F H Maffei

Santa Casa de São Paulo, San Paulo, São Paulo, Brazil

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Publications (59)96.41 Total impact

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    ABSTRACT: Abstract Arterial thrombosis is an important complication of diabetes and cancer, being an important target for therapeutic intervention. Crataeva tapia bark lectin (CrataBL) has been previously shown to have hypoglycemiant effect and also to induce cancer cell apoptosis. It also showed inhibitory activity against Factor Xa (Kiapp=8.6 μm). In the present study, we evaluated the anti-thrombotic properties of CrataBL in arterial thrombosis model. CrataBL prolongs the activated partial thromboplastin time on human and mouse plasma, and it impairs the heparin-induced potentiation of antithrombin III and heparin-induced platelet activation in the presence of low-dose ADP. It is likely that the dense track of positive charge on CrataBL surface competes with the heparin ability to bind to antithrombin III and to stimulate platelets. In the photochemically induced thrombosis model in mice, in the groups treated with 1.25, 5.0, or 10 mg/kg CrataBL, prior to the thrombus induction, the time of total artery occlusion was prolonged by 33.38%, 65%, and 66.11%, respectively, relative to the time of the control group. In contrast to heparin, the bleeding time in CrataBL-treated mice was no longer than in the control. In conclusion, CrataBL was effective in blocking coagulation and arterial thrombus formation, without increasing bleeding time.
    Biological chemistry. 09/2014; 395(9):1027-1035.
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    ABSTRACT: The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis.
    Thrombosis Research 01/2014; · 3.13 Impact Factor
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    ABSTRACT: BACKGROUND: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. OBJECTIVE: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. METHODS: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. RESULTS: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. CONCLUSIONS: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice.
    Annals of Vascular Surgery 01/2013; · 0.99 Impact Factor
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    ABSTRACT: Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.
    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 06/2012; 45(10):929-34. · 1.08 Impact Factor
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    ABSTRACT: Passion fruit (Passiflora edulis Sims f. flavicarpa) is popularly known for its sedative and calming properties and is consumed as a fresh fruit or as a juice. The clinical observation of blood incoagulability associated with excessive consumption of passion fruit juice, in a patient treated with warfarin, prompted the current study to investigate in vitro the presence of blood clotting inhibitors in Passiflora edulis Sims f. flavicarpa extract. After purification process, two compounds of distinct molecular weight and inhibitory action were better characterized. One is a trypsin inhibitor similar to inhibitors from Bowman-Birk family, named PeTI-I12, and other is a compound active in coagulation that prolongs aPTT and PT, but does not change TT. The aim of this study is to provide evidence that passion fruit extract's components play a role on hemostasis and therefore may be relevant in the handling of patients treated with anticoagulants or suffering hemorrhagic diseases.
    Protein and Peptide Letters 05/2012; 19(5):501-8. · 1.99 Impact Factor
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    ABSTRACT: Superficial thrombophlebitis (ST) ascending the lower limbs is a common disease, which may be associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). The aim of this study was to investigate the prevalence of DVT and PE as complications of ascending ST of the lower limbs in the great saphenous vein (GSV) or SSV (SSV) and probable risk factors. For this study 60 consecutive patients were enrolled with ascending ST of the GSV or SSV, seen between 2000 and 2003 at a public hospital in Botucatu, SP, Brazil. All patients were assessed clinically, by venous Duplex scanning of the lower limbs to confirm ST and test for DVT, and by means of pulmonary scintigraphy to test for PE. In 13 ST cases (21.67%) there was concomitant DVT and 17 ST patients (28.33%) also had PE. Eleven patients had a clinical status suggestive of DVT, but only in eight of these (61.5%), this clinical diagnosis was confirmed. Fourteen patients had a clinical status suggestive of PE, and this diagnosis was confirmed in six cases (35.30%). ST patients who also had DVT and/or PE were given anticoagulant treatment with heparin and warfarin. None of the variables studied was predictive of DVT or PE (P>0.05). However, the presence of varicose veins reduced the risk of patients having DVT (relative risk=9.09; 95%CI:1.75 - 50.00 and P=0.023). The prevalence rates of PE (28.3%) and DVT (21.6%) were elevated in this sample of ascending ST cases, indicating a need for detailed assessment of patients for signs of these complications, including for therapeutic management decision making.
