DEWTON DE MORAES VASCONCELOS

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Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina
LIM/31 - Laboratório de Genética e Hematologia Molecular, Hospital das Clínicas, Faculdade de Medicina

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Autor: MORAES-VASCONCELOS, Dewton de ×

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  • conferenceObject
    Ombination Efficacy of Voriconazole and Amphotericin B in the Experimental Disease In Immunodeficient Mice Caused by Fluconazole-Resistant Cryptococcus Neoformans
    (2012) SILVA, E. G.; SOARES, Maria Cecilia Pereira; MORAES-VASCONCELOS, Dewton de; DIAS, A. L. T.; CHANG, M. R.; RUIZ, L. S.; GAMBALE, Valderez; PRATES, R. A.; RIBEIRO, M. S.; PAULA, Claudete Rodrigues de
    The model of systemic cryptococcosis in BALB/c SCID mice is useful for immunological and therapeutic study of the disease in immunodeficient hosts. They are susceptible to experimental cryptococcosis by C. neoformans var. grubii and useful to evaluate treatment. All the treatments pro-longed the survival compared to the control groups (P < 0.05). Amphotericin B significantly prolonged the survival of the mice compared to all other treatments. The results obtained in this study, based on a significant increase in survival and significant reduction in the burden of yeasts in the lung and brain tissues, found in the groups treated with amphotericin B combined with voriconazole versus the groups treated only with amphotericin B or voriconazole, suggest that this therapy—using amphotericin B (1.5 mg/kg/ day) in association with voriconazole (40.0 mg/kg/day) —could be a promising alternative for the treatment of cryptococcosis, especially when fluconazole proves to be unsatisfactory.
  • article 3 Citação(ões) na Scopus
    Chronic mucocutaneous candidiasis and systemic lupus erythematosus: a new variant of chronic mucocutaneous candidiasis?
    (2012) MORAES-VASCONCELOS, Dewton de; DOMINGUES-FERREIRA, Mauricio; PIERI, Patricia de Campos; DUARTE, Alberto Jose da Silva
    Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to Candida infection of skin, nails, and mucous membranes. Autoimmune endocrinopathies are common in CMC patients, but there are no reports of the involvement of systemic autoimmune disorders. We present here the first case of this kind of association in a patient with an autosomal dominant variant of CMC. The individual had had this disorder since childhood and systemic lupus erythematosus with secondary antiphospholipid syndrome, as well as renal, articular and hepatic manifestations without thymoma.
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    Phenotypic and Genotypic Changes in CVID Patients
    (2012) COLLANIERI, Anna Cristina; SOARES, Maria Cecilia Pereira; ALMEIDA, Lais Pinto de; BEZERRA, Thiago de Almeida; DUARTE, Alberto Jose da Silva; MORAES-VASCONCELOS, Dewton de
    Common variable immunodeficiency (CVID) is a humoral immunodeficiency. In recent years, the discovery of related genes has broadened, including TACI, ICOS, CD19, CD20, CD81 and BAFF-R. We selected 20 CVID patients and 20 controls. We evaluated CD154 in T cells, markers in B cells (CD19, CD20, CD21, CD40, BAFF-R, CD5, CD27, IgM and IgD), PBMC cultures, and sequencing of the TACI, BAFF and BAFF-R genes. The genotyping of TACI showed 5/17 patients presented allelic variants: a non-pathogenic allelic variant in exon 2 (G>A in g19525, c94), a previously described mutation in exon 3 (g23216T>C; c310 T>C; p C104R), one intronic SNP in g23376 A>C, a heterozygous SNP at position g31695 A>T, possibly pathogenic and not previously described in exon 4, and a heterozygous SNP g32491T>C. The genotyping of BAFF showed one previously unpublished heterozygous allelic variant (g336A>G, c69A>G), but predicted to be a non-pathogenic polymorphism. The evaluation of BAFF-R genotype showed an intronic homozygous genetic variant in g1027T>A, between exons 2 and 3, not previously described and predicted as pathogenic, affecting the splice-site of exon 3.
