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1.
Sci Transl Med ; 13(616): eabj7843, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34669442

RESUMO

In 1967, two toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (FIRSV) in the United States died from enhanced RSV disease (ERD), a severe form of illness resulting from aberrant priming of the antiviral immune response during vaccination. Up to 80% of immunized children subsequently exposed to wild-type virus were hospitalized. These events hampered RSV vaccine development for decades. Here, we provide a characterization of the clinical, immunopathological, and transcriptional signature of fatal human ERD, outlining evidence for safety evaluation of RSV vaccines and a framework for understanding disease enhancement for pathogens in general.


Assuntos
Doenças Transmissíveis , Infecções por Vírus Respiratório Sincicial , Vacinas contra Vírus Sincicial Respiratório , Pré-Escolar , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios
3.
Pediatr Crit Care Med ; 12(6): 617-21, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21242857

RESUMO

OBJECTIVES: To describe the implementation of an educational program that achieved high compliance with autopsy requests and consents in a pediatric intensive care unit. To evaluate the concordance between clinical diagnoses and autopsy findings and to identify patient characteristics in which postmortem diagnosis elucidated the primary disease process. DESIGN: Retrospective, observational study. SETTING: A pediatric intensive care unit in a tertiary care teaching hospital. PATIENTS: All pediatric intensive care unit patients with autopsy reports from 2000 to 2005. INTERVENTIONS: An educational program and protocol were initiated in 1995-1996 to raise awareness and formalize the process for autopsy request. From 2000 to 2005, data were collected from medical records and pathology department autopsy reports. Premortem and postmortem diagnoses were compared utilizing the modified Goldman's classification. The associations of Goldman's classification with age of patients and length of stay were explored. MEASUREMENTS AND MAIN RESULTS: After the educational program was instituted, an autopsy rate of >50% was attained compared to 20%-30% in previous years (p < .05). From 2000 to 2005, 139 autopsies were performed. In 111 patients (79.8%), complete concordance of premortem and postmortem diagnoses was found; in 22 cases (16%), there was no concordance and in six cases the postmortem studies failed to explain the mechanism of death. Autopsies provided new and pertinent findings in 47.5% of all studies, with histologic information accounting for 58% of them. A relationship between short length of stay and the presence of autopsy findings elucidating the main disease process was found (p < .05). CONCLUSIONS: It is feasible to produce a sustainable increase in the rate of postmortem studies within an organization. Autopsy results added new information to almost half of the patients, particularly those who died soon after admission. A pediatric intensive care unit strategy to increase and maintain compliance with autopsy requests is an important practice with favorable clinical and educational repercussions.


Assuntos
Autopsia , Unidades de Terapia Intensiva Pediátrica , Causas de Morte , Criança , Chile , Erros de Diagnóstico , Hospitais de Ensino , Humanos , Capacitação em Serviço , Auditoria Médica , Patologia Clínica , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Pediatr Dev Pathol ; 13(2): 95-100, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19678719

RESUMO

Diagnosis of cardiac pathology, valvular stenosis, cardiac dilation, and/or cardiac hypertrophy is underestimated if measures of weight, wall thickness, and valve circumference are not obtained. Routine study methodology protocols allow us to obtain values of these measurements for a correct diagnosis of these cardiopathies. The aim of the study is to establish reference values for cardiac measurements in fetuses and to compare them with an international curve of reference. One hundred seventy-one autopsies from week 17 through 41 of gestation were performed on fetuses from the Pathology Unit at the Hospital Barros Luco in Santiago de Chile. Cases with malformations were not considered. Anthropometric and cardiac measurements for each gestational week were taken. A tabulation of data with values (in percentiles) of cardiac weight, valve circumference, and ventricular wall thickness was obtained. Values were similar to an international reference. The curves of values obtained allow for identification of normal parameters of heart weight, valve circumference, and ventricular wall thickness, thereby providing easily accessible data for each gestational week. Abnormal values that fall outside of the curve must be attributed to cardiac fetal pathology.


Assuntos
Coração Fetal/anatomia & histologia , Valvas Cardíacas/anatomia & histologia , Ventrículos do Coração/anatomia & histologia , Coração/anatomia & histologia , Chile , Feto , Idade Gestacional , Humanos , Valores de Referência
5.
J Infect Dis ; 199(8): 1128-38, 2009 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-19278337

RESUMO

Antiviral antibody production during respiratory syncytial virus (RSV) infection in infants is poorly understood. To characterize local B lymphocyte responses, lung tissue and secretions from infants with RSV bronchiolitis were analyzed for innate B cell-stimulating factors and antiviral antibodies. In lung tissues of infants with fatal RSV bronchiolitis, CD20(+) lymphocytes and IgM-positive, IgG-positive, and IgA-positive plasma cells were prominent but CD4(+) T lymphocytes were not. Type I interferon-induced proteins and B cell tropic factors, including B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), were colocalized in infected epithelium. In nasopharyngeal secretions from infants who survived RSV infection, class-switched antiviral and antinucleosomal antibodies were detected at presentation and correlated with BAFF and APRIL levels. Expression of APRIL and antiviral antibodies of IgA and IgM but not IgG isotype predicted better oxygen saturation. We conclude that B lymphocyte-stimulating factors derived from infected epithelium are primary determinants of the mucosal antibody response in infant RSV bronchiolitis.


Assuntos
Anticorpos Antivirais/sangue , Linfócitos B/fisiologia , Imunidade Inata/imunologia , Infecções por Vírus Respiratório Sincicial/imunologia , Transdução de Sinais/imunologia , Anticorpos Antivirais/metabolismo , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/metabolismo , Lactente , Pulmão/imunologia , Pulmão/patologia , Oxigênio/metabolismo , Infecções por Vírus Respiratório Sincicial/patologia , Linfócitos T/fisiologia
6.
J Infect Dis ; 198(12): 1783-93, 2008 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-18980502

RESUMO

Although respiratory syncytial virus (RSV) infection is the most important cause of bronchiolitis in infants, the pathogenesis of RSV disease is poorly described. We studied histopathologic changes in a panel of lung tissue specimens obtained from infants with fatal cases of primary RSV infection. In these tissues, airway occlusion with accumulations of infected, apoptotic cellular debris and serum protein was consistently observed. Similar observations were found after RSV infection in New Zealand black (NZB) mice, which have constitutive deficiencies in macrophage function, but not in BALB/c mice. A deficiency in the number of alveolar macrophages in NZB mice appears to be central to enhanced disease, because depletion of alveolar macrophages in BALB/c mice before RSV exposure resulted in airway occlusion. In mice with insufficient numbers of macrophages, RSV infection yielded an increased viral load and enhanced expression of type I interferon-associated genes at the height of disease. Together, our data suggest that innate, rather than adaptive, immune responses are critical determinants of the severity of RSV bronchiolitis.


Assuntos
Obstrução das Vias Respiratórias/patologia , Obstrução das Vias Respiratórias/virologia , Bronquiolite/complicações , Macrófagos/fisiologia , Infecções por Vírus Respiratório Sincicial/complicações , Animais , Ácido Clodrônico/farmacologia , Humanos , Imunidade Inata , Recém-Nascido , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NZB , Vírus Sincicial Respiratório Humano
7.
J Infect Dis ; 195(8): 1126-36, 2007 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-17357048

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. METHODS: We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. RESULTS: Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. CONCLUSIONS: Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.


Assuntos
Influenza Humana/imunologia , Orthomyxoviridae/patogenicidade , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/patogenicidade , Infecções Respiratórias/imunologia , Antígenos CD/análise , Antígenos Virais/análise , Secreções Corporais/imunologia , Caspase 3/análise , Quimiocinas/análise , Citocinas/análise , Feminino , Granzimas/análise , Humanos , Lactente , Influenza Humana/fisiopatologia , Células Matadoras Naturais/imunologia , Pulmão/patologia , Pulmão/virologia , Masculino , Orthomyxoviridae/imunologia , Vírus Sinciciais Respiratórios/imunologia , Infecções Respiratórias/virologia , Fatores de Tempo
8.
Rev. chil. cardiol ; 25(1): 57-64, ene.-mar. 2006. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-485649

RESUMO

Antecedentes: El ventrículo izquierdo no compactado (VINC) corresponde a una miocardiopatía caracterizada por trabeculaciones prominentes con recesos intertrabeculares en continuidad con la cavidad ventricular. Objetivo: Identificar características clínicas, métodos de diagnóstico, seguimiento y analizar índices fijos y variables de pruebas diagnósticas. Material y método: Ocho niños con diagnóstico de VINC entre octubre de 2001 a diciembre de 2004. Se registraron datos clínicos, electrocardiograma (ECG), ecocardiograma bidimensional Doppler color, en siete resonancias nucleares magnéticas (RNM) y biopsia miocárdica. Seguimiento a la totalidad del grupo. Comparación de proporciones según t de student e índices kappa para análisis de concordancia interobservador y cálculo de índices fijos y variables. Resultados: Edad media de 5,9 años. En 4 pacientes la primera manifestación clínica fue insuficiencia cardíaca, y ECG anormal en 8 niños. En 6 pacientes el compromiso ecocardiográfico fue de ventrículo izquierdo (VI) en forma aislada (p<0.01). La fracción de acortamiento de ventrículo izquierdo (FAVI) media fue de 25 por ciento. El radio no compactado/compactado promedio fue de 2.8, mientras que la localización de las trabeculaciones fueron: pared apical (100 por ciento), pared lateral (75 por ciento) Sensibilidad de un 100 por ciento con valor predictivo positivo de 0.83. En 2 niños la FAVI se recuperó en forma significativa durante el primer año de seguimiento. Un fallecimiento por insuficiencia cardíaca refractaria.Conclusiones: VINC constituye un nuevo tipo de enfermedad miocárdica cuyas manifestaciones clínicas no difieren de las de otra etiología, constituyendo la insuficiencia cardíaca la presentación más frecuente. La ecocardiografía es una buena técnica diagnóstica y presenta un alto grado de acuerdo con la RNM y los hallazgos histológicos.


