RESUMO
The purpose of this study was to evaluate the applica-bility of ultrasound-guided percutaneous biopsy for the diagnosis and differentiation of various pulmonary lesions in a Chinese population. A total of 338 pulmonary lesions were biopsied with 18-gauge cutting needles, guided by ultrasound, and sent for histopathological analy-sis. The ultrasonographic characteristics of these lesions, procedure complications, and histopathological diagnoses were analyzed. Suffi-cient specimen for histopathologic analysis was obtained in 95.64% (351/367), and mild complications occurred in 2.72% (10/367) of the patients. Accurate diagnosis was obtained in 94.03% (315/335) of the patients; 16 were lost to follow-up. Using the combination of shape and echogenicity to distinguish benign vs malignant lesions, diagnos-tic sensitivity and specificity were 57.39 and 95.65%, respectively. No significant difference was found between malignant and benign lesions in blood flow signals. Ultrasound-guided core biopsy is valuable for the diagnosis, management, and prognosis of unknown pulmonary lesions. Shape and echogenicity on ultrasonography correlate well with histo-pathology and provide useful information for distinguishing between benign and malignant lesions. On the contrary, color Doppler is of little value for this purpose.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Humanos , Biópsia Guiada por Imagem , Lactente , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Ultrassonografia , Adulto JovemRESUMO
To define the molecular basis of secondary resistance to epidermal growth factor receptor (EGFR)-specific antibodies is crucial to increase clinical benefit in patients. The limited access to posttreatment tumor samples constitutes the major barrier to conduct these studies, representing preclinical experimentation as a useful alternative. Anti-EGFR antibody-based therapy has been reported to mediate tumor regression by interrupting oncogenic signals and, more recently, by inducing antitumor immunological responses. However, resistance models have been focused only on tumor escape associated with EGFR blockade, whereas studies describing immune-associated escape mechanisms have not been reported thus far. To address this idea, we modeled resistance induction in D122 metastasis-bearing C57BL/6 mice treated with 7A7 (an anti-murine EGFR antibody). Similarly to patients receiving EGFR-specific antibodies, 7A7 resistance promotion represents an important drawback to successful therapy. Characterization of primary cultures derived from metastasis in 7A7-treated mice revealed a high frequency of tumor variants resistant to in vivo and in vitro antibody treatment. We showed, for the first time, the convergence of alterations in oncogenic and immunological pathways in 7A7-resistant variants. To identify key molecules behind resistance, seven 7A7-resistant variants were screened. HER3 overexpression and PTEN deficiency leading to hyperactivation of protumoral downstream signaling were found in these variants as a consequence of 7A7-mediated EGFR inhibition. Concomitantly, we found a high percentage of resistant variants carrying abnormalities in the constitutive and/or interferon gamma (IFN-γ)-inducible major histocompatibility complex I (MHC-I) expression. A significant decrease in mRNA levels for MHC-I heavy chains, ß2-microglogulin and antigen processing machinery genes as well as transcriptional alterations in IFN-γ pathway components were identified as the main mechanisms underlying MHC-I expression defects in 7A7-resistant variants. Notably, these defects have not been previously associated with EGFR-specific antibody resistance, providing novel immunological escape mechanisms. This study has strong implications for the development of new combination strategies to overcome anti-EGFR antibodies refractoriness.
