Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Laryngoscope ; 129(5): 1113-1116, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30284247

RESUMO

OBJECTIVES/HYPOTHESIS: Evaluate bone resorption in free fibular grafts and document resorption behavior as compared to dentulous and edentulous autochthonous mandibular bone. STUDY DESIGN: Retrospective Chart review. METHODS: Postoperative computed tomography images were used to evaluate fibular graft resorption rates and corresponding sites of the dentulous or edentulous mandible. Bone height, width, and cortical thickness were measured. RESULTS: Eighteen patients underwent fibula free flap reconstruction following resection of a primary head and neck cancer. Mandibular defects were classified using Jewer's classification. The average interval loss of osseous height was 0.23 ± 0.09 mm/yr for fibula flap, 0.55 ± 0.13 mm/yr for dentulous native mandible, and 0.98 ± 0.41 mm/yr in edentulous native mandible. Change in osseous width was 0.19 ± 0.08 mm/yr, 0.55 ± 0.33 mm/yr, and 0.73 ± 0.15 mm/yr, respectively. Rate of superior cortical resorption was 0.33 ± 0.34 mm/yr, 0.35 ± 0.13 mm/yr, and 0.53 ± 0.11 mm/yr in fibula flap, dentulous, and edentulous mandible, respectively. Inferior cortical resorption rates were quantified as 0.30 ± 0.11 mm/yr, 0.35 ± 0.08 mm/yr, and 0.51 ± 0.08 mm/yr. CONCLUSIONS: Fibula free flap reconstruction of the mandible provides excellent functional results and allows for stable outcomes. Bone resorption is significantly lower in fibular graft compared with both edentulous and dentulous mandible. Edentulous bone displays significantly increased rates of atrophy in comparison to the dentulous mandible. This may have implications with regard to long-term viability of both the fibular flap and native mandible. The role of dental restoration on overall osseous stability warrants further research. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1113-1116, 2019.


Assuntos
Reabsorção Óssea , Fíbula/transplante , Retalhos de Tecido Biológico , Neoplasias Mandibulares/cirurgia , Reconstrução Mandibular/métodos , Seguimentos , Humanos , Arcada Edêntula , Mandíbula , Estudos Retrospectivos , Fatores de Tempo
2.
Sci Rep ; 8(1): 17239, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30467317

RESUMO

The development of new treatments for castrate resistant prostate cancer (CRPC) must address such challenges as intrinsic tumor heterogeneity and phenotypic plasticity. Combined PTEN/TP53 alterations represent a major genotype of CRPC (25-30%) and are associated with poor outcomes. Using tumor-derived, castration-resistant Pten/Tp53 null luminal prostate cells for comprehensive, high-throughput, mechanism-based screening, we identified several vulnerabilities among >1900 compounds, including inhibitors of: PI3K/AKT/mTOR, the proteasome, the cell cycle, heat shock proteins, DNA repair, NFκB, MAPK, and epigenetic modifiers. HSP90 inhibitors were one of the most active compound classes in the screen and have clinical potential for use in drug combinations to enhance efficacy and delay the development of resistance. To inform future design of rational drug combinations, we tested ganetespib, a potent second-generation HSP90 inhibitor, as a single agent in multiple CRPC genotypes and phenotypes. Ganetespib decreased growth of endogenous Pten/Tp53 null tumors, confirming therapeutic activity in situ. Fifteen human CRPC LuCaP PDX-derived organoid models were assayed for responses to 110 drugs, and HSP90 inhibitors (ganetespib and onalespib) were among the select group of drugs (<10%) that demonstrated broad activity (>75% of models) at high potency (IC50 <1 µM). Ganetespib inhibits multiple targets, including AR and PI3K pathways, which regulate mutually compensatory growth and survival signals in some forms of CRPC. Combined with castration, ganetespib displayed deeper PDX tumor regressions and delayed castration resistance relative to either monotherapy. In all, comprehensive data from near-patient models presents novel contexts for HSP90 inhibition in multiple CRPC genotypes and phenotypes, expands upon HSP90 inhibitors as simultaneous inhibitors of oncogenic signaling and resistance mechanisms, and suggests utility for combined HSP90/AR inhibition in CRPC.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antagonistas de Receptores de Andrógenos/farmacologia , Animais , Benzamidas/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Genótipo , Ensaios de Triagem em Larga Escala/métodos , Humanos , Isoindóis/farmacologia , Masculino , Camundongos , PTEN Fosfo-Hidrolase/metabolismo , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Próstata/efeitos dos fármacos , Próstata/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Triazóis/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
4.
Int Forum Allergy Rhinol ; 8(7): 850-856, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29543388

