PAULO CALEB JUNIOR DE LIMA SANTOS
Projetos de Pesquisa
Unidades Organizacionais
LIM/13 - Laboratório de Genética e Cardiologia Molecular, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Non-HFE hemochromatosis(2012) SANTOS, Paulo Caleb Júnior de Lima; DINARDO, Carla Luana; CANÇADO, Rodolfo Delfini; SCHETTERT, Isolmar Tadeu; KRIEGER, José Eduardo; PEREIRA, Alexandre CostaHereditary hemochromatosis (HH) is an autosomal recessive disorder classically related to HFE mutations. However, since 1996, it is known that HFE mutations explain about 80% of HH cases, with the remaining around 20% denominated non-HFE hemochromatosis. Nowadays, four main genes are implicated in the pathophysiology of clinical syndromes classified as non-HFE hemochromatosis: hemojuvelin (HJV, type 2Ajuvenile HH), hepcidin (HAMP, type 2B juvenile HH), transferrin receptor 2 (TFR2, type 3 HH) and ferroportin (SLC40A1, type 4 HH). The aim of this review is to explore molecular, clinical and management aspects of non-HFE hemochromatosis.
- Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population(2013) ALVIM, Rafael de Oliveira; SANTOS, Paulo Caleb Junior Lima; MUSSO, Mariane Manso; CUNHA, Roberto de Sa; KRIEGER, Jose Eduardo; MILL, Jose Geraldo; PEREIRA, Alexandre CostaBackground: Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods: A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV >= 12 m/s. Results: In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions: These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.
- MTRR rs326119 polymorphism is associated with plasma concentrations of homocysteine and cobalamin, but not with congenital heart disease or coronary atherosclerosis in Brazilian patients(2017) HORITA, Melanie; BUENO, Carolina Tosin; HORIMOTO, Andrea R.; LEMOS, Pedro A.; MORANDINI-FILHO, Antonio A.; KRIEGER, Jose E.; SANTOS, Paulo C. J. L.; PEREIRA, Alexandre C.Background: Differences in the distribution of the MTRR rs326119 polymorphism (c.56+ 781 A>C) between patients with congenital heart disease (CHD) and controls have been described in Chinese individuals. The association is thought to be due to deregulation of homocysteine-cobalamin pathways. This has not been replicated in other populations. The primary objective of this study was to assess the influence of the MTRR rs326119 polymorphism on biochemical parameters of vitamin B12 metabolism, coronary lesions, and congenital heart disease in Brazilian subjects. Methods: We selected 722 patients with CHD, 1432 patients who underwent coronary angiography, and 156 blood donors. Genotyping for the MTRR polymorphism was evaluated by high-resolution melting analysis, and biochemical tests of vitamin B12 metabolism were measured. Results: Subjects carrying the AC or CC genotypes had higher homocysteine concentrations (9.7 +/- 0.4 mu mol/L and 10.1 +/- 0.6 mu mol/L) and lower cobalamin concentrations (260.5 +/- 13.3 pmol/L and 275.6 +/- 19.9 pmol/L) compared with the subjects carrying the AA genotype (8.7 +/- 0.5 mu mol/L and 304.8 +/- 14.7 pmol/L), respectively. A multiple linear regression model also identified a significant association between the number of C variant alleles with the concentrations of homocysteine and cobalamin. Nonetheless, the allelic and genotypic distributions for MTRR rs326119 were not associated with CHD or coronary atherosclerosis in the studied samples. Conclusion: Our findings indicate that the MTRR rs326119 variant might be a genetic marker associated with homocysteine and cobalamin concentrations, but not a strong risk factor for CHD or coronary atherosclerosis in the Brazilian population. (C) 2016 The Authors.
