Previous analyses of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) identified four main dietary patterns (DP). The aim of this study was to explore the association between the previously defined DP and renal function (RF). A cross-sectional study using the ELSA-Brasil baseline data was carried out. DP (“traditional”, “fruits and vegetables”, “bakery”, and “low sugar/low fat), metabolic syndrome (MS) using the Joint Interim Statement criteria, microalbuminuria (MA), and glomerular filtration rate (eGFR) through the CKD-EPI equation were evaluated. Abnormal RF was defined as eGFR<60 mL·min-1·(1.73 m2)-1 and MA≥3.0 mg/dL. Factors associated with RF were determined and mediation analysis was performed to investigate the association between DP, MS, and RF. A total of 15,105 participants were recruited, with a mean age of 52±9 years; 8,134 participants (54%) were females. The mediation analysis identified indirect associations between “bakery” and “fruits and vegetables”, and both were associated with decreased eGFR and albuminuria in both genders, compared with “traditional” and “low sugar/low fat” patterns in the general population. There was a direct association of the “bakery” pattern with MA in men (OR: 1.17, 95%CI: 1.92-1.48). The “fruits and vegetables” pattern also showed a direct association with reduced eGFR in women (OR: 1.65, 95%CI: 1.28-2.12), although there was no significance after adjustment. The “fruits and vegetables” and “bakery” DPs were associated with renal dysfunction. The only independent, direct association was between “bakery” DP and MA in men, raising concerns about DP and renal damage in men.

Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

Biomarkers have been identified for pulmonary arterial hypertension, but are less well defined for specific etiologies such as congenital heart disease-associated pulmonary arterial hypertension (CHDPAH). We measured plasma levels of eight microvascular dysfunction markers in CHDPAH, and tested for associations with survival. A cohort of 46 inoperable CHDPAH patients (age 15.0 to 60.2 years, median 33.5 years, female:male 29:17) was prospectively followed for 0.7 to 4.0 years (median 3.6 years). Plasma levels of von Willebrand factor antigen (VWF:Ag), tissue plasminogen activator (t-PA) and its inhibitor (PAI-1), P-selectin, reactive C-protein, tumor necrosis factor alpha, and interleukin-6 and -10 were measured at baseline, and at 30, 90, and 180 days in all subjects. Levels of six of the eight proteins were significantly increased in patients versus controls (13 to 106% increase, P < 0.003). Interleukin-10 level was 2.06 times normal (P = 0.0003; Th2 cytokine response). Increased levels of four proteins (t-PA, PAI-1, P-selectin, and interleukin-6) correlated with disease severity indices (P < 0.05). Seven patients died during follow-up. An average VWF:Ag (mean of four determinations) above the level corresponding to the 95th percentile of controls (139 U/dL) was independently associated with a high risk of death (hazard ratio = 6.56, 95%CI = 1.46 to 29.4, P = 0.014). Thus, in CHDPAH, microvascular dysfunction appears to involve Th2 inflammatory response. Of the biomarkers studied, plasma vWF:Ag was independently associated with survival.

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively). Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively) and second phase (73, 57, and 66% inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.

We investigated whether chronic rosuvastatin administration could improve the abnormalities of the circulating levels of vascular dysfunction markers in pulmonary arterial hypertension (PAH). Sixty patients, aged 13 to 60 years, with idiopathic (N = 14) or congenital heart disease-associated PAH (N = 46) were equally but randomly assigned to rosuvastatin treatment (10 mg a day, orally) or placebo for 6 months in a blind fashion. Plasma levels of P-selectin, tissue-plasminogen activator and its inhibitor as well as von Willebrand factor antigen were measured by enzyme-linked immunoassay before and after 1, 3, and 6 months of treatment. Baseline levels of biomarkers were elevated (68, 16, 45 and 46% increase relative to controls, for P-selectin, von Willebrand factor antigen, tissue-plasminogen activator and its inhibitor, respectively; P < 0.001). P-selectin values at baseline, 1, 3, and 6 months were 39.9 ± 18.5, 37.6 ± 14.6, 34.8 ± 14.6, and 35.4 ± 13.9 ng/mL, respectively, for the rosuvastatin group and 45.7 ± 26.8, 48.0 ± 26.9, 48.1 ± 25.7, and 45.7 ± 25.6 ng/mL for the placebo group. The P-selectin level was lower in the rosuvastatin group compared with placebo throughout treatment (P = 0.037, general linear model). A trend was observed towards a decrease in tissue-plasminogen activator in the statin group (16% reduction, P = 0.094), with no significant changes in the other markers. Since P-selectin is crucial in inflammation and thrombosis, its reduction by rosuvastatin is potentially relevant in the pathophysiological scenario of PAH.

