Cezar Augusto Muniz Caldas

Zika virus epidemic in Brazil. I. Fatal disease in adults: Clinical and laboratorial aspects

BACKGROUND Zika virus (ZIKV) was first detected in Brazil in May 2015 and the country experienced an explosive epidemic. However, recent studies indicate that the introduction of ZIKV occurred in late 2013. Cases of microcephaly and deaths associated with ZIKV infection were identified in Brazil in November, 2015. OBJECTIVES To determine the etiology of three fatal adult cases. STUDY DESIGN Here we report three fatal adult cases of ZIKV disease. ZIKV infection in these patients was confirmed by cells culture and/or real-time reverse transcriptase polymerase chain reaction (RT-qPCR) and by antigen detection using immunohistochemical assay. Samples of brain and other selected organs taken at autopsy from three patients were also analyzed by histopathological and immunohistological examination. RESULTS The first patient, a 36-year-old man with lupus and receiving prednisone therapy, developed a fulminant ZIKV infection. At autopsy, RT-qPCR of blood and tissues was positive for ZIKV RNA, and the virus was cultured from an organ homogenate. The second patient, a previously healthy female, 16 years of age, presented classic symptoms of Zika fever, but later developed severe thrombocytopenia, anemia and hemorrhagic manifestations and died. A blood sample taken on the seventh day of her illness was positive RT-PCR for ZIKV RNA and research in the serum was positive for antinuclear factor fine speckled (1/640), suggesting Evans syndrome (hemolytic anemia an autoimmune disorder with immune thrombocytopenic purpura) secondary to ZIKV infection. The third patient was a 20-year-old woman hospitalized with fever, pneumonia and hemorrhages, who died on 13days after admission. Histopathological changes were observed in all viscera examined. ZIKV antigens were detected by immunohistochemistry in viscera specimens of patients 1 and 3. These three cases demonstrate other potential complications of ZIKV infection, in addition to microcephaly and Guillain-Barre syndrome (GBS), and they suggest that individuals with immune suppression and/or autoimmune disorders may be at higher risk of developing severe disease, if infected with ZIKV.

The role of environmental factors in the pathogenesis of non-organ-specific autoimmune diseases

The immune system must be able to discriminate between self and non-self. However, mechanisms of doing so sometimes fail, causing the activation and clonal expansion of autoreactive lymphocytes and the development of autoimmune conditions. Although some autoimmune diseases have heritable components, these components are not sufficient to develop an autoimmune condition. A variety of environmental factors have been described as possible triggers of autoimmune diseases, including drugs, infectious agents, smoking, vaccination and adjuvants. The aim of this chapter is to review the most common environmental factors associated with autoimmune diseases.

IL28B gene polymorphisms and Th1/Th2 cytokine levels might be associated with HTLV-associated arthropathy

The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-β (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-β and IFN-γ levels.

Cardiovascular comorbidities in antiphospholipid syndrome.

Antiphospholipid syndrome is an autoimmune disease characterized by venous and/or arterial thrombosis and/or recurrent fetal loss and the presence of antiphospholid antibodies. Among the causes of death of antiphospholipid syndrome there are the myocardial infarction and stroke. Comorbidities could worsen the evolution of these patients, and the knowledge about these situations could prevent or minimizethe risks associated with the disease. In this article, we review the literature about cardiovascular comorbidities, such as traditional risk factors for atherosclerosis, metabolic syndrome and vitamin D deficiency, and how these could influence the prognosis of antiphospholipid syndrome patients.Antiphospholipid syndrome is an autoimmune disease characterized by venous and/or arterial thrombosis and/or recurrent fetal loss and the presence of antiphospholid antibodies. Among the causes of death of antiphospholipid syndrome there are the myocardial infarction and stroke. Comorbidities could worsen the evolution of these patients, and the knowledge about these situations could prevent or minimizethe risks associated with the disease. In this article, we review the literature about cardiovascular comorbidities, such as traditional risk factors for atherosclerosis, metabolic syndrome and vitamin D deficiency, and how these could influence the prognosis of antiphospholipid syndrome patients.