- Juvenile hemochromatosis: HAMP mutation and severe iron overload treated with phlebotomies and deferasirox(2017) LESCANO, Manuel A.; TAVARES, Leticia C.; SANTOS, Paulo C. J. L.Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. JH usually affects people under the age of 30 and presents symptoms such as chronic liver damage, hypogonadotropic hypogonadism, cardiac diseases and endocrine dysfunctions. The present case reports a 29-year-old Brazilian woman with JH condition due to HAMP mutation (g. 47G> A), treated with phlebotomies and deferasirox. She presented symptoms such as weakness, skin hyperpigmentation, joint pain in the shoulders and hands and amenorrhea. First laboratory tests showed altered biochemical parameters [ serum ferritin (SF): 5696 ng/mL, transferrin saturation (TS): 85%]. After sessions of phlebotomies (450 mL every 15 d), the patient presented partial symptomatic improvements and biochemical parameters (SF: 1000 ng/mL, Hb: 11 g/dL). One year later, deferasirox (15 mg/kg per day) was introduced to the treatment, and the patient showed total symptomatic improvement, with significant clearing of the skin, SF: 169 ng/mL, and TS: 50%. Furthermore, after the combined deferasirox-phlebotomy therapy, magnetic resonance imaging measurements revealed normalized level for liver iron (30 ae mol/g; reference value < 36 ae mol/g). In conclusion, combined deferasirox-phlebotomy treatment was able to normalize iron levels and improve symptoms.
- Genomic ancestry as a predictor of haemodynamic profile in heart failure(2016) BERNARDEZ-PEREIRA, Sabrina; GIOLI-PEREIRA, Luciana; MARCONDES-BRAGA, Fabiana G.; SANTOS, Paulo Caleb Junior Lima; SPINA, Joceli Mabel Rocha; HORIMOTO, Andrea Roseli Vancan Russo; SANTOS, Hadassa Campos; BACAL, Fernando; FERNANDES, Fabio; MANSUR, Alfredo Jose; PIETROBON, Ricardo; KRIEGER, Jose Eduardo; MESQUITA, Evandro Tinoco; PEREIRA, Alexandre CostaObjective: The aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF). Methods: Observational, cross-sectional study. Eligible participants were aged between 18 and 80 years; ejection fraction was <= 50%. Patients underwent genetic analysis of ancestry informative markers, echocardiography and impedance cardiography (ICG). Race was determined by self-classification into two groups: white and non-white. Genomic ancestry was estimated using a panel of 101 348 polymorphic markers and three continental reference populations (European, African and Native American). Results: Our study included 362 patients with HF between August 2012 and August 2014. 123 patients with HF declared themselves as white and 234 patients declared themselves as non-white. No statistically significant differences were found regarding the ICG parameters according to self-declared race. The Amerindian ancestry was positively correlated with systolic time ratio (r=0.109, p<0.05). The thoracic fluid content index (r=0.124. p<0.05), E wave peak (r=0.127. p<0.05) and E/e' ratio (r=0.197. p<0.01) were correlated positively with African ancestry. In multiple linear regression, African ancestry remained associated with the E/e0 ratio, even after adjustment to risk factors. Conclusions: The African genetic ancestry was associated with worse parameters of diastolic function; the Amerindian ancestry correlated with a worse pattern of ventricular contractility, while self-declared colour was not helpful to infer haemodynamic profiles in HF.
- CHRNA4 rs1044396 is associated with smoking cessation in varenicline therapy(2015) SANTOS, Juliana Rocha; TOMAZ, Paulo R. X.; ISSA, Jaqueline S.; ABE, Tania O.; KRIEGER, Jose E.; PEREIRA, Alexandre C.; SANTOS, Paulo C. J. L.Background: The large individual variability in response to drugs for smoking cessation suggests that specific treatments can be more effective in particular subgroups of smokers. In the context of personalized medicine, the main aim of the present study was to evaluate whether the CHRNA4 and CHRNB2 polymorphisms are associated with response to smoking cessation therapies in patients from a smoker assistance program. Methods: This cohort study enrolled 483 smoking patients who received behavioral counseling and drug treatment (varenicline, bupropion, and/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerstrom test for nicotine dependence (FTND) and lssa situational smoking scores were analyzed for nicotine dependence. The CHRNA4 (rs1044396 and rs2236196) and CHRNB2 (rs2072660 and rs2072661) polymorphisms were genotyped by high resolution melting analysis. Results: Patients with rs1044396 CC genotype had lower success rate in treatment with varenicline (29.5%) compared with carriers of CT or TT genotypes (50.9%; p = 0.007, n = 167). The CT or TT genotypes were associated with higher odds ratio for success (OR = 1.67, 95% CI = 1.10-2.53, p = 0.02), in a multivariate model. We did not observe significant differences in the FTND and lssa scores according to the studied polymorphisms. Conclusion: The CHRNA4 rs1044396 is associated with smoking cessation in individuals on varenicline therapy. We suggest that this polymorphism influences the varenicline response, but replications of this finding are needed.
