RESUMO
BACKGROUND: Efficacy testing of immunotherapy in field studies is often hampered by variation of airborne allergens. Standardized allergen exposure in challenge chamber settings might be an alternative. Therefore, we developed a universal technique to create an atmosphere loaded with allergen particles of adjustable size from aqueous solutions of licensed allergen extracts. OBJECTIVE: The aim of this study was to apply this technique and test the safety and efficacy of challenges with house dust mite (HDM) allergen in the Fraunhofer allergen challenge chamber. METHODS: Aerosol particles carrying HDM allergen were produced by spray-drying of an aqueous solution containing HDM allergen and lactose. In a monocenter, placebo-controlled, single-blind, dose-escalation pilot study, 18 subjects with perennial allergic rhinitis and sensitization to HDM were exposed to HDM allergen for 4 h at either 250, 500, 1000 SQE/m3 or lactose alone (0 SQE/m3 ) 7 days apart. The dose of 500 SQE/m³ was repeated to investigate reproducibility. Total nasal symptom score (TNSS) was the primary endpoint. RESULTS: Exposure to HDM increased TNSS (mean ± SD) to 3.4 ± 1.8, 3.3 ± 2.1, and 3.6 ± 2.0 at 250, 500 and 1000 SQE/m3 , respectively, while lactose alone did not change TNSS (0.7 ± 0.6). The results were reproducible at 500 SQE/m3 . Pulmonary function and adverse event frequency did not change with escalation of allergen dose. CONCLUSION: This HDM allergen particle generation is safe, specific and reproducible and can therefore be used for efficacy testing of immunotherapy and for basic clinical research.
Assuntos
Antígenos de Dermatophagoides/imunologia , Imunização , Pyroglyphidae/imunologia , Adulto , Animais , Antígenos de Dermatophagoides/administração & dosagem , Antígenos de Dermatophagoides/efeitos adversos , Dessensibilização Imunológica , Expiração , Feminino , Humanos , Imunização/métodos , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Óxido Nítrico/metabolismo , Testes de Função Respiratória , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: The ozone challenge model can be used to assess the efficacy of anti-inflammatory compounds in early phases of clinical drug development. PUR118, a calcium salt based formulation engineered in the iSPERSE(TM) dry powder delivery technology, is a novel anti-inflammatory drug for COPD. Here we evaluated the efficacy and safety of three doses of PUR118 in attenuating ozone-induced airway inflammation in healthy volunteers. METHODS: In a single-blind, phase 1B proof of concept study, 24 subjects were enrolled to sequentially receive three doses of PUR118 (5.5 mg, n = 18; 11.0 mg, n = 18; 2.8 mg, n = 16). Each dose was inhaled 3 times (1, 13, 25 h, preceded by 2 puffs salbutamol) before the ozone exposure (250 ppb, 3 h intermittent exercise). Sputum was induced 3 h after the end of exposure. RESULTS: Sputum neutrophils, sputum CD14+ cells, as well as concentrations of IL1B, IL6, IL8, MMP9, and TNFA in sputum supernatant significantly increased after ozone exposure (n = 24). The percentage of sputum neutrophils (n = 12 who completed all treatments) did not change following treatment with different doses of PUR118. The high dose treatment group (n = 16) showed a decrease in the percentage and number of sputum macrophages (p ≤ 0.05) as well as a decrease in blood neutrophils (p = 0.04), and an increase in blood CD14 + cells (p = 0.04) compared to baseline. All dosages of PUR118 were safe and well tolerated. CONCLUSION: Ozone challenge resulted in the expected and significant increase of sputum inflammatory parameters. Treatment with multiple rising doses of PUR118 was safe and three applications within 25 h prior to the ozone challenge had small effects on ozone-induced airway inflammation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01690949. Registered 12 September 2012.
