced intraoperative antibiotic use ( p = 0.01). Geographic location significantly affected postoperative antibiotic use ( p = 0.01). Postoperative antibiotic duration was significantly affected by presence of chronic otitis media, cerebrospinal fluid leak, and surgeon training ( p = 0.02, p = 0.01, and p = 0.006, respectively). Logistic regression modeling showed that the motivation to reduce infection significantly impacted postoperative antibiotic use ( p = 0.03). Conclusion This study demonstrates significant variations in intraoperative and postoperative antibiotic use in LSBS among the NASBS membership. Appropriate guidelines for optimal perioperative antibiotic use patterns should be determined with randomized studies in the future.

7.
Am J Otolaryngol ; 42(4): 102993, 2021.
Article in English | MEDLINE | ID: mdl-33640801

ABSTRACT

OBJECTIVE: The association between obstructive sleep apnea (OSA) and Eustachian tube dysfunction (ETD) is well known. When both exist in a single pediatric patient, one of the expected culprits is adenoid enlargement. We hypothesize, in contrast, that the negative pharyngeal pressure found in OSA may be transmitted to the middle ear as negative middle ear pressure (MEP), which subsequently results in pathology. The objective of this study was to determine whether the degree of OSA and MEP are associated while using MEP as a quantifiable measurement of ETD. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic center (Jan 2000-Jan 2018). SUBJECTS AND METHODS: The relationship between apnea-hypopnea index (AHI) and MEP was examined. A non-anatomic model was utilized to support causality. RESULTS: Thirty-four pediatric patients and twenty-three adult patients were included in the analysis. REM AHI showed a moderate negative correlation with MEP in children (r = -0.265), and a weak positive correlation with MEP in adults (r = 0.171). Children with an AHI in the severe OSA category had a more negative mean MEP than those in the mild category (p = 0.36). Adults with an AHI in the severe OSA category had a more positive mean MEP than those in the mild category (p = 0.11). CONCLUSION: In children, increasing severity of OSA is associated with a negative MEP, suggesting that negative pressure associated with OSA may be transmitted to the middle ear. In adults, increasing severity of OSA is associated with a more positive MEP.


Subject(s)
Ear Diseases/etiology , Ear, Middle/physiopathology , Pharynx/physiopathology , Pressure , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Adult , Age Factors , Aged , Child , Child, Preschool , Ear Diseases/physiopathology , Eustachian Tube , Female , Humans , Male , Middle Aged , Retrospective Studies , Severity of Illness Index
8.
Front Psychol ; 11: 1155, 2020.
Article in English | MEDLINE | ID: mdl-32655436

ABSTRACT

The ability to distinguish among different types of sounds in the environment and to identify sound sources is a fundamental skill of the auditory system. This study tested responses to sounds by stimulus category (speech, music, and environmental) in adults with normal hearing to determine under what task conditions there was a processing advantage for speech. We hypothesized that speech sounds would be processed faster and more accurately than non-speech sounds under specific listening conditions and different behavioral goals. Thus, we used three different task conditions allowing us to compare detection and identification of sound categories in an auditory oddball paradigm and in a repetition-switch category paradigm. We found that response time and accuracy were modulated by the specific task demands. The sound category itself had no effect on sound detection outcomes but had a pronounced effect on sound identification. Faster and more accurate responses to speech were found only when identifying sounds. We demonstrate a speech processing "advantage" when identifying the sound category among non-categorical sounds and when detecting and identifying among categorical sounds. Thus, overall, our results are consistent with a theory of speech processing that relies on specialized systems distinct from music and other environmental sounds.

9.
Article in English | MEDLINE | ID: mdl-32596655

ABSTRACT

The petrous apex is a difficult to reach surgical area due to its deep position in the skull base and many vital surrounding structures. Petrous apex pathology ranges from extradural cholesterol granulomas, cholesteatomas, asymmetric pneumatization, and osteomyelitis to intradural meningiomas and schwannomas. Certain lesions, such as cholesterol granulomas, can be managed with drainage while neoplastic lesions must be completely resected. Surgical options use open, endoscopic, and combined techniques and are categorized into anterior, lateral, and posterior approaches. The choice of approach is determined by the nature of the pathology and location relative to vital structures and extension into surrounding structures and requires thorough preoperative evaluation and discussion of surgical goals with the patient. The purpose of this state-of-the-art review is to discuss the most commonly used surgical approaches to the petrous apex, and the anatomy on which these approaches are based.

