Navegando por Palavras-chave "Immunosuppression"

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    Alterações no perfil lipídico durante o primeiro ano após o transplante renal: Fatores de risco e a influência do regime imunossupressor
    (Universidade Federal de São Paulo (UNIFESP), 2010-07-28) Spinelli, Glaucio Amaral [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Aim: Dyslipidemia is a recognized risk factor associated with cardiovascular events after kidney transplantation, Cyclosporine (CSA), tacrolimus (TAC), mycophenolate (MMF), sirolimus (SRL), everolimus (EVR) and prednisone have differential effects on the development of dyslipidemia, This study analyzed the incidence, time-course, severity and risk factors associated with dyslipidemia during the first year after kidney transplantation, Methods: In a cohort of 474 kidney transplant recipients [CSA/SRL (n=137), CSA/MMF (n=58), CSA/EVR (n=47), SRL/MMF (n=32), TAC/SRL (n=86), TAC/MMF (n=114)] we evaluated the influence of demographics, clinical ouCOLomes and statin use on lipid profile changes [total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, non-HDL-C, COL/HDL-C, LDL-C/HDL-C, TG/HDL-C] during the first year after transplantation, Results: Lipid profile was within recommended ranges in 28% of patients pretransplant and in 10% at one year, with 27% of them receiving statins, LDL-C could not be measured due to high TG concentrations in 20% of patients, At one year, LDL-C < 100 mg/dl was observed in 31,8% of patients, Within this group around 35% of patients still showed lipid fractions or ratios outside recommended target concentrations, Age, gender, time on dialysis, new onset diabetes mellitus, use of CSA or SRL/EVR and dose of prednisone were independent risk factors associated with dyslipidemia at one year, Conclusion: One year after transplant dyslipidemia is almost universal, Modifiable risk factors include the type and dose of immunosuppressive drugs, he variable changes in all lipid fractions and ratios may limit proper therapeutic interventions.
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    Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats
    (Springer, 2012-03-01) Araujo, Leandro Pires [UNIFESP]; Truzzi, Renata Ramos; Florido Mendes, Gloria Elisa; Mendes Luz, Marcus Alexandre; Burdmann, Emmanuel A.; Oliani, Sonia Maria [UNIFESP]; São Paulo State Univ UNESP; Universidade Federal de São Paulo (UNIFESP); Sao Jose do Rio Preto Med Sch; Universidade de São Paulo (USP)
    Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. the most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity.Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups.CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration.ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.
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    Atividade inflamatória, oxidante e proliferativa em fígado e rim de ratos expostos ao crack
    (Universidade Federal de São Paulo, 2021-09-29) Souza, Daniel Vitor de [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; Peres, Rogerio Correa [UNIFESP]; http://lattes.cnpq.br/9555994793258800; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/7955161915979529; Universidade Federal de São Paulo (UNIFESP)
    O crack é uma das drogas ilícitas mais utilizadas ao redor do mundo, sendo o consumo e a disseminação desenfreada representam grande problema de saúde pública. O objetivo do presente estudo foi investigar os efeitos da exposição subaguda de crack no contexto inflamatório, oxidativo e proliferativo em fígado e rim de ratos Wistar. Para tanto, o trabalho foi dividido em 4 capítulos a citar: o Capítulo I foi dedicado a estabelecer uma revisão de literatura acerca do assunto; o Capítulo II apresentamos uma revisão de literatura intitulada “Genotoxicity, oxidative stress and inflammatory response induced by crack cocaine: relevance to carcingoenesis” publicada na Revista Environmental Science and Pollution Research; o Capítulo III apresentamos o artigo intitulado “Histopathological and inflammatory response in multiple organs of rats exposed to crack“, que foi aceito para a publicação na Revista International Journal of Environmental Health Research e finalmente o Capítulo IV apresentamos o artigo intitulado “Genomic instability suppresses toll like signaling pathway in rat liver exposed to crack cocaine, que foi aceito para publicação na revista In Vivo.