Especialidade médica: escolhas e influências

Objetivou-se identificar as especialidades mais desejadas pelos alunos de Medicina do Centro Universitario do Estado do Para (Cesupa) e fatores determinantes dessa escolha. Trata-se de um estudo transversal, descritivo e analitico, realizado mediante aplicacao de questionarios a alunos do primeiro, quarto e sexto anos, no periodo de novembro de 2012 a marco de 2013. A maioria dos alunos era do sexo masculino (59,2%), com media de idade de 22 ± 2 anos, possuindo renda familiar acima de dez salarios minimos e apresentando pelo menos um parente medico. As principais especialidades escolhidas foram: Cirurgia Plastica (10,4%), Endocrinologia (15,7%), e Oftalmologia (14,0%) no primeiro, quarto e sexto anos, respectivamente. O principal fator influenciador na escolha no primeiro ano foi a influencia dos pais (17,2%), e no quarto e sexto anos o fator financeiro, com 15,8% e 22,8%, respectivamente. Conclui-se que muitos fatores influenciam a escolha de especialidades, sendo necessario buscar formas de atrair alunos para areas de carater mais generalista.

Correlation between clinical symptoms and peripheral immune response in HAM/TSP

HTLV-1 infects principally CD4+ T cells that are the main reservoirs of the virus in vivo, which play an important role in the immunological response. Most of the infected patients are asymptomatic. However, 2-3% of patients will develop HAM/TSP or Adult T lymphoma. HAM/TSP is a chronic inflammatory disease of the central nervous system, which is characterized by unremitting myelopathic symptoms. Studies have shown that cytokines levels alterations (IFN-γ and TNF-α) were associated with tissue injury in HAM/TSP. The aims of this study were to compare the gene expression of IFN-γ, IL-4 and IL-10 of asymptomatic and HAM/TSP HTLV-1 infected patients, and to correlate the gene expression with those of clinical symptoms. 28 subjects were included, 20 asymptomatic HTLV-1 and 8 with HAM/TSP. Spasticity was evaluated using the Modified Ashworth Scale and the degree of walking aid was classified on a progressive scale. The relative gene expression of IFN-γ, IL-4, and IL-10 was measured by Real-Time PCR. Results showed high gene expression of IFN-γ for all patients, but it was higher among HAM/TSP. A significant correlation was observed between IFN-γ gene expression and the degree of walking aid, and IFN-γ gene expression was higher among wheelchair users compared to non-wheelchair users. No association was found with IL-4 and IL-10. These findings indicate that HAM/TSP patients express higher amounts of IFN-γ than asymptomatic patients, and more importantly, the expression of this cytokine was strongly correlated with the need of walking aid.

Relationship between the education level and dermatological lesions in feet of diabetic patients

Background Diabetes mellitus is a heterogeneous group of metabolic disorders that result in hyperglycemia by defects in insulin secretion or action, or both. This disease has a direct association with long-term damage to the body, including vascular disease and peripheral neuropathy, increasing the risk of foot ulcers and amputations. There are several risk factors that contribute to the development of diabetic foot ulcers, such as the duration of the disease, uncontrolled metabolism and the mishandling of the foot. Effective health actions related to education about the disease and, more specifically, on the diabetic foot may avoid or delay diabetic foot ulcers.

Antiphospholipid syndrome and polyarteritis nodosa: a diagnostic and therapeutic challenge.

