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1.
Ann Otol Rhinol Laryngol ; 125(3): 247-56, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26530091

RESUMO

OBJECTIVES: The pathophysiology of recurrent laryngeal nerve (RLN) transection injury is rare in that it is characteristically followed by a high degree of spontaneous reinnervation, with reinnervation of the laryngeal adductor complex (AC) preceding that of the abducting posterior cricoarytenoid (PCA) muscle. Here, we aim to elucidate the differentially expressed myogenic factors following RLN injury that may be at least partially responsible for the spontaneous reinnervation. METHODS: F344 male rats underwent RLN injury (n = 12) or sham surgery (n = 12). One week after RLN injury, larynges were harvested following euthanasia. The mRNA was extracted from PCA and AC muscles bilaterally, and microarray analysis was performed using a full rat genome array. RESULTS: Microarray analysis of denervated AC and PCA muscles demonstrated dramatic differences in gene expression profiles, with 205 individual probes that were differentially expressed between the denervated AC and PCA muscles and only 14 genes with similar expression patterns. CONCLUSIONS: The differential expression patterns of the AC and PCA suggest different mechanisms of reinnervation. The PCA showed the gene patterns of Wallerian degeneration, while the AC expressed the gene patterns of reinnervation by adjacent axonal sprouting. This finding may reveal important therapeutic targets applicable to RLN and other peripheral nerve injuries.


Assuntos
Músculos Laríngeos/inervação , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Transcriptoma , Animais , Masculino , Análise em Microsséries , Modelos Animais , Ratos Endogâmicos F344 , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
Ann Otol Rhinol Laryngol ; 123(2): 124-34, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24574468

RESUMO

OBJECTIVES: As an initial step toward our goal of developing a completely tissue-engineered larynx, the aim of this study was to describe and compare three strategies of creating tissue-engineered muscle-polymer constructs for hemilaryngeal reconstruction. METHODS: Cartilage-mimicking polymer was developed from electrospun poly(D,L-lactide-co-ε-caprolactone) (PCL). Primary muscle progenitor cell cultures were derived from syngeneic F344 rat skeletal muscle biopsies. Twenty F344 rats underwent resection of the outer hemilaryngeal cartilage with the underlying laryngeal adductor muscle. The defects were repaired with muscle stem cell-derived muscle-PCL constructs (5 animals), myotube-derived muscle-PCL constructs (5 animals), motor end plate-expressing muscle-PCL constructs (5 animals), or PCL alone (controls; 5 animals). The outcome measures at 1 month included animal survival, muscle thickness, and innervation status as determined by electromyography and immunohistochemistry. RESULTS: All of the animals survived the 1-month implant period and had appropriate weight gain. The group that received motor end plate-expressing muscle-PCL constructs demonstrated the greatest muscle thickness and the strongest innervation, according to electromyographic activity and the percentage of motor end plates that had nerve contact. CONCLUSIONS: Although all of the tissue-engineered constructs provided effective reconstruction, those that expressed motor end plates before implantation yielded muscle that was more strongly innervated and viable. This finding suggests that this novel approach may be useful in the development of a tissue-engineered laryngeal replacement.


Assuntos
Laringe , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Masculino , Placa Motora , Fibras Musculares Esqueléticas , Mioblastos Esqueléticos , Poliésteres , Ratos Endogâmicos F344
3.
Ann Otol Rhinol Laryngol ; 122(10): 653-63, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24294689

RESUMO

OBJECTIVES: Recurrent laryngeal nerve (RLN) and vagus nerve (VN) injuries characteristically are followed by differing degrees of spontaneous reinnervation, yet laryngeal muscle neurotrophic factor (NF) expression profiles after RLN and VN injuries have not been well elucidated. This study's objective was to determine the relative changes in gene expression of 5 well-characterized NFs from laryngeal muscle after RLN or VN injuries in a time-dependent fashion, and demonstrate how these changes correspond with electromyography-assessed innervation status. METHODS: Thirty-six male rats underwent left RLN transection (12 rats), left VN transection (12 rats), or a sham procedure (12 rats). The primary outcomes included electromyographic assessment and laryngeal muscle NF expression quantification with reverse transcription polymerase chain reaction at 3 days and at 1 month. RESULTS: Electromyography at 3 days demonstrated electrical silence in the VN injury group, normal activity in the sham group, and nascent units with decreased recruitment in the RLN injury group. Reverse transcription polymerase chain reaction demonstrated that changes in NF gene expression from laryngeal muscles varied depending on the type of nerve injury (RLN or VN) and the specific laryngeal muscle (posterior cricoarytenoid or adductor) assessed. CONCLUSIONS: Laryngeal muscle NF expression profiles after cranial nerve X injury depend both upon the level of nerve injury and upon the muscles involved.