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    Avaliação da tolerabilidade do micofenolato de sódio com revestimento entérico em receptores de transplante renal
    (Universidade Federal de São Paulo (UNIFESP), 2016-12-31) Hiramoto, Liliane Lumi [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; http://lattes.cnpq.br/7250195328752808; http://lattes.cnpq.br/8553448242624876; Universidade Federal de São Paulo (UNIFESP)
    Introduction: The enteric coated mycophenolate sodium (EC-MPS) is an antiproliferative prodrug which acts in the biosynthesis of purines. A major limitation of the EC-MPS is the occurrence of gastrointestinal adverse events mostly. Thus, the modification of EC-MPS dose may be sufficient to relieve symptoms, but can result in subtherapeutic levels and increase the risk of acute rejection. Objectives: This study aims to evaluate the EC-MPS tolerability associated with TAC and PRED in renal transplant recipients. Methods: A retrospective study of a cohort of kidney transplants with living or deceased donors made between 01/01/2007 and 31/12/2011 at the Hospital do Rim to evaluate the tolerability of the EC-MPS and classification into five subgroups according to type of modification made (temporary reduction, definitive reduction, temporary interruption, definitive interruption and without modification). Results: The modification-free survival dose of EC-MPS was 49.8%. According to CTCAE, the gastrointestinal system had the highest incidence and was observed at all dose modification subgroups, with an incidence of 50% to TR, 47.3% for DR, 46.8% for TI and 37.0% for the subgroup DI. The main adverse events reported were diarrhea, CMV infection, and leukopenia. Secondary endpoints of incidence of BPAR were worse for the DI subgroup when compared to the others (DI 46.3% vs TR 28.6% vs DR 41.1% vs WM 25.8%; p <0.05). Conclusion: 50.2% of patients did not tolerate the use of EC-MPS and the three main causes of dose changes were gastrointestinal, infections and infestations and hematological changes. The adverse event of diarrhea was observed in over 37% of cases in all subgroups. The subgroup DI showed poor graft survival (44.4%) and patients survival (59.3%), and 40.9% of the patients had the infection as the main factor of drug discontinuation. In addition, the DI subgroup showed higher incidence of BPAR (46.3%) when compared to WM subgroup (25.8%), which may be associated with increased incidence of infectious adverse events type.
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    Cyclosporin A Treatment and Decreased Fungal Load/Antigenemia in Experimental Murine Paracoccidioidomycosis
    (Springer, 2011-03-01) Massuda, T. Y. C.; Nagashima, L. A.; Leonello, P. C.; Kaminami, M. S.; Mantovani, M. S.; Sano, A.; Uno, J.; Venancio, E. J.; Camargo, Z. P. [UNIFESP]; Itano, E. N.; Universidade Estadual de Londrina (UEL); Chiba Univ; Universidade Federal de São Paulo (UNIFESP)
    Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb). the cyclosporin A (CsA) is an immunosuppressant drug that inhibits calcineurin and has been described as a potential antifungal drug. the present study investigated the effect of CsA on the immune response, fungal load/antigenemia in experimental murine PCM. It was used four groups of BALB/c mice: (a) infected with 1 x 10(5) Pb18 yeast cells (Pb), (b) infected and treated with CsA every other day 10 mg/kg of CsA (s.c.) during 30 days (Pb/CsA), (c) treated with CsA (CsA) and (d) no infected/treated (PBS). the immune response was evaluated by lymphocyte proliferation, DTH assays to exoAgs, ELISA for IgG anti-gp43 (specific immune responses) and cytokine serum levels (IFN-gamma, TNF-alpha, IL-4 and IL-10). Fungal load was determined by lung colony-forming units (CFU) counts, lung and liver histopathology analysis and antigenemia determined by inhibition-ELISA. As expected, CsA was able to inhibit the specific cellular and humoral immune response (P < 0.05), with decrease in serum IFN-gamma, TNF-alpha and IL-4 levels (P < 0.05). Cyclosporin A treatment also resulted in significantly decreased lung Pb CFU (P < 0.05) as well as a lower number of yeasts in the lung and liver (P < 0.05) by histopathology. in concordance, the decreased antigenemia was observed in Pb/CsA group (P < 0.05). in conclusion, even with immunosuppressive action, treatment with CsA results in decreased lung fungal load/antigenemia in experimental PCM in BALB/c mice. Further study is required to determine whether this represents less severe disease or protection by CsA.