    International angiology: a journal of the International Union of Angiology 10/2009; 28(5):400-8. · 1.46 Impact Factor
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    ABSTRACT: Effective strategies for prevention of venous thromboembolism (VTE) are widely available, but still remain underused, mainly in our country. Our aim was to verify whether the implementation of a guideline for VTE prophylaxis for surgical patients influenced the prescription of prophylaxis by the medical staff. This was a retrospective preintervention-postintervention study. Charts of 150 patients before guideline implementation (BGI) and 150 after (AGI) were randomized among all patients admitted during one year in each period. Inclusion criteria: >40 years-old, major abdominal or orthopedic surgeries. Exclusion criteria: Incomplete files and use of anticoagulants for any reason at admission. Data registered: demographic data, reference to VTE risk factors, VTE prophylaxis prescription, diagnosis of deep venous thrombosis or pulmonary embolism during hospitalization. Results. The two groups, BGI and AGI were similar for demographic data and duration of prophylaxis (5.6 x 6.6 days). Frequency of prophylaxis in percentages was BGI x AGI respectively, before surgery: pharmacologic prophylaxis (PP), 6 x 9; graduated compression stockings (GCS), 4 x 3; intermittent pneumatic compression (IPC), 2 x 3. After surgery: PP, 53 x 53; GCS, 23 x 40 (P<0.05); IPC, 26 x 32. Including all patients, prophylaxis was prescribed for 60.5% BGI and 66.5% AGI, but was considered adequate only in 34% BGI and 32% AGI. Adoption of a guideline, although increasing concern about prophylaxis, expressed by greater use of GCS, only minimally improved quality of prophylaxis , indicating that other active and continuous interventions are necessary to enforce compliance.
    Revista da Associação Médica Brasileira 12/2008; 55(5):587-92. · 0.77 Impact Factor
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    ABSTRACT: This study aimed at assessing the accuracy of ultrasound (US) in the diagnosis of recent deep vein thrombosis (DVT) in an experimental study in dogs. Design: blinded and randomized experimental study. Twenty dogs were randomly divided in two groups: control group (CG) and thrombosis group (TG). US was performed in the pre- and postoperative period. Phlebography was performed immediately prior to the postoperative US. After the second US, a surgery was performed to detect whether thrombus was present or not. US results were compared to those of phlebography and surgical findings. In all dogs, inferior vena cava (IVC) was compressible. The relations of IVC diameter with the aorta were higher (P<0.005) in TG than in CG. Spectral Doppler in spontaneous breathing, tissue harmonic imaging, power Doppler and B flow showed sensitivity, specificity and accuracy of 1. Phlebography presented sensitivity of 90%, specificity of 80% and accuracy of 85%, when compared to surgical finding. For the diagnosis of recent DVT in the experimental model used, venous compressibility proved to be inefficient. The ratio of IVC diameter to aorta, when increased, suggests thrombosis. The use of new US technological advances increases accuracy. Phlebography was less accurate than US.
    International angiology: a journal of the International Union of Angiology 12/2008; 27(6):466-74. · 1.46 Impact Factor
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    Jornal Vascular Brasileiro 01/2008; 7(2).