Assuntos
Compostos de Cálcio/administração & dosagem , Compostos de Cálcio/farmacologia , Inflamação/prevenção & controle , Lactatos/administração & dosagem , Lactatos/farmacologia , Ozônio/efeitos adversos , Sistema Respiratório/efeitos dos fármacos , Administração por Inalação , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Biomarcadores/metabolismo , Compostos de Cálcio/efeitos adversos , Compostos de Cálcio/uso terapêutico , Feminino , Humanos , Inflamação/induzido quimicamente , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Lactatos/efeitos adversos , Lactatos/uso terapêutico , Receptores de Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Método Simples-Cego , Fator de Necrose Tumoral alfa/metabolismo , Adulto JovemRESUMO
Non-invasive pulmonary diagnostics is a promising and interesting field in respiratory medicine. Beside exhaled breath condensate, there is an increasing interest in alternative and faster techniques such as electronic noses (EN). EN aim to mimic or improve the sense of smelling. Different types of EN have been employed in research so far. In addition to ion mobility spectrometry and mass spectrometry, ENs that consist of various biopolymer sensors for the sensing of volatile organic compounds (VOCs) have been tested. VOCs bind to the sensors depending on size, structure, hydrogen binding and polarity. This leads to physical alterations, e.âg., swelling resulting in a change of resistance. The smell print represents composite patterns in contrast to single compounds, and the distinction between different categories is achieved by pattern recognition algorithms. Other types of EN like mass spectrometry and ion mobility spectrometry are capable of identifying even single analyte fractions provided that their characteristics have been saved in data repositories. The non-invasive nature, onsite availability and relatively cheap sampling are advantages of ENs that underly the increasing interest in their use for medical purposes. Some promising results have already been published. This review aims to describe the state of the art in brief form.
Assuntos
Materiais Biomiméticos , Técnicas Biossensoriais , Testes Respiratórios/instrumentação , Gases/análise , Pneumopatias/diagnóstico , Olfato , Compostos Orgânicos Voláteis/análise , Biomarcadores/análise , Humanos , Pneumopatias/metabolismoRESUMO
BACKGROUND: Volatile organic compounds (VOCs) can be used as biomarkers in exhaled air. VOC profiles can be detected by an array of nanosensors of an electronic nose. These profiles can be analysed using bioinformatics. It is, however, not known whether different devices of the same model measure identically and to which extent different set-ups and the humidity of the inhaled air influence the VOC profile. METHODS: Three different measuring set-ups were designed and three healthy control subjects were measured with each of them, using four devices of the same model (Cyranose 320™, Smiths Detection). The exhaled air was collected in a plastic bag. Either ambient air was used as reference (set-up Leipzig), or the reference air was humidified (100% relative humidity) (set-up Marburg and set-up Munich). In the set-up Marburg the subjects inhaled standardised medical air (Aer medicinalis Linde, AGA AB) out of a compressed air bottle through a demand valve; this air (after humidification) was also used as reference. In the set-up Leipzig the subjects inhaled VOC-filtered ambient air, in the set-up Munich unfiltered room air. The data were evaluated using either the real-time data or the changes in resistance as calculated by the device. RESULTS: The results were clearly dependent on the set-up. Apparently, humidification of the reference air could reduce the variance between devices, but this result was also dependent on the evaluation method used. When comparing the three subjects, the set-ups Munich and Marburg mapped these in a similar way, whereas not only the signals but also the variance of the set-up Leipzig were larger. CONCLUSION: Measuring VOCs with an electronic nose has not yet been standardised and the set-up significantly affects the results. As other researchers use further methods, it is currently not possible to draw generally accepted conclusions. More systematic tests are required to find the most sensitive and reliable but still feasible set-up so that comparability is improved.