10.
Laryngoscope ; 130(3): 615-621, 2020 03.
Article in English | MEDLINE | ID: mdl-31099417

ABSTRACT

OBJECTIVES/HYPOTHESIS: To examine the perspectives of current otolaryngology-head and neck surgery residents and faculty members on educational formats and approaches. To assess the effects of a novel integrative educational curriculum for residents by examining results from the otolaryngology training examination (OTE). We hypothesized that altering the current curriculum to accentuate resident participation would result in improved performance on the OTE. STUDY DESIGN: Prospective cohort study. METHODS: We conducted a study from June 2015 to July 2018. All faculty attendings and residents were asked to participate in the study and were included. A novel educational curriculum founded on the principles of experiential learning and utilizing the PulseQD app to facilitate collaborative learning was implemented. The results of a questionnaire distributed within the department and yearly OTE scores were collected. RESULTS: Residents and faculty attendings reported comparable exposure to educational formats throughout their training, although residents had more experience with flipped classroom settings. Both groups had similar attitudes toward the importance and effectiveness of educational opportunities. There was a statistically significant improvement in OTE scores in each of the 2 years after implementation of the educational changes (P = .0296 and P = .00237, respectively), with all current residents improving their scores on the most recent OTE. CONCLUSIONS: Through implementation of this integrative educational curriculum our residents showed significant improvement in OTE scores. Our results suggest that this type of curriculum, which combines a variety of approaches including a flipped classroom model with active participation and integrates app technology, can improve resident performance on educational assessments. LEVEL OF EVIDENCE: 2 Laryngoscope, 130:615-621, 2020.


Subject(s)
Curriculum , Education, Medical, Graduate/methods , Internship and Residency/methods , Otolaryngology/education , Problem-Based Learning/methods , Adult , Clinical Competence , Educational Measurement , Faculty, Medical/psychology , Female , Humans , Male , Middle Aged , Prospective Studies , Students, Medical/psychology , Surveys and Questionnaires
11.
Int Forum Allergy Rhinol ; 9(10): 1196-1204, 2019 10.
Article in English | MEDLINE | ID: mdl-31442001

ABSTRACT

BACKGROUND: There is a paucity of data evaluating antibiotic use in anterior skull-base surgery (ASBS). The goal of this study was to determine antibiotic prescribing patterns and factors that influence antibiotic use in ASBS. METHODS: An online-based survey was distributed to the membership of the North American Skull Base Society in 2018. Outcomes included practitioner preference regarding intraoperative and postoperative antibiotic use, practice location and environment, surgeon experience, and patient factors influencing antibiotic use. RESULTS: There were 208 respondents (25.6% response rate) of which 182 (87.5%) performed ASBS; 60.4% were in academic institutions. Respondents were neurosurgeons (59.3%) or otolaryngologists (40.7%), and 75.3% were fellowship-trained in ASBS. Most surgeons (95.0%) gave intraoperative antibiotics. Academic surgeons were 4 times more likely to prescribe intraoperative antibiotics than private practitioners (odds ratio [OR] 3.98; 95% confidence interval [CI], 1.53 to 10.36; p = 0.005). Among surgeons who did not routinely prescribe intraoperative antibiotics, regression analysis indicated that the presence of actively infected sinuses, transplantation, diabetes, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and pulmonary disease influenced decision-making (p < 0.03). Postoperative antibiotics were prescribed by 73.6% of respondents. European surgeons were 3 times less likely to prescribe postoperative antibiotics (OR 0.34; 95% CI, 0.15 to 0.80; p = 0.01). Regression modeling indicated that HIV/AIDS, cystic fibrosis, diabetes, transplantation, and pulmonary disease, as well as the use of absorbable packing influenced the decision to use postoperative antibiotics (p < 0.003). CONCLUSION: This study demonstrates the significant variation in intra- and postoperative antibiotic use among surgeons performing ASBS. Prospective randomized studies are necessary to establish evidence-based practice guidelines for perioperative antibiotic use in ASBS.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Neurosurgical Procedures , Otolaryngologists , Postoperative Complications/prevention & control , Skull Base/surgery , Surgeons , Antibiotic Prophylaxis , Female , Humans , Infection Control , Male , Practice Patterns, Physicians' , Prospective Studies , Societies, Medical , Surveys and Questionnaires
12.
Int J Pediatr Otorhinolaryngol ; 123: 63-65, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31075708

ABSTRACT

We describe the case of a young boy with severe clinical symptoms which mimicked several findings consistent with a peritonsillar abscess (PTA). After the patient exhibited no improvement with medical management, imaging revealed an intramuscular medial pterygoid abscess secondary to parapharyngeal space lymphadenitis. This is the first reported case of a patient with a medial pterygoid abscess secondary to lymphadenitis. We also describe a minimally invasive surgical approach for incision and drainage of the abscess that has not previously been described in the literature.