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    ABSTRACT: Background Diet composition is one of the factors that may contribute to intraindividual variability in the anticoagulant response to warfarin. Aim of the study To determine the associations between food pattern and anticoagulant response to warfarin in a group of Brazilian patients with vascular disease. Methods Recent and usual food intakes were assessed in 115 patients receiving warfarin; and corresponding plasma phylloquinone (vitamin K1), serum triglyceride concentrations, prothrombin time (PT), and International Normalized Ratio (INR) were determined. A factor analysis was used to examine the association of specific foods and biochemical variables with anticoagulant data. Results Mean age was 59 ± 15 years. Inadequate anticoagulation, defined as values of INR 2 or 3, was found in 48% of the patients. Soybean oil and kidney beans were the primary food sources of phylloquinone intake. Factor analysis yielded four separate factors, explaining 56.4% of the total variance in the data set. The factor analysis revealed that intakes of kidney beans and soybean oil, 24-h recall of phylloquinone intake, PT and INR loaded significantly on factor 1. Triglycerides, PT, INR, plasma phylloquinone, and duration of anticoagulation therapy loaded on factor 3. Conclusions Fluctuations in phylloquinone intake, particularly from kidney beans, and plasma phylloquinone concentrations were associated with variation in measures of anticoagulation (PT and INR) in a Brazilian group of patients with vascular disease.
    European Journal of Nutrition 06/2007; 46(3):147-154. · 3.13 Impact Factor
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    Jornal Vascular Brasileiro 03/2007; 6(1):7-16.
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    ABSTRACT: Venous thrombosis (VT) and inflammation are two closely related entities. In the present investigation we assessed whether there is a relation between genetic modifiers of the inflammatory response and the risk of VT. 420 consecutive and unrelated patients with an objective diagnosis of deep VT and 420 matched controls were investigated. The frequencies of the following gene polymorphisms were determined in all subjects: TNF-alpha-308 G/A, LT-alpha+252 A/G, IL-6-174 G/C, IL1-ra 86 bp VNTR, IL-10-1082 A/G and CD-31 125 C/G. Overall odds ratio (OR) for VT related to TNF-alpha-308 G/A, LT-alpha+252 A/G, IL-6-174 G/C, A1 allele (4 bp repeat) of the IL1-ra 86 bp VNTR, IL-10-1082 A/G and CD-31 125 C/G were respectively: 1.0 (CI95: 0.8-1.5), 1.3 (CI95: 1.0-1.7), 1.1 (CI95: 0.9-1.5), 1.6 (CI95: 1-2.5), 1.2 (CI95: 0.8-1.7) and 0.8 (CI95: 0.6-1.1). A possible interaction between polymorphisms was observed only for the co-inheritance of the mutant alleles of the LT-alpha+252 A/G and IL-10-1082 G/A polymorphisms (OR=2; CI95: 1.1-3.8). The risk of VT conferred by factor V Leiden and FII G20210A was not substantially altered by co-inheritance with any of the cytokine gene polymorphisms. Cytokine gene polymorphisms here investigated did not significantly influence venous thrombotic risk.
    Thrombosis Research 02/2007; 120(2):221-9. · 3.13 Impact Factor
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    Thrombosis Research 02/2007; 119(2):183-8. · 3.13 Impact Factor
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    ABSTRACT: The risk for venous thromboembolism (VTE) in medical patients is high, but risk assessment is rarely performed because there is not yet a good method to identify candidates for prophylaxis. To perform a systematic review about VTE risk factors (RFs) in hospitalized medical patients and generate recommendations (RECs) for prophylaxis that can be implemented into practice. A multidisciplinary group of experts from 12 Brazilian Medical Societies searched MEDLINE, Cochrane, and LILACS. Two experts independently classified the evidence for each RF by its scientific quality in a standardized manner. A risk-assessment algorithm was created based on the results of the review. Several VTE RFs have enough evidence to support RECs for prophylaxis in hospitalized medical patients (eg, increasing age, heart failure, and stroke). Other factors are considered adjuncts of risk (eg, varices, obesity, and infections). According to the algorithm, hospitalized medical patients > or =40 years-old with decreased mobility, and > or =1 RFs should receive chemoprophylaxis with heparin, provided they don't have contraindications. High prophylactic doses of unfractionated heparin or low-molecular-weight-heparin must be administered and maintained for 6-14 days. A multidisciplinary group generated evidence-based RECs and an easy-to-use algorithm to facilitate VTE prophylaxis in medical patients.