Assuntos
Poluentes Ocupacionais do Ar/análise , Técnicas Biossensoriais/instrumentação , Testes Respiratórios/instrumentação , Compostos Orgânicos Voláteis/análise , Adulto , Gráficos por Computador , Desenho de Equipamento , Feminino , Humanos , Umidade , Masculino , Microcomputadores , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Angiotensin converting enzyme (ACE) is thought to influence susceptibility, disease progression, and/or outcome of sarcoidosis by functional mutations/polymorphisms of the ACE gene, such as the ACE gene deletion/insertion (D/I) polymorphism or the angiotensin receptors like the angiotensin II receptor type 1 (AT2R1) A1166 --> C polymorphism. The aim of our study was to examine the distribution of the ACE D/I genotypes and the AT2R1 A1166 --> C genotypes in sarcoidosis and healthy controls, and to test their influence on disease progression. In this study, we assessed ACE and AT2R1 genotypes by PCR in 264 healthy Caucasians and 95 sarcoidosis patients. Serum ACE levels were determined using a kinetic test. Genotyping sarcoidosis patients for the AT2R1 A166 --> C polymorphism revealed an increase in homozygous genotypes CC (sarcoidosis: 11.6%, controls: 9.2%) and AA (sarcoidosis: 61.1%, controls: 47.3%) but a lower frequency in heterozygous genotypes (sarcoidosis: 27,4%, controls: 43,5%; p = 0.024) which was more pronounced in male patients. The co-incidence of DI and AC was less frequent in patients with sarcoidosis, suggesting protection by the combination of DI and AC. The AT2R1 A1166 --> C gene polymorphism modulated the effect of the ACE D/I polymorphism on serum ACE levels with the A allele promoting its influence and the C allele reducing it. We conclude that neither the ACE D/I nor the AT2R1 A1166 --> C polymorphism has a role in sarcoidosis disease progression. In males, the homozygous AT2R1 genotypes CC and AA possibly increase the risk for sarcoidosis. Co-incidence of the heterozygous genotypes DI and AC might be protective against sarcoidosis.
Assuntos
DNA/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Receptor Tipo 2 de Angiotensina/genética , Sarcoidose/genética , Adulto , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Peptidil Dipeptidase A/sangue , Reação em Cadeia da Polimerase , Receptor Tipo 2 de Angiotensina/sangue , Sarcoidose/sangueRESUMO
BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is one of the most common causes of chronic morbidity and mortality. The "Burden of Obstructive Lung Disease" (BOLD) initiative was established as an international study collecting data about the prevalence of COPD. The Medical University of Hanover took part in this study collecting data representative for Germany. METHODS: 683 individuals aged = 40 years from the city and region of Hannover were included in the study. On the basis of standardized questionnaires data were collected on general health, physical and mental capability, smoking habits and occupational exposure to dust. All participants performed spirometry before and after inhalation of salbutamol. RESULTS: The prevalence of COPD, GOLD (Global Health Initiative on Obstructive Lung Disease) severity stage = I, was 13.2% (GOLD stage I: 7.4%; GOLD stage II: 5.0%, GOLD stage III or IV: 0.8%). There was a marked increase of the prevalence of COPD depending on age and smoking habits. The percentage of active smokers in the sample was 20.6 %. Among younger participants the percentage of female smokers was noticeable higher than in older subjects. Although clinical symptoms of COPD, GOLD stage = III correlated with disease severity, only persons with COPD reported reduced physical capability. CONCLUSION: COPD is a highly prevalent disease. With regard to the increasing life expectancy and the change of smoking habits of the population, a further increase of morbidity and mortality due to COPD must be expected, especially in women.
Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/epidemiologia , Adulto , Fatores Etários , Idoso , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Qualidade de Vida , Índice de Gravidade de Doença , Fatores Sexuais , EspirometriaRESUMO
The deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene has the greatest impact on serum ACE level in Caucasians of any factor yet discovered. The aim of the present study was to establish new ACE genotype-corrected normal ranges for serum ACE level in a population of central European origin. After a medical examination, 159 healthy Caucasians volunteered to donate blood for the study. ACE genotypes were assessed by PCR and serum ACE levels were determined using two different kinetic tests. The distribution of the D/I polymorphism of the ACE gene was in accordance with the Hardy-Weinberg equilibrium. Serum ACE levels and ACE genotypes correlated significantly, with the highest serum ACE levels in subjects with ACE genotype D/D, and the lowest serum ACE levels in subjects with genotype I/I (mean+/-sd, assay 1: D/D 59.3+/-15.1 U x L(-1), D/I 45.5+/-15.2 U x L(-1), I/I 34.8+/-13.7 U x L(-1); assay 2: D/D 43.7+/-14.1 U x L(-1), D/I 33.7+/-12.1 U x L(-1), I/I 25.4+/-9.5 U x L(-1)). Although they gave different absolute values of serum ACE levels, the results of the two test kits correlated significantly. In conclusion, the present authors recommend the use of new, genotype-specific reference values for serum angiotensin-converting enzyme levels, especially to improve the sensitivity and specificity of tests for angiotensin-converting enzyme in the follow-up of sarcoidosis.
