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1.
Am J Otolaryngol ; 45(1): 104052, 2024.
Article in English | MEDLINE | ID: mdl-37801744

ABSTRACT

PURPOSE: Patients often have basic audiometry (BA) but not objective diagnostic tests of the vestibular system (VNG) when complaining of symptoms of a vestibular disorder. The relationship of BA results to VNG results is unknown. This study sought to determine if BA scores are related to impaired VNG scores. MATERIALS AND METHODS: We reviewed electronic medical records at a tertiary care center, for patients seen between 2015 and 2021 who had had both a BA and a VNG (n = 651). BA subtests were pure tone averages, word recognition, and tympanogram. VNG subtests were cervical vestibular evoked myogenic potentials, Dix-Hallpike maneuvers, and bi-thermal caloric tests. All tests were summarized as normal/abnormal. RESULTS: More subjects had abnormal BA than abnormal VNG scores. Age but not sex was significantly related to abnormal scores. High BP was a significant comorbidity in 15 % of the sample, more in patients with abnormal than normal VNG scores. Although the abnormal BA and abnormal VNG were significantly related, pure tone averages and tympanogram scores were not related to VNG subtests. Abnormal word recognition with both ears combined was significantly related to normal and abnormal bi-thermal caloric tests. CONCLUSIONS: If the clinician needs to know of any VNG impairment, in general, then performing a BA without a VNG might suffice. If the clinician needs information about the details of possible vestibular impairment, then a VNG should be performed.


Subject(s)
Vestibular Diseases , Vestibular Evoked Myogenic Potentials , Vestibule, Labyrinth , Humans , Vertigo/diagnosis , Hearing , Vestibular Diseases/diagnosis , Caloric Tests , Vestibular Function Tests
2.
Angiogenesis ; 19(4): 463-86, 2016 10.
Article in English | MEDLINE | ID: mdl-27338829

ABSTRACT

Desmogleins (DSG) are a family of cadherin adhesion proteins that were first identified in desmosomes and provide cardiomyocytes and epithelial cells with the junctional stability to tolerate mechanical stress. However, one member of this family, DSG2, is emerging as a protein with additional biological functions on a broader range of cells. Here we reveal that DSG2 is expressed by non-desmosome-forming human endothelial progenitor cells as well as their mature counterparts [endothelial cells (ECs)] in human tissue from healthy individuals and cancer patients. Analysis of normal blood and bone marrow showed that DSG2 is also expressed by CD34(+)CD45(dim) hematopoietic progenitor cells. An inability to detect other desmosomal components, i.e., DSG1, DSG3 and desmocollin (DSC)2/3, on these cells supports a solitary role for DSG2 outside of desmosomes. Functionally, we show that CD34(+)CD45(dim)DSG2(+) progenitor cells are multi-potent and pro-angiogenic in vitro. Using a 'knockout-first' approach, we generated a Dsg2 loss-of-function strain of mice (Dsg2 (lo/lo)) and observed that, in response to reduced levels of Dsg2: (i) CD31(+) ECs in the pancreas are hypertrophic and exhibit altered morphology, (ii) bone marrow-derived endothelial colony formation is impaired, (iii) ex vivo vascular sprouting from aortic rings is reduced, and (iv) vessel formation in vitro and in vivo is attenuated. Finally, knockdown of DSG2 in a human bone marrow EC line reveals a reduction in an in vitro angiogenesis assay as well as relocalisation of actin and VE-cadherin away from the cell junctions, reduced cell-cell adhesion and increased invasive properties by these cells. In summary, we have identified DSG2 expression in distinct progenitor cell subpopulations and show that, independent from its classical function as a component of desmosomes, this cadherin also plays a critical role in the vasculature.


Subject(s)
Desmoglein 2/metabolism , Endothelial Cells/metabolism , Neovascularization, Physiologic , Animals , Cell Differentiation , Cells, Cultured , Desmoglein 2/deficiency , Desmoglein 2/genetics , Endothelial Cells/cytology , Female , Gene Knockdown Techniques , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Neovascularization, Physiologic/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Small Interfering/genetics
3.
Otolaryngol Head Neck Surg ; 168(4): 814-820, 2023 04.
Article in English | MEDLINE | ID: mdl-35414323