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.

The objective of the present study was to establish a method for quantitative analysis of von Willebrand factor (vWF) multimeric composition using a mathematical framework based on curve fitting. Plasma vWF multimers from 15 healthy subjects and 13 patients with advanced pulmonary vascular disease were analyzed by Western immunoblotting followed by luminography. Quantitative analysis of luminographs was carried out by calculating the relative densities of low, intermediate and high molecular weight fractions using laser densitometry. For each densitometric peak (representing a given fraction of vWF multimers) a mean area value was obtained using data from all group subjects (patients and normal individuals) and plotted against the distance between the peak and IgM (950 kDa). Curves were constructed for each group using nonlinear fitting. Results indicated that highly accurate curves could be obtained for healthy controls and patients, with respective coefficients of determination (r²) of 0.9898 and 0.9778. Differences were observed between patients and normal subjects regarding curve shape, coefficients and the region of highest protein concentration. We conclude that the method provides accurate quantitative information on the composition of vWF multimers and may be useful for comparisons between groups and possibly treatments.

OBJETIVO: Avaliar retrospectivamente a associação entre raça e incidência de doença renal terminal (DRT) em pacientes com glomerulonefrites em um Hospital Universitário do estado da Bahia. MÉTODOS: A amostra foi composta de 79 pacientes com esclerose glomerular focal (EGF), 50 com glomerulonefrite membranoproliferativa (GNMP) e 44 com outros tipos de glomerulonefrites (OTGN), acompanhados entre 1970 e 1996 por pelo menos 6 meses. Não foram incluídos os pacientes com glomerulonefrite aguda, formas crescênticas, lesão mínima, doenças do colágeno e com níveis de creatinina sérica maior ou igual a 4 mg/dl. Quanto à raça, os pacientes foram classificados em brancos, mulatos ou negros. Para idades superiores a 18 anos e na ausência de uso de anti-hipertensivos, definiu-se como hipertensos pacientes que tiveram médias das três primeiras determinações da pressão arterial sistólica ou diastólica iguais ou superiores a 140 e 90 mmHg, respectivamente; para idades igual ou abaixo de 18 anos foram utilizados critérios recomendados pela "Task Force on Blood Pressure in Children". RESULTADOS: No grupo de normotensos, a incidência de DRT foi 72% menor em mulatos e negros (risco relativo (RR)=0,28; intervalo de confiança (IC) 95%=0,11-0,67). No grupo de hipertensos, a associação entre raça e DRT apresentou direção inversa (RR=1,49; IC 95%=0,68-4,34; p=0,316) à observada em normotensos. Esta variação no RR de acordo com a presença ou ausência de HA foi estatisticamente significante (p=0,01). Entre os normotensos, parte da diferença racial na incidência de DRT pode ser explicada pela distribuição de tipos histológicos de glomerulonefrite entre o grupo de brancos e o grupo de negros e mulatos. CONCLUSÕES: Entre os normotensos com glomerulonefrite, a incidência de DRT foi significantemente maior em brancos do que em negros ou mulatos. Contrariamente, entre os hipertensos observou-se uma tendência para um risco maior de DRT no grupo de negros e mulatos. O estudo sugere que HA e o tipo histológico de glomerulonefrite influenciam a associação entre raça e DRT.

OBJECTIVE: To assess, retrospectively, the association between race and incidence of end-stage renal disease (ESRD) in patients with glomerulonephritis in a University Hospital of Bahia, Brazil. METHODS: The sample was comprised of 79 patients with focal segmental glomerulosclerosis (FSG), 50 with membranoproliferative glomerulonephritis (MPGN) and 49 with other types of glomerulonephritis (OTGN), followed-up between 1970 and 1996 for at least 6 months. It was not included patients with acute glomerulonephritis, minimal change disease, crescentic glomerulonephritis, connective tissue diseases or patients with serum creatinine level greater than or equal to 4.0 mg/dl. The patients were classified according to race as caucasian (white), mulatto or negro. For patients older than 18 yr, not taking antihypertensives drugs, hypertension was defined as a mean of three blood pressure measurements greater than or equal to 140 mmHg for systolic or 90 mmHg for diastolic; for ages <= 18 years. The definition was based on criteria recommended by the Task Force on Blood Pressure in Children. RESULTS: In the normotensive group, the incidence of ESRD was 72% lower in mulattos and negroes (relative risk (RR)=0.28; 95% confidence interval (CI)=0.11-0.67). In the group with hypertension, the direction of association between race and ESRD was opposite to that observed in the normotensive group (RR=1.49; 95% CI= 0.68-4.34). The modification in the RR depending on the presence or the absence of hypertension was statistically significant (p=0.01). In the normotensive group the RR shifted toward the null hypothesis after the inclusion of histologic type in the Cox model. CONCLUSIONS: Among normotensive patients with glomerulonephritis the incidence of ESRD was greater in caucasians (whites) than in negroes or mulattoes. By contrast among hypertensive patients there was a trend for a higher risk of ESRD in negroes. The study suggests that hypertension and the histologic type of glomerulonephritis influence the association between race and ESRD.