- Pharmaceutical Care Increases Time in Therapeutic Range of Patients With Poor Quality of Anticoagulation With Warfarin(2018) MARCATTO, Leiliane Rodrigues; SACILOTTO, Luciana; TAVARES, Leticia Camargo; FACIN, Mirella; OLIVETTI, Natalia; STRUNZ, Celia Maria Cassaro; DARRIEUX, Francisco Carlos Costa; SCANAVACCA, Mauricio Ibrahim; KRIEGER, Jose Eduardo; PEREIRA, Alexandre Costa; SANTOS, Paulo Caleb Junior LimaThromboembolic events are associated with high mortality and morbidity indexes. In this context, warfarin is the most widely prescribed oral anticoagulant agent for preventing and treating these events. This medication has a narrow therapeutic range and, consequently, patients usually have difficulty in achieving and maintaining stable target therapeutics. Some studies on the literature about oral anticoagulant management showed that pharmacists could improve the efficiency of anticoagulant therapy. However, the majority of these studies included general patients retrospectively. The aim of this study was to prospectively evaluate a pharmacist's warfarin management in patients with poor quality of anticoagulation therapy (Time in the Therapeutic Range-TTR < 50%). We included 268 patients with atrial fibrillation (AF) and without stable dose of warfarin (TTR < 50%, based on the last three values of International Normalized Ratio-INR). We followed them up for 12 weeks, INR values were evaluated and, when necessary, the dose adjustments were performed. During the first four visits, patient's INR was measured every 7 days. Then, if INR was within the target therapeutic range (INR: 2-3), the patient was asked to return in 30 days. However, if INR was out the therapeutic target, the patient was asked to return in 7 days. Adherence evaluation was measured through questionnaires and by counting the pills taken. Comparison between basal TTR (which was calculated based on the three last INR values before prospective phase) and TTR of 4 weeks (calculated by considering the INR tests from visits 0 to 4, in the prospective phase of the study) and basal TTR and TTR of 12 weeks (calculated based on the INR tests from visits 0 to 12, in the prospective phase of the study) revealed significant statistical differences (0.144 +/- 0.010 vs. 0.382 +/- 0.016; and 0.144 +/- 0.010 vs. 0.543 +/- 0.014, p < 0.001, respectively). We also observed that the mean TTR of 1 year before (retrospective phase) was lower than TTR value after 12 weeks of pharmacist-driven treatment (prospective phase) (0.320 +/- 0.015; 0.540 +/- 0.015, p < 0.001). In conclusion, pharmaceutical care was able to improve TTR values in patients with AF and poor quality of anticoagulation with warfarin.
- Surgery is unlikely to be enough for a patient to stop smoking 24 h prior to hospital admission(2018) MARINHO, Igor Maia; CARMONA, Maria Jose C.; BENSENOR, Fabio Ely Martins; HERTEL, Julia Mintz; MORAES, Marcos Fernando Breda de; SANTOS, Paulo Caleb Junior Lima; VANE, Matheus Fachini; ISSA, Jaqueline ScholzIntroduction: The need for surgery can be a decisive factor for long-term smoking cessation. On the other hand, situations that precipitate stress could precipitate smoking relapse. The authors decided to study the impact of a surgery on the patient's effort to cease smoking for, at least, 24 h before hospital admission and possible relapse on the last 24 h before hospital admission for ex-smokers. Methods: Smoker, ex-smokers and non-smokers adults, either from pre-anesthetic clinic or recently hospital admitted for scheduled elective surgeries that were, at most, 6 h inside the hospital buildings were included in the study. The patients answered a questionnaire at the ward or at the entrance of the operating room (Admitted group) or at the beginning of the first pre-anesthetic consultation (Clinic group) and performed CO measurements. Results: 241 patients were included, being 52 ex-smokers and 109 never smokers and 80 non-smokers. Smokers had higher levels of expired carbon monoxide than non-smokers and ex-smokers (9.97 +/- 6.50 vs. 2.26 +/- 1.65 vs. 2.98 +/- 2.69; p= 0.02). Among the smokers, the Clinic group had CO levels not statistically different of those on the Admitted group (10.93 +/- 7.5 vs. 8.65 +/- 4.56; p= 0.21). The ex-smokers presented with no significant differences for the carbon monoxide levels between the Clinic and Admitted groups (2.9 +/- 2.3 vs. 2.82 +/- 2.15; p= 0.45). Conclusion: A medical condition, such as a surgery, without proper assistance is unlikely to be enough for a patient to stop smoking for, at least, 24 h prior to admission. The proximity of a surgery was not associated with smoking relapse 24 h before the procedure. (C) 2018 Sociedade Brasileira de Anestesiologia.
