ABSTRACT Background: The establishment of regional development poles in the State of Pernambuco, Brazil was characterized by industrial expansion and consequent concerns about the increase in the occurrence of diseases, specifically those having long latency periods, as is the case of Chronic Myeloid Leukemia. Methods: The study included 367 patients diagnosed with Chronic Myeloid Leukemia over a ten-year period at a reference treatment center. Records of patient charts and the TerraView software were used, respectively, for data collection and geographic mapping of the cases from the twelve established State development regions. Results: A total incidence of 3.4 cases per 100,000 inhabitants was found, with a predominance of the disease among males, a median age of 47 years, a mestizo ethnicity, with elementary schooling and residence in urban area. Microregional incidence varied, but there was no significant variation in numbers over the years, and no relevant socio-environmental determinants were identified. Conclusion: The present study determined the incidence and characterized the spatial distribution of Chronic Myeloid Leukemia cases over a decade in a northeastern Brazilian state. The variation in the incidence rate by region of development is compatible with a homogeneous distribution of the cases. The work is a baseline study to be used for present and future analyses of the impact of the state economic development poles and the occurrence of this chronic malignant disease.

Abstract Objective: To evaluate factors predictive for relapse in a cohort of adult patients with acute promyelocytic leukemia monitored by molecular methods during consolidation and during at least one month of maintenance therapy. Methods: The charts and laboratory data of 65 adult patients with acute promyelocytic leukemia treated according to the International Consortium on Acute Promyelocytic Leukemia 2006 protocol were reviewed. The identification of the promyelocytic leukemia-retinoic acid receptor-alpha gene rearrangement at diagnosis, post-induction, post-consolidation and during maintenance treatment was performed by qualitative and quantitative reverse transcription polymerase chain reaction. Results: Eighty-nine patients were diagnosed with acute promyelocytic leukemia over a seven-year period and of these 65 were eligible for treatment with the protocol. Among the 45 patients who received consolidation and maintenance treatment, six (13%) relapsed, three of whom presented hematologic and three presented molecular relapse. The first relapses occurred at a median of 39 months. Relapsed patients were from all risk groups (low, intermediate and high) and both morphological types (M3 and M3variant) were found. Three of these patients are alive and in molecular remission after salvage treatment. There were no statistically significant differences regarding gender, age, risk group, morphology, promyelocytic leukemia breakpoint cluster region, use of all-trans retinoic acid, development of differentiation syndrome and number of days to complete remission between the patients who relapsed and those who did not. Conclusion: Our results reinforce the importance of prolonged monitoring of acute promyelocytic leukemia patients using molecular methods to detect relapse early.

Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL) rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%). The most common immunophenotype was B lineage (76%). BCR-ABL rearrangements was detected in 14 (34%) patients with the following distribution: p190 (28%), p210 (50%) and double positive (22%). Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44%) and positive BCR-ABL (28%). Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia.

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis.

INTRODUÇÃO: A doença tromboembólica é bastante freqüente, com incidência anual na população de 1 caso por mil indivíduos. Os fatores de risco para trombose incluem condições hereditárias e adquiridas. Uma mutação de ponto no fator II da coagulação, a protrombina G20210A (PTCR), constitui o segundo defeito genético mais comum associado à predisposição para trombose ou trombofilia. No Brasil, o estudo desse fator de risco é relativamente recente e se dispõe de poucos dados na literatura especializada. OBJETIVO: Este trabalho teve como objetivo determinar a freqüência da PTCR em 285 indivíduos sob investigação de trombofilia na Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE/PE). MATERIAL E MÉTODO: A técnica molecular utilizada foi a enzima de restrição/reação em cadeia da polimerase (RE/PCR), com primers específicos e a enzima Hind III. RESULTADOS: A freqüência encontrada da PTCR foi de 6% em heterozigose. A presença da mutação foi semelhante em indivíduos com idades tanto inferiores quanto superiores a 45 anos. DISCUSSÃO: A presença da PTCR pode ter sido determinante para o surgimento dos quadros trombóticos, e a baixa mediana de idade do grupo estudado sugere que outras causas genéticas de trombofilia devem ser investigadas, pois a maioria dos trabalhos associa a presença de fator de risco genético a eventos trombóticos em indivíduos com idade inferior a 45 anos. CONCLUSÕES: Os resultados da pesquisa mostraram que a freqüência da PTCR na população estudada é semelhante à descrita na literatura científica para indivíduos selecionados com tromboembolismo e confirmam a importância do estudo molecular em diferentes faixas etárias.