RESUMO

BACKGROUND: The objective of this work was to assess resident education regarding contemporary management of hereditary angioedema using a web-based survey. METHODS: An 11-item, multiple-choice, electronic questionnaire was sent to all 106 accredited otolaryngology training programs in November 2016. Questions focused on resident education, management principles, and formalized assessment. RESULTS: A total of 34 program directors responded, representing 32% of otolaryngology residences. Ninety-seven percent believed otolaryngology residents should be knowledgeable in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE). Specifically, 38% and 26% of program directors felt their residents were comfortable and very comfortable in C1-INH-HAE management, respectively. Of those surveyed, 18% have educational simulation activities and a protocol in place for C1-INH-HAE management. Forty-seven percent of respondents felt their training program provided adequate education and exposure to C1-INH-HAE. Over the last 5 years, 45% felt residents were exposed to 1 to 5 cases of C1-INH-HAE. Sixty-seven percent of residents were trained in the management of C1-INH-HAE through in-person lectures. Seventy-one percent of programs had no formal assessment of resident competency in C1-INH-HAE management. CONCLUSION: This study is the first to offer insight into C1-INH-HAE education and management principles in otolaryngology training programs. Surveyed program directors believe residents need a strong knowledge base in the management of C1-INH-HAE but less than half feel their trainees acquire the necessary exposure to this emergent disease process. Future research efforts in this area should aim to determine optimal educational activities as well as how to best incorporate this into otolaryngology residency curricula.


Assuntos
Angioedemas Hereditários/epidemiologia , Otolaringologia/educação , Educação , Educação de Pós-Graduação em Medicina , Humanos , Internato e Residência , Inquéritos e Questionários , Estados Unidos/epidemiologia
5.
Otolaryngol Head Neck Surg ; 158(2): 368-374, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28873028

RESUMO

Objective To establish the safety and efficacy of single-dose intraoperative intravenous (IV) acetaminophen in postoperative pain management following adenotonsillectomy in addition to a standardized regimen of oral pain medication. Study Design Randomized, controlled prospective clinical trial. Setting Single academic medical center. Subjects and Methods Patients between the ages of 3 and 17 years scheduled for tonsillectomy or adenotonsillectomy by a single surgeon between December 2014 and November 2016 were recruited. Patients were randomly assigned to 1 of 2 groups; group 1 received a single intraoperative dose of IV acetaminophen, and group 2 did not. Induction and maintenance of anesthesia, as well as operative technique, were standardized. Nursing pain scores, pain medications administered, and recovery times were reviewed during the 24-hour postoperative period. Postoperative pain regimen included standing alternating oral acetaminophen and ibuprofen. Results In total, 260 patients were included in the study, and 131 (50.4%) received a single intraoperative dose of IV acetaminophen. Patients receiving IV acetaminophen were more likely to experience postoperative nausea and vomiting than patients who did not receive IV acetaminophen (1.53% vs 0.00%, P = .016). There were no significant differences noted for postoperative pain scores, requirements for breakthrough pain medications, time to discharge from the recovery room or hospital, or postoperative complications. Conclusion The use of a single intraoperative dose of IV acetaminophen was associated with minimal additional adverse effects. However, a single intraoperative IV dose of acetaminophen added to standard narcotic and nonnarcotic pain medication does not provide a statistically significant improvement in pain control.


Assuntos
Acetaminofen/administração & dosagem , Adenoidectomia , Analgésicos não Entorpecentes/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Tonsilectomia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intravenosas , Cuidados Intraoperatórios , Masculino , Medição da Dor , Estudos Prospectivos
6.
Int J Pediatr Otorhinolaryngol ; 102: 103-107, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29106854

RESUMO

OBJECTIVE: To determine if salivary cotinine, a biomarker for tobacco smoke exposure, is elevated more often or to a higher degree in children meeting criteria for tonsillectomy or tympanostomy tube insertion. METHODS: Saliva samples were obtained from 3 groups of children for salivary cotinine measurement. Group 1 served as healthy controls. Group 2 consisted of subjects meeting tympanostomy tube criteria. Group 3 consisted of patients meeting tonsillectomy criteria. Environmental tobacco smoke (ETS) exposure was defined as a salivary cotinine concentration ≥1.0 ng/mL. Demographic data, smoke exposure history, and co-morbidities were also determined. RESULTS: 331 patients were included, with 112 in Group 1, 111 in Group 2, and 108 in Group 3. No differences were encountered for smoke exposure by history or smoker's identity, salivary cotinine level, or frequency of positive cotinine results. 42.6% of Group 1 had positive salivary cotinine compared to 51.8% of Group 2 and 47.7% of Group 3. Group 1 had a mean salivary cotinine level of 2.42 ng/mL compared to 2.54 ng/mL in Group 2 and 2.60 ng/mL in Group 3. The frequency of positive cotinine levels was higher than expected based on parental history. Among subjects with positive cotinine levels, 93 had no ETS exposure, and 64 had ETS exposure by history. CONCLUSION: Approximately 50% of children who undergo tonsillectomy and tympanostomy tube insertion have objective evidence of ETS exposure. Parental history underestimates passive smoke exposure, which can impact perioperative care.


