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Case studies in international tobacco surveillance: cigarette smuggling in Brazil
(Tobacco Control, 2002) Shafey, O; Cokkinides, V; Cavalcante, T M; Teixeira, M; Vianna, C; Thun, M
Objective: This article is the first in a series of international case studies developed by the American Cancer Society to illustrate use of publicly available surveillance data for regional tobacco control. Design: A descriptive analysis of Brazil and Paraguay cigarette production and trade data from offi- cial sources. Methods: Per capita cigarette consumption for Brazil and its neighbour was calculated from 1970 to 1998 using data on production, imports, and exports from NATIONS, the National Tobacco Information Online System. Results: A 63% decrease was observed in the estimate of per capita consumption of cigarettes in Bra- zil between 1986 and 1998 (from 1913 cigarettes per person in 1986 to 714 cigarettes per person in 1998) and a 16-fold increase in Paraguay was observed during the same period (from 678 ciga- rettes per person in 1986 to 10 929 cigarettes per person in 1998). Following Brazil’s 1999 passage of a 150% cigarette export tax, cigarette exports fell 89% and Brazil’s estimated per capita consump- tion rose to 1990 levels (based on preliminary data). Per capita consumption in Paraguay also fell to 1990 levels. Conclusions: These trends coincide with local evidence that large volumes of cigarettes manufactured in Brazil for export to Paraguay are smuggled back and consumed as tax-free contraband in Brazil. It is hoped that this case study will draw wider public attention to the problems that smuggling presents for tobacco control, help identify other countries confronting similar issues, and stimulate effective inter- ventions.
Impact of Carvedilol on QT Interval Dispersion in Patients with Chronic Heart Failure
(Journal of Cardiac Failure, 2003) Albuquerque, Denilson C.; Paola, Angelo A.V. de; Rocha, Ricardo M.; Tura, Bernardo; Albanesi Filho, Francisco M.; Veloso, Henrique H.
Background: The role of QT interval dispersion (QTD) in heart failure (HF) remains poorly defined and controversial. Our objective was to evaluate the impact of QTD in the clinical evolution of chronic HF patients under control due to the use of carvedilol (CVD). Methods: We selected 108 patients (22-82 years), 65.7% were male, 72.2% caucasians, with stable chronic HF and NYHA functional class (FC) II, III and IV on optimized treatment, with an left ventricle ejection fraction (LVEF) of 0.40 for therapy with CVD. All patients had complete history taken and physical exam performed, as well as, laboratorial evaluation, electrocardiogram, echocardiogram and followed-up at the HF clinic for an average period of 38.2 months. All used CVD at the maximum tolerated dose. The evaluated parameters were: general characteristics of the population, cardiopathy etiology, concomitant medication used, NYHA’s FC, maximum CVD dose, LVEF and QTD before and 6 months after CVD and deaths. Results: A QTD reduction (109ms to 72ms) and an increase in the LVEF (0.27 to 0.35) was found after 6 months of therapy with CVD (p 0.001). The general characteristics of the population (p 0.05), concomitant medications (p 0.05), CVD dose (p 0.80), cardiopathy etiology (p 0.959) did not influence in the QTD reduction. This reduction was related to the patients with worse NYHA FC pre-CVD (p 0.007) and with NYHA FC improvement (p 0.028). The ROC curve analysis post-CVD determined that QTD 90ms was a mortality predictor (p 0.034; OR 3.912) (AUC 0.061; sensibility 29.2%; specificity 90.5%; positive likelihood ratio 3.06; negative likelihood ratio 0.78). The multivariate analysis showed that the QTD reduction was an independent survival predictor (p 0.004; OR 5.48). Conclusions: CVD reduced the QTD and increased the LVEF in patients with chronic HF. We did not observe interaction among QTD reduction and population characteristics. The QTD reduction was not influenced by concomitant medications, cardiopathy etiology and CVD dose. The largest QTD reduction occurred specially in worst patients (NYHA FC III and IV). The presence of QTD reduction was an independent predictor of survival and the QTD 90ms post-CVD was predictor of mortality.
Como o ecocardiograma pode ser útil em predizer a morte em crianças com cardiomiopatia dilatada idiopática?