Assuntos
Expressão Gênica , Fatores de Crescimento Neural/genética , Traumatismos do Nervo Laríngeo Recorrente/genética , Traumatismos do Nervo Vago/genética , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Ciliar/genética , Eletromiografia , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator de Crescimento Insulin-Like I/genética , Músculos Laríngeos/fisiologia , Masculino , Marcadores do Trato Nervoso , Ratos , Ratos Endogâmicos F344 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/genética
4.
Laryngoscope Investig Otolaryngol ; 6(4): 780-785, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34226876

RESUMO

Objective: Describe safety practices for performing in-office laryngology procedures during clinical re-introduction amidst the coronavirus disease 2019 (COVID-19) pandemic. Methods: An anonymous survey in Qualtrics was created to evaluate demographics, preprocedure testing, practice settings, anesthesia, and personal protective equipment (PPE) use for five procedure categories (non-mucosal-traversing injections, mucosal-traversing injections, endoscopy without suction, endoscopy with suction/mucosal intervention via working channel, and laser via working channel). The survey was emailed to the Fall Voice Community on Doc Matter and to members of the American Broncho-Esophagological Association (ABEA) from May to June 2020. Results: Eighty-two respondents were analyzed (response rate: 10%). Respondents represented diverse locations, including international. Most reported academic (71%) or private practices (16%), laryngology fellowship training (76%), and a significant practice devotion to laryngology and broncho-esophagology. During the early re-introduction, most continued to perform all procedure categories. The office was preferred to the OR setting for most, though 36% preferred the OR for laser procedures. There was a preference for preprocedural SARS-Cov2 testing for procedures involving a working channel (>67%), and these procedures had the highest proportion of respondents discontinuing the procedure due to COVID-19. Various types of topical anesthesia were reported, including nebulizer treatments. The most common forms of personal protective equipment utilized were gloves (>95%) and N95 masks (>67%). Powered-air purifying respirators and general surgical masks were used infrequently. Conclusions: During the early re-introduction, respondents reported generally continuing to perform office laryngology procedures, while greater mucosal manipulation affected decisions to stop procedures due to COVID-19, perform preprocedural SARS-Cov2 testing, and alter topical anesthesia. Gloves and N95 masks were the predominate PPE. Level of Evidence: N/A.

5.
Ann Otol Rhinol Laryngol ; 118(10): 687-92, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19894394

RESUMO

OBJECTIVES: Although the Reflux Symptom Index (RSI) is a validated laryngopharyngeal reflux (LPR) outcomes tool, its predictive value for LPR is controversial. Because psychiatric problems may lead to exaggerated patient-perceived symptoms and RSI values,the aim of this study was to determine whether the positive predictive value of the RSI for pH probe-documented LPR is influenced by anxiety and depression. METHODS: We reviewed the charts of all patients who underwent pH probe testing for LPR between January 2006 and July 2008 at our institution. The RSI, Reflux Finding Score (RFS), medical history, and pH probe findings were recorded. Patients with anxiety or depression were included in the psychiatric disorder (+PSY) group, and those without anxiety or depression comprised the non-psychiatric disorder (-PSY) group. Predictive values of the RSI for pH probe-documented LPR were determined for each group. RESULTS: We included 51 patients: 30 patients (59%) in the -PSY group and 21 patients (41%) in the +PSY group. The mean RSI of the +PSY group was higher than that of the -PSY group (p < 0.05), but the +PSY patients actually had a lower incidence of abnormal probe studies (p < 0.02). The positive predictive value of an elevated RSI for an abnormal pH probe study was poor in the +PSY patients (p = 0.495), but strong in the -PSY group (p = 0.004). CONCLUSIONS: The presence of anxiety and depression impairs the predictive value of the RSI for LPR. This finding potentially explains some of the controversy over the diagnostic utility of the RSI.