Assuntos
Anticorpos Monoclonais/farmacologia , Carcinoma Pulmonar de Lewis/imunologia , Resistencia a Medicamentos Antineoplásicos/imunologia , Receptores ErbB/imunologia , Neoplasias Pulmonares/imunologia , Melanoma Experimental/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Animais , Apoptose , Western Blotting , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Movimento Celular , Proliferação de Células , Feminino , Citometria de Fluxo , Técnicas Imunoenzimáticas , Interferon gama/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Invasividade Neoplásica , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T Citotóxicos/imunologiaRESUMO
Introdução: as ações de promoção da saúde vocal devem atingir a população infantil, adulta e idosa, diante dos riscos que todos apresentam em desenvolver disfonia. Neste sentido, o Projeto Jovem Doutor propõe dinâmicas de capacitação para que adolescentes se tornem aptos a disseminar conhecimentos a respeito de temas em saúde para a comunidade. Objetivo: construir e avaliar o conteúdo de um Cybertutor, compondo um programa de capacitação sobre saúde vocal, seguindo a proposta do Projeto Jovem Doutor. Métodos: O Cybertutor de saúde vocal foi elaborado a partir da literatura científica. Posteriormente avaliado pelo Índice de Facilidade de Leitura de Flesch (IFLF) e por 14 alunos do ensinomédio de duas escolas. Esses alunos participaram do programa de capacitação, que consistiu de duas aulas presenciais, acesso ao cybertutor e oficina. Resultados: Os módulos obtiveram média geral de56,68% (dp±8,15) do IFLF caracterizado como nível Padrão. Quanto à avaliação subjetiva, 89,61% dos alunos classificaram a qualidade do cybertutor como excelente/satisfatório, sendo que os itens qualidadedas figuras e organização do conteúdo foram classifi cados como excelente/satisfatório em 100% da amostra. Completadas as atividades, os alunos receberam um jaleco e certificado, intitulando-os de Jovens Doutores, havendo disseminado o conhecimento adquirido para 1300 pessoas da comunidade. Conclusão: a construção e avaliação do cybertutor em saúde vocal expressou a linguagem no nível Padrão e alta satisfação dos alunos. O programa possibilitou a transmissão das informações sobre saúde vocal a um número expressivo de pessoas da comunidade pela ação intensa dos ?Jovens Doutores?...
Introduction: activities of vocal health promotion must reach the young, adult and elderly populations due to risks that everyone presents in the development of Dysphonia. In this purpose, the Young DoctorProject proposes dynamics of training to turn adolescents capable of disseminating, to the community, knowledge about health themes. Objective: to create and evaluate the content of a Cybertutor, composinga training program about vocal health, following the Young Doctor proposal. Methods: the cybertutor on vocal health was developed from the scientific literature. Subsequently, was evaluated by the Flesch Reading Facility Index (FRFI) and by 14 students of high school of two different schools. Those students participated of a training program, consisting in two classroom lectures, cybertutor access and workshop. Results: the modules obtained overall average of 56.68% (sd±8,15) of the FRFI featured as Standard level. Concerning the subjective assessment, 89.61% of students classifi ed the cybertutor quality as excellent/satisfactory, regarding that the items ?figures quality? and ?content organization? were classified as excellent/satisfactory in 100% of sample. In the end of the activities, the students received a white coat and a certificate were, named Young Doctors, disseminating the acquired knowledge to 1300 community people. Conclusion: the creation and evaluation of the cybertutor on vocal health expressed language in the Standard level and high satisfaction of students. The program enabled the communication of information about vocal health to an expressive number of community people by the intense action of the ?Young Doctors?...
Introducción: las acciones de promoción de la salud vocal deben ser llevadas a la población infantil, adulta y anciana delante de los riesgos que todos presentan para desarrolar disfonía. En este sentido, el Proyecto Joven Doctor propone dinámicas de capacitación para que adolescentes se vuelvan aptos para difundir el conocimiento sobre temas de salud para la comunidad. Objetivo: construir y evaluar el contenido de un Cybertutor, componiendo un programa de capacitación sobre la salud vocal, siguiendola propuesta del Proyecto Joven Doctor. Métodos: el Cybertutor de la salud vocal fue elaborado a partir de la literatura científica. Posteriormente evaluado por el Índice de Facilidad de Lectura Flesch (IFLF) y por 14 estudiantes de enseñanza media de dos escuelas. Estos estudiantes participaron del programa de capacitación que fue compuesto por dos clases, acceso al Cybertutor y un taller. Resultados: Los módulos obtuvieron media general de 56,68% (dp±8,15) del IFLF caracterizado como nivel Patrón. En la evaluación subjetiva, 89,61% de los estudiantes calificaron la calidad del Cybertutor como excelente/ satisfactorio, y la calidad de las figuras y organización del contenido se clasifican como excelente/ satisfactorio en 100% de la muestra. Terminadas las actividades, los estudiantes recibieron un guardapolvo y certificado, dándole el título Jóvenes Doctores, que difundieron los conocimientos adquiridos para 1300 personas de la comunidad. Conclusión: La construcción y evaluación del Cybertutor en la salud vocal expreso el lenguaje en el nivel Patrón y alta satisfacción de los alumnos. El programa permitió la transmisión de informaciones sobre la salud vocal para un número significativo de personas de la comunidad por la intensa acción de los ?Jóvenes Doctores?...