Subject(s)
Abscess/diagnostic imaging , Abscess/surgery , Lymphadenitis/diagnosis , Pterygoid Muscles , Abscess/etiology , Child , Drainage , Humans , Lymphadenitis/complications , Male , Tomography, X-Ray Computed
13.
Am J Otolaryngol ; 39(5): 527-530, 2018.
Article in English | MEDLINE | ID: mdl-29895431

ABSTRACT

INTRODUCTION: The development of portable, high resolution video displays such as video glasses allows clinicians the opportunity to offer patients an increased ability to visualize aspects of their physical examination in an ergonomic and cost-effective manner. The objective of this pilot study is to trial the use of video glasses for patients undergoing binocular microscopy as well as to better understand some of the potential benefits of the enhanced display option. METHODS: This study was comprised of a single treatment group. Patients seen in the otolaryngology clinic who required binocular microscopy for diagnosis and treatment were recruited. All patients wore video glasses during their otoscopic examination. An additional cohort of patients who required binocular microscopy were also recruited, but did not use the video glasses during their examination. Patients subsequently completed a 10-point Likert scale survey that assessed their comfort, anxiety, and satisfaction with the examination as well as their general understanding of their otologic condition. RESULTS: A total of 29 patients who used the video glasses were recruited, including those with normal examinations, cerumen impaction, or chronic ear disease. Based on the survey results, patients reported a high level of satisfaction and comfort during their exam with video glasses. Patients who used the video glasses did not exhibit any increased anxiety with their examination. Patients reported that video glasses improved their understanding and they expressed a desire to wear the glasses again during repeat exams. CONCLUSION: This pilot study demonstrates that video glasses may represent a viable alternative display option in the otolaryngology clinic. The results show that the use of video glasses is associated with high patient comfort and satisfaction during binocular microscopy. Further investigation is warranted to determine the potential for this display option in other facets of patient care as well as in expanding patient understanding of disease and anatomy.


Subject(s)
Anxiety/prevention & control , Eyeglasses/classification , Otoscopy/methods , Patient Comfort , Physical Examination/instrumentation , Adult , Ambulatory Care/methods , Cohort Studies , Female , Humans , Male , Microscopy/methods , Physical Examination/methods , Pilot Projects , Video Recording/methods
14.
Laryngoscope ; 128(6): 1340-1345, 2018 06.
Article in English | MEDLINE | ID: mdl-29214641

ABSTRACT

OBJECTIVE: Technological change is leading to an evolution in medical education. The objective of our study was to assess the impact of a medical knowledge app, called PulseQD, on resident education within our otolaryngology-head and neck surgery department at Montefiore Medical Center, Albert Einstein College of Medicine (Bronx, NY). METHODS: A prospective cohort study was conducted within the Department of Otolaryngology-Head and Neck Surgery from July 2016 to June 2017. All faculty attendings and residents were asked to participate in the study and were included. A Web and mobile-based app, PulseQD, that allowed for collaborative learning was implemented. Questionnaires were given at the beginning and end of the academic year. Otolaryngology Training Exam (OTE) scores were collected RESULTS: A total of 20 residents and 13 faculty members participated in the study. Residents used online sources of medical information significantly more often than faculty (90% and 54%, respectively, P = 0.0179). Residents and faculty felt that PulseQD offered a valuable perspective on clinically relevant medical information (P = 0.0003), was a great way to test clinical and medical knowledge (P = 0.0001), and improved the sharing and discussing of medical knowledge (P < 0.0001). There was a statistically significant 5.8% improvement in OTE scores (P = 0.0008) at the end of the academic year. CONCLUSION: The implementation of a novel mobile app, PulseQD, was well received by residents and faculty in the Department of Otolaryngology-Head and Neck Surgery. Preliminary data suggest that app-based learning may lead to improved performance on knowledge-based assessments. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1340-1345, 2018.