(Arquivos Brasileiros de Cardiologia, 2004) Azevedo, Vitor Manuel Pereira; Albanesi Filho, Francisco Manes; Santos, Marco Aurélio; Castier, Márcia Bueno; Tura, Bernardo Rangel
OBJETIVO: Determinar os fatores preditores ecocardiográficos de morte em crianças com cardiomiopatia dilatada idiopática. MÉTODOS: Estudo retrospectivo de 148 crianças com cardiomiopatia dilatada idiopática diagnosticadas entre setembro/1979 a março/2003. Critérios para inclusão: insuficiência cardíaca e redução da contratilidade no ecocardiograma, na ausência de cardiopatia congênita ou secundária. Foram analisados 470 exames, durante 244,8 meses de evolução. Parâmetros analisados: dimensão do átrio esquerdo (DAE), relação átrio esquerdo/aorta (DAE/Ao), dimensão sistólica (DSVE) e diastólica (DDVE) do VE, massa do VE (massa), dimensão do ventrículo direito (DVD), fração de ejeção do VE (FE), percentagem de encurtamento do VE (%EC), gravidade da insuficiência das valvas atrioventriculares e da valva pulmonar e medida da pressão sistólica (PsVD) e diastólica (PdVD) do VD. Foi considerado significativo erro alfa <0,05. RESULTADOS: Idade média de 2,37 anos, ocorridos 35 óbitos (23,7% - IC95=17,1% a 31,2%). ANOVA demonstrou: DAE (p<0,0001), DAE/Ao (p<0,0001), DSVE (p=0,0061), DDVE (p=0,0086), massa (p<0,0001), FE (p=0,0074), %EC (p=0,0072) e DVD (p<0,0001). O agravamento da insuficiência mitral (IM) (p=0,0113) e tricúspide (IT) (p=0,0044) foram marcadores de óbito e a presença de IM, IT e insuficiência pulmonar moderada/grave foram deletérias à sobrevida. A análise de Cox demonstrou como preditores independentes da morte: DAE/Ao (p=0,0487), FE (<0,0001) e presença de IM moderada/grave (p=0,0419). CONCLUSÃO: Os pacientes com aumento progressivo da DAE/Ao, redução da FE e agravamento progressivo da IM, a despeito do tratamento clínico, devem ser considerados precocemente em programa de transplante cardíaco.
Macrophage migration inhibitory factor is associated with positive cultures in patients with sepsis after cardiac surgery
(Shock, 2005) Mendonça-Filho, Hugo Tannus Furtado de; Gomes, Gleice Silva; Nogueira, Pedro Miguel Mattos; Fernandes, Marco Aurelio de Oliveira; Tura, Bernardo Rangel; Santos, Marisa; Castro-Faria-Neto, Hugo Caire
This prospective consecutive observational study describes the blood levels of macrophage migration inhibitory factor (MIF), other cytokines, and markers of acute-phase response in 49 consecutive patients who developed the clinical syndrome of sepsis after cardiac surgery. Before starting antimicrobial treatment, all patients underwent microbiologic screening, and blood samples were collected. These samples subsequently were assayed for MIF, macrophage chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and -10, procalcitonin (PCT), and C-reactive protein (CRP). Patients with positive cultures (n = 25) had a higher mortality (P = 0.046) and higher levels of MIF (P < 0.001) than those with negative cultures (n = 24). We could not detect significant difference between the groups concerning the levels of CRP, PCT, IL6, IL10, MCP-1, or TNF-alpha. MIF levels showed an area under receiver operator curve of 0.823 for the prediction of culture-proven bacterial infection, with the best cut-off value at 988.5 pg/mL. In conclusion, circulating levels of MIF could be indicated as a valuable marker of microbiologically documented sepsis in patients after cardiac surgery, which suggests that MIF may be prospectively explored as a useful diagnostic tool in this setting.