Assuntos
Humanos , Educação a Distância , Tecnologia da Informação , Telemedicina , Distúrbios da VozRESUMO
Introdução: as ações de promoção da saúde vocal devem atingir a população infantil, adulta e idosa, diante dos riscos que todos apresentam em desenvolver disfonia. Neste sentido, o Projeto Jovem Doutor propõe dinâmicas de capacitação para que adolescentes se tornem aptos a disseminar conhecimentos a respeito de temas em saúde para a comunidade. Objetivo: construir e avaliar o conteúdo de um Cybertutor, compondo um programa de capacitação sobre saúde vocal, seguindo a proposta do Projeto Jovem Doutor. Métodos: O Cybertutor de saúde vocal foi elaborado a partir da literatura científica. Posteriormente avaliado pelo Índice de Facilidade de Leitura de Flesch (IFLF) e por 14 alunos do ensinomédio de duas escolas. Esses alunos participaram do programa de capacitação, que consistiu de duas aulas presenciais, acesso ao cybertutor e oficina. Resultados: Os módulos obtiveram média geral de56,68% (dp±8,15) do IFLF caracterizado como nível Padrão. Quanto à avaliação subjetiva, 89,61% dos alunos classificaram a qualidade do cybertutor como excelente/satisfatório, sendo que os itens qualidadedas figuras e organização do conteúdo foram classifi cados como excelente/satisfatório em 100% da amostra. Completadas as atividades, os alunos receberam um jaleco e certificado, intitulando-os de Jovens Doutores, havendo disseminado o conhecimento adquirido para 1300 pessoas da comunidade. Conclusão: a construção e avaliação do cybertutor em saúde vocal expressou a linguagem no nível Padrão e alta satisfação dos alunos. O programa possibilitou a transmissão das informações sobre saúde vocal a um número expressivo de pessoas da comunidade pela ação intensa dos ?Jovens Doutores?.(AU)
Introduction: activities of vocal health promotion must reach the young, adult and elderly populations due to risks that everyone presents in the development of Dysphonia. In this purpose, the Young DoctorProject proposes dynamics of training to turn adolescents capable of disseminating, to the community, knowledge about health themes. Objective: to create and evaluate the content of a Cybertutor, composinga training program about vocal health, following the Young Doctor proposal. Methods: the cybertutor on vocal health was developed from the scientific literature. Subsequently, was evaluated by the Flesch Reading Facility Index (FRFI) and by 14 students of high school of two different schools. Those students participated of a training program, consisting in two classroom lectures, cybertutor access and workshop. Results: the modules obtained overall average of 56.68% (sd±8,15) of the FRFI featured as Standard level. Concerning the subjective assessment, 89.61% of students classifi ed the cybertutor quality as excellent/satisfactory, regarding that the items ?figures quality? and ?content organization? were classified as excellent/satisfactory in 100% of sample. In the end of the activities, the students received a white coat and a certificate were, named Young Doctors, disseminating the acquired knowledge to 1300 community people. Conclusion: the creation and evaluation of the cybertutor on vocal health expressed language in the Standard level and high satisfaction of students. The program enabled the communication of information about vocal health to an expressive number of community people by the intense action of the ?Young Doctors?.(AU)
Introducción: las acciones de promoción de la salud vocal deben ser llevadas a la población infantil, adulta y anciana delante de los riesgos que todos presentan para desarrolar disfonía. En este sentido, el Proyecto Joven Doctor propone dinámicas de capacitación para que adolescentes se vuelvan aptos para difundir el conocimiento sobre temas de salud para la comunidad. Objetivo: construir y evaluar el contenido de un Cybertutor, componiendo un programa de capacitación sobre la salud vocal, siguiendola propuesta del Proyecto Joven Doctor. Métodos: el Cybertutor de la salud vocal fue elaborado a partir de la literatura científica. Posteriormente evaluado por el Índice de Facilidad de Lectura Flesch (IFLF) y por 14 estudiantes de enseñanza media de dos escuelas. Estos estudiantes participaron del programa de capacitación que fue compuesto por dos clases, acceso al Cybertutor y un taller. Resultados: Los módulos obtuvieron media general de 56,68% (dp±8,15) del IFLF caracterizado como nivel Patrón. En la evaluación subjetiva, 89,61% de los estudiantes calificaron la calidad del Cybertutor como excelente/ satisfactorio, y la calidad de las figuras y organización del contenido se clasifican como excelente/ satisfactorio en 100% de la muestra. Terminadas las actividades, los estudiantes recibieron un guardapolvo y certificado, dándole el título Jóvenes Doctores, que difundieron los conocimientos adquiridos para 1300 personas de la comunidad. Conclusión: La construcción y evaluación del Cybertutor en la salud vocal expreso el lenguaje en el nivel Patrón y alta satisfacción de los alumnos. El programa permitió la transmisión de informaciones sobre la salud vocal para un número significativo de personas de la comunidad por la intensa acción de los ?Jóvenes Doctores?.(AU)
