NAIRO MASSAKAZU SUMITA
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
LIM/03 - Laboratório de Medicina Laboratorial, Hospital das Clínicas, Faculdade de Medicina
18 resultados
Resultados de Busca
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- UPLC-MS/MS assay validation for tacrolimus quantitative determination in peripheral blood T CD4+and B CD19+lymphocytes(2018) ROMANO, Paschoalina; FERNANDES, Maria da Luz; EBNER, Persio de Almeida Rezende; OLIVEIRA, Nayara Duarte de; OKUDA, Larissa Mitsue; AGENA, Fabiana; MENDES, Maria Elizabete; SUMITA, Nairo Massakazu; COELHO, Veronica; DAVID-NETO, Elias; GALANTE, Nelson ZocolerMonitoring tacrolimus (Tac) exposure in cell matrices enriched with lymphocytes can improve Tac therapeutic drug monitoring (TDM) in solid organ transplant recipients. An UPLC-MS/MS based assay for Tac quantification in peripheral blood T CD4+ and B CD19+ lymphocytes was developed. Peripheral blood mononuclear cells (PBMC) were obtained by density gradient centrifugation and highly purified (purity >90%) T CD4+ and B CD19+ cell suspensions were acquired by magnetic negative selection from whole blood of 6 healthy volunteers. The purity of lymphocyte suspensions was checked by flow cytometry. Tac extraction was performed in a liquid-liquid zinc sulfate, methanol and acetonitrile based medium. Ascomycin was used as internal standard. The equipment used was a Waters (R) Acquity (TM) UPLC system (Waters Corporation, Milford, MA, USA). The chromatographic run was performed on a Waters (R) MassTrak TDM C18 (2.1 x 10 mm) column (Waters Corporation, Milford, MA, USA). at a flow rate of 0.4 mL/min. The instrument was set in electrospray positive ionization mode. The method was validated according to Clinical Laboratory Standard Institute (CLSI) guidelines and showed a high sensitivity and specificity over a range of 0-5.2 ng/mL in PBMC, 0-5.0 ng/mL in T CD4+ Lymphocytes and 0-5.3 ng/mL in B CD19+ lymphocytes. Precision was appropriate with CV of intra-assay quantifications ranging from 4.9 to 7.4%, and of inter-assay quantifications from 7.2 to 13.9%. Limit of detection and quantification were 0.100 and 0.115 ng/mL in PBMC, 0.058 and 0.109 ng/mL in T CD4+ and 0.017 and 0.150 ng/mL in B CD19+ cells. Matrix effect was not significant among all the studied matrices. Samples showed stability for Tac quantification over a period of 90 days either at room temperature or at -30 degrees C storage conditions. The method was applied to clinical samples of 20 kidney transplant recipients. Concentrations ranged from 2.200 to 11.900 ng/mL in whole blood, from 0.005 to 0.570 ng/10(6) cells in PBMC, from 0.081 to 1.432 ng/10(6) cells in T CD4+, and from 0.197 to 1.564 ng/10(6) cells in B CD19+ cell matrices. The method has potential applicability for Tac TDM in solid organ transplant recipients.
- Diminished Mycophenolic Acid Exposure Caused by Omeprazole May Be Clinically Relevant in the First Week Posttransplantation(2012) DAVID-NETO, Elias; TAKAKI, Kelly M.; AGENA, Fabiana; ROMANO, Paschoalina; SUMITA, Nairo M.; MENDES, Maria E.; NERI, Leticia Aparecida Lopes; NAHAS, William C.Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant. Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC) 0-12h] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials. Results: For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC(0-12h) (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10-12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58-0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng.h/mL) was higher at most periods in the PPI group but again not statistically significant. Conclusions: These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.