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    Angioedema Due to Acquired C1-Inhibitor Deficiency
    (2012) BEZERRA, Thiago de Almeida; ALMEIDA, Lais Pinto de; PEREIRA, Juliana; DUARTE, Alberto Jose da Silva; MORAES-VASCONCELOS, Dewton de
    Angioedema due to acquired C1-inhibitor deficiency is a rare, life-threatening disease with poorly defined etiology, therapy, and prognosis. It is characterized by increase in vascular permeability (angioedema) of the skin, the gastrointestinal and oro-pharyngo-laryngeal mucosa. The mediator of symptoms is bradykinin, released from HMW kininogen, cleaved by plasma kallikrein, a serine protease controlled by C1-INH. We report one 58 years old female patient with acquired C1-INH deficiency. The age at onset of angioedema was 58 years (May, 2011). C1-INH function and C4 antigen quantitation were below 50% of normal. C1q was also reduced. Associated disease was a B cell follicular non-Hodgkin lymphoma. Autoantibodies inactivating C1-INH are detected in the majority of patients and account for the deficiency. Lymphoproliferative diseases, ranging from benign monoclonal gammopathies to malignant lymphoma, are frequently associated with AAE. Antifibrinolytic agents are more effective than attenuated androgens in long-term prophylaxis. Patients with acquired C1-INH deficiency may be resistant to replacement therapy with C1-INH plasma concentrate.
  • conferenceObject
    Description of ICOS and ICOS-L Mutations in CVID Patients
    (2012) SOARES, Maria Cecilia Pereira; COLLANIERI, Anna Cristina; YASUHARA, Fabiana; DUARTE, Alberto Jose da Silva; MORAES-VASCONCELOS, Dewton de
    Common variable immunodeficiency (CVID) is a humoral immunodeficiency. Recently the discovery of genes related to the cause of CVID has been reported, among them ICOS. ICOS is a co-stimulatory molecule expressed in T cells and interacts with ICOS-L, expressed in B and antigen-presenting cells. We selected 20 CVID and 20 controls. We evaluated CD154 in T cells, surface markers in B cells (CD19, CD20, CD21, CD40, BAFF-R, CD5, CD27, IgM and IgD), PBMC cultures, and sequencing of ICOS and ICOS-L genes. All patients had low Ig levels, recurrent infections and in 30%, autoimmune manifestations. CVID patient may present higher T CD8+ counts, as well as reduced expression of CD27+ in B cells. We found, in ICOS gene, an intronic allele variant in intron 3 (nt 2729G>A), predicted as non-pathogenic, in one patient. Another non-pathogenic allelic variant (nt 11843 A>G) was found in intron 7 in two sisters, homozygous in one and heterozygous in the other. This same genetic variant was found in one patient from another family (homozygous). We found another genetic variant in intron 7 (Nt 11859C>G), not previously described and predicted as pathogenic in two patients of the same family.
  • article 8 Citação(ões) na Scopus
    Primary Immunodeficiencies in a Mesoregion of Sao Paulo, Brazil: Epidemiologic, Clinical, and Geospatial Approach
    (2020) PEREIRA, Denise Helena Boton; PRIMO, Livia Souza; PELIZARI, Giovana; FLORES, Edilson; MORAES-VASCONCELOS, Dewton de; CONDINO-NETO, Antonio; PRESTES-CARNEIRO, Luiz Euribel
    Background: Primary immunodeficiencies (PIDs) are rare genetic disorders leading to immunologic abnormalities that can affect different organs and systems. We determined the epidemiology, clinical, and geospatial characteristics of PID disorders among patients diagnosed over a 5 year period in a reference hospital covering a mesoregion in Sao Paulo, Brazil. Methods: A retrospective analysis of 39 patients with recognizable PIDs according to the criteria of the European Society of Primary Immunodeficiencies were enrolled. Thirty-four patients came from outpatient immunodeficiency clinics and five patients from active search. Demographic, clinical, and immunologic data were collected, and maps were constructed using a geographic information system. Results: The ratio of females to males was 1.4:1, and 48.7% of patients were younger than 17 years of age. The mean age at the onset of symptoms in children was 2.0 years [standard error of the mean (SEM), 1.7 years] and the diagnosis lag was 5.1 years (SEM, 3.1 years); the mean age at diagnosis in adults was 16.3 years (SEM, 11.8 years) and the lag was 10.8 years (SEM, 10.9 years). Antibody deficiency and common variable immunodeficiencies were the most common categories and phenotypes, respectively. The need for intravenous antibiotics and respiratory tract infections were the most prevalent warning signs, with an overall mortality rate of 15.3%. Autoimmune diseases were diagnosed in 56.4% and visceral leishmaniasis in 5.1% of patients. In the active search, 29 patients were investigated and 17.2% were diagnosed; early diagnosis, the involvement of multidisciplinary professionals, and dissemination of knowledge achieved milestone benefits. The distribution of PID networks in Brazil shows great asymmetry between regions and at a regional level; it was shown that the patients lived mainly in Presidente Prudente municipality. Conclusions: The implementation of an immunodeficiency outpatient clinic in a referral hospital covering a mesoregion with a large population has led to the generation of policies and practices to improve the diagnosis, quality of life, and care of patients with PIDs and their families. Furthermore, the search for hospitalized patients with warning signs for PIDs showed great benefits. Inequality in the distribution of PID network centers in Brazil was demonstrated.