Este artigo foi escrito com o objetivo de descrever o conceito de Medicina Baseada em Evidências (MBE) e as competências necessárias para a sua prática. MBE deve ser vista como a integração da experiência clínica com a capacidade de analisar e aplicar racionalmente a informação científica ao cuidar de pacientes. A aplicação de métodos e estratégias para fortalecer o alicerce científico do médico, sem desprezar os valores humanitários da profissão, deverá contribuir para a melhoria da qualidade da assistência médica que é oferecida no Brasil. As Escolas e Associações Médicas podem desempenhar importantes papéis na promoção da MBE.

This article was written with the objective of describing the concept of Evidence Based Medicine (EBM) and the competences required for its practice. EBM should be viewed as an integration of clinical experience with the ability to analyze and rationally apply the scientific information while taking care of patients. The application of methods and strategies to enhance the scientific background of the physician while taking into account the humanitarian values of the medical profession should contribute to improve the quality of the medical care that is offered in Brazil. The Medical Schools and Associations may play important roles in the promotion of EBM.

OBJETIVO: Avaliar mudanças, ao longo dos anos, na freqüência de resistência à norfloxacina e ciprofloxacina em bactérias isoladas de uroculturas. MÉTODOS: Resultados de todas as uroculturas com crescimento bacteriano de pelo menos 10(5) unidades formadoras de colônias por mL de urina (UFC/mL), realizadas no Serviço de Nefrologia da Universidade Federal da Bahia durante o período 1983-1994, foram analisadas. As bactérias incluídas na análise foram aquelas mais freqüentemente isolados: Escherichia coli (n=668), Klebsiella spp. (n=286), Staphylococcus spp. (n=186), Proteus spp. (n=135) e Enterobacter spp. (n=129). RESULTADOS: A freqüência de bactérias resistentes à norfloxacina foi de 3,2%, no período 1983-1986; 5,9%, no período 1987-1990; e 9,1%, no período 1991-1994 (p<0,05). Klebsiella spp. e Enterobacter spp. foram as bactérias que apresentaram maiores aumentos na freqüência de resistência à norfloxacina. Para a ciprofloxacina, constatou-se resistência em 7,4% das bactérias isoladas, no período 1985-1989, e 16,5%, no período 1990-1994 (p<0,05). Esse aumento na freqüência de bactérias resistentes à ciprofloxacina foi mais marcante para Enterobacter spp. e Staphylococcus spp. CONCLUSÕES: Os resultados do presente estudo mostram um aumento gradual na freqüência de resistência à norfloxacina e ciprofloxacina entre as bactérias mais comumente isoladas em uroculturas. A influência do uso prévio de quinolonas e de peculiaridades da bactéria infectante, nesses achados, representa importante questão a ser investigada.

OBJECTIVE: To assess time trends in the frequency of norfloxacin and ciprofloxacin resistance of bacteria isolated from urine culture. METHODS: Results of all urine cultures with a bacterial growth of at least 10(5) colony-forming units per milliter, performed at the Renal Service of the Federal University of Bahia, Brazil, from 1983 to 1994 were analyzed. The bacteria considered for this analysis were those most often isolated: Escherichia coli (n=668), Klebsiella spp. (n=286), Staphylococcus spp. (n=186), Proteus spp. (n=135) and Enterobacter spp. (n=129). RESULTS: The frequencies of norfloxacin resistance for the periods 1983-1986, 1987-1990 and 1991-1994 were 3.2%, 5.9% and 9.1%, respectively (p-value<0.05). The most pronounced increases in the frequencies of norfloxacin-resistance were observed for Klebsiella spp. and Enterobacter spp. The frequency of ciprofloxacin resistance was 7.4% in the period 1985-1989 and 16.5% in the period 1990-1994 (p-value<0.05). This time trend in ciprofloxacin resistance was more striking for Enterobacter spp. and Staphylococcus spp. CONCLUSION: The results show a gradual increase in the frequency of norfloxacin and ciprofloxacin resistance of the bacteria most commonly isolated from urine cultures. The influence of previous treatment with quinolones and characteristics of the infecting bacteria on these findings are important questions to to be addressed in future investigations.