Assuntos
Genótipo , Peptidil Dipeptidase A/sangue , Polimorfismo Genético/genética , Adolescente , Adulto , Alelos , Biomarcadores/sangue , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Reação em Cadeia da Polimerase , Valores de Referência , Sarcoidose Pulmonar/sangue , Sarcoidose Pulmonar/diagnósticoRESUMO
It has been postulated that T lymphocytes orchestrate the chronic inflammation in bronchial asthma. In animal models, infiltration of CD8+ T lymphocytes into the bronchial mucosa prevented bronchial hyperresponsiveness and decreased early and late phase reaction. IFN-gamma antagonizes IL-4-dependent IgE production as well as IL-5-induced proliferation and activation of eosinophils. We therefore investigated the secretion of IFN-gamma of isolated CD8+ T lymphocytes from peripheral blood of patients with allergic asthma (n = 6) and from healthy controls (n = 7) in vitro. In this setting we compared the effect of stimulation with anti-CD3 antibodies with that of phorbol myristate acetate (PMA) and calcium-ionophore. As expected, CD8+ T lymphocytes from peripheral blood of healthy volunteers produced significantly more IFN-gamma in the presence of PMA and calcium-ionophore than after stimulation with anti-CD3 antibodies. However, in subjects with allergic asthma, IFN-gamma secretion of CD8+ T cells was significantly higher when incubated with anti-CD3 antibodies than after activation with PMA and calcium-ionophore. While IFN-gamma secretion of CD8+ T lymphocytes of patients with allergic asthma was lower than that of healthy controls in the presence of PMA/calcium-ionophore, it was significantly elevated when compared with normal controls after stimulation with anti-CD3 antibodies. Thus, potent activators of cytokine secretion, such as PMA and calcium-ionophore, induce a cytokine profile different from that induced by weaker stimulants, such as anti-CD3 antibodies. These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro.
Assuntos
Asma/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon gama/sangue , Adulto , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Calcimicina/farmacologia , Estudos de Casos e Controles , Citocinas/biossíntese , Feminino , Humanos , Técnicas In Vitro , Ionóforos/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/farmacologia , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
OBJECTIVE: To assess the diagnostic accuracy of fine-needle aspiration (FNA) and frozen section (FS) in nodular thyroid disease. SETTING: Tertiary care academic medical center. STUDY DESIGN: Retrospective review of 139 consecutive patients undergoing surgery for nodular thyroid disease. FNA and FS sensitivity, specificity, and accuracy were calculated with respect to permanent section histology. RESULTS: Among 63 patients with an FNA interpreted as either benign (n = 38) or malignant (n = 25), FNA was accurate (sensitivity 89%, specificity 97%, accuracy 94%). FS identified only one case of carcinoma missed by FNA. Among 76 patients with a "suspicious" FNA, FS was reasonably accurate (sensitivity 67%, specificity 100%, accuracy 89%), but was deferred in 50% of cases. CONCLUSION: Given high FNA accuracy, more selective use of FS is suggested. SIGNIFICANCE: The study results will assist with intra-institutional patient counseling and intraoperative decision-making with respect to FNA and FS results in patients with nodular thyroid disease.