ABSTRACT

OBJECTIVE: To present the surgical and quality of life (QOL) outcomes of patients who underwent blind sac closure of the external auditory canal (EAC) via a modified Rambo approach. STUDY DESIGN: Retrospective case review. SETTING: Tertiary academic referral center. METHODS: All patients who underwent EAC closure with a modified Rambo approach between 2015 and 2021 were evaluated. Complication rates, QOL estimations from a validated survey, and subjective cosmetic reports were analyzed. RESULTS: Thirty-five ears were closed in 31 patients. The most common indication for surgery was related to cochlear implantation and cochlear malformation or cholesteatoma (31.4%). No case involved an immediate complication requiring revision surgery, and 4 ears (11.4%) were suspected of having cholesteatoma within the surgical cavity at a mean 28.6-month follow-up. Adults (≥18 years) had significantly higher QOL scores than children in the medical resource subscale of the Chronic Ear Survey (P < .01), and patients undergoing concurrent EAC closure and skull base tumor removal scored higher than others (P = .04). Females reported higher cosmetic scores than males (P = .04). QOL and cosmetic scores compared favorably to previously published data involving the management of otologic disease. CONCLUSIONS: Ear canal closure can be a useful technique for select adult and pediatric patients. Patient and surgeon concerns regarding QOL and cosmesis in ear canal closure should be explored prior to employing this surgical technique, though the present data suggest that the modified Rambo approach to closure is generally associated with reasonable outcomes in both areas.


Subject(s)
Cholesteatoma, Middle Ear , Cholesteatoma , Cochlear Implantation , Otologic Surgical Procedures , Male , Female , Humans , Adult , Child , Ear Canal/surgery , Quality of Life , Retrospective Studies , Cochlear Implantation/methods , Otologic Surgical Procedures/methods , Cholesteatoma/surgery , Cholesteatoma, Middle Ear/surgery , Mastoid/surgery
4.
Ann Otol Rhinol Laryngol ; 121(10): 657-63, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23130540

ABSTRACT

OBJECTIVES: We compared the outcomes of cartilage tympanoplasty in nonsmokers and smokers. METHODS: We performed a retrospective chart review of patients who underwent cartilage tympanoplasty in a tertiary academic medical center from 1991 to 2010. There were 129 operations in 118 patients; 84 operations were performed in nonsmokers and 45 operations were performed in smokers. The primary outcome measure was the tympanic membrane graft take rate at the interval and most recent follow-up visits. Secondary measures included recurrence, the need for revision surgery, and hearing outcomes. RESULTS: Nonsmokers and smokers had comparable long-term rates of intact eardrums (90.6% versus 92.9%; p = 0.99). There was a trend toward a higher rate of recurrent or persistent disease requiring further operation for smokers (13.3% versus 4.7%; p = 0.09). Both groups had improvement in pure tone averages (12.1 dB in nonsmokers and 12.8 dB in smokers) and air-bone gaps (9.6 dB in nonsmokers and 5.1 dB in smokers), although the rates were not statistically significantly different from each other. The rates of success of cartilage tympanoplasty in smokers appear superior to previously published rates of noncartilage tympanoplasty. CONCLUSIONS: Cartilage tympanoplasty has success rates and postoperative audiological measures that are comparable between smokers and nonsmokers. In smokers, cartilage grafting is superior to noncartilage grafting and is recommended for any patient who smokes and is undergoing tympanoplasty.


Subject(s)
Cartilage/transplantation , Smoking , Tympanoplasty , Adolescent , Adult , Aged , Audiometry, Pure-Tone , Bone Conduction , Female , Graft Survival , Humans , Male , Middle Aged , Reoperation/statistics & numerical data , Retrospective Studies , Treatment Outcome , Young Adult
5.
Laryngoscope ; 131(6): 1382-1385, 2021 06.
Article in English | MEDLINE | ID: mdl-33635545

ABSTRACT

OBJECTIVES/HYPOTHESIS: To determine the value of standard clinic screening questions and vital signs in predicting abnormal vestibular function, indicated by standard objective diagnostic tests. STUDY DESIGN: Retrospective records review. METHODS: We reviewed electronic medical records of 150 patients seen by the neurotologists or the physician assistant they supervised, in an out-patient tertiary care clinic, between June 2018 and March 2020, and subsequently referred for the complete objective vestibular test battery (VB). RESULTS: Of standard questions asked during the initial exam about vertigo, disequilibrium, lightheadedness and oscillopsia, only vertigo predicted an abnormal response on the VB. More males than females had abnormal VB responses, P < .05. Pulse was not related to VB score. Significantly more subjects with blood pressure in the range for stage 2 hypertension (blood pressure [BP] stage 2) had abnormal than normal results on the VB, P < .00001. Subjects with BP stage 2 had high rates of diabetes (34.2%) and hypertension (68.4%) as diagnosed by their primary care physicians or cardiologists. CONCLUSION: Complaints of subjective vertigo and BP in the range of hypertension stage 2 are most likely to predict abnormal findings on the VB. Therefore, during an examination of a patient who comes in complaining of dizziness, two measures may be the most useful for screening: BP in the range of hypertension type 2, when BP is taken by a nurse, and a question to determine whether or not the patient has true vertigo. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1382-1385, 2021.