Assuntos
Refluxo Gastroesofágico/diagnóstico , Índice de Gravidade de Doença , Ansiedade/epidemiologia , Depressão/epidemiologia , Feminino , Refluxo Gastroesofágico/psicologia , Humanos , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos
6.
Ann Otol Rhinol Laryngol ; 118(12): 887-93, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20112524

RESUMO

OBJECTIVES: Persistent vocal fold motion impairment after recurrent laryngeal nerve (RLN) injury is not characteristically due to absent reinnervation, but often results from spontaneous aberrant reinnervation (synkinesis). We administered local neurotoxins to selected laryngeal muscles after RLN injury to determine whether aberrant reinnervation could be selectively inhibited. METHODS: Unilateral RLN transection was performed in 24 male rats. Three weeks later, the denervated laryngeal adductor complex was injected with phenol, high- or low-dose vincristine sulfate (VNC), or saline solution. One month later, rat larynges were evaluated via videolaryngoscopy and laryngeal electromyography (LEMG). Larynges from euthanized animals were analyzed via immunofluorescent staining for the presence of reinnervation. RESULTS: One animal that received phenol and 3 animals that received high-dose VNC died of toxicity-related complications. In the surviving neurotoxin-treated animals, videolaryngoscopy showed increased lateralization of the immobile vocal fold. Only 1 phenol-injected rat had adductor complex motor recruitment (score of 3+) with LEMG. The other neurotoxin-treated animals demonstrated an absence of adductor complex reinnervation, with only insertional activity and fibrillations (no motor units/recruitment). Spontaneous ipsilateral abductor reinnervation was not affected by the adductor injections. CONCLUSIONS: Low-dose VNC injections appear to be relatively safe and effective in selectively inhibiting spontaneous aberrant reinnervation after RLN injury in an animal model.


Assuntos
Fenol/uso terapêutico , Traumatismos do Nervo Laríngeo Recorrente , Soluções Esclerosantes/uso terapêutico , Sincinesia/prevenção & controle , Moduladores de Tubulina/uso terapêutico , Vincristina/uso terapêutico , Animais , Eletromiografia , Músculos Laríngeos/inervação , Laringoscopia , Masculino , Regeneração Nervosa/efeitos dos fármacos , Ratos , Prega Vocal/fisiopatologia
7.
Ann Otol Rhinol Laryngol ; 127(12): 926-930, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30235935

RESUMO

INTRODUCTION:: The aim of this study was to evaluate the current indications for and clinical factors influencing the use of transnasal esophagoscopy (TNE). METHODS:: An online survey was sent to American Broncho-Esophagological Association members, including questions on demographics, indications, and factors influencing the use of TNE. RESULTS:: Sixty of 251 members (24%) completed the survey. Ninety-three percent of respondents reported academic practices, while 98% practice in medium to large urban settings. Thirty-five (58%) completed laryngology fellowships. Mean monthly TNE procedure count was 7.15 (range, <1-35). The most common indications were dysphagia (82%), biopsy (50%), and laryngopharyngeal reflux (47%). Chronic cough, head and neck cancer screening, gastroesophageal reflux (GER), and tracheoesophageal puncture were also commonly reported indications (44% each). For laryngopharyngeal reflux and GER, most respondents perform TNE for recalcitrant disease following a medical trial of at least 3 months. Long-standing GER symptoms, documentation of GER on pH and impedance testing, and abnormal findings on previous esophagoscopy lead to greater TNE use. Specific dysphagia indications included abnormal esophagographic findings (70%), history or examination localizing to the esophagus (60%), solid dysphagia only (53%), and solid and/or liquid dysphagia (40%). The primary sites most likely to prompt TNE use for head and neck cancer surveillance were the esophagus (92.3%) and hypopharynx (84.6%). Balloon dilation was the most common indication for which respondents do not currently perform TNE but would like to (n = 8). CONCLUSIONS:: TNE indications have not been well established. According to respondents from the American Broncho-Esophagological Association, TNE is most commonly used for dysphagia and laryngopharyngeal reflux and slightly less so for GER and head and neck cancer screening and surveillance. Several clinical indicators were identified that influence the decision to perform TNE.


Assuntos
Transtornos de Deglutição/diagnóstico , Esofagoscopia , Neoplasias de Cabeça e Pescoço/diagnóstico , Refluxo Laringofaríngeo/diagnóstico , Nariz , Adulto , Assistência Ambulatorial/métodos , Biópsia/métodos , Detecção Precoce de Câncer/métodos , Esofagoscopia/métodos , Esofagoscopia/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos
8.
Laryngoscope ; 117(5): 917-22, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17473696