B-type natriuretic peptide: a novel early blood marker of acute myocardial infarction in patients with chest pain and no ST-segment elevation
(European Heart Journal, 2005) Bassan, Roberto; Potsch, Alfredo; Maisel, Alan; Tura, Bernardo; Villacorta, Humberto; Nogueira, Mônica Viegas; Campos, Augusta; Gamarski, Roberto; Masetto, Antonio Cláudio; Moutinho, Marco Aurélio
Aims: This study was undertaken to determine the diagnostic value of admission B-type natriuretic peptide (BNP) for acute myocardial infarction (AMI) in patients with acute chest pain and no ST-segment elevation. Methods and results: A prospective study with 631 consecutive patients was conducted in the emergency department. Non-ST elevation AMI was present in 72 patients and their median admission BNP level was significantly higher than in unstable angina and non-acute coronary syndrome patients. Sensitivity of admission BNP for AMI (cut-off value of 100 pg/mL) was significantly higher than creatine kinase-MB (CKMB) and troponin-I on admission (70.8 vs. 45.8 vs. 50.7%, respectively, P<0.0001) and specificity was 68.9%. Simultaneous use of these markers significantly improved sensitivity to 87.3% and the negative predictive value to 97.3%. In multiple logistic regression analysis, admission BNP was a significant independent predictor of AMI, even when CKMB and troponin-I were present in the model. Conclusion: BNP is a useful adjunct to standard cardiac markers in patients presenting to the emergency department with chest pain and no ST-segment elevation, particularly if initial CKMB and/or troponin-I are non-diagnostic.
Sintomas depressivos e óbito em síndromes coronarianas isquêmicas agudas
(Revista Brasileira de Psiquiatria. 2005;27(2):163-7, 2005) Lougon, Mauricio; Mattos, Marco Antonio de; Tura, Bernardo
Carta aos editores da Revista Brasileira de Psiquiatria
Multicenter randomized trial of cell therapy in cardiopathies - MiHeart Study
(Trials, 2007) Tura, Bernardo R; Martino, Helena F; Gowdak, Luis H; Santos, Ricardo Ribeiro dos; Dohmann, Hans F; Krieger, José E; Feitosa, Gilson; Vilas-Boas, Fabio; Oliveira, Sergio A; Silva, Suzana A; Bozza, Augusto Z; Borojevic, Radovan; Carvalho, Antonio C Campos de
Background: Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. Method/design: We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. Discussion: Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).
Is myocardial performance index an independent echocardiographic marker of death in children with idiopathic dilated cardiomyopathy?
(Clinical Cardiology, 2008) Azevedo, Vitor Manuel P; Albanesi Filho, Francisco M; Santos, Marco Aurélio; Castier, Márcia B; Tura, Bernardo R; Amino, José Geraldo; Cunha, Maria Ourinda Mesquita da
Background: Myocardial performance index (MPI) was reported as a parameter of ventricular systolic and diastolic function, as well as a useful tool to predict the outcome in patients with ventricular dysfunction. Hypothesis: To compare MPI with classical echocardiographic parameters as an independent marker of death in children with idiopathic dilated cardiomyopathy (IDCM). Methods: Fifty-five children (13 deaths) underwent 104 echocardiograms from January 1996 to May 2005. Right ventricle (RV) MPI and left ventricle (LV) MPI, and 9 classical echocardiographic parameters (left atrium [LA]/body surface area [BSA], distance between mitral E point and ventricular septum, LV mass/body surface area, RV shortening fraction, LV end-systolic and end-diastolic dimensions/body surface area, LV ejection fraction, fiber circumferential shortening velocity, and mitral deceleration time) were compared. Statistical analysis was performed by chi-square, Pearson's correlation and Student t-test, Kaplan-Meier method, Cox's method, and receiver operating curve (ROC). Statistical significance was considered with alpha<0.05 and p=0.80]. Results: Univariate analysis showed that all studied parameters were markers of death. There was a high correlation between RVMPI and LVMPI (r=0.847]-p=0.0001]); therefore, to avoid bias, RVMPI was discharged from multivariate analysis. In the deceased group, moderate/severe mitral regurgitation was frequent (76.9%; confidence interval [CI[ 95%=46.2%- 94.9%) and it was considered in multivariate analysis. In Cox's multivariate analysis, LVMPI was the only independent marker of death (p=0.0213]). The ideal cut-off was 0.63 with 92.3% sensitivity, 66.7% specificity, and fitted ROC area=0.918]. Conclusions: In children with IDCM, LVMPI is an independent marker of death.