article Pharmacokinetics of 6-thioguanine nucleotide and 6-methyl-mercaptopurine in a case of inadvertent combination therapy of azathioprine with allopurinol(2012) PACHECO-NETO, Maurílio; ALVES, Atecla N. L; FORTINI, Alexandre S.; SUMITA, Nairo M.; MENDES, Maria E.; TORRES, Larissa H. L.; DULEY, John A.; NAHAS, William C.; CHOCAIR, Pedro R.Background: Allopurinol was invented originally to improve response to thiopurine drugs, such as azathioprine (AZA) and mercaptopurine, but if they are given in combination then the thiopurine dose must be drastically reduced to about one third of a normal dose. Failure to reduce the thiopurine dose can cause severe toxicity, and has resulted in allopurinol usually being contraindicated for patients taking thiopurines. Case report: We present a case of a 44 year old female patient who received a renal transplant in 2001, with mycophenylate/tacrolimus/prednisolone immunosuppression. In 2004 the patient experienced gout symptoms and was prescribed 100 mg allopurinol per day. In 2008, her mycophenylate was replaced with 150 mg AZA. Within four weeks the patient was hospitalized suffering from severe myelotoxicity, with high blood levels of the AZA metabolite thioguanine nucleotide (6-TGN). AZA was stopped, with recovery of hematological parameters and elimination of AZA metabolites requiring a further two weeks. Discussion: This case demonstrates the risk of rapid-onset myelotoxicity due to AZA/ allopurinol co-therapy without correct dose adjustment of these drugs. The availability of routine analysis of AZA metabolites was useful for rapidly diagnosing the cause of the toxicity and monitoring recovery. Interestingly, the half-life of AZA metabolites after cessation of therapy (5.5 days for 6-TGN, 4 days for 6-MMP) was comparable to values in the absence of allopurinol: this excluded the elevation of 6-TGN being caused by an increased half-life.- Interferon lambda and hepatitis C virus core protein polymorphisms associated with liver cancer(2016) MOREIRA, Joao Paulo; MALTA, Fernanda de Mello; DINIZ, Marcio Augusto; KIKUCHI, Luciana; CHAGAS, Aline Lopes; LIMA, Livia de Souza Botelho; GOMES-GOUVEA, Michele Soares; CASTRO, Vanessa Fusco Duarte de; SANTANA, Rubia Anita Ferraz; SUMITA, Nairo Massakazu; VEZOZZO, Denise Cerqueira Paranagua; CARRILHO, Flair Jose; PINHO, Joao Renato RebelloBackground: Hepatitis C virus (HCV) infection is often persistent and gradually advances from chronic hepatitis to liver cirrhosis and hepatocellular carcinoma (HCC). Worldwide, hepatocellular carcinoma is the fifth most common neoplasm. Method of study: the Interferon lambda (IFNL) polymorphisms genotypes (rs8099917, rs12979860 and rs12980275) and the presence of mutations in HCV core protein were analyzed in 59 patients with HCC, and also in 50 cirrhotic patients (without HCC). Results: the rs12980275-AG genotype was associated with HCC on age-adjusted analysis (OR 2.42, 95% CI 1.03-5.69, P=0.043). Core substitutions R70Q and L91M were mainly found in genotype 1b isolates. Furthermore, a borderline level of statistical significance association was found among the presence of amino acid Glutamine (Q) in the position 70 and IFNL3 genotype AG (P=0.054). Conclusions: the screening of these polymorphisms and functional studies would be useful in clinical practice for identifying groups at high risk of HCC development.
- Validation protocol for multiple blood gas analyzers in accordance with laboratory accreditation programs(2015) EBNER, Pérsio A. R.; ROMANO, Paschoalina; SANT’ANNA, Alexandre; MENDES, Maria Elizabete; OLIVEIRA, Magna; SUMITA, Nairo M.Introduction: The results of blood gas analysis using different instrumentation can vary widely due to the methodological differences, the calibration procedures and the use of different configurations for each type of instrument. Objective: The objective of this study was to evaluate multiple analytical systems for measurement of blood gases, electrolytes and metabolites in accordance with the accreditation program (PALC) of Sociedade Brasileira de Patologia Clínica/Medicina Laboratorial (SBPC/ML). Materials and methods:20 samples were evaluated in three ABL800 Flex (Radiometer Medical ApS, Denmark) blood gas analyzers, and the results were compared with those of the device in use, which was considered the reference. The analysis of variance (Anova) was applied for statistical purposes, as well as the calculation of mean, standard deviation and coefficient of variation.Results:The p values obtained in the statistical analysis were: pH = 0.983, pO2 = 0.991, pCO2 = 0.353, lactate = 0.584, glucose = 0.995, ionized calcium = 0.983, sodium = 0.991, potassium = 0.926, chlorine = 0.029. Conclusion: The evaluation of multiple analytical systems is an essential procedure in the clinical laboratory for quality assurance and accuracy of the results.