Assuntos
Humanos , Telemedicina , Distúrbios da Voz , Educação a Distância , Tecnologia da InformaçãoRESUMO
The microbiology laboratory provides a strategic support for infectious disease diagnosis and also alerts the medical community about bacterial resistance to antibiotics. The microbiologists' training is a challenge in Brazil, a country with an extensive territory, a diverse population, and disparity of resource allocation. The aim of this study was to implement an interactive tele-educational course in clinical microbiology to reach distant laboratory workers and to improve their professional skills. The course scientific content was defined according to competences associated, distributed in 560 h, with laboratory practices (knowledge matrix-contextual education). The 11-module course structure comprised 70% distance learning, 22% on campus (integrated modules), and 8% monographs. The group included 7 physicians and 21 microbiologists from 20 different Brazilian cities. The time flexibility and location were the two main reasons for student participation, thus decreasing absences to the workplace, different from the traditional teaching methodologies. The group performance was measured by monthly evaluations, and 1 year postcourse, the researcher visited their workplace. There was significant improvement in microbiological practices performed before compared with after group participation. Therefore, 76.9% of laboratory practices were modified because of the knowledge acquired in the course. Students showed behavioral changes in relation to performance in infection control as well as on the dissemination of their knowledge. This specialization course using distance education did not compromise the quality. This educational methodology represents an alternative to teach clinical microbiology to laboratory workers from remote hospitals, as a nationwide continuing educational strategy.
Assuntos
Educação a Distância/métodos , Pessoal de Laboratório Médico/educação , Microbiologia/educação , Telemedicina , Brasil , Currículo , Médicos , Avaliação de Programas e Projetos de Saúde , População Rural , Universidades , Interface Usuário-ComputadorRESUMO
We established a Website which allowed clinical dermatology cases to be submitted, with digital images, through a simple online form. The case could then be managed within the public health service. A database containing 6000 drug interactions was also available on the Website to help clinical management. The Website was tested by 10 junior doctors, who examined dermatology patients, filled in the electronic form with their clinical observations and descriptions, and forwarded digital images. Five dermatologists then evaluated the 71 cases stored on the Website. The agreement between the virtual evaluation and the definitive diagnosis (on face-to-face examination) was 95%. The Website could be used in national health strategies, as a tool for promoting voluntary medical attendance, and for multicentre epidemiological surveillance.
Assuntos
Dermatologia/normas , Internet/normas , Consulta Remota/normas , Dermatopatias/diagnóstico , Bases de Dados como Assunto/normas , HumanosRESUMO
A Web-based educational model, called JUTE, was developed for the early diagnosis of melanoma. It was compared with a control Website composed of information available on the Internet for teaching undergraduate medical students. The JUTE model was designed to allow the student linear navigation of the main topics that were assumed to be important in learning to make a diagnosis. The rate of success in correctly deciding to refer pigmented lesions to a dermatologist was compared among 34 new medical students who were randomly divided into two groups. There was no significant difference between the JUTE and control groups in the pre-test. When comparing the pre- and post-tests, the number of correct decisions increased significantly only in the JUTE group. In the JUTE group there was a slight but significant improvement when comparing decisions about thin melanoma before and after the training. The educational approach chosen for the JUTE Website appears to be useful for teaching the early recognition of melanoma and could be used for larger educational campaigns of skin cancer prevention.