    Vascular Health and Risk Management 01/2007; 3(4):533-53.
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    ABSTRACT: Ximelagatran has been recently studied for prophylaxis in surgical orthopedic cases. We proposed to establish whether interventions involving ximelagatran, as compared with warfarin, would increase thromboembolic prophylaxis in patients undergoing major orthopedic knee surgery. Studies with random assignment were identified by an electronic search of the medical literature up to 2006. Data were double-entered into the Review Manager software, version 4.2.5. We included three well-conducted clinical trials involving 4,914 participants. Sub-groups with two dosages of ximelagatran (24 mg and 36 mg, b.i.d.), were defined. Ximelagatran showed significantly lower frequency of total venous thromboembolism (VTE) than warfarin, but only with the 36-mg dosage (risk relative, RR: 0.72; 95% confidence interval, CI: 0.64-0.81; p < 0.00001). For the 24-mg subgroup, total VTE frequency was similar (RR: 0.86; 95% CI: 0.73-1.01; p = 0.06). No significant differences were shown with either ximelagatran dosage for deep vein thrombosis (DVT), pulmonary embolism, any bleeding or severe bleeding. At the end of the treatment, alanine aminotransferase (ALT) elevation was less frequent in the 24-mg ximelagatran sub-group (RR: 0.33; 95% CI: 0.12-0.91; p = 0.03], but during the follow-up period, the ALT elevation rate was greater in the 36-mg ximelagatran group (RR: 6.97; 95% CI: 1.26-38.50; p = 0.03]. Ximelagatran appears to be more effective than warfarin when used in higher dosages (36 mg b.i.d.), but at the expense of increased frequency of ALT elevation during the follow-up period.
    Sao Paulo Medical Journal 11/2006; 124(6):355-61. · 0.59 Impact Factor
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    Antônio Tadeu de Souza Faleiros, Francisco Humberto de Abreu Maffei, Luiz Antonio de Lima Resende
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    ABSTRACT: This study investigates the role of cervical sympathectomy in the prevention of acute vasospasm induced by meningeal haemorrhage in rabbits. Sixteen adult English Norfolk rabbits were divided into 2 experimental groups: bilateral cervical sympathectomy of the superior sympathetic ganglion (SSSG, n=8), and bilateral SSSG and sympathectomy of the inferior sympathetic ganglion (SISG, n=8). Other 24 animals were used as controls. Basilar artery diameter was evaluated by angiography. SSSG protected the animals against developing cerebral vasospasm; SSSG associated with SISG did not increase this effect.
    Arquivos de Neuro-Psiquiatria 10/2006; 64(3A):572-4. · 0.83 Impact Factor
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    ABSTRACT: OBJECTIVE: To prospectively study the frequency of complications in patients treated with warfarin followed at Botucatu Medical School. METHODS: Patients randomly selected among those with appointments scheduled from June 2002 to February 2004. At the first appointment, a protocol was filled with identification and clinical data. At every return or when the patient went to the hospital due to clinical events, another form was filled with the international normalized ratio, existence and type of clinical event and the conditions of use of vitamin K antagonists. RESULTS: A total of 136 patients (61 men and 75 women), were followed; 99 patients with venous thromboembolism and 37 with arterial disease; 59 were from Botucatu and 77 were from other municipalities. Thirty clinical events were registered: nine of them were not related to the use of warfarin and 21 were hemorrhagic complications (38.8 per 100 patients-year). One hematemesis was considered severe (1.9 per 100 patients-year). The others were considered moderate or mild. There were no deaths, intracranial hemorrhage or cutaneous necrosis. The only significant association was frequency of hemorrhage and average international normalized ratio level. CONCLUSION: Our results demonstrate the feasibility of this treatment in vascular patients in our country, even in socially and economically poor populations, when treated in specialized clinics.
    Jornal Vascular Brasileiro 09/2006; 5(3):194-202.