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    Disseminated cryptococcosis with skin lesions: report of a case series
    (Soc Brasileira Dermatologia, 2017) Hayashida, Marina Zoega [UNIFESP]; Seque, Camila Arai [UNIFESP]; Pasin, Victor Pavan [UNIFESP]; Enokihara, Mílvia Maria Simões e Silva [UNIFESP]; Porro, Adriana Maria [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Cryptococcosis is a common fungal infection in immunocompromised patients, caused by genus Cryptococcus, presenting with meningitis, pneumonia, and skin lesions. Cutaneous presentation can be varied, but specifically in solid organ transplant recipients (iatrogenically immunocompromised), cryptococcosis should always be considered in the differential diagnosis of cellulitis-like lesions, since the delay in diagnosis leads to worse prognosis and fatal outcome. We report four cases of cryptococcosis with cutaneous manifestation not only for its rarity, but also to emphasize the important role of the dermatologist in the diagnosis of this disease.
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    Efeito de suplementação de probióticos sobre função de monócitos após exercício extenuante
    (Universidade Federal de São Paulo (UNIFESP), 2016-03-30) Silva, Edgar Tavares da [UNIFESP]; Santos, Ronaldo Vagner Thomatieli dos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The performance of strenuous physical exercise induces acute physiological and biochemical responses with several immunosuppressant powers. Probiotic supplementation is an attempt to mitigate the effects of exercise on the innate immune system. Thus, the objective of this study was to verify the effects of probiotics supplementation on the function of monocytes after an acute long-term strenuous exercise. For this, seven participants were supplemented during thirty days (2.0 g/day of probiotics) and seven participants were supplemented during thirty days with placebo (2.0 g/day of corn starch). Posteriorly, they ran a marathon (42,195 m). Before the race, immediately after the exercise session and 1 hour after exercise, 30 ml of blood were collected for determination of the cellular function of monocytes, also for plasma cytokine dosages. A questionnaire was applied about infections in the upper respiratory tract symptoms - URTS during seven days after the strenuous exercise. The normality of the data was checked using the Shapiro-Wilk?s test and for statistical analysis we used the analysis of repeated measures General Linear Model (GLM) or Student t-test, with Post-Hoc Fisher?s LSD. The level of significance was p ? 5%. To perform the analyses was used software IBM SPSS Statistics 20. In our results, the production of monocytes stimulated with LPS in the placebo group had significant increase of IL-6 after the race and significant decrease of TNF-alpha, not being watched modifications in the levels of IL-1 and IL-10 p ? 5% . In the probiotic group significant differences were not found on the levels of IL-1, IL-6 and TNF-alpha, however, the results point to a significant increase in the production of IL-10 after the race of Marathon p ? 5%. In plasma levels were not found significant differences in both groups at concentrations of IL-2, IL-4 and IL-6. However, in the placebo group was observed significant increase of IL-10 and in the probiotic group TNF-alpha increase after a marathon p ? 5%. Moreover, our results showed that the supplementation of probiotics is associated with a smaller amount of upper respiratory tract symptoms and severity when compared with the placebo group, besides presenting a shorter recovery and a lower percentage of incidence of opportunistic infections.
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    Effect of oral sirolimus therapy on inflammatory biomarkers following coronary stenting
    (Associação Brasileira de Divulgação Científica, 2010-08-01) Rosa, Werther Clay Monico [UNIFESP]; Campos, Alexandre Holthausen [UNIFESP]; Lima, Valter Correia [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal do Espírito Santo Hospital Universitário Cassiano Antonio de Morais Disciplina de Cardiologia
    We studied the effect of oral sirolimus, administered to prevent and treat in-stent restenosis (ISR), on the variation of serum levels of inflammatory markers following coronary stenting with bare metal stents. The mean age of the patients was 56 ± 13 years, 65% were males and all had clinically manifested ischemia. Serum levels of high sensitivity C-reactive protein (hs-CRP) concentration were determined by chemiluminescence and serum levels of all other biomarkers by ELISA. One group of patients at high risk for ISR received a loading oral dose of 15 mg sirolimus and 5 mg daily thereafter for 28 days after stenting (SIR-G). A control group (CONT-G) was submitted to stenting without sirolimus therapy. The increase in hs-CRP concentration was highest at 24 h after stenting in both groups. A significant difference between SIR-G and CONT-G was observed at 4 weeks (-1.50 ± 5.0 vs -0.19 ± 0.4, P = 0.008) and lost significance 1 month after sirolimus discontinuation (-1.73 ± 4.3 vs -0.01 ± 0.7, P = 0.0975). A continuous fall in MMP-9 concentration was observed in SIR-G, with the greatest reduction at 4 weeks (-352.9 ± 455 vs +395.2 ± 377, P = 0.0004), while a positive variation was noted 4 weeks after sirolimus discontinuation (227 ± 708 vs 406.2 ± 472.1, P = 0.0958). SIR-G exhibited a higher increase in P-selectin after sirolimus discontinuation at week 8 (46.1 ± 67.9 vs 5.8 ± 23.7, P = 0.0025). These findings suggest that the anti-restenotic actions of systemic sirolimus include anti-proliferative effects and modulation of the inflammatory response with inhibition of adhesion molecule expression.