Subject(s)
Mass Screening/statistics & numerical data , Physical Examination/statistics & numerical data , Surveys and Questionnaires/standards , Vestibular Diseases/diagnosis , Vestibular Function Tests/statistics & numerical data , Diagnosis, Differential , Female , Humans , Hypertension/complications , Hypertension/diagnosis , Male , Mass Screening/methods , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Vestibular Diseases/etiology , Vital Signs
6.
Nat Commun ; 12(1): 1434, 2021 03 04.
Article in English | MEDLINE | ID: mdl-33664264

ABSTRACT

Although melanoma is initiated by acquisition of point mutations and limited focal copy number alterations in melanocytes-of-origin, the nature of genetic changes that characterise lethal metastatic disease is poorly understood. Here, we analyze the evolution of human melanoma progressing from early to late disease in 13 patients by sampling their tumours at multiple sites and times. Whole exome and genome sequencing data from 88 tumour samples reveals only limited gain of point mutations generally, with net mutational loss in some metastases. In contrast, melanoma evolution is dominated by whole genome doubling and large-scale aneuploidy, in which widespread loss of heterozygosity sculpts the burden of point mutations, neoantigens and structural variants even in treatment-naïve and primary cutaneous melanomas in some patients. These results imply that dysregulation of genomic integrity is a key driver of selective clonal advantage during melanoma progression.


Subject(s)
Aneuploidy , DNA Copy Number Variations/genetics , Genome, Human/genetics , Melanoma/genetics , Skin Neoplasms/genetics , Disease Progression , Exome/genetics , Humans , INDEL Mutation/genetics , Melanocytes/pathology , Point Mutation/genetics , Polymorphism, Single Nucleotide/genetics , Exome Sequencing , Whole Genome Sequencing , Melanoma, Cutaneous Malignant
7.
Laryngoscope ; 122(3): 578-82, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22258933

ABSTRACT

OBJECTIVES/HYPOTHESIS: Examine the incidence of sharps exposures among otolaryngology residents, assess characteristics of exposures, and determine rates of reporting these potentially career- and life-impacting exposures. STUDY DESIGN: Cohort study of otolaryngology-head and neck surgery residents. METHODS: Survey was administered online to otolaryngology residents in the spring of 2008, gathering demographic information, characteristics of sharps exposures, and residents' self-reporting of sharps exposures. RESULTS: Among 1,407 otolaryngology residents nationwide, 231 completed the survey. Of these, 168 (72.7%) had at least one sharps exposure during residency, with most due to solid-bore needles (51.7%) and occurring in the operating room (67%). Fifty percent of residents reported exposures occurring in postgraduate year (PGY)-3 or PGY-4, whereas exposures occurred at slightly lower rates in the other PGYs. There was no difference in incidence of sharps exposures based on gender (Fisher exact test, P = .2742) or history of sharps exposure during medical school (Fisher exact test, P = .7559). Seventy-four participants had an exposure that they did not report to the hospital, with the most common reason for not reporting being the perceived burden of the hospital testing protocol. CONCLUSIONS: Otolaryngology residents report a high rate of sharps exposures during residency training, with a significant number of these exposures going unreported. Better education may be needed to help decrease these often preventable workplace exposures and to improve compliance with reporting and testing procedures.


Subject(s)
Internship and Residency , Needlestick Injuries/epidemiology , Occupational Exposure/statistics & numerical data , Otolaryngology/education , Otorhinolaryngologic Surgical Procedures/education , Female , Follow-Up Studies , Humans , Incidence , Male , Retrospective Studies , Surveys and Questionnaires , United States/epidemiology
8.
Arch Otolaryngol Head Neck Surg ; 137(1): 42-6, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21242545