- Proteína C reativa: aplicações clínicas e propostas para utilização racional(2013) AGUIAR, Francisco J. B.; FERREIRA-JUNIOR, Mario; SALES, Maria M.; CRUZ-NETO, Luiz M.; FONSECA, Luiz A. M.; SUMITA, Nairo M.; DUARTE, Nilo J. C.; LICHTENSTEIN, Arnaldo; DUARTE, Alberto J. S.C-reactive protein (CRP) is an acute-phase protein whose requests have been growing exponentially in several countries, including Brazil. In this study, the use of CRP in several clinical situations was reviewed by a group of physicians comprised by specialists in internal medicine, medical emergencies, intensive care, screening, and laboratory medicine, aiming to analyze the applicable literature and to propose guidelines for a more rational use of this laboratory test. The result was the creation of flowcharts guiding CRP request, adjusted to four different healthcare environments, namely, intensive care units, emergency room, wards; and outpatient clinics. These flowcharts, as well as a more detailed discussion on several clinical recommendations for the test, are presented in this study.
- N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis(2014) GUIMARAES, Luciana Pache de Faria; SEGURO, Antonio Carlos; SHIMIZU, Maria Heloisa Mazzola; NERI, Leticia Aparecida Lopes; SUMITA, Nairo Massakasu; BRAGANCA, Ana Carolina de; VOLPINI, Rildo Aparecido; SANCHES, Talita Rojas Cunha; FONSECA, Fernanda Andrade Macaferri da; MOREIRA FILHO, Carlos Alberto; VAISBICH, Maria HelenaNephropathic cystinosis is an autosomal recessive systemic severe disease characterized by intralysosomal cystine storage. Cysteamine is an essential component of treatment. There is solid evidence that cystine accumulation itself is not responsible for all abnormalities in cystinosis; there is also a deficiency of glutathione in the cytosol. Patients with cystinosis can be more susceptible to oxidative stress. The patient cohort comprised 23 cystinosis patients (16 males) aged < 18 years (mean age 8.0 +/- 3.6 years) with chronic kidney disease class I-IV with good adherence to treatment, including cysteamine. Oxidative stress was evaluated based on the levels of serum thiobarbituric acid-reactive substances (TBARS), and renal function was evaluated based on serum creatinine and cystatin C levels and creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant drug was given to all patients for 3 months (T1) at 25 mg/kg/day divided in three doses per day. The measured values at just before the initiation of NAC treatment (T0) served as the control for each patient. Median serum TBARS levels at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2) nmol/mL, respectively (p < 0.0001). In terms of renal function at T0 and T1, serum creatinine levels (1.1 +/- 0.5 vs. 0.9 +/- 0.5 mg/dL, respectively; p < 0.0001), creatinine clearance (69.7 +/- 32.2 vs. T1 = 78.5 +/- 33.9 mL/min/1.73 m(2), respectively; p = 0.006), and cystatin c level (1.33 +/- 0.53 vs. 1.15 +/- 0.54 mg/l, respectively; p = 0.0057) were all significantly different at these two time points. Serum creatinine measurements at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated. During the 3-month period that our 23 cystinosis patients were treated with NAC, oxidative stress was reduced and renal function significantly improved. No side-effects were detected. Larger and controlled studies are needed to confirm these findings.