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    Evolução da gravidez e resultados perinatais em transplantadas renais
    (Federação Brasileira das Sociedades de Ginecologia e Obstetrícia, 2005-06-01) Oliveira, Leandro Gustavo de [UNIFESP]; Sass, Nelson [UNIFESP]; Camano, Luiz [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    PURPOSE: to evaluate the relationship between renal transplantation and pregnancy through the analysis of clinical and obstetric intercurrent events and perinatal outcomes. METHODS: a retrospective series of 39 cases of pregnancy in 37 women with renal transplantation from January 1997 to December 2003 was evaluated. A control group consisted of 66 pregnant women with no previous clinical pathologies. This group received prenatal care and these patients delivered during 2002 and 2003. Preeclampsia, premature rupture of membranes, premature delivery, and intrauterine growth restriction were used to compare these variables. Demographic characteristics of these groups were related to the mean age at conception, ethnic characteristics and obstetric past. Regarding renal transplantation the type of donator and used immunosuppressive drugs were evaluated. The studied clinical variables were chronic hypertension, anemia and urinary tract infection. The interval between the surgery and conception, occurrence of dysfunction, rejection and loss of the allograft were characteristcs related to the allograft. Obstetric variables were related to the type of delivery, incidence of preeclampsia and premature rupture of membranes. Perinatal outcomes were premature delivery and intrauterine growth restriction and these results were compared with renal function. The used statistical methods were the chi2 and Fisher's exact tests. The significance level was fixed always as less than or equal to 0.05 (5%). RESULTS: the mean age at conception was 27 years. The live donator was the most frequent among the patients. Among the immunosuppressive drugs, cyclosporine was the most used. Chronic hypertension occurred in 82% of the cases, anemia in 77% and urinary tract infection in 38.5%. The incidence of renal dysfunction was 47.4% and preeclampsia was the main cause. The loss of the renal transplantation occurred in 10.2%. Delivery by cesarean section was performed in 53.8% of the patients, and the main causes were hypertensive syndromes. Preeclampsia occurred in 28.2%. Among the perinatal outcomes, premature delivery occurred in 46.1% of the cases, with a significant relation to creatinine level greater than or equal to 1.5 mg/dL at the start of prenatal care. Another observed intercurrent event was intrauterine growth restriction, which occurred in 41.0%, and here we found no relation between this event and creatinine levels. CONCLUSIONS: young patients constituted the study group. Chronic hypertension, anemia and urinary tract infection were very common. Renal dysfunction was frequent and must be investigated during prenatal care. There were four cases of loss of the transplant due to clinical or obstetric causes. Cesarean delivery had the highest incidence, but vaginal delivery should be the first choice in these cases. Preeclampsia occurred very frequently and this complication should be considered as a high risk. Preterm delivery and intrauterine growth restriction were the main perinatal complications. Premature deliveries before 37 weeks of gestation were related to allograft function.
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    Importance of exercise immunology in health promotion
    (Springer, 2011-11-01) Rosa Neto, José Cesar [UNIFESP]; Lira, Fabio Santos de [UNIFESP]; Mello, Marco Tulio de [UNIFESP]; Santos, Ronaldo Vagner Thomatieli dos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Chronic physical exercise with adequate intensity and volume associated with sufficient recovery promotes adaptations in several physiological systems. While intense and exhaustive exercise is considered an important immunosuppressor agent and increases the incidence of upper respiratory tract infections (URTI), moderate regular exercise has been associated with significant disease protection and is a complementary treatment of many chronic diseases. the effects of chronic exercise occur because physical training can induce several physiological, biochemical and psychological adaptations. More recently, the effect of acute exercise and training on the immunological system has been discussed, and many studies suggest the importance of the immune system in prevention and partial recovery in pathophysiological situations. Currently, there are two important hypotheses that may explain the effects of exercise and training on the immune system. These hypotheses including (1) the effect of exercise upon hormones and cytokines (2) because exercise can modulate glutamine concentration. in this review, we discuss the hypothesis that exercise may modulate immune functions and the importance of exercise immunology in respect to chronic illnesses, chronic heart failure, malnutrition and inflammation.
