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1.
Ear Nose Throat J ; 102(11): 739-741, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34218707

RESUMO

When in-person experiences were taken away from medical students and residency applicants during the COVID-19 pandemic, institutions had to pivot to virtual experiences. We present here a comprehensive overview of virtual engagement for medical students. As we increasingly embrace virtual opportunities, it may be possible to continue utilizing these programs for many years to come.


Assuntos
COVID-19 , Internato e Residência , Otolaringologia , Estudantes de Medicina , Humanos , Pandemias
2.
Ann Otol Rhinol Laryngol ; 132(1): 63-68, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35152774

RESUMO

OBJECTIVE(S): To compare otolaryngology program director, house-staff, and medical student perspectives on the score reporting change of USMLE Step 1 to pass/fail. METHODS: Separate electronic surveys were sent to program directors of ACGME-accredited otolaryngology programs (Cronbach's alpha = .87), otolaryngology house-staff (Cronbach's alpha = .91), and medical students interested in otolaryngology (Cronbach's alpha = .76). RESULTS: Among the 51 otolaryngology program directors that completed the survey (response rate of 46.8%), 17.6% favored reporting USMLE Step 1 as pass/fail. A majority believed the reporting change would make it more difficult to screen (74.5%) and objectively compare applicants (82.4%). Step 2 CK scores will be more important to most program directors due to the reporting change (83.7%). Of the 93 house-staff that completed surveys, most did not favor the reporting change (61.3%). Over half (54.0%) of the 87 medical students that completed surveys did not support the scoring change, and most (65.5%) did not feel that it would decrease anxiety around residency applications (65.5%). Most house-staff and medical students felt that the scoring change would put non-U.S. MD students at a disadvantage (65.6% of house-staff, 69.8% of medical students). CONCLUSION: Most survey respondents do not agree with the decision to report Step 1 as pass/fail. Despite its intended goals, most do not believe pass/fail Step 1 reporting will improve medical student well-being and believe it will put certain student populations at a greater disadvantage.


Assuntos
Internato e Residência , Otolaringologia , Estudantes de Medicina , Humanos , Estados Unidos , Avaliação Educacional , Otolaringologia/educação , Inquéritos e Questionários
3.
Neoreviews ; 23(9): e613-e624, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047759

RESUMO

Respiratory distress in the neonate is one of the most common reasons for referral to a tertiary NICU, accounting for more than 20% of admissions. (1) The cause of respiratory distress can range from parenchymal lung disease to anomalies of any portion of the neonatal airway including the nose, pharynx, larynx, trachea, or bronchi. This review will focus on airway anomalies at or immediately below the level of the larynx. Although rare, those with such congenital or acquired laryngotracheal anomalies often require urgent evaluation and surgical intervention. This review describes 1) the pathophysiology associated with congenital and acquired laryngotracheal deformities in the neonate, 2) the clinical presentation and diagnostic evaluation of these anomalies, and 3) the current medical and surgical strategies available in the NICU and after discharge.


Assuntos
Doenças do Recém-Nascido , Laringe , Síndrome do Desconforto Respiratório , Brônquios , Humanos , Recém-Nascido , Laringe/anormalidades , Laringe/cirurgia , Traqueia
4.
Int J Pediatr Otorhinolaryngol ; 158: 111191, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35636082

