Maria José Andrada-Serpa

Clinical and demographic features of HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Rio de Janeiro, Brazil.

In Rio de Janeiro (RJ) most cases of paraparesis of obscure origin are associated with the human T‐cell lymphotropic virus type I (HTLV‐I). Thirty‐four consecutive patients with HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) from RJ were evaluated. Most patients came from low socio‐economic levels. There was no difference in terms of gender. The main affected racial group was white. A history of sexually transmitted diseases was a major risk factor for HAM/TSP and a positive serology for syphilis was found in 26.5% of the patients. The major clinical findings were of a spastic paraparesis with generalized brisk tendon jerks and bilateral Babinkis sign. Sensation was abnormal in 25 patients (73.5%) and five (14.7%) had a sensory level. Three patients (8.8%) had optic atrophy. The cerebrospinal fluid showed a lymphocytic pleocytosis with a mean total protein content of 0.4 g/litre, and an increased intrathecal IgG synthesis in 59.4% of patients. HAM/TSP and multiple sclerosis (MS) occur indigenously in RJ and some HAM/TSP cases can be sometimes confused with MS. Therefore we propose that, in places where MS coexist with HAM/TSP, HTLV‐I antibodies should be sought routinely in those MS suspected cases with prominent spastic paraparesis.

Human T Lymphotropic Virus Type 1 (HTLV-1) Proviral Load in Asymptomatic Carriers, HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis, and Other Neurological Abnormalities Associated with HTLV-1 Infection

Recent reports have demonstrated that human T lymphotropic virus type 1 (HTLV-1) is associated with other neurological abnormalities in addition to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been well established that high HTLV-1 proviral loads are associated with the development of HAM/TSP. We now demonstrate, for the first time, to our knowledge, that HTLV-1 proviral loads in patients with other neurological abnormalities are also significantly higher than in asymptomatic HTLV-1 carriers.

Human Papillomavirus and Penile Cancers in Rio de Janeiro, Brazil: HPV Typing and Clinical Features

OBJECTIVE To determine the prevalence of human papillomavirus (HPV) DNA in penile cancers in Rio de Janeiro, Brazil. MATERIALS AND METHODS We studied, prospectively, 80 consecutive cases of patients with penile cancers who underwent surgical treatment at three different Hospitals in Rio de Janeiro between March 1995 and June 2000. Of these patients, 72 were diagnosed with invasive squamous cell carcinoma and 8 patients with verrucous carcinoma. The following parameters were observed: presence or absence of HPV DNA viral type, histological subtypes, clinical stage and overall survival. RESULTS HPV DNA was detected in 75% of patients with invasive carcinomas and in 50% of patients with verrucous carcinomas. High risk HPVs were detected in 15 of 54 (27.8%) patients with HPV positive invasive tumors and in 1 of 4 (25%) patients with HPV positive verrucous tumors. HPV 16 was the most frequent type observed. No correlation was observed between HPV status and histological subtype (p = 0.51) as well as HPV status and stage stratification (p = 0.88). HPV status was also not significantly associated with the presence of regional metastases (p = 0.89). The overall survival was related to the presence of lymph node metastases (p < 0.0001). CONCLUSIONS HPV infection may have contributed to malignant transformation in a large proportion of our penile cancer cases but only inguinal metastasis was a prognostic factor for survival in these patients with penile carcinoma.

Peripheral neuropathy in HTLV-I infected individuals without tropical spastic paraparesis/HTLV-I-associated myelopathy.

Tropical spastic paraparesis/ HTLV-I-associated myelopathy (TSP/HAM) is the classical neurological manifestation of HTLV-I. Only a few studies have described isolated peripheral neuropathy (PN) among HTLV-I infected individuals. 335 infected individuals without TSP/HAM were evaluated for the presence of PN and 45 of them showed evidences of peripheral nervous system involvement. Of these 21 patients had isolated PN, defined by clinical and/or electrophysiological criteria. Sural nerve biopsies revealed inflammatory infiltrates in 2, axonal degeneration in 2 and segmental demyelination in 1. Therefore, peripheral neuropathy can be found as an isolated manifestation of HTLV-I infection. We conclude that HTLV-I infection should be investigated in patients with PN of unknown origin.