- Evaluation of PSA requests in men under 40 years of age(2020) ARAÚJO, Fernando Antonio G. R; BITTENCOURT, Luana A; SUMITA, Nairo M; BARROSO JR., Ubirajara OABSTRACT Objectives: To evaluate the frequency of PSA requests in men under age 40 years; and to observe the possible influence of medical specialty of the requesting physician. Material and method: This is an observational, cross-sectional study using the database of a national clinical laboratory on PSA requests from October 1, 1997 until December 31, 2016. Descriptive statistics were used. The work was approved by the Ethics Committee of our institution. Results: 2,514,375 PSA requests were evaluated, 158,399 (6.3%) in men younger than 40 years old. These percentages did not vary significantly when observed over time (1998-2016). The prevalence of requests for patients under 40 years of age, was 18.2% among general practitioners; 16.5% among cardiologists, 8.4% among geriatricians and 6.8% among urologists. Conclusion: There is a very high frequency of PSA requests in men with low probability of benefiting from the test. It is necessary to invest in the dissemination of best practices related to prostate cancer screening, especially among clinicians and cardiologists.
- Perception of usefulness of laboratory tests ordering by internal medicine residents in ambulatory setting: A single-center prospective cohort study(2021) DOI, Dimitria; VALE, Romulo Ribeiro do; MONTEIRO, Jean Michell Correia; PLENS, Glauco Cabral Marinho; FERREIRA JUNIOR, Mario; FONSECA, Luiz Augusto Marcondes; PERAZZIO, Sandro Felix; BESEN, Bruno Adler Maccagnan Pinheiro; LICHTENSTEIN, Arnaldo; TANIGUCHI, Leandro Utino; SUMITA, Nairo Massakazu; CORA, Aline Pivetta; EISENCRAFT, Adriana Pasmanik; DUARTE, Alberto Jose da SilvaThe demand for high value health care uncovered a steady trend in laboratory tests ordering and inappropriate testing practices. Residents' training in laboratory ordering practice provides an opportunity for quality improvement. We collected information on demographics, the main reason for the appointment, preexisting medical conditions and presence of co-morbidities from first-visit patients to the internal medicine outpatient service of our university general hospital. We also collected information on all laboratory tests ordered by the attending medical residents. At a follow-up visit, we recorded residents' subjective perception on the usefulness of each ordered laboratory test for the purposes of diagnosis, prognosis, treatment or screening. We observed that 17.3% of all ordered tests had no perceived utility by the attending resident. Tests were usually ordered to exclude differential diagnoses (26.7%) and to help prognosis estimation (19.1%). Age and co-morbidity influenced the chosen category to legitimate usefulness of tests ordering. This study suggests that clinical objectives (diagnosis, prognosis, treatment or prevention) as well as personalization to age and previous health conditions should be considered before test ordering to allow a more appropriate laboratory tests ordering, but further studies are necessary to examine this framework beyond this medical training scenario.
- Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation(2022) BUSATTO, Geraldo F.; ARAUJO, Adriana Ladeira de; CASTALDELLI-MAIA, Joao Mauricio; DAMIANO, Rodolfo Furlan; IMAMURA, Marta; GUEDES, Bruno F.; PINNA, Fabio de Rezende; SAWAMURA, Marcio Valente Yamada; MANCINI, Marcio C.; SILVA, Katia R. da; GARCIA, Michelle L.; SUMITA, Nairo; BRUNONI, Andre Russowsky; DUARTE, Alberto J. da Silva; BURDMANN, Emmanuel A.; KALLAS, Esper G.; CERRI, Giovanni G.; NITRINI, Ricardo; BENTO, Ricardo F.; ROCHA, Vanderson Geraldo; SOUZA, Heraldo Possolo de; MIGUEL, Euripedes C.; CARVALHO, Carlos R. R. de; FORLENZA, Orestes V.; BATISTELLA, Linamara RizzoBackground Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. Methods We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 +/- 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. Results The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p <= 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. Conclusions Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.