RESUMO

OBJECTIVE: Autologous muscle stem cell (myoblast) therapy may be an ideal treatment for vocal fold paralysis because of its technical ease (administered by injection), its potential to restore muscular defects and dynamic function, and its autologous origin. The goal of this project was to determine whether autologous myoblast injection into the thyroarytenoid (TA) muscle after recurrent laryngeal nerve (RLN) injury could attenuate TA muscle atrophy and enhance spontaneous reinnervation. STUDY DESIGN: This was an animal experiment. METHODS: Unilateral RLN transection and sternocleidomastoid muscle (approximately 1 g) biopsies were performed in 16 male Wistar rats. Biopsies were used to create myoblast cultures for each animal. One month later, 10(6) autologous myoblasts labeled with fluorescent cell membrane marker (PKH26) were injected into the denervated TA of each study animal, with saline injected into controls. Animals were euthanized at 2 weeks and 2 months after myoblast injection. Outcomes included myoblast survival, TA fiber diameter and volume, and reinnervation status (motor endplate to nerve contact staining). RESULTS: All denervated TA study specimens demonstrated viable myoblasts under fluorescent microscopy, with the myoblasts demonstrating fusion with the TA myofibers at 2 months. The myoblast-treated group had greater mean TA fiber diameter than denervated TA controls at 2 months (25.1 vs. 21.1 microm; P = .04) but not at 2 weeks (25.7 microm vs. 23.5 microm; P = .06). Mean TA volumes were greater in the myoblast-treated groups at both time points. Two of the animals in the myoblast-treated group demonstrated adductor motion at 2 months, whereas none of the 2 week study animals or controls recovered adduction. Reinnervation was not significantly different between the myoblast-treated groups and the denervated controls. CONCLUSIONS: Autologous myoblast therapy may be a future treatment for vocal fold paralysis, with current findings demonstrating myoblast survival with attenuation of TA muscle atrophy.


Assuntos
Mioblastos/transplante , Paralisia das Pregas Vocais/terapia , Animais , Células Cultivadas , Denervação , Músculos Laríngeos/inervação , Músculos Laríngeos/fisiologia , Masculino , Projetos Piloto , Ratos , Ratos Wistar , Transplante Autólogo
9.
Otolaryngol Head Neck Surg ; 137(5): 792-7, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17967648

RESUMO

OBJECTIVE: Although cricopharyngeal electromyography (CP-EMG) is recognized as a diagnostic tool for dysphagia assessment, few reports in the literature characterize CP-EMG abnormalities in relation to clinical presentation. The aim of this study was to review a large series of CP-EMG studies, and compare the CP-EMG results with the patients' diagnoses. METHODS: A retrospective review of all CP-EMG performed at our institution over a 10-year period was executed. CP-EMG findings were then compared with the patients' clinical history, focusing on potential etiologies of neurogenic injury. RESULTS: Seventy CP-EMGs were reviewed, with 47 (67%) demonstrating neural injury. Of those cases with neural injury on EMG, 29 (60%) had known vagal injuries, 13 (28%) had idiopathic nerve palsies, and 5 (11%) had central etiologies, such as stroke. Each of these three neurogenic subgroups revealed a distinct pattern of EMG abnormalities. CONCLUSION: This study suggests there is an association between patterns of CP-EMG abnormalities and underlying etiology based on clinical history.


Assuntos
Eletromiografia , Esfíncter Esofágico Superior/fisiopatologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos do Nervo Vago
10.
Otolaryngol Head Neck Surg ; 137(4): 576-81, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17903573

RESUMO

OBJECTIVES: To determine the utility of spectral analysis in the differentiation of adductor-type spasmodic dysphonia (AdSD) from muscle tension dysphonia (MTD). STUDY DESIGN: Prospective blinded study. METHODS: Forty-seven samples of AdSD-connected speech spectrograms from 27 subjects and 17 samples of MTD-connected speech spectrograms from 15 subjects were selected from clinical charts and de-identified. These spectrograms were reviewed independently and blindly by two speech language pathologists experienced in spectrography. The speech language pathologists designated the spectrogram as consistent with AdSD and MTD, and these designations were compared with actual clinical diagnoses. RESULTS: The ability to differentiate AdSD from MTD with spectral analysis was 94% for rater #1 and 98% for rater #2. No MTD subjects were incorrectly diagnosed as having SD (100% specificity). CONCLUSIONS: This study suggests that experienced speech language pathologists can distinguish AdSD from MTD with a high degree of sensitivity and specificity based on spectral analysis. Spectral analysis is especially useful in cases where perceptual analysis and clinical evaluation alone are insufficient.