- Machine Learning for Prediction of Stable Warfarin Dose in US Latinos and Latin Americans(2021) STEINER, Heidi E.; GILES, Jason B.; PATTERSON, Hayley Knight; FENG, Jianglin; ROUBY, Nihal El; CLAUDIO, Karla; MARCATTO, Leiliane Rodrigues; TAVARES, Leticia Camargo; GALVEZ, Jubby Marcela; CALDERON-OSPINA, Carlos-Alberto; SUN, Xiaoxiao; HUTZ, Mara H.; SCOTT, Stuart A.; CAVALLARI, Larisa H.; FONSECA-MENDOZA, Dora Janeth; DUCONGE, Jorge; BOTTON, Mariana Rodrigues; SANTOS, Paulo Caleb Junior Lima; KARNES, Jason H.Populations used to create warfarin dose prediction algorithms largely lacked participants reporting Hispanic or Latino ethnicity. While previous research suggests nonlinear modeling improves warfarin dose prediction, this research has mainly focused on populations with primarily European ancestry. We compare the accuracy of stable warfarin dose prediction using linear and nonlinear machine learning models in a large cohort enriched for US Latinos and Latin Americans (ULLA). Each model was tested using the same variables as published by the International Warfarin Pharmacogenetics Consortium (IWPC) and using an expanded set of variables including ethnicity and warfarin indication. We utilized a multiple linear regression model and three nonlinear regression models: Bayesian Additive Regression Trees, Multivariate Adaptive Regression Splines, and Support Vector Regression. We compared each model's ability to predict stable warfarin dose within 20% of actual stable dose, confirming trained models in a 30% testing dataset with 100 rounds of resampling. In all patients (n = 7,030), inclusion of additional predictor variables led to a small but significant improvement in prediction of dose relative to the IWPC algorithm (47.8 versus 46.7% in IWPC, p = 1.43 x 10(-15)). Nonlinear models using IWPC variables did not significantly improve prediction of dose over the linear IWPC algorithm. In ULLA patients alone (n = 1,734), IWPC performed similarly to all other linear and nonlinear pharmacogenetic algorithms. Our results reinforce the validity of IWPC in a large, ethnically diverse population and suggest that additional variables that capture warfarin dose variability may improve warfarin dose prediction algorithms.
article 20 Citação(ões) na Scopus Simultaneous Use of Amiodarone Influences Warfarin Maintenance Dose but Is Not Associated with Adverse Events(2014) SANTOS, Paulo Caleb Junior Lima; SOARES, Renata Alonso Gadi; STRUNZ, Celia Maria Cassaro; GRINBERG, Max; FERREIRA, Joao Fernando M. .; CESAR, Luiz Antonio Machado; SCANAVACCA, Mauricio; KRIEGER, Jose Eduardo; PEREIRA, Alexandre CostaBACKGROUND: Drug interaction studies selecting patients in a real-life setting are scarce, and most studies to date are characterized by a small sample size. OBJECTIVE: To evaluate the effect of amiodarone on warfarin maintenance dose and adverse events in an anticoagulation cohort from a tertiary cardiovascular service. METHODS: This study recruited 866 patients, and oral anticoagulant therapy was monitored by the prothrombin time expressed as the international normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673 polymorphisms was performed. RESULTS: Of the 866 patients, 111 (12.8%) were taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the therapeutic target dose. The warfarin maintenance dose was significantly lower in patients simultaneously using amiodarone (23.8 +/- 11.3 mg/wk) compared with other patients (29.5 +/- 14.3 mg/wk; P < 0.001). Patients taking amiodarone had higher INR/current dose ratios (0.83 +/- 0.04 per mg) compared with patients not using amiodarone (0.71 +/- 0.02 per mg, P = 0.001). Adverse event frequency was not different between the groups (P = 0.40). No genotype effect was noted on the odds of bleeding associated with amiodarone use. CONCLUSIONS: Simultaneous use of amiodarone influences warfarin maintenance dose, but is not associated with adverse events.