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    Infections in heart transplant recipients in Brazil: the challenge of Chagas' disease
    (Elsevier B.V., 2010-03-01) Godoy, Henrique Luiz dos de [UNIFESP]; Guerra, Carla Morales [UNIFESP]; Viegas, Ruy Felipe Melo [UNIFESP]; Diniz, Rosiane Viana Zuza [UNIFESP]; Branco, João Nelson Rodrigues [UNIFESP]; Amato-Neto, Vicente; Almeida, Dirceu Rodrigues de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: Despite the high incidence of infections after heart transplantation, there is limited information about its epidemiology in patients from countries where Chagas' disease is endemic.METHODS: We analyzed the occurrence of infections in 126 patients aged older than 18 years who underwent transplantation from 1986 through 2007 at a Brazilian University Hospital and who survived at least 48 hours.RESULTS: Heart failure diagnoses before transplantation were idiopathic dilated cardiomyopathy (38.6%), Chagas' disease (34.9%), coronary artery disease (19.8%), and others (6.3%). the respiratory tract was the most common site of infections (40.9%), followed by surgical wound site (18.1%). Trypanosoma cruzi reactivations occurred in, 38.8% of Chagas' disease patients: 47.0% had myocarditis, 23.5% had skin lesions, and 29.4% had both. New-onset ventricular dysfunction was observed in 47.0%, with complete response after specific treatment, and 41.0% were asymptomatic cases, diagnosed by routine endomyocardial biopsies. No patient died from such events. No differences in survival were found after 5 years of follow-up between recipients with and without Chagas' disease (p = 0.231).CONCLUSIONS: in a heart transplant population from a developing country, infectious complications occurred at a high rate. Tropical illnesses were uncommon, except for the high rate of Chagas' disease reactivations. Despite that, the overall outcome of these patients was similar to that of recipients with other cardiomyopathies. J Heart Lung Transplant 2010;29:286-90 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved.
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    Interaction of the Anti-Inflammatory Annexin A1 Protein and Tacrolimus Immunosuppressant in the Renal Function of Rats
    (Karger, 2010-01-01) Araujo, Leandro P. [UNIFESP]; Truzzi, Renata R.; Mendes, Gloria E.; Luz, Marcus A. M.; Burdmann, Emmanuel A.; Oliani, Sonia M. [UNIFESP]; UNESP; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    Background: Tacrolimus (FK) is currently widely used in transplant immunosuppression and the treatment of autoimmune diseases. However, FK induces nephrotoxicity which is characterized by functional and structural renal injury. the ubiquitous protein annexin A1 (ANXA1) has potent anti-inflammatory effects and protects against ischemia/reperfusion injury. We investigated the effects of exogenous ANXA1 treatment in an experimental model of acute FK nephrotoxicity. Methods: Munich-Wistar rats received a low-salt diet for 1 week and were randomized to treatment with ANXA1 (Ac2-26 peptide 0.5 mg/kg/day s.c.), FK (6 mg/kg/day p.o.), association (FK+ANXA1) and vehicles (1 ml/kg/day) for 7 days. Results: FK induced a significant decrease in glomerular filtration rate and renal blood flow, and a significant increase in renal vascular resistance. in addition, FK caused extensive acute tubule-interstitial damage and an increase in anti-inflammatory ANXA1 expression in renal tissue. Exogenous ANXA1 treatment reduced FK-induced tubular dilatation and macrophage infiltration. for the first time, we observed that FK augmented ANXA1 expression in renal tissue. Conclusion: Exogenous ANXA1 treatment partially protected against FK-induced tubular injury and macrophage infiltration, and may be targeted in renal intervention strategies. Copyright (C) 2010 S. Karger AG, Basel
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    Interconsulta dermatológica a receptores de transplante renal hospitalizados: um estudo observacional
    (Universidade Federal de São Paulo (UNIFESP), 2017-02-24) Pereira, Amanda Regio [UNIFESP]; Tomimori, Jane [UNIFESP]; Porro, Adriana Maria [UNIFESP]; http://lattes.cnpq.br/7527051548277127; http://lattes.cnpq.br/1123390691453566; http://lattes.cnpq.br/3948704483698892; Universidade Federal de São Paulo (UNIFESP)