RESUMO

INTRODUCTION: Obstructive sleep apnea (OSA) is common in autism spectrum disorder (ASD). Children with OSA can present with a range of symptoms including loud snoring, excessive daytime sleepiness, and changes in cognitive function. Some of these symptoms can overlap with and exacerbate symptoms of ASD, potentially delaying OSA diagnosis in children with both conditions. OBJECTIVE: The primary objective of this study was to assess between-group difference in OSA symptomatology and age at OSA diagnosis in children with and without ASD. METHODS: A retrospective chart review was conducted on 166 pediatric patients (<18 years) with OSA undergoing adenotonsillectomy at a single academic institution between 2019 and 2021. The control group consisted of 91 patients (54.9% male) without ASD. The ASD group included 75 patients (88.0% male). Autism severity was scored on a 1-4 scale using a novel methodology. Statistical analyses included Wilcoxon rank sum tests for continuous variables, chi-squared tests for categorical variables, and multivariable analyses as needed. RESULTS: There was a significant between-group difference in total number of reported OSA symptoms (p < 0.001), with more symptoms reported in patients with ASD. Within the ASD group, lower autism severity was associated with an increased number of reported OSA symptoms (p = 0.006). There was not a significant between-group difference in age at OSA diagnosis (p = 0.999); however, lower autism severity was associated with an increased age at diagnosis (p = 0.002). CONCLUSION: These findings suggest that OSA may present with a higher symptom burden in children with ASD, particularly for children with lower ASD severity, who often experience delays in OSA diagnosis. These findings and their clinical implications merit further explanation.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Apneia Obstrutiva do Sono , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Transtorno Autístico/complicações , Transtorno Autístico/diagnóstico , Transtorno Autístico/epidemiologia , Criança , Feminino , Humanos , Masculino , Polissonografia/métodos , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
5.
Ear Nose Throat J ; : 1455613211052337, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34693791

RESUMO

The COVID-19 pandemic led to a suspension of visiting student rotations across the United States. For senior medical students applying into surgical subspecialties, such as otolaryngology, these away rotations serve a vital role in the residency application process. Prior to the pandemic, there was not a virtual alternative to in-person visiting student rotations for applicants. We developed a replicable and expandable program focused on helping prospective otolaryngology applicants (fourth-year medical students) gain exposure to the experiences typically offered via in-person rotations. The goal was to improve otolaryngology-specific knowledge and to help applicants demonstrate specific program interest, without the financial and logistical challenges associated with in-person away rotations.

6.
Int J Pediatr Otorhinolaryngol ; 150: 110864, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34411868

RESUMO

OBJECTIVES: Risk factors for middle ear disease necessitating myringotomy with tympanostomy tube placement after a tracheostomy have not been thoroughly explored. This study investigates the incidence and risk factors for ear tube placement in pediatric patients with a tracheostomy. METHODS: Pediatric patients under age 18 who underwent tracheotomy between 2002 and 2010 at two institutions were identified. Patients were excluded if they had undergone myringotomy prior to, or at the same time as, the tracheotomy, or did not have at least two years of follow-up clinic visits. The presence of other comorbidities was recorded. Descriptive statistics and logistic regression models were used to assess the impact of clinical characteristics on outcomes. RESULTS: A total of 214 patients met inclusion criteria. Median patient age at time of tracheotomy was 6 months (IQR 2-17), median patient age at time of myringotomy with tubes was 12 months (IQR8-17), and median time between tracheotomy and myringotomy with tube placement was 8 months (IQR 5-11). Sixty-seven (31%) patients required myringotomy with tympanostomy tube placement within the first two years after tracheotomy. Fifty-eight (87%) patients who underwent myringotomy with tympanostomy tubes were younger than 2 years at the time of the procedure. Logistical regression found younger age at time of tracheotomy to be a risk factor (OR: 0.71, 95% CI: 0.5-0.9, p < 0.006). The combination of tracheostomy with gastric tube increased the risk of requiring myringotomy with tubes 2.79 fold (p < 0.009). Craniofacial abnormalities (p < 0.001), known genetic syndrome (p = 0.009), cleft palate (p < 0.001), age at time of tracheotomy (p < 0.001) and gastric tubes (p = 0.002) were all independently found to increase risk of myringotomy with tubes. Patients' gestational age (p = 0.411), ventilator dependence (p = 0.33), and airway structural abnormalities (p = 0.632) did not increase this risk. CONCLUSION: This study reports a high incidence of myringotomy with tubes in children with tracheostomy relative to the general pediatric population. Many comorbid conditions that often accompany the need for tracheotomy place these patients at a higher risk for ear disease requiring surgical intervention. Risk factors for operative middle ear disease in this population included age at time of tracheostomy, craniofacial abnormalities, and presence of a G-tube.