Influência da Terapia com Espironolactona sobre Níveis Sangüíneos de Tiamina em Pacientes com Insuficiência Cardíaca
(Arquivos Brasileiros de Cardiologia, 2008) Rocha, Ricardo Mourilhe; Silva, Guilherme Vianna e; Albuquerque, Denilson Campos de; Tura, Bernardo Rangel; Albanesi Filho, Francisco Manes
FUNDAMENTO: Estudos do manejo não-farmacológico da insuficiência cardíaca (IC) têm sido muito escassos. A importância de micronutrientes como tiamina há muito é conhecida, uma vez que sua deficiência está associada com o desenvolvimento de IC de alto débito. OBJETIVO: Nós estudamos a relação entre adicionar à inibição da ECA uma supressão adicional da aldosterona com espironolactona e níveis sangüíneos de tiamina (pmol/ml). MÉTODOS: Um total de 22 pacientes (pc) com IC (classes III/IV da NYHA) foi dividido em dois grupos [grupo I - espironolactona 25mg/dia (n=11) e grupo II - sem espironolactona (n=11)]. Determinamos os níveis de tiamina pelo uso da atividade da transcetolase eritrocitária. Os grupos foram comparados com relação à ingesta alimentar, demografia, doses de furosemida e níveis sangüíneos de tiamina, usando os testes de Mann-Whitney e t de Student. Analisamos as proporções com testes de qui-quadrado e de Kruskal-Wallis para associarmos a tiamina com fatores demográficos e usamos as doses de furosemida como variáveis dependentes. RESULTADOS: Os grupos I e II eram similares em relação à ingesta alimentar, doses diárias de furosemida (110,9±30,2 e 105,5±26,9 mg, respectivamente; p>0,05), demografia (etiologia, idade, hipertensão, diabete, tabagismo, abuso de álcool, dislipidemia e tratamento adjuvante da IC com drogas). Os pacientes do grupo I mostraram níveis de tiamina significativamente superiores, comparados com aqueles do grupo II (277,2±89,8 e 154,7±35,7, respectivamente) (p<0,001). Nenhuma das variáveis dependentes citadas acima estava associada com a tiamina. CONCLUSÃO: Em uma coorte de pacientes ambulatoriais com IC tratados com alta dose de diuréticos de alça, o uso de espironolactona está associado com níveis sangüíneos superiores de tiamina. A importância deste achado ainda deverá ser estabelecida por estudos futuros com desenho prospectivo e amostras maiores.
Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study
(Trials, 2008) Dohmann, Hans F R; Silva, Suzana A; Sousa, André L S; Braga, Alcione M S; Castelo Branco, Rodrigo V; Haddad, Andréa F; Oliveira, Mônica A; Moreira, Rodrigo C; Tuche, Fabio A A; Peixoto, Cíntia M; Tura, Bernardo R; Borojevic, Radovan; Ribeiro, Jorge P; Nicolau, José C; Nóbrega, Antonio C; Carvalho, Antonio C C
Background: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required. Trial register: This trial is registered at the NIH registry under the number NCT00350766
Custo-efetividade da trombólise pré-hospitalar vs intra-hospitalar no infarto agudo do miocárdio
(Arquivos Brasileiros de Cardiologia, 2008) Araújo, Denizar Vianna; Tura, Bernardo Rangel; Brasileiro, Antonio Luiz; Luz Neto, Heitor; Pavão, Ana Luiza Braz; Teich, Vanessa
FUNDAMENTO: Existe evidência de que a trombólise pré-hospitalar melhora os desfechos no infarto agudo do miocárdio (IAM) com supradesnivelamento do segmento ST. OBJETIVO: Comparar as relações de custo-efetividade entre trombólise pré-hospitalar e trombólise intra-hospitalar para o IAM com supradesnivelamento do segmento ST, pela perspectiva do Sistema Único de Saúde. MÉTODOS: Modelo analítico de decisão foi utilizado para comparar as duas estratégias. O desfecho do estudo foi "anos de vida ganhos". O uso de recursos e os custos foram estimados pela perspectiva do Sistema Único de Saúde. Árvore de decisão e modelo de Markov foram construídos com resultados de ensaios clínicos publicados. Os custos foram valorados em real (R$), para o ano de 2005. RESULTADOS: Para um horizonte de tempo de vinte anos, a expectativa de vida média com a trombólise pré-hospitalar foi de 11,48 anos e a trombólise intra-hospitalar proporcionou expectativa de vida média de 11,32 anos. Os custos foram de R$ 5.640,00 para a trombólise pré-hospitalar e de R$ 5.816,00 para a trombólise intra-hospitalar. Houve custo adicional de R$ 176,00 por paciente com a trombólise intra-hospitalar. A trombólise pré-hospitalar proporcionou adicional de 0,15 ano de expectativa de vida comparado à trombólise intra-hospitalar. CONCLUSÃO: Esse modelo sugere que, pela perspectiva do Sistema Único de Saúde, implementar a trombólise pré-hospitalar para o IAM com supradesnivelamento do segmento ST pode representar sobrevida extra e menor custo que comparativamente à trombólise intra-hospitalar.