Assuntos
Espectrografia do Som/métodos , Distúrbios da Voz/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Músculos Laríngeos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tono Muscular/fisiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Método Simples-Cego , Espasmo/fisiopatologia , Patologia da Fala e Linguagem , Voz/fisiologia , Distúrbios da Voz/fisiopatologia
11.
Otolaryngol Head Neck Surg ; 137(1): 146-51, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17599582

RESUMO

BACKGROUND: Unsedated office-based laser surgery (UOLS) of the larynx and trachea has significantly improved the treatment options for patients with laryngotracheal pathology including recurrent respiratory papillomas, granulomas, leukoplakia, and polypoid degeneration. UOLS delivered by flexible endoscopes has dramatically impacted office-based surgery by reducing the time, costs, and morbidity of surgery. OBJECTIVES: To review our experience with 443 laryngotracheal cases treated by UOLS. METHODS: The laser logbooks at the Center for Voice and Swallowing Disorders were reviewed for UOLS, and the medical and laryngological histories were detailed, as were the treatment modalities, frequencies, and complications. RESULTS: Of the 443 cases, 406 were performed with the pulsed-dye laser, 10 with the carbon-dioxide laser, and 27 with the thulium: yttrium-aluminum-garnet laser. There were no significant complications in this series. A review of indications and wavelength selection criteria is presented. CONCLUSION: Unsedated, office-based, upper aerodigestive tract laser surgery appears to be a safe and effective treatment option for many patients with laryngotracheal pathology.


Assuntos
Procedimentos Cirúrgicos Ambulatórios , Doenças da Laringe/cirurgia , Terapia a Laser/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glote/cirurgia , Granuloma/cirurgia , Humanos , Edema Laríngeo/cirurgia , Neoplasias Laríngeas/cirurgia , Laringoscópios , Lasers/classificação , Leucoplasia/cirurgia , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico , Papiloma/cirurgia , Estudos Retrospectivos , Segurança , Doenças da Traqueia/cirurgia , Neoplasias da Traqueia/cirurgia , Resultado do Tratamento
12.
Ann Otol Rhinol Laryngol ; 116(8): 582-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17847725

RESUMO

OBJECTIVES: Laryngopharyngeal sensory discrimination threshold (LPSDT) testing is a method used to detect sensory deficits in patients in whom swallowing disorders are suspected. LPSDTs have been used to stratify patient risk status with regard to aspiration and to guide dietary management. The aim of this pilot study was to evaluate the intraobserver and interobserver reliability of LPSDT testing among a group of examiners with differing levels of testing experience. METHODS: Twenty-seven healthy volunteers were enrolled in the study to elicit LPSDTs for intraobserver and interobserver reliability measurements. The examiners represented 3 levels of testing experience: an attending laryngologist, a laryngology fellow, and an otolaryngology resident. With the examiners blinded to test results, each subject was examined twice by one examiner and once by a different examiner in an alternating fashion. RESULTS: Six subjects were unable to tolerate the examinations because of coughing and gagging. Spearman rank correlations revealed strong intraobserver reliability for the experienced endoscopists (ie, attending and fellow) but poor reliability for the novice endoscopist (ie, resident). Poor interobserver reliability regardless of endoscopy experience was found. Eighteen percent of the participants demonstrated LPSDTs of more than 4.0 mm Hg (above normal). CONCLUSIONS: 1) Intraobserver reliability was good for experienced endoscopists. 2) Interobserver LPSDT agreement between endoscopists was poor. 3) Eighteen percent of the subjects demonstrated elevated LPSDT thresholds of more than 4 mm Hg.


Assuntos
Transtornos de Deglutição/etiologia , Laringe/fisiopatologia , Neurônios Motores/fisiologia , Faringe/inervação , Células Receptoras Sensoriais/fisiopatologia , Adulto , Deglutição/fisiologia , Transtornos de Deglutição/fisiopatologia , Feminino , Humanos , Nervos Laríngeos/fisiopatologia , Masculino , Variações Dependentes do Observador , Faringe/fisiopatologia , Estimulação Física , Valor Preditivo dos Testes , Valores de Referência , Reflexo/fisiologia , Aspiração Respiratória/fisiopatologia , Aspiração Respiratória/prevenção & controle , Fatores de Risco , Limiar Sensorial/fisiologia , Prega Vocal/inervação , Prega Vocal/fisiopatologia
13.
J Neurosurg ; 127(6): 1219-1230, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28059653

RESUMO

OBJECTIVE Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)-a constituent of cruciferous vegetables with a multitargeted effect-as a therapeutic agent for GBM. METHODS The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models. RESULTS SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell-induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10. CONCLUSIONS These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.