Assuntos
Otopatias , Otite Média com Derrame , Adolescente , Criança , Humanos , Lactente , Ventilação da Orelha Média , Otite Média com Derrame/cirurgia , Traqueostomia , Traqueotomia/efeitos adversos
7.
Children (Basel) ; 7(11)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33227920

RESUMO

Parental attitudes regarding pain interventions and perceptions of their child's pain intensity likely influence the decision to administer postoperative analgesics. Our study examined the impact of daily fluctuations in child pain intensity and parental attitudes regarding complementary and alternative medicine (CAM) on analgesic administration following pediatric tonsillectomy. Parents of children undergoing tonsillectomy (n = 33) completed a survey assessing CAM attitudes and a 7-day postoperative electronic daily diary to record their child's daily pain intensity and analgesic medications (acetaminophen, ibuprofen, or oxycodone). Generalized linear mixed models with Poisson distributions evaluated the effects of within-person (child's daily pain intensity) and between-person (average postoperative pain, parental CAM attitudes) components on the number of medication doses administered. Higher daily pain intensity was associated with more oxycodone doses administered on a given day, but not acetaminophen or ibuprofen. Positive parental CAM attitudes were associated with less oxycodone use, beyond the variations accounted for by the child's daily pain intensity and average postoperative pain. Both parental CAM attitudes and their child's daily pain intensity were independently associated with parental decisions to administer opioids following tonsillectomy. Understanding factors influencing individual variability in analgesic use could help optimize children's postoperative pain management.

8.
Ann Otol Rhinol Laryngol ; 129(11): 1071-1077, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32483986

RESUMO

OBJECTIVES: (1) To identify clinical factors and perioperative practices that correlate with longer length of stay (LOS) in the post-anesthesia care unit (PACU) after adenotonsillectomy (T&A) in pediatric populations.(2) To understand the relationship between family presence and PACU LOS for pediatric patients after T&A. METHODS: Pediatric patients (ages 3-17) who underwent T&A between February 2016 and December 2016 were retrospectively reviewed. Factors assessed for impact on PACU LOS included BMI, preoperative medications, intraoperative medications/narcotics, postoperative medications/narcotics, method of postoperative medication administration, and family presence in the PACU. Kruskal-Wallis and Spearman tests were used to assess correlations. Statistical significance was set a priori at P < .05. RESULTS: Our cohort included 500 patients. Patients were in the PACU for an average of 135.4 minutes (±65.8). Subset analyses of the type of medications administered intra-operatively and in the PACU show that the intraoperative administration of sedatives is associated with increased LOS (P = .014). Postoperative administration of any medications (P < .001), and specifically, postoperative administration of narcotics (P < .001), analgesics (P = .043), antihistamines (P < .001), and dopamine antagonists (P = .011), are associated with increased LOS. Administration of PACU medications by IV was also correlated with shorter LOS compared to oral administration of PACU medications (P = .016). A comparison of patients who received PACU medications to those who did not demonstrated that intraoperative administration of acetaminophen was associated with a reduced need for PACU medication administration (P = .012). Shorter waiting times for family arrival in the PACU was also associated with shorter LOS (P < .001). CONCLUSION: Our results suggest that postoperative medication administration and time until family arrival in the PACU are associated with significant differences in LOS. We also find that intraoperative administration of acetaminophen is correlated with reduced need for postoperative medication administration. Standardizing postoperative practices to minimize PACU LOS could result in a more efficient recovery for pediatric patients undergoing T&A.


Assuntos
Adenoidectomia/métodos , Período de Recuperação da Anestesia , Tempo de Internação/tendências , Dor Pós-Operatória/terapia , Cuidados Pós-Operatórios/métodos , Tonsilectomia/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Medição da Dor , Dor Pós-Operatória/diagnóstico , Prognóstico
9.
Int J Pediatr Otorhinolaryngol ; 107: 31-36, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29501307

RESUMO

OBJECTIVES: To characterize postoperative respiratory complications following adenotonsillectomy (AT) in children with obstructive sleep apnea (OSA) and to identify variables associated with pediatric intensive care unit (PICU) admission. METHODS: Retrospective analysis of 133 pediatric OSA patients with prior AT. Assessment of the postoperative hospital course informed patient stratification based on respiratory event severity, PICU admission status, and unscheduled escalation of care. RESULTS: Thirty-six (26.8%) patients were admitted to the PICU. Compared to non-PICU admissions, these patients were significantly younger and with greater preoperative apnea-hypopnea indices, comorbidities, and percentage of post-anesthesia care unit (PACU) time requiring supplemental oxygen. Seventy-one respiratory events occurred in 59 patients, with 60.6% affecting PICU patients. Fifteen severe events occurred, affecting 31% of PICU patients. Of 14 unscheduled escalations of care, 7 were PICU admissions who, compared to planned PICU admissions, spent significantly more time in the PACU and exhibited a trend towards greater PACU time on supplemental oxygen. CONCLUSIONS: Pediatric patients requiring post-AT PICU care have more risk factors for respiratory compromise. Total PACU time and total PACU time requiring supplemental oxygen may indicate patient risk for postoperative respiratory complications and need for intensive care. Future work includes prospective determination of appropriate post-AT PICU admission.