Práticas cirúrgicas baseadas em evidências: tomografia computadorizada helicoidal no diagnóstico da apendicite aguda
(Revista do Colégio Brasileiro de Cirurgiões, 2008) Guimarães, Carlos Alberto; Santos, Bráulio dos
Os cirurgiões são instados a não somente ler os artigos dos periódicos, mas também a compreendê-los e analisá-los criticamente quanto à validade. Eles cuidam melhor dos seus pacientes se são capazes de analisar criticamente a literatura e aplicar os resultados a sua prática. Este é o segundo artigo de uma série - Práticas Cirúrgicas Baseadas em Evidência - que tem por objetivo apresentar a avaliação crítica de um teste diagnóstico.
Evolução para hipertensão arterial em pacientes com diabetes tipo 1
(Arquivos Brasileiros de Endocrinologia & Metabologia, 2008) Cobas, Roberta; Santos, Bráulio; Braga, Luiza; Cunha, Edna Ferreira; Gomes, Marilia de Brito
Purpose: Check the evolution of type 1(T1) diabetic patients to hypertension and prehypertension and baseline factors related to final blood pressure levels (BP). Methods: Observational study involving 127 T1 diabetic patients submitted to clinical and laboratory evaluation and followed by for 5 (2.4-9.2) years. Results: From the initially normotensive patients, 21.7% developed prehypertension, 4.7% developed hypertension and 73.6% remained with normal BP. From the prehypertensive patients, 35% returned to normal BP, 50% remained prehypertensive and 15% developed hypertension. The relative risk for hypertension development was 3.2 (0.8-12.3) in the prehypertensive compared to the normotensive group. The prevalence of prehypertension and hypertension increased from 15.7% to 26% and 0.8% to 7% respectively. Levels of serum creatinine predicted final levels of systolic and diastolic BP. Conclusion: It is emphasized the importance of renal function and BP evaluation even when they are in normal range to minimize the deleterious effects of hypertension in the development of nephropathy and cardiovascular disease.
Práticas cirúrgicas baseadas em evidências: apendicectomia laparoscópica versus a céu aberto
(Revista do Colégio Brasileiro de Cirurgiões, 2008) Santos Junior, Bráulio dos; Guimarães, Carlos Alberto
Os cirurgiões são instados a não somente ler os artigos dos periódicos, mas também a compreendê-los e analisá-los criticamente quanto à validade. Eles cuidam melhor dos seus pacientes se são capazes de analisar criticamente a literatura e aplicar os resultados a sua prática. Este é o primeiro artigo de uma série - Práticas Cirúrgicas Baseadas em Evidência - que tem por objetivo apresentar tópicos de Cirurgia Baseada em Evidências.