Subject(s)
Clinical Competence/statistics & numerical data , Internship and Residency/methods , Mobile Applications , Otolaryngology/education , Adult , Aged , Cohort Studies , Educational Measurement/methods , Humans , Middle Aged , Prospective Studies , Surveys and Questionnaires
16.
J Neurosci ; 34(50): 16688-97, 2014 Dec 10.
Article in English | MEDLINE | ID: mdl-25505321

ABSTRACT

Cholinergic inhibition of hair cells occurs by activation of calcium-dependent potassium channels. A near-membrane postsynaptic cistern has been proposed to serve as a store from which calcium is released to supplement influx through the ionotropic ACh receptor. However, the time and voltage dependence of acetylcholine (ACh)-evoked potassium currents reveal a more complex relationship between calcium entry and release from stores. The present work uses voltage steps to regulate calcium influx during the application of ACh to hair cells in the chicken basilar papilla. When calcium influx was terminated at positive membrane potential, the ACh-evoked potassium current decayed exponentially over ∼100 ms. However, at negative membrane potentials, this current exhibited a secondary rise in amplitude that could be eliminated by dihydropyridine block of the voltage-gated calcium channels of the hair cell. Calcium entering through voltage-gated channels may transit through the postsynaptic cistern, since ryanodine and sarcoendoplasmic reticulum calcium-ATPase blockers altered the time course and magnitude of this secondary, voltage-dependent contribution to ACh-evoked potassium current. Serial section electron microscopy showed that efferent and afferent synaptic structures are juxtaposed, supporting the possibility that voltage-gated influx at afferent ribbon synapses influences calcium homeostasis during long-lasting cholinergic inhibition. In contrast, spontaneous postsynaptic currents ("minis") resulting from stochastic efferent release of ACh were made briefer by ryanodine, supporting the hypothesis that the synaptic cistern serves primarily as a calcium barrier and sink during low-level synaptic activity. Hypolemmal cisterns such as that at the efferent synapse of the hair cell can play a dynamic role in segregating near-membrane calcium for short-term and long-term signaling.


Subject(s)
Calcium/physiology , Hair Cells, Auditory/physiology , Organ of Corti/physiology , Synapses/physiology , Animals , Calcium Channels/physiology , Calcium Channels/ultrastructure , Chick Embryo , Female , Hair Cells, Auditory/ultrastructure , Male , Organ of Corti/ultrastructure , Synapses/ultrastructure
17.
Otol Neurotol ; 35(10): e331-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25275864

ABSTRACT

OBJECTIVE: To develop a cadaveric temporal bone preparation to compare the strength of superior semicircular canal dehiscence (SCD) repair techniques. BACKGROUND: Superior semicircular canal dehiscence syndrome is a clinical condition with a variety of auditory and vestibular symptoms resulting from a mobile third window into the inner ear. Patients with incapacitating symptoms often undergo surgical repair. There have been no previous studies to directly assess the strength of techniques used for repair of SCD. METHODS: The ability of repair techniques to withstand prolonged pressure application was measured in prepared temporal bones (n = 5). Pressure changes were compared with the superior semicircular canal intact and with the dehiscence repaired via three repair techniques (resurfacing, plugging, and combined plugging and resurfacing). RESULTS: Each of the three repair techniques resisted loss of applied pressure as well as the closed system before creation of the dehiscence at pressures comparable to high-normal intracranial pressure (23-25 cm H2O). At supra-physiologic pressure levels (45-55 cm H2O), the combined plugging and resurfacing technique showed consistent resistance to loss of pressure as compared to instances of failure with either of the single repair approaches. CONCLUSION: Findings from the cadaveric temporal bone preparations revealed that even immediately after repair, each of the three main techniques are equally resistant to the application of high-normal intracranial pressure levels. However, with consistent resistance to loss of pressure across all trials, the combined plugging and resurfacing technique may offer improved resistance in instances where supra-physiologic pressures are encountered.


Subject(s)
Labyrinth Diseases/surgery , Otologic Surgical Procedures/methods , Semicircular Canals/surgery , Temporal Bone/surgery , Humans , Labyrinth Diseases/pathology , Pressure , Semicircular Canals/pathology , Syndrome , Temporal Bone/pathology
18.
Oral Oncol ; 48(11): 1136-45, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22732263

ABSTRACT

OBJECTIVE: Targeting the epidermal growth factor receptor (EGFR) using the tyrosine kinase inhibitor (TKI) erlotinib has demonstrated activity in aerodigestive tract malignancies. Co-targeting of the G-protein-coupled receptor cyclooxygenase (COX) with EGFR inhibitors has shown promise in preclinical models and early phase clinical studies. MATERIALS AND METHODS: We studied the modulation of serum proteins after neoadjuvant treatment with erlotinib with or without sulindac in head and neck cancer patients. In a prospective, randomized, double-blind clinical trial, paired serum samples were obtained before and after neoadjuvant treatment in three groups of patients (n = 23 total), who were randomized to receive 7-14 consecutive days of erlotinib alone, erlotinib plus sulindac, or placebo. Two separate multiplexed ELISA systems (SearchLight™ or Luminex™) were used to measure serum biomarkers. HGF and IL-6 levels were tested on both systems, and validated using single analyte ELISAs. RESULTS: Several analytes were significantly altered (generally decreased) post-treatment, in patients who received erlotinib (with or without sulindac) as well as in the placebo groups. No single analyte was differentially altered across the three treatment groups using either multiplex platform. Single HGF ELISA suggested a nonspecific decrease in all patients. CONCLUSION: These results demonstrate the importance of a placebo group when assessing changes in expression of serum biomarkers. While multiplex platforms can provide quantitative information on a large number of serum analytes, results should be cautiously compared across platforms due to their intrinsic features. Furthermore, the dynamic range of expression of a single analyte is constrained in multiplex versus standard ELISA.