Assuntos
Anticarcinógenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Glioblastoma/metabolismo , Isotiocianatos/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Glioblastoma/patologia , Humanos , Camundongos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sulfóxidos
14.
Laryngoscope ; 116(9): 1539-52, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16954976

RESUMO

OBJECTIVES/HYPOTHESIS: Vocal fold paralysis continues to be a dominant topic in laryngology. Although the majority of cases can be attributed to a known etiology, a significant number of patients present without a clear precipitating event. Over 1,500 studies regarding vocal fold paralysis exist in the medical literature, although only a small percentage report on the use of serum or radiographic testing for the evaluation of idiopathic paralysis. Despite this, patients are routinely subjected to diagnostic evaluation to investigate the underlying cause. To characterize contemporary practice, a national survey of the American Broncho-Esophagological Association (ABEA) membership was undertaken. It is hypothesized that the current practice of diagnostic testing for idiopathic vocal fold paralysis is not well supported by an evidence-based medicine (EBM) review of the available medical literature. STUDY DESIGN: The authors conducted a national survey, systematic EBM review of existing literature. METHODS: Surveys were mailed to all active ABEA members; responses regarding practice specialization as well as serum/radiographic diagnostic preferences for idiopathic vocal fold paralysis were tabulated and subjected to statistical analysis. To compare contemporary practice with evidence in the available literature, an EBM review was first performed. Articles for evaluation were selected from a Medline search of English-language abstracts related to adult vocal fold paralysis. The publications were individually reviewed and an EBM level and grade were assigned and compared with the survey results. RESULTS: Eighty-four of 249 active members responded with 76 (31%) replies submitted for analysis. Specific serum tests were advocated by 41 of 76 (54%) respondents, although the majority (52 of 65 [80%]) felt that they were only "occasionally" or "never" necessary. The most common tests were rheumatoid factor (38%), Lyme titer (36%), erythrocyte sedimentation rate (34%), and antinuclear antibody (33%). Fifty-one of 71(72%) felt that computed tomography (CT) was "always" or "often" necessary and 50 of 72 (69%) replied that chest radiography (CXR) was "always" or "often" necessary. There was no significant difference between CT and CXR ordering (P < .51). In contrast, magnetic resonance imaging (MRI) was described as "always" or "often" necessary in 28 of 71 (39%) of the surveys, significantly less than CT (P < .0001). There was no statistical impact of practice specialization on ordering of serum tests (P = .25) or imaging (P = .50 for CT; P = .46 for CXR; P = .45 for MRI). Following analysis of 1,510 vocal fold paralysis abstracts, 19 publications were found to be appropriate for an EBM review of serum testing with 15 available for review of radiographic imaging. Only one study presented level III evidence; the remainder were levels IV and V comprised of retrospective series and case reports. The evidence supporting serum or radiographic testing toward the evaluation of idiopathic vocal fold paralysis is given an overall grade of "C." CONCLUSIONS: Serum and radiographic testing for the evaluation of vocal fold paralysis is supported by grade "C" evidence only. There are no existing prospective studies estimating the clinical impact of testing on diagnosis or patient outcome. Current practice, as estimated by a survey of the ABEA membership, is not well founded for serum testing and only by retrospective case series with regard to imaging. Further study into the nature of idiopathic vocal fold paralysis and outcomes assessment of diagnostic paradigms may improve clinical practice.


Assuntos
Medicina Baseada em Evidências , Padrões de Prática Médica/estatística & dados numéricos , Paralisia das Pregas Vocais/diagnóstico , Adulto , Distribuição de Qui-Quadrado , Humanos , Inquéritos e Questionários , Estados Unidos
15.
Laryngoscope ; 116(2): 303-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16467724

RESUMO

OBJECTIVES: The symptoms, patterns of reflux, and clinical manifestations of laryngopharyngeal reflux (LPR) differ from those of gastroesophageal reflux disease (GERD) in many ways. The purposes of this study were to determine the prevalence of Barrett's esophagus in patients with LPR using transnasal esophagoscopy (TNE) and to determine if there is agreement between TNE clinical findings and pathology results when using TNE for Barrett's screening. STUDY DESIGN: This study involved a retrospective review of the records of 200 consecutive patients with LPR undergoing esophageal screening. METHODS: The prevalence of patients with findings clinically suspicious for Barrett's and the biopsy results for those patients were reviewed. RESULTS: Of the 200 patients with LPR who were screened with TNE, 10% (20 of 200) had findings suspicious for Barrett's esophagus, and, of those, only 30% (six of 20) had biopsy-proven Barrett's metaplasia. CONCLUSION: Although TNE may be a useful screening tool for Barrett's, there is incongruence between TNE findings and biopsy results, which likely reflects suboptimal biopsy methods with TNE. New biopsy techniques such as the CDx brush biopsy may enhance the sensitivity of TNE biopsies, and future studies are needed in this area.