Assuntos
Biomarcadores/metabolismo , Cotinina/metabolismo , Otorrinolaringopatias/metabolismo , Saliva/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Criança , Exposição Ambiental , Feminino , Humanos , Masculino , Ventilação da Orelha Média/estatística & dados numéricos , Pais , Tonsilectomia/estatística & dados numéricos
7.
J Child Adolesc Psychopharmacol ; 26(4): 372-9, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26783833

RESUMO

OBJECTIVE: We sought to evaluate the neurophysiology of mindfulness-based cognitive therapy for children (MBCT-C) in youth with generalized, social, and/or separation anxiety disorder who were at risk for developing bipolar disorder. METHODS: Nine youth (mean age: 13 ± 2 years) with a generalized, social, and/or separation anxiety disorder and a parent with bipolar disorder completed functional magnetic resonance imaging (fMRI) while performing a continuous processing task with emotional and neutral distractors (CPT-END) prior to and following 12 weeks of MBCT-C. RESULTS: MBCT-C was associated with increases in activation of the bilateral insula, lentiform nucleus, and thalamus, as well as the left anterior cingulate while viewing emotional stimuli during the CPT-END, and decreases in anxiety were correlated with change in activation in the bilateral insula and anterior cingulate during the viewing of emotional stimuli (p < 0.05, uncorrected; p < 0.005 corrected; cluster size, 37 voxels). CONCLUSIONS: MBCT-C treatment in anxious youth with a familial history of bipolar disorder is associated with increased activation of brain structures that subserve interoception and the processing of internal stimuli-functions that are ostensibly improved by this treatment.


Assuntos
Transtornos de Ansiedade/terapia , Transtorno Bipolar/prevenção & controle , Terapia Cognitivo-Comportamental/métodos , Atenção Plena/métodos , Adolescente , Transtornos de Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Criança , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Fatores de Risco , Resultado do Tratamento
8.
Early Interv Psychiatry ; 10(5): 426-34, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-25582800

RESUMO

AIM: Children and adolescents with bipolar parents have an elevated risk for anxiety disorders. However, antidepressant medications commonly used to treat symptoms of anxiety may accelerate the onset of mania in these already at-risk youth. Therefore, studies evaluating innovative non-pharmacologic treatments for anxiety in this population are urgently needed. METHODS: Subjects participated in 12 weekly sessions of mindfulness-based cognitive therapy for children (MBCT-C), a manualized group psychotherapeutic intervention utilizing cognitive behavioural principles and mindfulness exercises to increase regulation of attention and non-judgmental acceptance of present moment thoughts, emotions and experiences. Independent raters administered symptoms rating scales prior to each treatment session. Spearman correlations and paired-samples signed rank tests were used to examine outcomes. After-intervention surveys and session transcripts were reviewed to assess feasibility and acceptability of the intervention. RESULTS: Participants included 10 youth (meanage = 13.2; 80% girls; 40% biracial) with generalized, social and/or separation anxiety disorders, and a parent with bipolar disorder. Clinician-rated anxiety was significantly reduced after intervention (meanbefore = 11.1; meanafter = 4.3; P < 0.01), as well as youth-rated trait anxiety (P = 0.03). Parent-rated emotion regulation significantly increased from before to after intervention (P = 0.05). Increases in mindfulness were associated with decreases in anxiety (P = 0.03). Finally, children and parents/guardians reported high levels of feasibility, acceptability and usefulness of the intervention. CONCLUSION: Findings support the feasibility, acceptability and preliminary efficacy of MBCT-C for treating anxiety in youth at risk for bipolar disorder. Future controlled and larger studies are needed to confirm these preliminary findings.


Assuntos
Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Atenção Plena , Adolescente , Transtorno Bipolar/psicologia , Criança , Feminino , Humanos , Masculino , Pais/psicologia , Projetos Piloto , Psicoterapia de Grupo
10.
Hypertens Res ; 33(8): 808-13, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20520615