Assuntos
Adenoidectomia/efeitos adversos , Apneia Obstrutiva do Sono/cirurgia , Tonsilectomia/efeitos adversos , Criança , Pré-Escolar , Comorbidade , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
10.
Pathog Dis ; 75(1)2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27956464

RESUMO

The inflammatory middle ear disease known as otitis media can become chronic or recurrent in some cases due to failure of the antibiotic treatment to clear the bacterial etiological agent. Biofilms are known culprits of antibiotic-resistant infections; however, the mechanisms of resistance for non-typeable Haemophilus influenzae biofilms have not been completely elucidated. In this study, we utilized in vitro static biofilm assays to characterize clinical strain biofilms and addressed the hypothesis that biofilms with greater biomass and/or thickness would be more resistant to antimicrobial-mediated eradication than thinner and/or lower biomass biofilms. Consistent with previous studies, antibiotic concentrations required to eliminate biofilm bacteria tended to be drastically higher than concentrations required to kill planktonic bacteria. The size characterizations of the biofilms formed by the clinical isolates were compared to their minimum biofilm eradication concentrations for four antibiotics. This revealed no correlation between biofilm thickness or biomass and the ability to resist eradication by antibiotics. Therefore, we concluded that biofilm size does not play a role in antibiotic resistance, suggesting that reduction of antibiotic penetration may not be a significant mechanism for antibiotic resistance for this bacterial opportunist.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/fisiologia , Humanos , Testes de Sensibilidade Microbiana , Otite Média/tratamento farmacológico , Otite Média/microbiologia
11.
PLoS One ; 10(6): e0128606, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26039250

RESUMO

Otitis media is a prominent disease among children. Previous literature indicates that otitis media is a polymicrobial disease, with Haemophilus influenzae, Streptococcus pneumoniae, Alloiococcus otitidis and Moraxella catarrhalis being the most commonly associated bacterial pathogens. Recent literature suggests that introduction of pneumococcal conjugate vaccines has had an effect on the etiology of otitis media. Using a multiplex PCR procedure, we sought to investigate the presence of the aforementioned bacterial pathogens in middle ear fluid collected from children undergoing routine tympanostomy tube placement at Wake Forest Baptist Medical Center during the period between January 2011 and March 2014. In purulent effusions, one or more bacterial organisms were detected in ~90% of samples. Most often the presence of H. influenzae alone was detected in purulent effusions (32%; 10 of 31). In non-purulent effusions, the most prevalent organism detected was A. otitidis (26%; 63 of 245). Half of the non-purulent effusions had none of these otopathogens detected. In purulent and non-purulent effusions, the overall presence of S. pneumoniae was lower (19%; 6 of 31, and 4%; 9 of 245, respectively) than that of the other pathogens being identified. The ratio of the percentage of each otopathogen identified in purulent vs. non-purulent effusions was >1 for the classic otopathogens but not for A. otitidis.


Assuntos
Infecções Bacterianas/microbiologia , Carnobacteriaceae/isolamento & purificação , Haemophilus influenzae/isolamento & purificação , Ventilação da Orelha Média , Moraxella catarrhalis/isolamento & purificação , Otite Média com Derrame/microbiologia , Streptococcus pneumoniae/isolamento & purificação , Infecções Bacterianas/patologia , Infecções Bacterianas/cirurgia , Carnobacteriaceae/crescimento & desenvolvimento , Pré-Escolar , Orelha Média/microbiologia , Orelha Média/patologia , Orelha Média/cirurgia , Feminino , Haemophilus influenzae/crescimento & desenvolvimento , Humanos , Lactente , Masculino , Moraxella catarrhalis/crescimento & desenvolvimento , Otite Média com Derrame/patologia , Otite Média com Derrame/cirurgia , Estudos Retrospectivos , Streptococcus pneumoniae/crescimento & desenvolvimento , Supuração
13.
Clin Pediatr (Phila) ; 54(7): 629-34, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25972051