Subject(s)
Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/blood , Head and Neck Neoplasms/blood , Adult , Aged , Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Double-Blind Method , Enzyme-Linked Immunosorbent Assay/methods , ErbB Receptors/blood , Erlotinib Hydrochloride , Female , Head and Neck Neoplasms/drug therapy , Hepatocyte Growth Factor/blood , Humans , Interleukin-6/blood , Male , Middle Aged , Neoadjuvant Therapy/methods , Pilot Projects , Placebos/administration & dosage , Prospective Studies , Protein Kinase Inhibitors/administration & dosage , Quinazolines/administration & dosage , Sulindac/administration & dosage , Transforming Growth Factor alpha/blood
19.
Am J Otolaryngol ; 32(3): 259-62, 2011.
Article in English | MEDLINE | ID: mdl-20444524

ABSTRACT

The differential diagnosis of middle ear masses encompasses a wide variety of pathologic conditions. In this report, we describe the case of a 6-year-old girl who presented with facial nerve weakness and was found to have a middle ear mass. The mass was excised, and final pathology revealed hemangioendothelioma. This report describes the youngest patient with this diagnosis presenting as a middle ear mass in the Western literature. This article provides this patient's presentation, imaging and histopathologic findings, and clinical course and reviews the current literature on this unique pathologic diagnosis.


Subject(s)
Ear Neoplasms/diagnosis , Ear Neoplasms/surgery , Ear, Middle , Hemangioendothelioma, Epithelioid/diagnosis , Hemangioendothelioma, Epithelioid/surgery , Biopsy, Needle , Child , Ear Neoplasms/pathology , Female , Follow-Up Studies , Hemangioendothelioma, Epithelioid/pathology , Humans , Immunohistochemistry , Neoplasm Staging , Otologic Surgical Procedures/methods , Risk Assessment , Tomography, X-Ray Computed , Treatment Outcome
20.
Mol Pharmacol ; 68(3): 866-75, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15939800

ABSTRACT

The rat mu-opioid receptor clone in which novel exon 5 was found in the place of exon 4 (MOR-1B) was one of the first MOR-1 variants described. We now have identified the mouse homolog of the rat MOR-1B as well as four additional variants derived from splicing from exon 3 into different sites within exon 5. The sequences of all of the variants were identical except for the intracellular tip of the C terminus encoded by exon 5, where each variant predicted a unique amino acid sequence ranging from 2 to 39 amino acids. All of the mMOR-1B variants were selective for mu-opioids in receptor-binding assays, as anticipated, because they all have identical binding pockets defined by the transmembrane domains. However, the relative potency and efficacy of mu-agonists to each other varied from variant to variant in guanosine 5'-O-(3-[35S]thio)triphosphate-binding studies, as shown by morphine-6beta-glucuronide, which was the most efficacious agent against mouse MOR-1B1 (mMOR-1B1) and the least efficacious agent against mMOR-1B2. mMOR-1B4 was quite unusual. Although mMOR-1B4 was mu-selective in receptor-binding studies and antagonists labeled mMOR-1B4 well, the binding affinities of most of the mu-agonists were far lower than those seen with mMOR-1, suggesting that the 39 amino acids at the C terminus of mMOR-1B4 influences the conformation of the receptor and its ligand recognition site itself either directly or through its interactions with other proteins. In conclusion, alterations in the amino acid sequence of the C terminus do not alter the mu-specificity of the receptor but they can influence the binding characteristics, efficacy, and potency of mu-opioids.


Subject(s)
Exons , RNA Splicing , Receptors, Opioid, mu/genetics , Animals , Base Sequence , Blotting, Northern , DNA , Guanosine 5'-O-(3-Thiotriphosphate)/metabolism , Mice , Molecular Sequence Data , Protein Binding , Receptors, Opioid, mu/metabolism , Reverse Transcriptase Polymerase Chain Reaction
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