Assuntos
Secções Congeladas , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Adenoma/patologia , Adenoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma Papilar, Variante Folicular/patologia , Carcinoma Papilar, Variante Folicular/cirurgia , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
The pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II-III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49.3 +/- 21.3% versus 14.5 +/- 15.6%), IFN-gamma (75.5 +/- 14.9% versus 32.6 +/- 18.7%) and TNF-alpha (68.3 +/- 18.7% versus 36.8 +/- 20.8%) was significantly higher in patients with sarcoidosis than in normal controls (each P < 0.005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-gamma and TNF-alpha, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-gamma, and TNF-alpha in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/metabolismo , Sarcoidose/imunologia , Células Th1/imunologia , Adulto , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Estudos de Casos e Controles , Contagem de Células , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Sarcoidose/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: To report our experience in a case series of 5 posterior scalping flaps. DESIGN: Retrospective review of a case series. SETTING: A tertiary academic care otolaryngology-head and neck surgery referral center. PATIENTS: Five patients having undergone posterior scalping flap reconstruction of cutaneous midface defects. METHODS: Reconstruction was performed for 4 cheek defects, 1 of which included the lateral third of the upper and lower lips, and 1 combined midfacial and lateral nasal wall defect. RESULTS: All 5 patients had excellent cosmetic and functional results. The only complication was a single case of partial-thickness distal flap necrosis. CONCLUSION: The posterior scalping flap offers a reliable source of skin with appropriate color and texture and minimal donor-site morbidity.
Assuntos
Malformações Arteriovenosas/cirurgia , Bochecha/irrigação sanguínea , Neoplasias Faciais/cirurgia , Neoplasias Cutâneas/cirurgia , Retalhos Cirúrgicos , Adulto , Idoso , Carcinoma Basocelular/cirurgia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Couro Cabeludo/transplante , Resultado do TratamentoRESUMO
Phonation after partial laryngeal ablative surgery has not often been examined. Videolaryngostroboscopic recordings made after vertical partial laryngectomy (VPL) were retrospectively reviewed and correlated with patient historical and operative factors. Among VPL patients (n = 42), the most common site of vibration during phonation was the contralateral false vocal fold (17/42 patients or 40.5%), followed by the contralateral arytenoid mucosa (10/42 or 23.8%) and the contralateral true vocal fold (8/42 patients or 19.0%). There was no overall difference in vocal quality judgment with respect to site of vibration (ANOVA, p = .373). Vocal quality scores were similar with use of the pyriform mucosal flap versus other reconstructive methods (Student's t-test, p = .568). This study highlights the fact that reconstruction of a new vibratory source after VPL is important for voice production. Because VPL patients infrequently demonstrated true vocal fold vibration, alternative sites (ie, false vocal fold, arytenoid mucosa) must be considered as new phonatory sources after VPL.
Assuntos
Laringectomia , Laringe/fisiologia , Fonação/fisiologia , Prega Vocal/fisiologia , Cartilagem Aritenoide/fisiologia , Cartilagem Aritenoide/cirurgia , Feminino , Glote/fisiologia , Humanos , Laringoscopia , Laringe/efeitos da radiação , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vibração , Gravação em Vídeo , Qualidade da Voz/fisiologiaRESUMO
Most of the sounds of human speech are produced by vibration of the vocal folds, yet the biomechanics and control of these vibrations are poorly understood. In this study the muscle within the vocal fold, the thyroarytenoid muscle (TA), was examined for the presence and distribution of slow tonic muscle fibers (STF), a rare muscle fiber type with unique contraction properties. Nine human TAs were frozen and serially sectioned in the frontal plane. The presence and distribution pattern of STF in each TA were examined by immunofluorescence microscopy using the monoclonal antibodies (mAb) ALD-19 and ALD-58 which react with the slow tonic myosin heavy chain (MyHC) isoform. In addition, TA muscle samples from adjacent frozen sections were also examined for slow tonic MyHC isoform by electrophoretic immunoblotting. STF were detected in all nine TAs and the presence of slow tonic MyHC isoform was confirmed in the immunoblots. The STF were distributed predominantly in the medial aspect of the TA, a distinct muscle compartment called the vocalis which is the vibrating part of the vocal fold. STF do not contract with a twitch like most muscle fibers, instead, their contractions are prolonged, stable, precisely controlled, and fatigue resistant. The human voice is characterized by a stable sound with a wide frequency spectrum that can be precisely modulated and the STF may contribute to this ability. At present, the evidence suggests that STF are not presented in the vocal folds of other mammals (including other primates), therefore STF may be a unique human specialization for speech.