BACKGROUND: Thromboembolic disease is very common, with a yearly incidence in the general population of approximately 1 case per a thousand individuals. The risk factors for thrombosis include both hereditary and acquired conditions. A point mutation in coagulation factor II, prothrombin G20210A (PTCR), constitutes the second most prevalent genetic defect associated with the predisposition to thrombosis or thrombophilia. In Brazil, the study of this risk factor is relatively recent and there is little available data in medical literature. OBJECTIVE: The aim of this study was to determine the frequency of PTCR in 285 individuals being investigated for thrombophilia at Fundação de Hematologia e Hemoterapia de Pernambuco (HEMOPE/PE). MATERIAL AND METHOD: The molecular biology technique used was restriction enzyme/polymerase chain reaction (RE/PCR), using specific primers and the Hind III enzyme. RESULTS: The frequency of PTCR was 6% in heterozygosis. The presence of the mutation was similar among individuals under and over 45 years old. DISCUSSION: The presence of PTCR may have been a relevant factor for the episodes of thrombosis, and the low median age of the group suggests that other genetic causes of thrombophilia must be investigated inasmuch as most publications associate the presence of genetic risk factor with thrombotic events in individuals under 45 years old. CONCLUSIONS: Our findings showed that the frequency of PTCR in the studied population is similar to the results published in medical literature for selected patients with thromboembolism and they confirm the importance of molecular testing at different age groups.

O gene híbrido PML-RARalfa é o marcador molecular presente na maioria dos casos de leucemia aguda promielocítica (LAP), sendo útil ao diagnóstico e ao estudo da doença residual mínima. A técnica molecular empregada como rotina laboratorial é a reação em cadeia da polimerase com transcrição reversa (RT-PCR) qualitativa, porém com o surgimento da PCR em tempo real (Q-PCR), foram descritas abordagens de detecção do gene PML-RARalfa possibilitando a quantificação de transcritos, com a vantagem metodológica da eliminação do processamento pós-PCR. No entanto, os protocolos relatam o uso de sondas fluorescentes de custo elevado para a rotina clínica, limitando sua aplicação. Este estudo teve como objetivo otimizar o método de detecção do gene PML-RARalfa para Q-PCR, utilizando como sistema de marcação fluorescente o intercalante SYBR® Green. A análise foi realizada com cDNA da linhagem celular NB4, tendo sido testados protocolos de termociclagem, síntese de cDNA com primer randômico ou específico e diferentes concentrações de MgCl2 e primers para amplificação. Os resultados mostraram amplificação mais eficiente nas seguintes condições: 2 mM MgCl2, 10 pmol de primers e cDNA sintetizado com primer específico. Não houve diferença na utilização de etapas para anelamento (58°C/30 s) seguido de extensão (72°C/30 s) ou etapa única de anelamento associado à extensão (60°C/45 s). Esses resultados demonstram a otimização da detecção do gene PML-RARalfa para Q-PCR através de um método considerado sensível e de baixo custo para a rotina laboratorial.

Hybrid gene PML-RARalpha is the molecular target found in most cases of acute promyelocytic leukemia (APL) and has been used for diagnosis and minimal residual disease studies. The standard molecular technique employed is qualitative reverse transcriptase-polymerase chain reaction (RT-PCR), but with the emergence of real time PCR (Q-PCR), PML-RARalpha gene detection approaches have been described allowing transcript detection, with the methodological advantage of eliminating post-PCR processing. However, current protocols report the use of expensive fluorescent labeled probes, limiting its routine application in the laboratory. The objective of this study was to optimize PML-RARalpha gene detection method for Q-PCR, using SYBR® Green fluorescent dye. The analysis was performed with NB4 cellular lineage cDNA. Thermal cycling protocols, cDNA synthesis with random or specific primer and different MgCl2 and amplification primers concentrations were tested. Results show that amplification improved in the following conditions: 2 mM MgCl2, 10 pmol primers and cDNA synthesized with specific primer. There were no significant differences using annealing temperature (58°C/30 s) followed by extension (72°C/30 s) or annealing associated with extension as a single step (60°C/45 s). This paper demonstrates the optimization of PML-RARalpha gene detection for Q-PCR studies using a technique considered sensitive and less expensive for routine use in the laboratory.

A problemática de grupos populacionais expostos a situações de risco que afetam o sistema sangüíneo e a gravidade dos danos causados à saúde faz com que este tema ganhe relevância para a saúde pública. A compreensão do comportamento epidemiológico de doenças hematológicas relacionadas ao ambiente/ocupação é fundamental para a instituição de medidas protetoras da saúde. A informação em epidemiologia depende de dados fidedignos sobre os diversos agravos. Este estudo verificou em prontuários de pacientes de um centro de referência o registro de condições de risco ambiental, em um período de dez anos. As patologias selecionadas foram as mais freqüentemente assistidas e que apresentam na literatura maiores evidências de associação com exposições a riscos químicos e/ou físicos de origem ambiental. As mesmas apresentaram-se com alta letalidade (52% da casuística). Para todas houve um grande sub-registro das situações de nocividade e de outros condicionantes de vulnerabilidade, revelando uma despreocupação dos profissionais de saúde com os aspectos da causalidade, no sentido de orientar a prevenção de novos casos. No momento em que o Ministério da Saúde reconhece a relevância desta problemática mediante recentes normatizações, é fundamental aprimorar o registro de situações de risco e agravos possivelmente relacionados a estes, especialmente nos serviços que podem identificar casos sentinelas, auxiliando, assim, a efetivação da vigilância epidemiológica e da saúde para grupos de expostos.

The problems of population groups exposed to risk situations that affect the blood system and the seriousness of the damages caused to health make this theme highly relevant in public health. The understanding of the epidemiological behavior of hematological diseases related to the environment/occupation is a priority for the implementation of health protective measures. Epidemiological information depends on reliable data on several conditions. This study investigated patient medical records of a reference center, records of environmental risk, covering a period of ten years. The conditions selected were those that were the most frequently seen in this facility and those that presented the strongest evidence of association with occupational/environmental risks in the specialized literature. These conditions presented high lethality (52% of all cases). For all these diseases, there was significant under-recording of potentially harmful situations and conditions of vulnerability, showing a lack of concern by healthcare professionals with the causes and prevention of new cases. The Ministry of Health has recently acknowledged the relevance of this problem as shown in its standardizations. For this reason, it has now become paramount to improve the recording of risk exposures and their related damages, especially in the healthcare services that can identify sentinel cases, so as to help in the implementation of epidemiological and health surveillance for exposed groups.

A problemática de grupos populacionais expostos a situações de risco que afetam o sistema sangüíneo e a gravidade dos danos causados à saúde faz com que este tema ganhe relevância para a saúde pública. A compreensão do comportamento epidemiológico de doenças hematológicas relacionadas ao ambiente/ocupação é fundamental para a instituição de medidas protetoras da saúde. A informação em epidemiologia depende de dados fidedignos sobre os diversos agravos. Este estudo verificou em prontuários de pacientes de um centro de referência o registro de condições de risco ambiental, em um período de dez anos. As patologias selecionadas foram as mais freqüentemente assistidas e que apresentam na literatura maiores evidências de associação com exposições a riscos químicos e/ou físicos de origem ambiental. As mesmas apresentaram-se com alta letalidade (52% da casuística). Para todas houve um grande sub-registro das situações de nocividade e de outros condicionantes de vulnerabilidade, revelando uma despreocupação dos profissionais de saúde com os aspectos da causalidade, no sentido de orientar a prevenção de novos casos. No momento em que o Ministério da Saúde reconhece a relevância desta problemática mediante recentes normatizações, é fundamental aprimorar o registro de situações de risco e agravos possivelmente relacionados a estes, especialmente nos serviços que podem identificar casos sentinelas, auxiliando, assim, a efetivação da vigilância epidemiológica e da saúde para grupos de expostos.

The problems of population groups exposed to risk situations that affect the blood system and the seriousness of the damages caused to health make this theme highly relevant in public health. The understanding of the epidemiological behavior of hematological diseases related to the environment/occupation is a priority for the implementation of health protective measures. Epidemiological information depends on reliable data on several conditions. This study investigated patient medical records of a reference center, records of environmental risk, covering a period of ten years. The conditions selected were those that were the most frequently seen in this facility and those that presented the strongest evidence of association with occupational/environmental risks in the specialized literature. These conditions presented high lethality (52% of all cases). For all these diseases, there was significant under-recording of potentially harmful situations and conditions of vulnerability, showing a lack of concern by healthcare professionals with the causes and prevention of new cases. The Ministry of Health has recently acknowledged the relevance of this problem as shown in its standardizations. For this reason, it has now become paramount to improve the recording of risk exposures and their related damages, especially in the healthcare services that can identify sentinel cases, so as to help in the implementation of epidemiological and health surveillance for exposed groups.

Resumo: Objetivo: caracterizar o desenvolvimento de pesquisas pelos docentes do curso médico da Universidade de Pernambuco (UPE). Material e método: estudo descritivo, censitário, com 246 docentes da Faculdade de Ciências Médicas e do Instituto de Ciências Biológicas. Quatro alunos de iniciação científica utilizaram dois instrumentos para coleta; as questões abertas foram submetidas à análise de conteúdo. Resultados: 74,4% desses docentes eram professores, 47,1% especialistas, 34,5% mestres e 14,2% doutores; 82,5% já realizaram pesquisa, 51,2% com iniciação científica. De janeiro de 1999 a agosto de 2002, 68,3% desenvolveram pesquisa, 48,8% com iniciação científica: 48,3% referiram falta de financiamento como o maior obstáculo: apenas 30,9% tiveram financiamento, sendo o CNPq a principal fonte (42,3%). O interesse científico motivou pesquisas (76,8%), esperavam fazer descobertas científicas (53,0%) e adquirir novos conhecimentos (41,7%). Metade dos projetos divulgou seus resultados, sobretudo em eventos científicos nacionais. Conclusões: é preciso estimular as potencialidades da UPE para que constitua um recanto privilegiado de interação professor-aluno no processo de ensino-aprendizagem-pesquisa.

Abstract: The objective of this article was to characterize the development of research by the medical school faculty of the University of Permmbuco (UPE), Brazi1. This was a descriptive survey with a total of 246 faculty members (professor and instructors), at the School of Medicine and Institute of Biological Science. Four first-year science fellows used two instruments for the suvey. The open questions were submitted to a content analysis. Of the faculty members, 74.4% had professor status, 47.1% were specialists, 34.5% had Master’s degrees, and 14.2% were PhDs; 82,5% had conducted research, 51.2% of whom with science initiation grants. From january 1999 to august 2002, 68.3% conducted rescarch, 48.8%, with Science initiation grants; 48.3% reported lack of funding as the main obstacl to conducting research; only 30.9% received funding with the National Research Council (CNPq) as the main sorce (42.3%). Motivations for the research included scientific interest (76.8%), the expectation of making scientific discoveries (53.0%), and the hope of acquiring new knowledge (41.7%). Half of the projects had their results disseminated, especially at national scientific events. The authors conclude that it is neressary to sstimulate the potentialities at UPE in order for it to become a prime center for faculty-study interaction in the teaching-learning-research.