RESUMO

OBJECTIVE: To investigate the associations between patient age, sociological factors, and the microbiology of pediatric neck infections. METHODS: Retrospective chart review of children up to 5 years old who underwent surgical management of suppurative cervical lymphadenitis. RESULTS: A total of 76 individuals met inclusion criteria; 93% of culture-positive infections were caused by Staphylococcus aureus in infants, compared with 59% in children between 13 months and 5 years of age (P = .002). Of the S aureus isolates, 51% were methicillin-resistant S aureus (MRSA) and 49% were methicillin-sensitive S aureus. Methicillin resistance was associated with African American race (P = .004); 67% of participants received empirical antibiotics prior to admission. Of these, 73% received antibiotics in the ß-lactam class, and 25% received treatment with clindamycin. CONCLUSIONS: Incidence of MRSA is high in infants with cervical lymphadenitis who fail empirical antibiotic therapy and require surgical management. Empirical coverage for cervical lymphadenitis with ß-lactam antibiotics may provide inadequate coverage for early infection in this population.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Linfadenite/epidemiologia , Infecções Estafilocócicas/epidemiologia , Fatores Etários , Antibacterianos/uso terapêutico , Causalidade , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/cirurgia , Feminino , Humanos , Lactente , Linfadenite/tratamento farmacológico , Linfadenite/cirurgia , Masculino , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Grupos Raciais/estatística & dados numéricos , Estudos Retrospectivos , Fatores Socioeconômicos , Sociologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/cirurgia
15.
Ann Otol Rhinol Laryngol ; 121(7): 442-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22844863

RESUMO

OBJECTIVES: We report outcomes of balloon dilation in the endoscopic management of pediatric subglottic stenosis (SGS) and discuss the role of balloon dilation in both primary and adjuvant therapy. METHODS: We performed a retrospective review of treatment with noncompliant, high-pressure balloons for SGS in the past 2 years at a tertiary pediatric hospital. Fifty-one dilations were performed in 28 children with SGS. The children's mean age was 42 months. The mean SGS grade was 2.46. RESULTS: Fifteen children had primary balloon dilation, and 13 had adjuvant balloon dilation. Overall, 16 children (57.1%) had successful balloon dilation. Of those who underwent primary dilation, 9 (60.0%) were able to avoid open reconstruction or tracheotomy and 6 had their symptoms temporarily improved (average, 36 days) until definitive open reconstruction. Of the patients who underwent adjuvant dilation, 7 (53.8%) were successfully decannulated. Nine of the 12 failed balloon dilations were in children who had concomitant airway disorders; in contrast, only 6 of 16 children in whom treatment was successful had concomitant airway disorders (p = 0.048). There was no statistical association between successful versus failed treatment and age (51.6 versus 27.9 months; p = 0.23), degree of stenosis (grade 2.3 versus grade 2.6; p = 0.41), presence of lung disease (33.3% versus 70%; p = 0.07), or soft versus firm stenosis (60.0% versus 53.1%; p = 0.71). CONCLUSIONS: Balloon dilation plays an important role in the primary and adjuvant management of pediatric SGS. The presence of concomitant airway lesions is significantly associated with failure of balloon dilation treatment. Meticulous surveillance of the dilated airway is necessary, given this failure rate.


Assuntos
Cateterismo , Laringoestenose/terapia , Adolescente , Obstrução das Vias Respiratórias/etiologia , Obstrução das Vias Respiratórias/terapia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Laringoscopia , Laringoestenose/complicações , Masculino , Doenças Respiratórias/complicações , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
16.
Laryngoscope ; 119(12): 2315-23, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19693929