RESUMO

Omega-3 polyunsaturated fatty acid deficiency, particularly during the prenatal period, can cause hypertension in later life. This study examined the effect of different sources of alpha-linolenic acid (canola oil or flaxseed oil) in the prevention of hypertension and other metabolic symptoms induced by an omega-3 fatty acid-deficient diet. Dams were provided one of three experimental diets from 1 week before mating. Diets were either deficient (10% safflower oil-DEF) or sufficient (7% safflower oil+3% flaxseed oil-SUF-F; or 10% canola oil-SUF-C) in omega-3 fatty acids. The male offspring were continued on the maternal diet from weaning for the duration of the study. Body weight, ingestive behaviors, blood pressure, body composition, metabolic rate, plasma leptin and brain fatty acids were all assessed. The DEF animals were hypertensive at 24 weeks of age compared with SUF-F or SUF-C animals; this was not evident at 12 weeks. These results suggest that different sources of ALA are effective in preventing hypertension related to omega-3 fatty acid deficiency. However, there were other marked differences between the DEF and, in particular, the SUF-C phenotype including lowered body weight, adiposity, leptin and food intake in SUF-C animals. SUF-F animals also had lower, but less marked reductions in adiposity and leptin compared with DEF animals. The differences observed between DEF, SUF-F and SUF-C phenotypes indicate that body fat and leptin may be involved in omega-3 fatty acid deficiency hypertension.


Assuntos
Ração Animal , Deficiências Nutricionais , Hipertensão , Efeitos Tardios da Exposição Pré-Natal , Ácido alfa-Linoleico/farmacologia , Animais , Pressão Sanguínea/fisiologia , Composição Corporal/fisiologia , Peso Corporal/fisiologia , Encéfalo/metabolismo , Calorimetria , Deficiências Nutricionais/complicações , Deficiências Nutricionais/dietoterapia , Deficiências Nutricionais/metabolismo , Metabolismo Energético/fisiologia , Ácidos Graxos Monoinsaturados/farmacologia , Feminino , Frequência Cardíaca/fisiologia , Hipertensão/dietoterapia , Hipertensão/etiologia , Hipertensão/metabolismo , Leptina/sangue , Óleo de Semente do Linho/farmacologia , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/dietoterapia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Óleo de Brassica napus , Ratos , Ratos Sprague-Dawley , Óleo de Açafrão/farmacologia
11.
Am J Hypertens ; 23(2): 125-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19893499

RESUMO

BACKGROUND: Dietary omega-3 fatty acid deficiency can lead to hypertension in later life; however, hypertension is affected by numerous other dietary factors. We examined the effect of altering the dietary protein level on blood pressure in animals deficient or sufficient in omega-3 fatty acids. METHODS: Female rats were placed on one of four experimental diets 1 week prior to mating. Diets were either deficient (10% safflower oil; DEF) or sufficient (7% safflower oil, 3% flaxseed oil; SUF) in omega-3 fatty acids and contained 20 or 30% casein (DEF20, SUF20, DEF30, SUF30). Offspring were maintained on the maternal diet for the duration of the experiment. At 12, 18, 24, and 30 weeks, blood pressure was assessed by tail cuff plethysmography. RESULTS: At both 12 and 18 weeks of age, no differences in blood pressure were observed based on diet, however, by 24 weeks hypertension was evident in DEF30 animals; there were no blood pressure differences between the other groups. This hypertension in DEF30 group was increased at 30 weeks, with systolic, diastolic, and mean arterial pressure all elevated. CONCLUSIONS: These results indicate that the hypertension previously attributed to omega-3 fatty acid deficiency is dependent on additional dietary factors, including protein content. Furthermore, this study is the first to plot the establishment of omega-3 fatty acid deficiency hypertension over time.


Assuntos
Proteínas na Dieta/efeitos adversos , Ácidos Graxos Ômega-3/metabolismo , Hipertensão/etiologia , Envelhecimento/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Caseínas/farmacologia , Dieta , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/fisiopatologia , Masculino , Pletismografia , Ratos , Ratos Sprague-Dawley
12.
Curr Opin Investig Drugs ; 9(1): 57-64, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18183532

RESUMO

Research has established that docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), plays a fundamental role in brain structure and function. Epidemiological and cross-sectional studies have also identified a role for long-chain omega-3 PUFA, which includes DHA, eicosapentaenoic acid, and docosapentaenoic acid, in the etiology of depression. In the past ten years, there have been 12 intervention studies conducted using various preparations of longchain omega-3 PUFA in unipolar and bipolar depression. The majority of these studies administered long-chain omega-3 PUFA as an adjunct therapy. The studies have been conducted over 4 to 16 weeks of intervention and have often included small cohorts. In four out of the seven studies conducted in depressed individuals and in two out of the five studies in bipolar patients, individuals have reported a positive outcome following supplementation with ethyl-eicosapentaenoic acid or fish oil containing long-chain omega-3 PUFA. In the three trials that researched the influence of DHA-rich preparations, no significant effects were reported. The mechanisms that have been invoked to account for the benefits of long-chain omega-3 PUFA in depression include reductions in prostaglandins derived from arachidonic acid, which lead to decreased brain-derived neurotrophic factor levels and/or alterations in blood flow to the brain.


Assuntos
Ácidos Graxos Ômega-3/fisiologia , Transtornos do Humor/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Transtornos do Humor/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA