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2.
Rheumatol Int ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375886

RESUMO

Chronic nonbacterial osteomyelitis (CNO) is a primary autoinflammatory bone disease that presents more frequently in children and is characterized by inflammatory bone lesions in the absence of an infectious etiology. There is little information of this disease in Latin America. The objective of the study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of pediatric CNO patients. The clinical records of 19 patients with CNO diagnosed between 2007 and 2019 at three tertiary centers in Santiago, Chile were reviewed. The median age of onset was 10 years and 47% were female. Median delay in diagnosis was 12 months. All patients had a pattern of recurrent multifocal disease. 37% of patients had positive antinuclear antibodies and 16% HLA-B27 positivity. 21% of patients presented arthritis or other rheumatologic comorbidity, although no association with psoriasis, inflammatory bowel disease (IBD) or palmoplantar pustulosis (PPP) was observed. Eighteen patients received treatment with nonsteroidal anti-inflammatory drugs with partial response. Twelve patients received methotrexate, and half of them received steroids at the same time reaching remission in 50%. Of the five patients who received bisphosphonates, 60% achieved remission. All four patients who received adalimumab had comorbid arthritis and 75% achieved remission. In a series of Chilean children with CNO, all patients presented with multifocal lesions. Comorbid autoimmune diseases including arthritis were frequent, but no association was observed with psoriasis, IBD, or PPP.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31419546

RESUMO

Severe combined immunodeficiency (SCID) represents the most lethal form of primary immunodeficiency, with mortality rates of greater than 90% within the first year of life without treatment. Hematopoietic stem cell transplantation and gene therapy are the only curative treatments available, and the best-known prognostic factors for success are age at diagnosis, age at hematopoietic stem cell transplantation, and the comorbidities that develop in between. There are no evidence-based guidelines for standardized clinical care for patients with SCID during the time between diagnosis and definitive treatment, and we aim to generate a consensus management strategy on the supportive care of patients with SCID. First, we gathered available information about SCID diagnostic and therapeutic guidelines, then we developed a document including diagnostic and therapeutic interventions, and finally we submitted the interventions for expert consensus through a modified Delphi technique. Interventions are grouped in 10 topic domains, including 123 "agreed" and 38 "nonagreed" statements. This document intends to standardize supportive clinical care of patients with SCID from diagnosis to definitive treatment, reduce disease burden, and ultimately improve prognosis, particularly in countries where newborn screening for SCID is not universally available and delayed diagnosis is the rule. Our work intends to provide a tool not only for immunologists but also for primary care physicians and other specialists involved in the care of patients with SCID.

4.
Pediatr Pulmonol ; 54(9): 1466-1473, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270969

RESUMO

OBJECTIVE: To evaluate trends and geographic distribution of infant bronchiolitis hospitalizations in Chile, a country with large variation in solar radiation (SR) and high rates of urban air pollution. METHODS: We performed a nationwide ecological study of bronchiolitis hospitalizations from 2001 to 2014. We investigated the associations of regional SR (a proxy of vitamin D status) and regional fine particulate matter (PM2.5) air pollution with bronchiolitis hospitalizations. We also evaluated the role of sociodemographic factors, including regional poverty, education, indigenous population, and rurality rates. RESULTS: During the study period, 119 479 infants were hospitalized for bronchiolitis in Chile; 59% were boys. The mean bronchiolitis hospitalization rate increased from 29 to 41 per 1000 infants per year (P = .02). There was an inverse correlation between regional SR and incidence of hospital admissions for bronchiolitis (r = -0.52, P = .049), accounting for 27% of these hospitalizations. There was also a significant direct correlation between regional ambient PM2.5 and bronchiolitis hospitalizations (R = 0.68, P = .006), accounting for 42% of the variation in admission rate. High firewood and/or coal residential use for heating, high regional poverty, lower years of education, and high rurality rates were also significantly correlated with bronchiolitis hospitalization rates. None of the environmental or sociodemographic factors evaluated were correlated with regional case fatality rates or length of stay at the hospital. CONCLUSIONS: This ecological study revealed significant associations between regional SR, air pollution, and sociodemographic factors with infant bronchiolitis hospitalizations in Chile, suggesting that these factors play a major role in the incidence and severity of respiratory infections in early childhood.

6.
Microbes Infect ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31128278

RESUMO

H. pylori infection shows an inverse relationship with allergies. Dendritic cells regulate mucosal immune responses including the induction of T regulatory cells which are fundamental in Helicobacter pylori-induced dampening of allergies. In this respect expression of high-affinity IgE receptor (FcεRI) has been associated with a regulatory dendritic cell profile. Therefore we aimed to evaluate possible mechanisms by which H. pylori infection might modify atopy in pediatric patients. Here we show that H. pylori-infected children exhibited both increased expression of FcεRI on peripheral myeloid and plasmacytoid dendritic cells and higher levels of Foxp3 and Latency Associated Peptide on T regulatory cells. Moreover, exposure to H. pylori drove increased FcεRI expression and IL-10 secretion by both pediatric H. pylori-exposed monocyte derived dendritic cells and T cells. Finally, we show a positive correlation between expression of FcεRI in circulating myeloid DCs and total Treg cells, suggesting that in children, H. pylori infection may have a modulating role in atopy, mediated by both altered surface expression of FcεRI on children's DC and an increased T regulatory cell profile.

8.
Exp Dermatol ; 28(3): 308-311, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30624829

RESUMO

Vitamin D (VD) deficiency has been associated with increased incidence and severity of atopic dermatitis (AD), but the mechanisms through which VD may ameliorate AD are unclear. We compared the phenotypic characteristics of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs, respectively) of children with AD vs healthy controls (HC) and evaluated if VD can modulate the allergic phenotype of circulating DCs in AD patients. Although there was no difference in frequency of circulating DCs between groups, among children with AD there was an inverse correlation between SCORAD and circulating total DCs and mDCs. In AD, serum IgE concentration correlated with FcεRI and surface-bound IgE expression on mDCs and pDCs; pDCs expressing FcεRI and IgE were significantly increased compared to HC. Ex vivo, 1,25(OH)2 D3 significantly decreased FcεRI expression on mDCs and surface-bound IgE on mDCs and pDCs. Oral VD supplementation reduced expression of surface-bound IgE on pDCs in children with AD. In summary, VD decreases the allergic phenotype of circulating DCs in children with AD, a potential mechanism for how VD supplementation may improve AD severity. Future studies are needed to further assess the role of VD supplementation as an immunomodulatory therapy for AD.

9.
Rev Chil Pediatr ; 89(5): 630-637, 2018 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-30571806

RESUMO

INTRODUCTION: Food protein-induced allergic proctocolitis (FPIAP) is the most frequent presenta tion of non-IgE mediated food allergy (FA). The diagnosis is made by oral food challenge, however, non-invasive diagnostic tests are not available. In Chile, the fecal occult blood test (FOBT) is fre quently used to confirm FPIAP, however, there are no studies that support this practice. OBJECTIVE: To establish the diagnostic validity of FOBT in the evaluation of infants with FPIAP. PATIENTS AND METHOD: Case-control study with prospective recruitment of infants with rectal bleeding and suspicion of FPIAP, and controls were healthy infants, in whom the FOBT was conducted. All cases underwent an elimination diet, after which the diagnosis of FPIAP was confirmed by oral food cha llenge. RESULTS: 25 cases and 29 controls were included without significant differences in age, gen der, type of delivery, feeding, and maternal age. The cases had higher rates of allergic comorbidities, medication use, and family history of allergy. The FOBT was positive in 84% of cases and in 34% of controls (p < 0.001). The sensitivity of the FOBT for the diagnosis of FPIAP was 84%, specificity was 66%, positive predictive value 68%, and the negative predictive value 83%. The area under the ROC curve was 0.75 (CI 95% 0.61-0.88). CONCLUSIONS: Although the FOBT has an adequate sensitivity to diagnose FPIAP in infants with rectal bleeding, this test had abnormal results in more than a third of healthy infants. Therefore, the routine use of FOBT is not recommended for the diagnosis of FPIAP.


Assuntos
Hipersensibilidade Alimentar/diagnóstico , Hemorragia Gastrointestinal/etiologia , Sangue Oculto , Proctocolite/etiologia , Estudos de Casos e Controles , Feminino , Hipersensibilidade Alimentar/complicações , Humanos , Lactente , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade
10.
Rev Chil Pediatr ; 89(4): 448-453, 2018 Aug.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30571817

RESUMO

BACKGROUND: Food allergy (FA) is an entity of high and growing prevalence, which can be mediated by IgE or cellular immunity. It can have a wide range of symptoms and be triggered by multiple food antigens, which vary in different geographical areas. OBJECTIVES: To describe clinical characteristics of Chilean patients with IgE-mediated FA. PATIENTS AND METHOD: Retrospective review of patients with IgE-mediated FA treated at a tertiary healthcare center in Santiago, Chile, between 2006 and 2016. Demographic characteristics, clinical manifestations, and trigger foods were evaluated. RESULTS: A to tal of 282 patients diagnosed with IgE-mediated FA were included. 89% had FA onset before 18 years of age and most of these before one year of age (median of age: one year; range: one month-55 years). The most common clinical manifestations were hives, angioedema, dyspnea, and vomiting. 40% had symptoms compatible with anaphylaxis. The foods most frequently involved were egg, cow's milk, peanut, shellfish, walnut, tomato, wheat, avocado, fish, and legumes. Egg, cow's milk, and peanut allergies were the most frequent at pediatric age, while seafood allergy was the most frequent among adults. CONCLUSION: Foods causing IgE-mediated FA in Chile were similar to those described in other countries, although the frequency of tomato and avocado allergy, which are unusual in international series, stands out. Anaphylaxis incidence was high, emphasizing the need for epinephrine autoinjec tors in Chile.


Assuntos
Hipersensibilidade Alimentar/diagnóstico , Imunoglobulina E/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Chile/epidemiologia , Feminino , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Int J Dermatol ; 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30471085

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease with frequent hypersensitivity to allergens. However, the role of exposure to indoor allergens on AD severity is unclear. METHODS: Children aged 0-17 years with active AD from central Chile were recruited; disease severity was evaluated with SCORAD and POEM scores. A home environment survey was applied to parents. Bedroom dust samples were collected for all subjects and analyzed by multiplex assay to quantify dust mite (Der p1, Der f1), dog (Can f1), cat (Fel d1), and alternaria alternata (Alt a1) allergens. RESULTS: Twenty-five children aged 3.9 ± 3.8 years were included. Fifty-two percent were female. Mean SCORAD was 29 ± 14 (range 11-61), and mean POEM was 10.7 ± 6.2. No direct association was found between tobacco exposure, pet ownership, aerosol use, visible dust, or home carpets/rugs with SCORAD (all P > 0.05). Dust samples from all homes had Can f1 and Fel d1 allergens, regardless of pet ownership. Homes that had indoor dogs or cats had significantly higher amounts of these allergens (P < 0.001). Forty percent of homes had dust mite allergens, and none had alternaria alternata. Children with AD living in homes with elevated dust mite and animal dander allergen concentrations had higher SCORAD than those from homes with low allergen concentrations (40 ± 13 vs. 26 ± 13, P = 0.025). CONCLUSIONS: High concentrations of indoor allergens may influence AD severity in children. Further studies assessing indoor allergens and allergen sensitization are warranted to fully evaluate the role of indoor allergens on AD.

13.
Rev. chil. pediatr ; 89(5): 630-637, oct. 2018. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-978135

RESUMO

Resumen: Introducción: La proctocolitis alérgica inducida por proteína alimentaria (PCA) es la forma más fre cuente de alergia alimentaria no mediada por IgE. El diagnóstico se realiza por prueba de provocación oral, sin embargo, no existe una prueba diagnóstica no invasiva para su diagnóstico. Frecuentemente en Chile se utiliza la prueba de hemorragia oculta fecal (PHOF) para confirmar PCA, pero no hay estudios que respalden su indicación. Objetivo: Determinar la validez diagnóstica de la PHOF en la evaluación de lactantes con PCA. Pacientes y Método: Estudio de casos y controles con recluta miento prospectivo de lactantes con rectorragia y sospecha de PCA y lactantes sanos, en quienes se realizó una PHOF. Se indicó dieta de exclusión a los casos y luego se confirmó diagnóstico de PCA mediante contraprueba. Resultados: Se incluyó a 25 casos y 29 controles sin diferencias signi ficativas en edad, sexo, tipo de parto, alimentación o edad materna. Los casos presentaron con mayor frecuencia comorbilidades alérgicas, uso de medicamentos y antecedentes familiares de alergia. La PHOF fue positiva en 84% de casos y en 34% de controles (p<0,001). La sensibilidad de la PHOF para diagnosticar PCA fue 84%, especificidad 66%, valor predictivo positivo 68% y valor predictivo nega tivo 83%. El área bajo la curva ROC fue de 0,75 (IC 95% 0,61-0,88). Conclusiones: Si bien la PHOF tiene sensibilidad adecuada para detectar PCA en lactantes con rectorragia, resulta alterada en más de un tercio de lactantes sanos por lo que no se recomienda su uso habitual para el diagnóstico de PCA.


Abstract: Introduction: Food protein-induced allergic proctocolitis (FPIAP) is the most frequent presenta tion of non-IgE mediated food allergy (FA). The diagnosis is made by oral food challenge, however, non-invasive diagnostic tests are not available. In Chile, the fecal occult blood test (FOBT) is fre quently used to confirm FPIAP, however, there are no studies that support this practice. Objective: To establish the diagnostic validity of FOBT in the evaluation of infants with FPIAP. Patients and Method: Case-control study with prospective recruitment of infants with rectal bleeding and suspicion of FPIAP, and controls were healthy infants, in whom the FOBT was conducted. All cases underwent an elimination diet, after which the diagnosis of FPIAP was confirmed by oral food cha llenge. Results: 25 cases and 29 controls were included without significant differences in age, gen der, type of delivery, feeding, and maternal age. The cases had higher rates of allergic comorbidities, medication use, and family history of allergy. The FOBT was positive in 84% of cases and in 34% of controls (p < 0.001). The sensitivity of the FOBT for the diagnosis of FPIAP was 84%, specificity was 66%, positive predictive value 68%, and the negative predictive value 83%. The area under the ROC curve was 0.75 (CI 95% 0.61-0.88). Conclusions: Although the FOBT has an adequate sensitivity to diagnose FPIAP in infants with rectal bleeding, this test had abnormal results in more than a third of healthy infants. Therefore, the routine use of FOBT is not recommended for the diagnosis of FPIAP.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30170123

RESUMO

BACKGROUND: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. OBJECTIVES: We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. METHODS: Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. RESULTS: Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. CONCLUSION: These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.

15.
Clin Immunol ; 197: 40-44, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30145329

RESUMO

B cell activation by Toll-like receptor 9 (TLR9) ligands is dependent on STAT3 and is important for optimal antibody responses to microbial antigens. B cells from patients with common variable immune deficiency (CVID) have impaired proliferation and differentiation in response to the TLR9 ligand CpG, despite normal levels of TLR9 expression. We demonstrate that CpG-driven STAT3 phosphorylation, but not activation of NFκB and p38, is selectively impaired in B cells from CVID patients. These results suggest that defective STAT3 activation contributes to the defective TLR9 and antibody response of B cells in CVID.

16.
Rev. chil. pediatr ; 89(4): 448-453, ago. 2018. tab, graf
Artigo em Espanhol | LILACS-Express | ID: biblio-959545

RESUMO

Resumen: Introducción: La alergia alimentaria (AA) es una entidad de elevada y creciente prevalencia, pudiendo ser mediada por IgE o inmunidad celular. Puede presentar amplia sintomatología y ser gatillada por múltiples antígenos alimentarios, lo que varía en diversas zonas geográficas. Objetivo: Describir las características clínicas de pacientes chilenos con AA IgE-mediada. Pacientes y Método: Revisión retrospectiva de pacientes con AA IgE-mediada atendidos en un centro terciario de salud de Santiago, Chile entre los años 2006 y 2016. Se evaluaron características demográficas, manifestaciones clínicas y alimentos gatillantes. Resultados: Se incluyeron 282 pacientes con diagnóstico de AA IgE-mediada. El 89% debutó con AA antes de los 18 años de edad y de estos, la mayoría antes del año (mediana: 1 año; rango: 1 mes - 55 años). Las manifestaciones clínicas más frecuentes fueron urticaria, angioedema, disnea y vómitos. Un 40% tenía historia compatible con anafilaxia. Los alimentos más frecuentes fueron huevo, leche de vaca, maní, mariscos, nuez, tomate, trigo, palta, pescados y legumbres. Alergia a huevo, leche de vaca y maní fueron más frecuentes en edad pediátrica, mientras que en adultos fueron los mariscos. Conclusiones: Los alimentos causantes de AA IgE-mediada en Chile fueron similares a los descritos en otros países, aunque destaca la elevada frecuencia de alergia a tomate y palta, poco habituales en series internacionales. La incidencia de anafilaxia fue alta, lo que instala la necesidad de contar con autoinyectores de adrenalina a nivel nacional.