Documento de discussão – saúde, nutrição e população (HNP) Controle do tabagismo no Brasil: resumo executivo
(Epidemologia e Serviço de Saúde, 2008) Iglesias, Roberto; Jha, Prabhat; Pinto, Márcia; Silva, Vera Luiza da Costa e; Godinho, Joana
Meta-analysis of factors related to health services that predict treatment default by tuberculosis patients
(Cadernos de Saúde Pública, 2008) Brasil , Pedro Emmanuel Alvarenga Americano do; Braga, José Ueleres
The identification of factors that predict tuber- culosis (TB) treatment default can help control this problem. The current study used a systematic review to investigate associations between TB treatment default and previously studied factors related to health services. Abstracts were searched in the MEDLINE and LILACS databases and in the bibliography of the full texts under evalua- tion. Studies were included if TB treatment de- fault was evaluated by comparing two or more groups and data could be extracted. A total of 41 studies were included for combining data. It was possible to combine five exposures: “difficult ac- cess to health services”; “need for hospitalization”; “training or support for adherence”; “delay in initiating treatment”; “long wait before medical attendance”. “Difficult access to health services”, “training or support for adherence”, and “need for hospitalization” were associated with TB treat- ment default. All exposures demonstrated hetero- geneity, which was only explained in one. Publi- cation bias was only detected for one exposure.
Role of p53 in the induction of cyclooxygenase-2 by cisplatin or paclitaxel in non-small cell lung cancer cell lines
(Cancer Letters, 2009) Duarte, Mariana Lemos; Moraes, Emanuela de; Pontes, Elizangela; Schluckebier, Luciene; Moraes, Joyce Luana de; Hainaut, Pierre; Ferreira, Carlos Gil
Non-small cell lung Cancer (NSCLC) is extremely resistant to chemotherapeutic agents, such as cisplatin. High expression of the inflammatory enzyme Cyclooxygenase-2 (COX- 2) has been shown to inhibit chemotherapy-induced apoptosis, but little is known about COX-2 regulation upon drug treatment. Recent data indicate the tumor suppressor protein p53 as an important regulator of COX-2. Therefore, TP53 status could change tumor sensi- tivity to chemotherapy through induction of the anti-apoptotic protein COX-2. The main objective of this work was to analyze the effect of chemotherapy on the expression of COX-2, according to TP53 status. We report herein that lung cancer cell lines expressing wild-type p53, when exposed to cisplatin treatment, induced COX-2 (mRNA and protein), with concurrent synthesis of prostaglandins (PGE2). In contrast, COX-2 expression was not changed after cisplatin treatment of cells containing an inactive form of p53. Further, after silencing of wild-type p53 expressed in A549 cells by RNA interference, cisplatin was no longer able to induce COX-2 expression. Therefore, we suggest that induction of COX-2 by cisplatin in NSCLC cell lines is dependent on p53. For paclitaxel treatment, an increase in COX-2 mRNA expression was observed in H460 and A549 (wild-type p53 cell lines). Moreover, paclitaxel treatment increased COX-2 expression in ACC-LC-319 cell lines (p53 null), showing a p53-independent effect. These data may have therapeutic implica- tions in the selection of patients and strategy for future COX-2 inhibition trials.
Embolia pulmonar: registro multicêntrico da prática clínica em hospitais terciários
(Revista Brasileira de Terapia Intensiva, 2009) Volschan, André; Albuquerque, Denilson Campos de; Tura, Bernardo Rangel; Knibel, Marcos de Freitas; Souza, Paulo César Pereira da Silva e; Toscano, Maria Luiza
INTRODUÇÃO: O perfil clínico e as estratégias diagnósticas e terapêuticas nos pacientes com embolia pulmonar demonstram a prática clínica na abordagem da doença. Essas informações, escassas nos estudos nacionais, possibilitam melhor conhecimento da embolia pulmonar. MÉTODOS: Estudo multicêntrico de 727 pacientes admitidos em unidades de emergência ou terapia intensiva, com o diagnóstico de embolia pulmonar confirmado por um ou mais dos seguintes exames: arteriografia pulmonar angiotomografia computadorizada helicoidal angioressonância magnética, ecodopplercardiograma, cintilografia pulmonar ou duplex-scan venoso. Dados demográficos, comorbidades, manifestações clínicas e métodos complementares foram analisados. RESULTADOS: A média de idade foi 68 anos, sendo 42% homens. Os fatores de risco mais prevalentes foram: idade > 40 anos, repouso no leito e neoplasia. A dispnéia, taquipnéia, taquicardia, dor torácica, foram as manifestações clínicas mais frequentes. O eletrocardiograma apresentou alterações em 30%, a radiografia de tórax em 45%, o duplex-scan venoso em 69% e o ecodopplercardiograma em 37%. O D-dímero a troponina e a CKMB foram positivos em respectivamente 93, 9 e 8%. Os métodos mais utilizados para o diagnóstico foram: tomografia computadorizada: 47%, duplex-scan venoso: 14% e cintilografia pulmonar: 14%. As formas mais freqüentes de tratamento foram: heparina não fracionada 50%, heparina de baixo peso molecular 30% e trombolítico 12%. A mortalidade intra-hospitalar foi de 19,5%. CONCLUSÕES: Observou-se que a idade > 40 anos, imobilização prolongada e neoplasia foram os fatores de risco de maior prevalência e a dispnéia a apresentação clínica mais freqüente. A angiotomografia computadorizada helicoidal foi o método mais utilizado para o diagnóstico e a heparina não fracionada a principal forma de tratamento.