Dermatological Findings of Human T Lymphotropic Virus Type 1 (HTLV-I)-Associated Myelopathy/Tropical Spastic Paraparesis

Dermatological findings for patients with human T lymphotropic virus type 1(HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) were investigated and were compared with dermatological findings for a control group. Only xerosis, cutaneous candidiasis, and palmar erythema were significantly associated with HAM/TSP. Histopathological patterns of cutaneous lymphoma were seen in 25% of 32 patients who underwent biopsy, and, thus, the cutaneous alterations in HAM/TSP can be classified into nonspecific lesions, infectious lesions, immune-inflammatory-mediated lesions, and premalignant or malignant lesions.

Tropical spastic paraparesis/HTLV-I-associated myelopathy in Brazil.

Brazil, the largest Latin American country, is highly heterogeneous, both demographically and socioeconomically. The overall human T-cell lymphotropic virus type I (HTLV-I) seroprevalence among blood donors is approximately 0.45%. These rates are highly variable, from 0 to 1.8%. Since 1989, many series of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) cases have appeared in the literature, with high variation in the prevalence of HTLV-I among TSP patients (14.7-57%). The main clinical features of Brazilian TSP/HAM are similar to those in other endemic countries, but sensory signs are more frequent. Recently, the presence of peripheral nerve and muscular involvement has been characterized. The first nationwide study on the disease has been recently completed: it enrolled 163 patients and concluded that TSP/HAM is common in Brazil, mainly in the northeast and southeast regions; it predominates among women and whites; the most important risk factors for infection are sexual promiscuity and blood transfusion; and, although a remarkably uniform disease throughout the country, some statistically significant differences were detected, such as a higher proportion of females over males in the northeast region, a higher proportion of whites the southeast and the south and mulattos in the northeast, and, finally, a high rate of venereal diseases in the southeast region and of intravenous drug use in the south. Brazil seems to be a perfect setting for future epidemiologic, clinical, basic, and therapeutic studies on TSP/HAM.

Inhibitory Effect of Extracts of Brazilian Marine Algae on Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)-Induced Syncytium Formation In Vitro

Extracts from four species of Brazilian marine algae collected from the Rio de Janeiro State coast were screened to determine the inhibitory effect on HTLV-1-induced syncytium formation. Before performing the syncytium inhibition assay the 50% cytotoxic dose (CyD50) of the algal extracts was evaluated. The antiviral test was carried out in HeLa cells co-cultured with HTLV-I infected T-cell line (C91/PL cells) in the presence of marine algal extracts in the concentration inferior to that corresponding to the CyD50. It was observed that co-cultured cells exposed to Ulva fasciata extract showed 60.2% syncytium inhibition at a concentration of 2.5%. At 5% concentration, Sargassum vulgare and Vidalia obtusiloba extracts presented 78.8 and 76% syncytium inhibition, respectively. The best inhibitory activity was observed with Laminaria abyssalis that presented 100% syncytium inhibition at a concentration of 2.5%. This work shows that extracts of marine algae, mainly L. abyssalis extract, are able to inhibit the cell-to-cell contact essential for the spreading of the virus and could be useful to prevent the infection.

Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil

The aim of the present work was to examine possible genetic risk factors related to the occurrence of cerebrovascular disease (CVD) in Brazilian population, the frequency of β(S)-globin gene haplotypes and co-inheritance with α-thalassemia (-α(3.7kb)) and single nucleotide polymorphism of methylenetetrahydrofolate reductase (MTHFR-C677T), Factor V Leiden (FV-G1691A) and prothrombin (PT-G20210A) genes in children from Rio de Janeiro. Ninety four children with sickle cell anemia (SCA) were included, 24 patients with cerebrovascular involvement and 70 patients without CVD as control group. The mean age of children at the time of the cerebrovascular event was similar to the control group. The frequency of -α(3.7kb) thalassemia was similar in both groups (p=0.751). Children with Bantu/Atypical β(S)-globin gene haplotype presented 15 times more chance (OR=15.4 CI 95% 2.9-81.6) of CVD than the other β(S)-globin gene haplotypes. The C677T polymorphism of MTHFR gene was similar in both groups (p=0.085). No mutation in the FV Leiden or PT genes was found. A large study seems necessary to establish the role of these genetic polymorphisms in Brazilian miscegenated population.

Sickle cell disease: acute clinical manifestations in early childhood and molecular characteristics in a group of children in Rio de Janeiro

Objectives To describe clinical events of sickle cell disease and the correlation with β-globin haplotypes and α-thalassemia in under 6-year-old children. Methods A retrospective study was conducted of under 6-year-old children from the neonatal screening program in Rio de Janeiro. Forty-eight male and 48 female children were enrolled in this study, 79 with sickle cell anemia and 17 with hemoglobin SC. The mean age was 29.9 (standard deviation = 20.9) months, 62 (16.2 ± 8.6) were aged between 0-3 years old and 34 (54.9 ± 11.3) were from 3-6 years old. Painful events, acute splenic sequestration, hemolytic crises, hand-foot and acute chest syndromes and infections were evaluated. Results The events were more frequent in under 3-year-old children, 94% of children had at least one episode. Infection was the most common event affecting 88.5% of children. Acute splenic sequestration took place earlier, while painful crises and acute chest syndromes in under 6-year-old children. Thal-α 3.7 was observed in 20.9% of cases. Bantu was the most frequent haplotype found, followed by Benin. No correlation was observed between clinical events and β-globin haplotypes. Children with sickle cell anemia and α-thalassemia have less infectious events. No correlation was found among these polymorphisms and clinical events, however, the majority of children with Bantu/Bantu and without α-thalassemia had more clinical events.

Mutações no gene TP53 em tumores malignos de mama: associação com fatores de risco e características clínico-patológicas, inclusive risco de óbito, em pacientes residentes no Rio de Janeiro

No Brasil, o câncer de mama e a primeira causa de obito por câncer entre mulheres, sendo o Rio de Janeiro o Estado que apresenta o maior coeficiente de mortalidade do pais. Estudos que avaliam a sobrevida por câncer de mama tem indicado que varios fatores de ordem genetica e molecular podem influenciar a evolucao dos casos. O objetivo deste trabalho foi descrever mutacoes no gene TP53 em 120 pacientes com diagnostico de carcinoma invasivo de mama, recrutadas no Instituto Nacional de Câncer (INCA), Rio de Janeiro, entre 1995 a 1997, e analisar as possiveis associacoes entre fatores de risco e presenca de mutacao e entre caracteristicas do tumor, incluindo estas mutacoes e o risco de obito. A analise molecular detectou 24 mutacoes no gene TP53 em 22 casos (18,3%), sendo que 2 casos apresentaram 2 mutacoes cada e, em um caso observamos o polimorfismo no exon 6. As mutacoes encontradas eram: 14 com troca de sentido; 2 sem sentido; 2 silenciosas; 2 delecoes; 1 insercao e 3 localizadas em intron. Em relacao aos fatores de risco estudados em associacao a presenca de mutacao, observou-se que apenas o consumo de tabaco mostrou associacao negativa (OR ajustado= 0,24 (0,06-0,88)). A analise multivariada utilizada para avaliar as caracteristicas tumorais associadas ao risco de obito mostrou que apenas a agressividade do tumor apresentou OR indicativo de risco (3,98, IC 95% 1,25-12,72). Estes resultados corroboram outros estudos que mostram que a mutacao no gene TP53 pode ser um indicador de tumores de mama biologicamente mais agressivos, apesar de nao ser o unico parâmetro a ser considerado.