RESUMO

OBJECTIVES/HYPOTHESIS: To develop a reliable modeling system for head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Laboratory-based translational study. METHODS: HNSCC tissue was obtained from patients at biopsy/resection, cultured, and implanted into mice. In vivo, tumor growth, and survival was monitored by bioluminescence imaging. Histology and immunohistochemistry (IHC) were used to confirm HNSCC and human origin. RESULTS: Short-term culture techniques were optimized allowing survival of primary HNSCC cells more than 7 days in 76% of tumors. The size of the tumor biopsy collected did not correlate with the success of short-term culture or xenograft establishment. Xenograft modeling was attempted in primary HNSCCs from 12 patients with a success rate of 92%. Immunostaining confirmed human origin of epithelial tumor cells within the modeled tumor. Bioluminescence and Ki67 IHC suggested tumor proliferation within the model. Luciferase expression was maintained for as long as 100 days in modeled tumors. CONCLUSIONS: The techniques developed for short-term primary tumor culture followed by xenograft modeling provide a low-cost and tractable model for evaluation of HNSCC response to standard and novel therapies. The high success rate of human-in-mouse tumor formation from primary HNSCC suggests that selection pressures for tumor growth in this model may be less than those observed for establishment of cell lines. Bioluminescent imaging provides a useful tool for evaluating tumor growth and could be expanded to measure response of the modeled tumor to therapy. This model could be adapted for xenograft modeled growth of other primary tumor types.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Experimentais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biópsia , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Ratos , Traqueia/citologia , Traqueia/transplante , Transplante Heterólogo , Células Tumorais Cultivadas
17.
Cancer Res ; 67(9): 4227-35, 2007 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-17483334

RESUMO

Invadopodia are branched actin-rich structures associated with extracellular matrix (ECM) degradation that collectively form the invasive machinery of aggressive cancer cells. Cortactin is a prominent component and a specific marker of invadopodia. Amplification of cortactin is associated with poor prognosis in head and neck squamous cell carcinomas (HNSCC), possibly because of its activity in invadopodia. Although the role of cortactin in invadopodia has been attributed to signaling and actin assembly, it is incompletely understood. We made HNSCC cells deficient in cortactin by RNA interference knockdown methods. In these cortactin knockdown cells, invadopodia were reduced in number and lost their ability to degrade ECM. In the reverse experiment, overexpression of cortactin dramatically increased ECM degradation, far above and beyond the effect on formation of actin/Arp3-positive invadopodia puncta. Secretion of matrix metalloproteinases (MMP) MMP-2 and MMP-9, as well as plasma membrane delivery of MT1-MMP correlated closely with cortactin expression levels. MMP inhibitor treatment of control cells mimicked the cortactin knockdown phenotype, with abolished ECM degradation and fewer invadopodia, suggesting a positive feedback loop in which degradation products from MMP activity promote new invadopodia formation. Collectively, these data suggest that a major role of cortactin in invadopodia is to regulate the secretion of MMPs and point to a novel mechanism coupling dynamic actin assembly to the secretory machinery, producing enhanced ECM degradation and invasiveness. Furthermore, these data provide a possible explanation for the observed association between cortactin overexpression and enhanced invasiveness and poor prognosis in HNSCC patients.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Cortactina/metabolismo , Matriz Extracelular/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Metaloproteinases da Matriz/metabolismo , Actinas/metabolismo , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Membrana Celular/enzimologia , Membrana Celular/metabolismo , Cortactina/biossíntese , Neoplasias de Cabeça e Pescoço/enzimologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Metaloproteinase 14 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz
18.
Artigo em Inglês | MEDLINE | ID: mdl-15467340

RESUMO

Health status instruments are questionnaires that are utilized to assess changes in health status of individuals. These surveys are increasingly of importance as health care providers are challenged to justify treatment approach and rationale. Objective criteria (e.g. CT scan of the sinuses) can be used to determine whether there is clinical evidence of disease. However, the impact of the disease on the individual's life is not included in such a clinical assessment. The use of validated and reliable health instruments is directed at measuring this impact in a reproducible and valid fashion. In patient-centered research, 'experimental' conditions are constantly changing because we are dealing with human beings with values, feelings, and perspectives. It is especially important to use valid measurement tools when assessing these impacts. This article outlines the principles of the development and validation of health status instruments and offers examples of such instruments from the otolaryngology literature.


Assuntos
Nível de Saúde , Otolaringologia/métodos , Inquéritos e Questionários , Humanos , Psicometria/métodos , Qualidade de Vida , Reprodutibilidade dos Testes
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