Background: Isolated non-compactation of left ventricular myocardium is a rare congenital cardiomyopathy resulting from an arrest in normal endomyocardial embryogenesis. The characteristic echocardiographic findings consist of multiple, prominent myocardial trabeculations and deep intertrabecular recesses communicating with the left ventricular cavity. Aim: The purpose of this study was to identify the clinical characteristics and follow up in children with left ventricular no compaction (LVNC) and analyze fixed and variable indexes of different diagnostics test. Methods: Eight children with LVNC from October 2001 to December 2004 were included. Review of Clinical data, electrocardiogram and echocardiography were consigned. In seven patients Magnetic Resonance Imaging was done and myocardial biopsy in six. Proportion comparison with t student test, Kappa index comparison for concordance (acceptable agreement degree of >0.8) and fixed and variable calculation were made. Results: Six patients were male. Median age of presentation was 5.9 years (range 0.3 -11 years). In four patients the first clinical manifestation was heart failure, two in functional capacity III-IV (NYHA). Six patients presented ecocardiographic compromise of the left ventricle only (p< 0.01). Median shortening fraction (SF) at diagnosis was 25 percent (range 15 percent-30 percent) Average no compaction/ compaction ratio was 2.8 (range 2.1-4). Localization of the non compactation in the left ventricle was located at the apical wall (100 percent) and lateral wall (75 percent). In comparison to myocardial biopsy Echocardiography sensitivity was 100 percent with positive predictive value of 0.83. Median follow up was 30.7 months (range 1- 50 months). In two children SF improved during follow up. One patient required the implant of a cardiac defibrillator. One death was due to refractory heart failure. Conclusions: Heart failure was the most frequent presentation of LVNC and the cause of...


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda , Ventrículos do Coração/patologia , Ventrículos do Coração , Disfunção Ventricular Esquerda/diagnóstico , Ecocardiografia Doppler em Cores , Seguimentos , Valor Preditivo dos Testes , Sensibilidade e Especificidade
9.
J Infect Dis ; 191(1): 122-6, 2005 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-15593013

RESUMO

Fresh-frozen lung and tracheal-aspirate specimens obtained from 112 infants who died in Santiago, Chile, during 1998-2000 were analyzed for the presence of Pneumocystis DNA, by use of nested DNA amplification of the large subunit mitochondrial rRNA, and for the presence of viruses, by use of culture and immunofluorescence. Pneumocystis DNA was detected in specimens from 45 (51.7%) of 87 infants who died in the community and from 5 (20%) of 25 infants who died in the hospital (P=.006). Primary infection with Pneumocystis was highly frequent among infants who die unexpectedly in the community. Infection with viruses was more common in infants who died in the hospital.


Assuntos
Imunocompetência , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/epidemiologia , Morte Súbita do Lactente/etiologia , Viroses/epidemiologia , Vírus/isolamento & purificação , DNA Fúngico/análise , DNA Mitocondrial/análise , DNA Ribossômico/análise , Imunofluorescência , Humanos , Lactente , Recém-Nascido , Pulmão/microbiologia , Pulmão/virologia , Pneumocystis carinii/genética , Traqueia/microbiologia , Traqueia/virologia , Vírus/genética , Vírus/crescimento & desenvolvimento
11.
Rev. chil. radiol ; 9(4): 206-210, 2003. ilus
Artigo em Espanhol | LILACS | ID: lil-435668

RESUMO

Se presenta el caso de una escolar, de sexo femenino, de 12 años de edad, con un osteosarcoma convencional de pelvis estadio IV, que evoluciona en forma natural por 11 meses, con compromiso bilateral de las raíces sacras y que se manifiesta clínicamente como paraparesia, vejiga neurogénica y mielitis transversa. El estudio de imágenes tanto anatómico como funcional (TC de tórax y pelvis, RM de pelvis y cintigrama óseo), permitió su correcta estadificación y selección de quimioterapia paliativa. Se analiza el caso desde el punto de vista de las imágenes destacando el aporte de la medicina nuclear.


Assuntos
Humanos , Feminino , Criança , Osso e Ossos , Neoplasias Ósseas/diagnóstico , Osteossarcoma , Região Lombossacral , Região Lombossacral , Tomografia Computadorizada de Emissão , Biópsia , Estadiamento de Neoplasias/métodos , Imageamento por Ressonância Magnética , Medicina Nuclear , Neoplasias Ósseas/patologia , Pelve , Pelve , Radiografia Torácica
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