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    ABSTRACT: Although effective strategies for the prevention of venous thromboembolism (VTE) are widely available, a significant number of patients still develop VTE because appropriate thromboprophylaxis is not correctly prescribed. We conducted this study to estimate the risk profile for VTE and the employment of adequate thromboprophylaxis procedures in patients admitted to hospitals in the state of São Paulo, Brazil. Four hospitals were included in this study. Data on risk factors for VTE and prescription of pharmacological and non-pharmacological thromboprophylaxis were collected from 1454 randomly chosen patients (589 surgical and 865 clinical). Case report forms were filled according to medical and nursing records. Physicians were unaware of the survey. Three risk assessment models were used: American College of Chest Physicians (ACCP) Guidelines, Caprini score, and the International Union of Angiololy Consensus Statement (IUAS). The ACCP score classifies VTE risk in surgical patients and the others classify VTE risk in surgical and clinical patients. Contingency tables were built presenting the joined distribution of the risk score and the prescription of any pharmacological and non-pharmacological thromboprophylaxis (yes or no). According to the Caprini score, 29% of the patients with the highest risk for VTE were not prescribed any thromboprophylaxis. Considering the patients under moderate, high or highest risk who should be receiving prophylaxis, 37% and 29% were not prescribed thromboprophylaxis according to ACCP (surgical patients) and IUAS risk scores, respectively. In contrast, 27% and 42% of the patients at low risk of VTE, according to Caprini and IUAS scores, respectively, had thromboprophylaxis prescribed. Despite the existence of several guidelines, this study demonstrates that adequate thromboprophylaxis is not correctly prescribed: high-risk patients are under-treated and low-risk patients are over-treated. This condition must be changed to insure that patients receive adequate treatment for the prevention of thromboembolism.
    Journal of Thrombosis and Haemostasis 07/2006; 4(6):1266-70. · 6.08 Impact Factor
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    ABSTRACT: To compare the efficacy and safety of a low molecular weight heparin (enoxaparin) with unfractionated heparin (UH) in this prophylaxis. Seventy five patients (59 men and 16 women), undergoing major lower extremity amputation (30 above-knee and 45 below-knee), were randomized to be treated with subcutaneous UH (5,000 IU t.i.d.) or enoxaparin (40 mg/day) during hospitalization. Prophylaxis was started 12 hours before surgery or, in emergency cases, in the first postoperative day. The two groups were comparable with regard to baseline characteristics. Evaluation of DVT was performed by daily clinical examination and by duplex scanning before and 5 to 8 days after surgery. DVT was documented in the operated limb in 9.75% in patients treated with enoxaparin and in 11.76% in patients treated with UH (p=0.92) and there was one bilateral thrombosis in each group . Bleeding complications were not observed in both groups. Enoxaparin and UH were both efficient and safe for the prophylaxis of DVT in patients submitted to lower extremity amputation.
    Acta Cirurgica Brasileira 01/2006; 21(3):184-6. · 0.63 Impact Factor
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    Jornal Vascular Brasileiro 01/2006; 5(3).

Publication Stats

400 Citations
96.41 Total Impact Points

Institutions

  • 2012
    • Santa Casa de São Paulo
      San Paulo, São Paulo, Brazil
  • 2007
    • Duke University
      Durham, North Carolina, United States
  • 1987–2007
    • São Paulo State University
      • • Faculdade de Medicina de Botucatu
      • • Department of Surgery and Orthopaedics
      San Paulo, São Paulo, Brazil
  • 2006
    • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
    • Hospital Sirio Libanes
      Potengy, Rio Grande do Norte, Brazil
  • 2002
    • Instituto Butantan
      • Laboratório de Farmacologia
      São Paulo, Estado de Sao Paulo, Brazil
  • 1999–2001
    • University of São Paulo
      • Faculdade de Medicina de Ribeirão Preto (FMRP)
      São Paulo, Estado de Sao Paulo, Brazil