Rationale, design, and baseline characteristics of the Acetylcystein for Contrast-Induced nephropaThy (ACT) Trial: a pragmatic randomized controlled trial to evaluate the efficacy of acetylcysteine for the prevention of contrast-induced nephropathy
(Trials, 2009) ACT Trial Investigators; Tura, Bernardo R; Cramer, Helena; Santos Jr., Bráulio
Background: Aceltylcysteine has been evaluated in several small trials as a means of reducing the risk of contrast-induced nephropathy (CIN), however systematic reviews of these studies do not provide conclusive answers. Therefore, a large randomized controlled trial (RCT) is needed to provide a reliable answer as to whether acetylcysteine is effective in decreasing the risk of CIN in high-risk patients undergoing angiographic procedures. Methods: ACT is a RCT of acetylcysteine versus placebo in 2,300 patients at-risk for CIN undergoing an intravascular angiographic procedure. The randomization list will be concealed. Participants, health care staff, investigators and outcome assessors will be blinded to whether patients receive acetylcysteine or placebo. All analysis will follow the intention-to-treat principle. The study drugs (acetylcysteine 1200 mg or placebo) will be administered orally twice daily for two doses before and two doses after the procedure. The primary outcome is the occurrence of CIN, defined as a 25% elevation of serum creatinine above baseline between 48 and 96 hours after angiography. Discussion: The first patient entered the trial on September, 2008. Up to April 7, 2009, 810 patients had been included in 35 centers. The mean age was 69 (Standard deviation: 10), 18% had a baseline serum creatinine >1.5 mg/dL, 57% were diabetics and 13% had a history of heart failure. The ongoing ACT Trial is the largest multicentre RCT that will determine whether acetylcysteine is effective in decreasing the risk of CIN in patients at risk undergoing angiography. Trial registration: Clinicaltrials.gov NCT00736866.
Pharmaceutical assistance within the SUS: the experience of students in Rural Internship from a Pharmacy Course
(Brazilian Journal of Pharmaceutical Sciences, 2009) Saturnino, Luciana Tarbes Mattana; Luz, Zélia Profeta; Perini, Edson; Modena, Celina Maria
The 2002 Brazilian Curricular Lines established a new curriculum for Pharmacy Programs, including amplified information about the Unified Health System (SUS). Following this, some Colleges have implemented a Rural Internship (RI) discipline, as a way to promote: a) adequate information on the SUS, and b) students’ interaction with pharmaceutical assistance. In this study we analyzed the perceptions of students enrolled in the Rural Internship program of the undergraduate Pharmacy Program at the Federal University of Minas Gerais. Eight students participated in this study and their perceptions and ideas were obtained by focus groups, both before and after the RI. This information was analyzed by content analysis. The students had a fragmented, distorted view on assistance, before as well as after taking the RI. Nevertheless, the RI provided students with a view of the professional realities and difficulties routinely faced by pharmacists in the public health system. The RI course of the Pharmacy Programs was viewed as an opportunity to improve the professional work within the SUS.

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