Assuntos
Esôfago de Barrett/diagnóstico , Esofagoscopia , Refluxo Gastroesofágico/complicações , Esôfago de Barrett/epidemiologia , Esôfago de Barrett/etiologia , Esôfago de Barrett/patologia , Feminino , Refluxo Gastroesofágico/diagnóstico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência
16.
Otolaryngol Head Neck Surg ; 135(4): 590-4, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17011423

RESUMO

OBJECTIVE: To compare practices of the American Broncho-Esophagological Association (ABEA) membership regarding the evaluation and management of unilateral vocal fold motion impairment (UVFMI) in adult versus pediatric populations. STUDY DESIGN AND SETTING: An 18-item adult survey and 16-item pediatric survey were administered to ABEA members. RESULTS: Seventy-six adult (31%) and 35 pediatric surveys (43%) were completed. Key differences are highlighted. With respect to etiology, the most common reported childhood cause is idiopathic; adults more often suffer iatrogenic paralysis. Children more commonly experience reflux disease, feeding difficulties, and choking. Preferred testing involves flexible laryngoscopy and chest x-ray; however, laboratory tests are carried out less often in children (51% vs 71%) and medical intervention is advocated by fewer pediatric practitioners (39% vs 57%). CONCLUSION: Significant disparities exist in the etiology, presenting symptoms, diagnostic testing, and medical treatment between children and adults with UVFMI. SIGNIFICANCE: Clinicians' perceptions regarding UVFMI may reflect the differing impact of vocal paralysis in the pediatric versus adult populations.


Assuntos
Pediatria , Paralisia das Pregas Vocais/diagnóstico , Paralisia das Pregas Vocais/terapia , Adulto , Criança , Humanos , Padrões de Prática Médica , Inquéritos e Questionários
17.
Otolaryngol Head Neck Surg ; 134(6): 1023-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16730550

RESUMO

INTRODUCTION: Recent advances in technology have facilitated a movement toward unsedated in-office treatment of laryngeal, tracheal, and esophageal lesions. The objective of this study was to determine patient tolerance of in-office pulsed-dye laser (PDL) treatment of upper aerodigestive tract pathoses via the transnasal esophagoscope. METHODS: Three hundred twenty-eight unsedated in-office PDL cases were performed at a university-based tertiary referral center in 131 patients. These procedures were performed for various upper aerodigestive pathoses, including recurrent respiratory papillomatosis, chronic granulomas, and recurrent leukoplakia. Eighty-nine subjects completed a phone survey concerning their discomfort level after the PDL procedure. They were also asked specific questions about recovery time, pain medication, and preference of operating room versus in-office procedures. RESULTS: The average comfort score was 7.4 (10 being minimal discomfort). Eighty-four percent did not use any pain medication; 87% stated that, if possible, they would prefer to undergo unsedated in-office procedures rather than surgeries under general anesthesia for further treatment of their upper aerodigestive tract pathosis. CONCLUSIONS: Unsedated transnasal treatment of upper aerodigestive tract pathoses is readily accepted and well-tolerated by otolaryngology patients. Patients overwhelmingly prefer the in-office PDL over surgeries under general anesthesia. EBM RATING: C-4.


Assuntos
Procedimentos Cirúrgicos Ambulatórios/psicologia , Esofagoscopia/psicologia , Terapia a Laser/psicologia , Pacientes Ambulatoriais/psicologia , Trato Gastrointestinal Superior/cirurgia , Adulto , Procedimentos Cirúrgicos Ambulatórios/métodos , Sedação Consciente , Esofagoscopia/métodos , Esôfago/cirurgia , Feminino , Humanos , Laringe/cirurgia , Terapia a Laser/métodos , Masculino , Satisfação do Paciente , Inquéritos e Questionários , Traqueia/cirurgia
18.
Ann Otol Rhinol Laryngol ; 115(2): 97-102, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16514790

RESUMO

OBJECTIVES: Despite the belief that it represents a central neurologic dysfunctional process, adductor-type spasmodic dysphonia without tremor is usually effectively treated by injection of botulinum toxin A; however, in most cases such injections must be repeated every few months. A promising new surgical procedure is herein reported. METHODS: Under local anesthesia with intravenous sedation, a large laryngoplasty window is created, and under direct vision with intraoperative voice monitoring, fibers from the thyroarytenoid and lateral cricoarytenoid muscles are removed until breathiness occurs. The two sides are staged; that is, one side is done at a time, with surgery on the second side being performed 3 to 6 months after that on the first side, if needed. RESULTS: This was a retrospective, unblinded study of 5 patients who underwent myectomy of the thyroarytenoid and lateral cricoarytenoid muscles. The preliminary results show improved voice fluency in all patients at 5 to 19 months of follow-up. There was no period of prolonged breathiness or dysphagia in any of the patients, and there were no surgical complications. CONCLUSIONS: Myectomy of the thyroarytenoid and lateral cricoarytenoid muscles is a promising new surgical treatment for adductor-type spasmodic dysphonia that may effectively mimic "permanent" botulinum toxin injections.


