Luiz Augusto Marcondes Fonseca

Mortality trends from uterine cervical cancer in the city of São Paulo from 1980 to 1999

Uterine cervical cancer shows a higher incidence in some Brazilian cities. It is a common cause of death in women from developing countries, despite the longstanding availability of an effective screening test, the Pap smear. This study aimed to evaluate the temporal trends of crude, age-adjusted, and age-specific mortality rates from cervical cancer, endometrial cancer, and cancer of the uterus not otherwise specified (NOS) in the city of São Paulo from 1980 to 1999. Results showed a slight reduction in cervical cancer rates, a decrease in NOS uterine cancer rates, and an increase in endometrial cancer mortality rates. The fall in mortality from NOS uterine cancer indicates an improvement in diagnostic accuracy and quality of information on death certificates and may point to an increase in coverage of cervical cancer screening using the Pap smear.

Identification of novel consensus CD4 T-cell epitopes from clade B HIV-1 whole genome that are frequently recognized by HIV-1 infected patients.

Objective:To identify promiscuous and potentially protective human CD4 T-cell epitopes in most conserved regions within the protein-coding genome of HIV-1 clade B consensus sequence. Design:We used the TEPITOPE algorithm to screen the most conserved regions of the whole genome of the HIV-1 subtype B consensus sequence to identify promiscuous human CD4 T-cell epitopes in HIV-1. The actual promiscuity of HLA binding of the 18 selected peptides was assessed by binding assays to nine prevalent HLA-DR molecules. Synthetic peptides were tested with interferon-γ ELISPOT assays on peripheral blood mononuclear cells (PBMC) from 38 HIV-1 infected patients and eight uninfected controls. Results:Most peptides bound to multiple HLA-DR molecules. PBMC from 91% of chronically HIV-1 infected patients recognized at least one of the promiscuous peptides, while none of the healthy controls recognized peptides. All 18 peptides were recognized, and each peptide was recognized by at least 18% of patients; 44% of the patients recognized five or more peptides. This response was not associated to particular HLA-DR alleles. Similar responses were obtained in CD8 T-cell-depleted PBMC. Conclusion:In silico prediction of promiscuous epitopes led to the identification of naturally immunodominant CD4 T-cell epitopes recognized by PBMC from a significant proportion of a genetically heterogeneous patient population exposed to HIV-1. This combination of CD4 T-cell epitopes – 11 of them not described before – may have the potential for inclusion in a vaccine against HIV-1, allowing the immunization of genetically distinct populations.

Qualidade da certificação médica da causa de morte em São Paulo, Brasil

Foi feita analise dos atestados de obito, do preenchimento dos seus itens e da declaracao da causa basica da morte. Foi estudada uma amostra de obitos ocorridos em hospitais e pronto socorros no periodo de 1.o de marco de 1971 a 29 de fevereiro de 1972. Foram colhidas informacoes adicionais, para cada caso, a partir dos prontuarios medicos, o que permitiu conhecer a verdadeira causa basica da morte e comparar com o que foi declarado no atestado. Verificou-se que somente 4,0% dos atestados apresentaram informacoes sobre o intervalo de tempo entre o inicio da doenca e a morte e sobre o exame complementar que confirmou o diagnostico, sendo que 65,5% nao apresentaram ambas as informacoes. O item mais negligenciado foi o referente ao intervalo de tempo, pois em 93,5% dos atestados este item nao se encontrava preenchido; 68,0% dos atestados nao tinha preenchido o item sobre exame complementar que confirmou o diagnostico. Quanto a declaracao da verdadeira causa basica foi verificado que 31,4% dos atestados nao a apresentavam registrada e 6,5%, ainda que a tivessem registrada, nao era selecionada como a causa primaria da morte para finalidades de estatistica de mortalidade. Conclui-se que nao e boa a qualidade dos atestados de obitos na cidade de Sao Paulo, e comparando os resultados com os de estudo semelhante feito em 1962/1963, verifica-se que nao houve melhora na certificacao medica da causa de morte nos ultimos 10 anos.