Assuntos
Fibras Musculares de Contração Lenta/citologia , Fibras Musculares de Contração Lenta/fisiologia , Fala/fisiologia , Prega Vocal/anatomia & histologia , Prega Vocal/fisiologia , Adulto , Idoso , Animais , Anticorpos Monoclonais , Cartilagem Aritenoide/anatomia & histologia , Fenômenos Biomecânicos , Feminino , Expressão Gênica , Humanos , Masculino , Mamíferos , Camundongos , Microscopia de Fluorescência , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismoRESUMO
OBJECTIVE: To report on the clinical behavior, histopathology, treatment, and prognosis of laryngeal, hypopharyngeal, and cervical esophageal liposarcomas. STUDY DESIGN: Retrospective reviews of pathology files and hospital records at a tertiary care hospital and a retrospective search of the English-language literature. METHODS: Cases of upper aerodigestive tract (UADT) liposarcoma with adequate histopathologic documentation and clinical information were included for review. RESULTS: Four cases of UADT liposarcomas were identified. The literature review revealed 26 cases of laryngeal liposarcomas, 7 cases of hypopharyngeal liposarcomas, and 6 cases of esophageal liposarcomas: the mean age at presentation was 55.8 years, the male:female ratio was 5:1, and 60% of the patients presented with dysphagia. Eighty-six percent of tumors had low-grade histologic findings. The recurrence rate after primary resection was 50%. Recurrence correlated with surgical procedure rather than with histologic subtype; 94.7% of recurrences happened after simple excision. Distant metastases occurred in three patients; two of them died of the disease. CONCLUSIONS: The literature supports that UADT liposarcomas are rare and usually of low-grade histologic type. The rate of metastatic disease and tumor-related mortality is low. However, high recurrence rates have been noted, particularly when less radical surgery is employed.
Assuntos
Neoplasias Hipofaríngeas/patologia , Neoplasias Laríngeas/patologia , Lipossarcoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Endoscopia/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Rouquidão/etiologia , Humanos , Neoplasias Hipofaríngeas/complicações , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Laríngeas/complicações , Neoplasias Laríngeas/cirurgia , Lipossarcoma/complicações , Lipossarcoma/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Prognóstico , Estudos RetrospectivosRESUMO
Glottic exposure and entry for vertical partial laryngectomy procedures has traditionally been through the subglottis. Although this approach is generally satisfactory for the resection of unilateral vocal cord lesions, it may be unsafe in cases in which tumors extend across the midline and/or subglottically. In these instances, we prefer the superior transverse infrahyoid approach to the glottis, which transects the petiole of the epiglottis and reflects the contents of the preepiglottic space posterior and superior. This improved visualization of the larynx has permitted precise tumor excision without sacrifice of uninvolved segments of the vocal cords. This procedure has been performed 35 times over a 15-year period at our institution for the resection of bilateral glottic tumors, with and without subglottic extension. In none of the cases in which it has been employed was there a positive surgical margin.