Abstract: Background: Food allergy (FA) is an entity of high and growing prevalence, which can be mediated by IgE or cellular immunity. It can have a wide range of symptoms and be triggered by multiple food antigens, which vary in different geographical areas. Objectives: To describe clinical characteristics of Chilean patients with IgE-mediated FA. Patients and Method: Retrospective review of patients with IgE-mediated FA treated at a tertiary healthcare center in Santiago, Chile, between 2006 and 2016. Demographic characteristics, clinical manifestations, and trigger foods were evaluated. Results: A to tal of 282 patients diagnosed with IgE-mediated FA were included. 89% had FA onset before 18 years of age and most of these before one year of age (median of age: one year; range: one month-55 years). The most common clinical manifestations were hives, angioedema, dyspnea, and vomiting. 40% had symptoms compatible with anaphylaxis. The foods most frequently involved were egg, cow's milk, peanut, shellfish, walnut, tomato, wheat, avocado, fish, and legumes. Egg, cow's milk, and peanut allergies were the most frequent at pediatric age, while seafood allergy was the most frequent among adults. Conclusion: Foods causing IgE-mediated FA in Chile were similar to those described in other countries, although the frequency of tomato and avocado allergy, which are unusual in international series, stands out. Anaphylaxis incidence was high, emphasizing the need for epinephrine autoinjec tors in Chile.

17.
An Bras Dermatol ; 93(1): 80-85, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29641703

RESUMO

Orofacial granulomatosis is a nonspecific term that contains a wide variety of granulomatous entities, which share a clinical and histopathological presentation. It manifests as persistent or recurrent orofacial swelling, amongst other findings. Idiopathic orofacial granulomatosis, characterized by an absence of systemic granulomatous disease, is a diagnosis of exclusion. The main differential diagnosis is Crohn's disease. Its pathogenesis is unknown, however, it seems to be immune-mediated. Patch-test sensitivity to multiple allergens is well documented. Currently, therapeutic options consider restrictive diets, topical, intralesional, and systemic agents. First-line therapy is currently a matter of debate. We present a review of the value of diet therapy in this syndrome, along with two illustrative cases.


Assuntos
Granulomatose Orofacial/dietoterapia , Adolescente , Adulto , Granulomatose Orofacial/diagnóstico , Granulomatose Orofacial/patologia , Humanos , Imunoglobulina E/sangue , Masculino , Mucosa Bucal/patologia , Testes Cutâneos , Adulto Jovem
18.
Expert Rev Clin Immunol ; 14(5): 367-378, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29681186

RESUMO

INTRODUCTION: The prevalence of peanut allergy (PA) has increased, affecting approximately 1.1% of children in Western countries. PA causes life-threatening anaphylaxis and frequently persists for life. There are no standardized curative therapies for PA, and avoidance of peanuts remains the main therapeutic option. A better understanding of the pathogenesis of PA is essential to identify new treatment strategies. Intestinal dendritic cells (DCs) are essential in the induction and maintenance of food tolerance because they present dietary allergens to T cells, thereby directing subsequent immune responses. Areas covered: In this review, we discuss the factors related to the acquisition of oral tolerance to peanut proteins. We focus on intestinal DC-related aspects, including the latest advances in the biology of intestinal DC subtypes, effect of tolerance-inducing factors on DCs, effect of dietary components on oral tolerance, and role of DCs in peanut sensitization. Expert commentary: Given the increasing prevalence of PA, difficulty of avoiding peanut products, and the potentially serious accidental reactions, the development of novel therapies for PA is needed. The ability of DCs to trigger tolerance or immunity makes them an interesting target for new treatment strategies against PA.

19.
An. bras. dermatol ; 93(1): 80-85, Jan.-Feb. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-887135

RESUMO

Abstract: Orofacial granulomatosis is a nonspecific term that contains a wide variety of granulomatous entities, which share a clinical and histopathological presentation. It manifests as persistent or recurrent orofacial swelling, amongst other findings. Idiopathic orofacial granulomatosis, characterized by an absence of systemic granulomatous disease, is a diagnosis of exclusion. The main differential diagnosis is Crohn's disease. Its pathogenesis is unknown, however, it seems to be immune-mediated. Patch-test sensitivity to multiple allergens is well documented. Currently, therapeutic options consider restrictive diets, topical, intralesional, and systemic agents. First-line therapy is currently a matter of debate. We present a review of the value of diet therapy in this syndrome, along with two illustrative cases.

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