Assuntos
Músculos Laríngeos/cirurgia , Espasmo/cirurgia , Distúrbios da Voz/cirurgia , Idoso , Anestesia Intravenosa , Anestesia Local , Cartilagem Aritenoide/cirurgia , Cartilagem Cricoide/cirurgia , Endoscopia , Feminino , Seguimentos , Humanos , Músculos Laríngeos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fonação/fisiologia , Estudos Retrospectivos , Espectrografia do Som , Espasmo/fisiopatologia , Resultado do Tratamento , Prega Vocal/fisiopatologia , Distúrbios da Voz/fisiopatologia
19.
Ann Otol Rhinol Laryngol ; 115(4): 312-6, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16676829

RESUMO

OBJECTIVES: We reviewed a large series of cricopharyngeal (CP) muscle electromyography (EMG) results and compared them with the EMG results from the inferior constrictor (IC), thyroarytenoid, (TA), cricothyroid (CT), and posterior cricoarytenoid (PCA) muscles. METHODS: We performed a retrospective review of all CP muscle EMG reports from studies performed between January 1996 and June 2003. All of the tested elements from the CP muscle EMG reports were recorded. The EMG results were recorded for the ipsilateral IC, TA, CT, and PCA muscles if they were simultaneously tested. Each muscle result was classified as normal, neurogenic inactive axonal injury (IAI), or neurogenic active axonal injury (AAI), and the muscle findings were compared. A patient chart review was performed to determine a clinical correlation. RESULTS: Fifty-nine patients underwent CP muscle EMG. Eighteen patients had bilateral EMG studies, making a total of 77 CP muscle studies. Nineteen sets of CP muscle results were normal, 43 demonstrated neurogenic IAI, and 15 demonstrated neurogenic AAI. The ipsilateral IC and CP muscles had the same innervation status in 27 of 28 studies (p < .0001). When the ipsilateral TA muscle was studied simultaneously with the CP muscle, 31 of 50 studies had the same innervation status (p = .005). The ipsilateral CT and CP muscles demonstrated the same innervation status in 40 of 50 studies (p < .0001). The correlations between the CP and IC muscle findings and between the CP and CT muscle findings were both stronger than the correlation between the CP and TA muscle findings (p < .0001 and p = .024, respectively). The chart review demonstrated the clinical findings to be consistent with the EMG results. CONCLUSIONS: The EMG studies demonstrated that CP muscle findings have the strongest correlation with IC muscle findings, followed by the CT and TA muscles. This outcome does not support theories indicating that the recurrent laryngeal nerve innervates the CP muscle in all cases.


Assuntos
Esfíncter Esofágico Superior/fisiologia , Músculos Laríngeos/fisiologia , Músculos Faríngeos/fisiologia , Eletromiografia , Esfíncter Esofágico Superior/fisiopatologia , Humanos , Doenças da Laringe/diagnóstico , Músculos Laríngeos/fisiopatologia , Doenças Faríngeas/diagnóstico , Músculos Faríngeos/fisiopatologia , Estudos Retrospectivos
20.
Laryngoscope ; 115(6): 1051-4, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15933519

RESUMO

BACKGROUND: Medialization laryngoplasty (ML) is a commonly performed procedure for vocal fold motion impairment with glottic incompetence. Although implant extrusion is a well-known risk of ML, management of this complication is rarely mentioned in the literature. The aim of this study was to review our experience with endoscopic implant retrieval for a group of patients with extruding ML implants. METHODS: All patients identified in our institution from January 1989 through August 2004 with a history of ML and extruded implants were identified. Case management was reviewed, including information on presentation, management techniques, and outcomes. RESULTS: Five patients presented with extruding ML (Gore-Tex [n = 2] or silastic [n = 3]) implants. All patients presented with worsening dysphonia and evidence of fullness and/or granulation tissue at the extrusion site. Endoscopic removal was performed using either sharp dissection or CO2 laser dissection. After removal, four patients underwent vocal fold injection augmentation. CONCLUSIONS: Endoscopic removal appears to be a safe, effective, and even preferred alternative to external transcervical removal in selected cases of extruding implants.


Assuntos
Endoscopia , Laringe/cirurgia , Próteses e Implantes/efeitos adversos , Adulto , Dimetilpolisiloxanos , Dispneia/etiologia , Feminino , Glote , Humanos , Doenças da Laringe/cirurgia , Politetrafluoretileno , Falha de Prótese , Silicones , Paralisia das Pregas Vocais/cirurgia
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