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    HLA Class I Deficiency Resembling Wegener's Granulomatosis: Report of Two Cases
    (2012) ALMEIDA, Lais Pinto de; LEITE, Olavo Henrique Munhoz; NICODEMO, Antonio Carlos; ORII, Noemia Mie; DIAS, Alana dos Santos; MORAES-VASCONCELOS, Dewton de
    HLA class I deficiency is a rare immunodeficiency characterized by recurrent respiratory infections and skin ulcers with granuloma. Herein we describe two patients with HLA class I deficiency with skin lesions and sinopulmonary disease. They were initially diagnosed as having WG and treated with immunosuppressive medication, without response. Patient 1: 25-year-old woman with previous diagnosis of TAP-1 deficiency (c2239 G>A, generating a premature stop codon). She had presented multiple ulcers on the legs, 2 episodes of severe pansinusitis, and chronic lung disease. At age 14 she was diagnosed as having WG. Patient 2: 36 year-old woman, with severe sinopulmonary disease leading to a sinuso-facial fistula and destruction of the uvula, besides chronic deep ulcers of her legs. The laboratorial features included negative c-ANCA, low CD8+ T cell counts and reduced expression of MHC class I in mononuclear cells. There are less than 30 MHC class I deficient patients described. The rarity of the syndrome turns our report interesting, in order to improve the knowledge of the disease.
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    Hereditary Angioedema: Report from 62 Cases
    (2012) GRUMACH, Anete Sevciovic; BARROS, Noac Chuffi; DOMINGUES-FERREIRA, Mauricio; ALMEIDA, Lais Pinto de; BEZERRA, Thiago de Almeida; LEVY, Ariel; MADALENA, Cintia Vargas; DUARTE, Alberto Jose da Silva; MORAES-VASCONCELOS, Dewton de
    Hereditary angioedema (HAE) is characterized by deficiency of the C1 esterase inhibitor. This protein controls the activation of complement and also the process of coagulation, fibrinolysis, and bradykinin pathway. It is characterized by attacks of angioedema affecting the subcutaneous tissue, the respiratory and gastrointestinal tracts. The frequency of HAE is estimated in 1 in 10,000 or 50,000 and respiratory involvement is fatal in 25–40% of untreated cases. We collected data of 62 patients followed at the ADEE-3003. There was female predominance (42/62), with wide variation in age (8–70 years), symptom onset in childhood and adolescence in most cases. 17% of patients had at least one episode of edema, the triggers were trauma (13/62), stress (4/62), and menstrual cycle (3/62). Family history was positive in 40/54. Quantitative defect was confirmed in all. Although there are several reports of cases of HAE in other countries, this diagnosis is rarely recognized in our country. Although the sample includes adult patients the first symptoms appear in childhood and adolescence. The family history was crucial in the investigation of immunodeficiency.
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    EVALUATION OF ANTIVIRAL IMMUNITY IN NASAL WASH OF PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY ALONG WITH VIRAL RHINOSINUSITIS.
    (2017) BEZERRA, Thiago de Almeida; MORAES-VASCONCELOS, Dewton de; PONTILLO, Alessandra; DUARTE, Alberto Jose da Silva; MACHADO, Clarisse Martins; VOAS, Lucy Santos Vilas