AIDS Incidence and Mortality in a Hospital-Based Cohort of HIV-1–Seropositive Patients Receiving Highly Active Antiretroviral Therapy in São Paulo, Brazil

Brazilian AIDS and HIV-1-seropositive patients have had free access to highly active antiretroviral therapy (HAART) since November 1996. Although secondary data based on official mortality statistics indicate a sharp decrease in AIDS mortality, few if any studies tried to estimate the prognosis for patients with HIV who have been followed from the beginning of the HAART era. An observational study, with retrospective and prospective components, was done in 233 adult HIV-1-infected subjects who were recruited in the last 10 years at the outpatient sector of the Secondary Immunodeficiencies Clinic of the Department of Dermatology, Hospital das Clinicas da FMUSP, Sao Paulo, Brazil. The definition of AIDS followed the guidelines issued by the Centers for Disease Control (CDC) in 1987. One hundred sixty patients were asymptomatic, 46 had AIDS, 24 had AIDS-related complex, and 3 presented with acute infection at study entry. Twenty-nine (18%) of the asymptomatic subjects developed AIDS during follow-up, with 5 (3%) deaths. Among the 46 AIDS cases at entry, 7 (17%) died during follow-up. Thus, a total of 12 people (5.2%) died of AIDS in this cohort over a mean follow-up of 5.2 years and 24 people were lost to follow-up (10.3%). Ninety percent of the survivors were on combined therapy (82% with 3 or more drugs, and 8% with 2 drugs), while 10% were not taking antiretrovirals. People with AIDS at entry were 5 times more likely to die during this period compared to patients who were asymptomatic at entry (p = 0.006). Women showed better outcomes than men, reflecting differences in CD4+ T-cell counts at study entry. All but 1 patient progressed to AIDS during the pre-HAART era (before 1996). In spite of its recent decline, mortality from AIDS-related conditions remains an important public health issue.

Specific immunotherapy using Hymenoptera venom: systematic review

CONTEXT AND OBJECTIVE The only effective treatment for patients who have severe reactions after Hymenoptera stings is venom immunotherapy. The aim of this study was to review the literature to assess the effects of venom immunotherapy among patients presenting severe reactions after Hymenoptera stings. DESIGN AND SETTING Randomized controlled trials in the worldwide literature were reviewed. The manuscript was produced in the Discipline of Allergy and Clinical Immunology, Universidade de São Paulo (USP). METHODS Randomized controlled trials involving venom immunotherapy versus placebo or only patient follow-up were evaluated. The risk of systemic reactions after specific immunotherapy was evaluated by calculating odds ratios (OR) and their 95% confidence intervals. RESULTS 2,273 abstracts were identified by the keywords search. Only four studies were included in this review. The chi-square test for heterogeneity showed that two studies were homogeneous and could be included in a meta-analysis. By combining the two studies, the odds ratio became significant: 0.29 (0.10-0.87). However, analysis on the severity of the reactions after immunotherapy showed that the benefits may not be so significant because the reactions were mostly similar to or milder than the original reaction. CONCLUSIONS Specific immunotherapy should be recommended for adults and children with moderate to severe reactions, but there is no need to prescribe it for children with skin reactions alone, especially if the exposure is very sporadic. On the other hand, the risk-benefit relation should always be assessed in each case.

CD4+ T-Cell Recovery and Clinical Outcome in HIV-1-Infected Patients Exposed to Multiple Antiretroviral Regimens: Partial Control of Viremia Is Associated with Favorable Outcome

The goal of antiretroviral therapy is clinical benefit through the suppression of viral replication and the immunologic reconstitution of HIV-1-infected patients. In spite of the availability of different highly active antiretroviral therapy only some patients sustain undetectable plasma viremia. We performed an observational study from October 1987 to February 2001 on immunologic and clinical outcome of 148 HIV-1-infected patients from an open clinical cohort at São Paulo University, Brazil. The median T CD4+ at starting first monitored regimen was 227 cells per microliter, with 65% of patients previously exposed to antiretroviral regimens, mostly dual therapy. Virologic response to antiretroviral therapy, after a median period of 179 weeks of monitored treatment, allowed classifying patients as aviremic (RNA plasma viremia below 500 copies per milliliter); viremic (current viral load at historic levels), and viremic-attenuated groups (detectable viremia, but > 1 log viral suppression). HIV RNA viral load, T CD4+ cells count, HIV-1 pol sequencing, inflammatory parameters, and clinical events were documented during a median follow-up of 251 weeks. This study observed better clinical and immunologic responses in the aviremic group, but the viremic-attenuated group showed a significant gain in CD4+ cells (p < 0.013) and a decreased number of cases progressing to an AIDS-defining clinical condition (p < 0.001) compared to the viremic group.

Mortalidade por diabetes mellitus no município de São Paulo (Brasil): evolução em um período de 79 anos (1900-1978) e análise de alguns aspectos sobre associação de causas

The trend of the mortality from diabetes mellitus in the city of S. Paulo, Brazil, is presented through a historical series of 79 years (1900 to 1978). A progressive increase in mortality rates was noted until 1960, when they showed a tendency to become stable around 20 per 100.000 inhabitants. The proportional mortality ratio from diabetes mellitus increased more than the rates. For a given point in the period studied (1974/75), mortality from diabetes mellitus was analysed according to the methodology of the multiple causes of death, which made possible the study of the more frequent underlying causes in diabetics and also of the more important associations of causes. In both cases cardiovascular diseases proved to be the most frequent, especially ischemic heart and cerebrovascular diseases, while arterial hypertension was very important as an associated cause.A evolucao da mortalidade por diabetes mellitus no municipio de Sao Paulo, Brasil, e apresentada atraves de uma serie historica de 79 anos (1900-1978). Dentro desse periodo, verificou-se uma ascensao progressiva dos coeficientes ate por volta de 1960, quando tenderam a estabilizar-se em valores proximos a 20 por 100 mil habitantes. Tambem e analisada a mortalidade proporcional pela doenca, verificando-se que ela aumentou mais que o proprio risco de morrer, medido pelo coeficiente de mortalidade. Para um ponto do periodo estudado (1974/75), a mortalidade por diabetes mellitus foi analisada segundo a metodologia das causas multiplas de morte, o que permitiu verificar quais as causas basicas de morte mais frequentes nos diabeticos e quais as associacoes de causas mais frequentes. Nos dois casos, destacaram-se as doencas do aparelho circulatorio, notadamente a doenca isquemica do coracao, as doencas cerebrovasculares, enquanto a hipertensao arterial se destaca como causa associada bastante frequente.

Education Level Explains Differences in Stroke Incidence among City Districts in Joinville, Brazil: A Three-Year Population-Based Study

Background: Current evidence suggests an inverse association between socioeconomic status and stroke incidence. Our aim was to measure the variation in incidence among different city districts (CD) and their association with socioeconomic variables. Methods: We prospectively ascertained all possible stroke cases occurring in the city of Joinville during the period 2005–2007. We determined the incidence for each of the 38 CD, age-adjusted to the population of Joinville. By linear regression analysis, we correlated incidence data with mean years of education (MYE) and mean income per month (MIPM). Results: Of the 1,734 stroke cases registered, 1,034 were first-ever strokes. In the study period, the crude incidence in Joinville was 69.5 per 100,000 (95% confidence interval, 65.3–73.9). The stroke incidence among CD ranged from 37.5 (22.2–64.6) to 151.0 per 100,000 (69.0–286.6). The stroke incidence was inversely correlated with years of education (r = –0.532; p < 0.001). MYE and MIPM were strongly related (R = 0.958), resulting in exclusion of MIPM by collinearity. Conclusions: Years of education can explain a wide incidence variation among CD. These results may be useful to guide the allocation of resources in primary prevention policies.

Proteína C reativa: aplicações clínicas e propostas para utilização racional

C-reactive protein (CRP) is an acute-phase protein whose requests have been growing exponentially in several countries, including Brazil. In this study, the use of CRP in several clinical situations was reviewed by a group of physicians comprised by specialists in internal medicine, medical emergencies, intensive care, screening, and laboratory medicine, aiming to analyze the applicable literature and to propose guidelines for a more rational use of this laboratory test. The result was the creation of flowcharts guiding CRP request, adjusted to four different healthcare environments, namely, intensive care units, emergency room, wards, and outpatient clinics. These flowcharts, as well as a more detailed discussion on several clinical recommendations for the test, are presented in this study.

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

Background The polymorphisms of IL28B have been described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) are associated with HAM/TSP. Methods The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96–4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82–31.72). Conclusion Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of such finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.