ABSTRACT

OBJECTIVE: To compare the use of flexible laryngeal mask airway (LMA) and endotracheal tube (ETT) in pediatric adenotonsillectomy. DESIGN: Prospective randomized trial. SETTING: Tertiary care hospital. PATIENTS: One hundred thirty-one children (aged 2-12 years). Exclusion criteria were body mass index (calculated as the weight in kilograms divided by the height in meters squared) greater than 35 and craniofacial anomalies. Obstructive sleep apnea was the most common indication for surgery. INTERVENTION: Children undergoing adenotonsillectomy were randomized to use of an LMA or ETT. A standardized anesthesia protocol was used. MAIN OUTCOME MEASURES: Primary outcome measure was laryngospasm. Secondary measures included anesthesia, operative, and recovery times. RESULTS: Sixty children were randomized to the LMA group and 71 to the ETT group. There was no difference between groups with regard to age (P = .76), ethnicity (P = .75), body mass index (P = .99), or American Society of Anesthesiologists grade (P = .46). Incidence of postoperative laryngospasm between LMA (12.5%) and ETT (9.6%) was similar (P = .77). In 10 patients, the LMA was changed to ETT intraoperatively owing to tube kinking or difficulty with visualization. Mean (SD) surgical times for LMA and ETT groups were 33.35 (13.39) and 37.76 (18.26) minutes, respectively (P = .15). Time from surgery end to extubation was significantly shorter in patients who used LMA (P = .01) by 4.06 minutes. There were no differences (P = .49) in postanesthesia care unit recovery times. CONCLUSIONS: An LMA is an efficient alternative to ETT in pediatric adenotonsillectomy. When comparing LMA and ETT, there is no difference in rates of laryngospasm. Time to extubation is significantly shorter in patients using LMA. Before adopting the routine use of LMA in pediatric adenotonsillectomy, further study is needed to address visualization and kinking issues associated with this device.


Subject(s)
Intubation, Intratracheal/methods , Laryngeal Masks , Laryngismus/prevention & control , Adenoidectomy/methods , Anesthesia/methods , Anesthesia Recovery Period , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Intubation, Intratracheal/instrumentation , Laryngismus/epidemiology , Laryngismus/etiology , Male , Postoperative Complications/prevention & control , Prospective Studies , Risk Factors , Tonsillectomy/methods , Treatment Outcome
9.
Int J Pediatr Otorhinolaryngol ; 73(12): 1817-20, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19819032

ABSTRACT

Blunt neck trauma is an infrequent cause of injury in the pediatric population; however, significant injury is possible even with minor trauma to the neck. The authors present the previously unreported case of a combined laryngotracheal and esophageal disruption as well as a severe laryngeal crush injury in a pediatric patient following a blunt, clothesline neck injury. Immediate management of laryngotracheal or esophageal separation is frequently discussed, but little information exists concerning long-term treatment and management of total laryngotracheal disruption and crush injuries in pediatric patients. A review of the literature is presented to address these concerns.


Subject(s)
Esophagus/injuries , Larynx/injuries , Neck Injuries/surgery , Trachea/injuries , Wounds, Nonpenetrating/complications , Accidents, Traffic , Catheterization/methods , Child , Combined Modality Therapy , Esophagus/surgery , Follow-Up Studies , Humans , Injury Severity Score , Laryngoscopy/methods , Larynx/surgery , Male , Multiple Trauma/diagnosis , Multiple Trauma/surgery , Neck Injuries/etiology , Risk Assessment , Trachea/surgery , Tracheostomy/methods , Treatment Outcome , Vocal Cords/injuries
10.
Clin Orthop Relat Res ; (415): 279-85, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14612657

ABSTRACT

Osteomyelitis is a difficult problem for orthopaedic surgeons. The current standard of treatment requires high doses of antibiotic to be administered parenterally, which can damage vital organs. A local drug delivery system, which targets only the infected tissues, would eliminate some of the complications associated with extended courses of parenteral antibiotic treatment. In the current study, biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. Various formulations of microspheres were tested for in vitro elution characteristics to determine the optimum formulation for linear release of antibiotic for at least 4 weeks. The optimal formulation then was implanted into a pouch created in the quadriceps muscle of mice to evaluate the in vivo elution of the antibiotic and the inflammatory response elicited by the microspheres. Results indicate that a sustained linear release of antibiotic from the microspheres is possible for a period of at least 4 weeks and that the inflammatory response was within levels required for the microspheres to be considered biocompatible.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Biocompatible Materials/therapeutic use , Microspheres , Osteomyelitis/drug therapy , Polyethylene Glycols/therapeutic use , Polyglactin 910/therapeutic use , Tobramycin/therapeutic use , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/chemistry , Biocompatible Materials/adverse effects , Biocompatible Materials/chemistry , Chemistry, Pharmaceutical , Delayed-Action Preparations , Drug Carriers , Drug Evaluation, Preclinical , Female , Fluorescence Polarization Immunoassay , Inflammation/chemically induced , Mice , Mice, Inbred ICR , Molecular Weight , Muscle, Skeletal/drug effects , Polyethylene Glycols/adverse effects , Polyethylene Glycols/chemistry , Polyglactin 910/adverse effects , Polyglactin 910/chemistry , Tobramycin/adverse effects , Tobramycin/chemistry
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