Assuntos
Glote/cirurgia , Osso Hioide/cirurgia , Neoplasias Laríngeas/cirurgia , Adulto , Idoso , Feminino , Humanos , Laringectomia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Terminologia como AssuntoRESUMO
It is not understood how different parts of the thyroarytenoid muscle contribute to vocal fold vibration. This study investigated the medial part of the thyroarytenoid muscle, the vocalis compartment, for anatomic differences that might suggest functionally distinct areas. Twenty human vocal folds were frontally sectioned and stained with hematoxylin and eosin. A single section from the middle of each vocal fold was magnified, and the muscle fascicles of the most superficial 25% of the vocalis compartment were then examined. In all 20 specimens the vocalis compartment could be separated into 2 plainly distinct subcompartments: the inferior vocalis compartment was composed of a single large muscle fascicle that contained densely packed muscle fibers of similar size; the superior vocalis compartment was composed of multiple small fascicles in which the muscle fibers were loosely arranged and varied greatly in size. On average, the inferior vocalis subcompartment composed 60% of the medial surface of the thyroarytenoid muscle. The superior subcompartment composed the remaining 40% of the medial surface, but also continued past the vocal ligament to make up the superior surface of the thyroarytenoid muscle. It is concluded that 2 distinct entities make up the vocalis compartment of the thyroarytenoid muscle. Their anatomy is so markedly different it suggests that they may function independently. One possibility is that they reflect the 2 masses observed in the superior and inferior aspects of the vocal fold during vibration.
Assuntos
Músculos Laríngeos/anatomia & histologia , Prega Vocal/anatomia & histologia , Voz/fisiologia , Humanos , Fibras Musculares Esqueléticas/ultraestrutura , Ventilação Pulmonar/fisiologia , Valores de Referência , VibraçãoRESUMO
It is hypothesized that different parts of the thyroarytenoid muscle (TA) are functionally specialized. Specifically, the TA is divided into a lateral muscularis compartment and a medial vocalis compartment. This study examined the distribution of muscle spindles throughout the human TA as an indicator of these functional differences. Histological cross-sections from the anterior, middle, and posterior regions of five human membranous vocal folds were examined for the number and location of muscle spindles. There was an average of 6.1 muscle spindles in sections from each region with no significant variation between the different regions (p < .05). However, in sections from all three regions, the muscle spindles were always found to be concentrated in the superior medial quadrant of the TA (mean 85.9%, p < .01). The inferior medial, superior lateral, and inferior lateral quadrants of the TA contained 11.96%, 2.17%, and 0%, respectively, of the total muscle spindles. Within the superior medial quadrant, most of the muscle spindles were localized in the most superficial part of the muscle. The results of this study demonstrate that the majority of TA muscle spindles are concentrated in its superior medial quadrant, an area we have termed the superior vocalis subcompartment (SC). This finding suggests that the superior vocalis SC is functionally distinct from the remainder of the TA. It is hypothesized that tension in the superior vocalis SC can be controlled independently from the remainder of the TA, and this capability is used to effect the biomechanics of vocal fold vibration during phonation.
Assuntos
Músculos Laríngeos/anatomia & histologia , Músculos Laríngeos/fisiologia , Fusos Musculares/anatomia & histologia , Prega Vocal/anatomia & histologia , Prega Vocal/fisiologia , HumanosRESUMO
The objective of this study was to determine whether botulinum toxin types A and D reduced the production of saliva from the submandibular glands of 18 dogs. The left submandibular glands of 8 dogs were injected with increasing doses of botulinum type A toxin (range 10 to 70 units), and the left glands of 10 dogs were injected with botulinum type D toxin (50 or 100 units). The right gland of each dog was injected with equivalent volumes of saline solution to serve as control. Six days after the injection, the lingual nerve was electrically stimulated for 10 minutes (3 mAmp, 20 Hz). The resulting volume of saliva was collected and weighed. Overall, the glands injected with types A or D toxin produced significantly less saliva than comparable glands injected with saline solution. Six of 8 dogs injected with type A toxin showed a significant decrease in saliva production (range 10.1% to 19.2%, one-sided p value = 0.0375) when compared with the controls. Nine of 10 dogs injected with type D toxin demonstrated a highly significant reduction in saliva production (total average decrease = 60%, two-sided pvalue = 0.001) when compared with the controls. We concluded that intraglandular injections of botulinum toxin types A and D significantly reduced the production of saliva from canine submandibular glands. The potential applications of intraglandular injections of botulinum toxin are discussed.
Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Toxinas Botulínicas/farmacologia , Antagonistas Colinérgicos/farmacologia , Salivação/efeitos dos fármacos , Glândula Submandibular/efeitos dos fármacos , Animais , Betanecol/farmacologia , Cães , Relação Dose-Resposta a Droga , Estimulação Elétrica , Injeções , MasculinoRESUMO
OBJECTIVES: To evaluate the complications of head and neck reconstruction using microvascular free tissue transfers (MFTTs) performed in an elderly population and to determine whether these complications are more common than in a younger population. SETTING: Tertiary referral center. PATIENTS AND DESIGN: Retrospective, consecutive chart review of patients older than 70 years who underwent MFTT in the past 5 years (group 1). The complications in this population were compared with those in a second group (group 2) of consecutive patients younger than 70 years who were matched according to the site of the primary tumor. MAIN OUTCOME MEASURES: Surgical and medical complications. RESULTS: The median age for group 1 was 74 years and for group 2, 55 years. The overall complication rate for group 1 was 48%, compared with 57% for group 2. In group 1, surgical morbidity was less common and medical morbidity was more common than in group 2. Mortality rate was 6% for group 1 and 0% for group 2. The types of complications were similar for both groups. There was no difference in complication rates when complications were classified by site of the defect, patient status determined by American Society of Anesthesiologists classification, or use of preoperative radiation. The overall success rate of MFTT was 100% for group 1 and 94% for group 2. CONCLUSIONS: Microvascular free tissue transfers for head and neck reconstruction can be safely performed in the elderly. An age older than 70 years does not increase the rate of surgical complications following head and neck reconstruction with MFTT. Medical complications, however, are more common and are equally divided between bronchopulmonary and cardiovascular effects.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Microcirurgia/métodos , Neoplasias Otorrinolaringológicas/cirurgia , Complicações Pós-Operatórias/etiologia , Retalhos Cirúrgicos/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Feminino , Seguimentos , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Otorrinolaringológicas/patologia , Complicações Pós-Operatórias/mortalidade , Fluxo Sanguíneo Regional/fisiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To review the experience of 1 microvascular surgeon during an 11-year period in performing 210 vascularized bone-containing free flaps for oromandibular reconstruction. DESIGN: Retrospective medical records review of patients who underwent primary and secondary oromandibular reconstruction with the use of vascularized bone free flaps. SETTING: Academic medical center. PATIENTS: A total of 201 patients underwent 210 composite free-flap reconstructions of the mandible for various disorders and with a range of bony and soft tissue defects. INTERVENTION: All patients underwent the microvascular transfer of vascularized bone flaps from the ilium, fibula, or scapula. In selected cases, 2 simultaneous free flaps were transferred to achieve an optimal bone and soft tissue reconstruction. Endosteal dental implants were used in 81 patients, with a total of 360 fixtures placed during these 11 years. MAIN OUTCOME MEASURES: The success of microvascular free tissue transfer, dental implant extrusion, and short- and long-term complications at the recipient and donor sites. RESULTS: Of the 210 mandibular reconstructions that were performed, 202 were successful in reestablishing mandibular continuity. Reexploration for vascular-related complications was done in 16 patients, 8 of whom were successfully treated, yielding an overall success rate of 96%. The overall success rate for endosteal dental implants was 92%. The implant success rate was 86% when the bone in which the fixtures were placed was irradiated postoperatively. The success rate was 64% in the 14 fixtures that were placed into previously irradiated bone. CONCLUSIONS: The success of the use of vascularized bone free flaps in restoring continuity to the mandible is clearly demonstrated in this series. There was an acceptable incidence of donor- and recipient-site complications that resulted in minimal long-term morbidity. The careful selection of a donor site(s) for oromandibular reconstruction allows for an optimal restoration of bony and soft tissue defects. Dental implants can be safely used in oromandibular reconstruction with a high level of success. Placing these implants during the initial surgery shortens the duration for achieving dental rehabilitation and enhances the success of the implants when postoperative radiotherapy is administered.