Antiphospholipid syndrome (APS) can be primary, when it is not associated with another connective tissue disease, or can be secondary, especially associated with systemic lupus erythematosus. In a cohort of 1,000 APS patients, only seven (0.7 %) were associated with systemic vasculitis [1]. In the literature, there are few articles about the association of polyarteritis nodosa with APS comprising a total of 19 cases [2–8]. This study reports two additional cases with this rare condition, APS and polyarteritis nodosa. A 40-year-old Caucasian man was admitted after two epileptic crises. One year before, he reported unintentional weight loss of 47 kg and onset of livedo reticularis. His past medical history included arterial hypertension. Creatinine was 1.3 mg/dl. An arteriography showed multiple small aneurysms in the renal arteries. Antineutrophil cytoplasmic antibody (ANCA) and hepatitis B surface antigen were negative, and hepatitis B core antibody and hepatitis B surface antibody were positive. A diagnosis of polyarteritis nodosa was performed, and he was treated with prednisone 60 mg/day and azathioprine (150 mg/ day). After 5 years, he experienced abrupt ataxia, and magnetic resonance imaging of the brain revealed caudate nucleus and cerebellum infarction. At this occasion, he had positive IgG anticardiolipin ([120GPL) and IgM ([120MPL) antibodies, and aspirin (300 mg/day) was then added to the therapeutical scheme. He experienced complete recovery of this neurological symptom after one month. After 12 weeks, as IgG and IgM anticardiolipin antibodies continued highly positive, APS diagnosis was done. Currently, he is well, asymptomatic, using azathioprine (100 mg/day) and aspirin. The other case is a 43-year-old Caucasian man presented with ulcers on his legs, systemic hypertension and livedo reticularis. Since three years before, he had limb paresthesia in left leg. Electroneuromyography showed mononeuritis multiplex with sensitive and motor nerve fibers involvement in left ulnar nerve, and left posterior tibial and peroneal nerve. The histopathologic features of skin biopsy showed leukocytoclastic vasculitis with perivascular neutrophilic inflammation and necrosis of vessel wall. ANCA was positive. He had a good evolution, with healing of his ulcers. One year later, the patient presented infectious ulcer on hallux, which led to necrosis and amputation. He was treated with antibiotics, prednisone 70 mg/day associated with cyclophosphamide, but these treatments did not demonstrate any efficacy. A new ulcer biopsy was performed and demonstrated leukocytoclastic vasculitis with perivascular neutrophilic inflammation, necrosis of vessel wall and vascular thrombosis. Lupus anticoagulant was positive. APS diagnosis was then performed, and heparin followed by warfarin was started, and he experienced marked improvement of his ulcers. After 12 weeks, lupus anticoagulant continued positive. Nowadays, he is asymptomatic, without ulcers, using azathioprine 75 mg/day and warfarin with INR target of 3–4. C. A. M. Caldas Internal Medicine Department, Centro Universitario do Estado do Para, Universidade Federal do Para, Belem, PA, Brazil

A reumatologia em um curso de medicina com aprendizagem baseada em problemas

ABSTRACT Objective : To present the experience of a Brazilian institution in the learning of Rheumatology at medical school and whose teaching project is structured into active learning methodologies. Me thods : Derived from a descriptive study with a qualitative approach to content related to Rheumatology in the medicine course of CESUPA. Results : The musculoskeletal system is discussed in the second and seventh terms as part of the modules related to the locomotor system and Internal Medicine II, respectively, and each stage and activity has specific minimum objectives. In addition to the theoreti-cal content, in the seventh term the students conduct Rheumatology ambulatory care where the focus is on preparing proper anamnesis and physical examination. During internship the students resume Rheumatology ambulatory care and at this point their diagnostic, investigative and therapeutic skills are the most required. Conclusion : There still is much to evolve in terms of finding an ideal model for teaching Rheumatology. However, by complying with the principal recommendations available for good medicine school teaching practices, we are able to offer future doctors the knowledge, skills and experiences that will potentially support them when treating rheumatology patients.

Data Mining Applied to Diagnose Diseases Caused by Lymphotropic Virus: a Performance Analysis

This paper proposes a new methodology to diagnose the rheumatology manifestations and HTLV-I-Associated Myelopathy/Tropical Spastic Paraparesis, or HAM/TSP, in patients who have Lymphotropic virus of T cells in Humans or HTLV of type I and II. Computational intelligence algorithms are used to classify HTLV patient carriers with or without the presence of rheumatology manifestations and of HAM / TSP. A benchmarking is performed among artificial neural intelligence, naive bayes, Bayesian networks and decision tree to evaluate the most suitable technique for solving this application issue. The obtained results demonstrate the potential of the methodology on the helping non-specialist doctors to classify the patient with the disease suspicion.