Assuntos
Instrução por Computador/métodos , Educação de Graduação em Medicina/métodos , Educação em Saúde/métodos , Melanoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Instrução por Computador/normas , Educação de Graduação em Medicina/normas , Humanos , Internet , Modelos Educacionais , Estatísticas não ParamétricasRESUMO
The development of a Web site to enable nonmedical health professionals to screen skin potentially malignant skin lesions is described. A nurse assistant and a dermatologist tested the Web site. An electronic clinical form was developed to allow a nurse assistant to send case reports and photographs for remote diagnosis by a dermatologist. The nurse assistant photographed the lesions of 92 patients who presented some kind of dermatological condition. The images were then sent for evaluation by the dermatologist followed by in person examination by the same physician. The diagnoses, which resulted from the examination in person and, in some cases, the biopsy results, were compared with the diagnostic impressions of the nurse assistant and with the diagnostic hypothesis of the dermatologist at a distance. The lesions were classified as either malignant or nonmalignant. Kappa statistics showed a high association between the suspected malignity and nonmalignity of the lesions between the dermatologist (p = 6.01 x 10(-9)) and the nurse assistant and between the diagnosis at distance and in person (p < 1.0 x 10(-14)). The Web site allowed a nurse assistant to screen for potentially malignant skin lesions and, thus, proved to be appropriate for a large-scale test.
Assuntos
Pessoal Técnico de Saúde/educação , Dermatologia/educação , Internet , Neoplasias Cutâneas/diagnóstico , Telemedicina/métodos , Pessoal Técnico de Saúde/organização & administração , Humanos , Assistentes de Enfermagem/educaçãoRESUMO
The quality of Brazilian health services, including clinical microbiology laboratories, varies enormously. We established a Website to provide different professionals with up-to-date information and to create a virtual Brazilian microbiology community. The Website became operational in February 2000 and had 198,976 hits in the subsequent 20 months. There were 1031 user registrations in its virtual community. Different microbiology topics were discussed and three virtual training courses (representing about 300 printed pages of information) were given. The e-learning centre and the Brazilian virtual community created by this Website have facilitated distance learning, and have encouraged professional integration within Brazilian clinical microbiology.
Assuntos
Internet , Microbiologia/organização & administração , Interface Usuário-Computador , Brasil , Educação a Distância/métodos , Humanos , Serviços de Informação/organização & administraçãoRESUMO
We have explored in detail the determinants of specificity for the hydrolysis by human tissue kallikrein (hK1) of substrates containing the Phe-Phe amino acid pair, after which hK1 cleaves kallistatin (human kallikrein-binding protein), a specific serpin for this protease, as well as somatostatin 1-14. Internally quenched fluorogenic peptides were synthesized with the general structure Abz-peptidyl-EDDnp [Abz, o-aminobenzoic acid; EDDnp, N-(2, 4-dinitrophenyl)ethylenediamine], based on the natural reactive-centre loop sequence of kallistatin from P9 to P'13, and the kinetic parameters of their hydrolysis by hK1 were determined. All these peptides were cleaved after the Phe-Phe pair. For comparison, we have also examined peptides containing the reactive-centre loop sequences of human protein-C inhibitor (PCI) and rat kallikrein-binding protein, which were hydrolysed after Phe-Arg and Leu-Lys bonds, respectively. Hybrid peptides containing kallistatin-PCI sequences showed that the efficiency of hK1 activity on the peptides containing kallistatin and PCI sequences depended on both the nature of the P1 amino acid as well as on residues at the P- and P'-sides. Moreover, we have made systematic modifications on the hydrophobic pair Phe-Phe, and on Lys and Ile at the P3 and P4 positions according to the peptide substrate, Abz-AIKFFSRQ-EDDnp. All together, we concluded that tissue kallikrein was very effective on short substrates that are cleaved after the Phe-Arg pair; however, hydrolysis after Phe-Phe or other hydrophobic pairs of amino acids was more restrictive, requiring additional enzyme-substrate interaction and/or particular substrate conformations.