    Background: Considering the rise in number and survival of solid organ transplant recipients (SOTR), there is a growing need for outpatient and inpatient services specialized in the care of these individuals. Dermatological abnormalities are highly prevalent in the hospital setting and can represent cutaneous findings of potentially severe systemic diseases, especially among immunocompromised patients. Literature about inpatient dermatology is scarce and no research was found concerning dermatology consultations specifically for SOTR. Objective: To evaluate the performance of dermatology consultation for renal transplant recipients (RTR) hospitalized in a Brazilian tertiary referral hospital for kidney transplantation (Hospital do Rim e Hipertensão – HRH). Methods: This is a clinical, observational, retrospective and descriptive study. All dermatology consultations performed at HRH for RTR over 36 consecutive months were included. Data were gathered from an electronic database and patient charts. Results: A total of 180 dermatology consultations were requested, 176 of these for a RTR. Four patients which were not RTR were excluded from the analysis. Male (64.2%) and young (average ± standard-deviation: 46.9 ± 15.6 years) patients predominated. In most cases, the dermatological complaint had arisen before admission (71.6%) and had been present for 30 days or less (59.7%). Infectious dermatoses motivated more than half of the consultations (52.3%), followed by inflammatory skin conditions (14.2%), neoplasms (12.5%) and drug reactions (8.5%). Herpes simplex, dermatophytosis and prurigo were the commonest diagnoses. There were some differences between ours and other studies from general hospitals, such as: the larger proportion of infectious dermatoses and neoplasms; the lower proportion of inflammatory diseases; the higher percentage of patients submitted to skin biopsy (40.3%); the lower proportion of consultations that were managed with a single visit (43.8%) and the higher probability of a systemic treatment being recommended (45.5%). There was diagnostic agreement between the requesting team and dermatologists in only 38.1% of the cases. Dermatology assessment changed the admission diagnosis in 11.4% of the consultations. Most of the requests were motivated by disorders of secondary relevance considering the main clinical scenario. However, the dermatology consultation was classified as extremely relevant or important in 75% of the cases. It was possible to manage skin conditions that are relatively uncommon in different settings, what highlights the educational potential of the consultations in this setting. Conclusion: Hospitalized RTR have specific dermatological demands and peculiarities when compared to general inpatients. It was observed a higher proportion of cases that demanded skin biopsy, systemic treatment for the dermatological condition and more than one visit to conclude dermatological evaluation. These findings possibly suggest a higher level of complexity in this sample. Different clinical and epidemiological presentations were also detected, such as the larger proportion of infectious dermatoses and cutaneous malignancies. Most of the consultations were motivated by common dermatologic conditions, not related to the admission diagnosis. However, the specificities of the inpatients, as well as the low proportion of diagnostic agreement between requesting and consulting teams, justify the need for dermatology consultation in high complexity hospitals, such as HRH.
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    Pharmacokinetic/pharmacodynamic relationships of FTY720 in kidney transplant recipients
    (Associação Brasileira de Divulgação Científica, 2005-05-01) Park, Sung In [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Machado, Paula Goulart Pinheiro [UNIFESP]; Garcia, Riberto [UNIFESP]; Skerjanec, Andrej; Schmouder, Robert; Tedesco-Silva Junior, Hélio [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Novartis Pharmaceuticals
    FTY720 is a new and effective immunosuppressive agent, which produces peripheral blood lymphopenia through a lymphocyte homing effect. We investigated the relationship between the dose of FTY720 or blood concentration (pharmacokinetics, PK) and peripheral lymphopenia (pharmacodynamics, PD) in 23 kidney transplant recipients randomized to receive FTY720 (0.25-2.5 mg/day) or mofetil mycophenolate (2 mg/day) in combination with cyclosporine and steroids. FTY720 dose, blood concentrations and lymphocyte counts were determined weekly before and 4 to 12 weeks after transplantation. The effect of PD was calculated as the absolute lymphocyte count or its reductions. PK/PD modeling was used to find the best-fit model. Mean FTY720 concentrations were 0.36 ± 0.05 (0.25 mg), 0.73 ± 0.12 (0.5 mg), 3.26 ± 0.51 (1 mg), and 7.15 ± 1.41 ng/ml (2.5 mg) between 4 and 12 weeks after transplantation. FTY720 PK was linear with dose (r² = 0.98) and showed low inter- and intra-individual variability. FTY720 produced a dose-dependent increase in mean percent reduction of peripheral lymphocyte counts (38 vs 42 vs 56 vs 77, P < 0.01, respectively). The simple Emax model [E = (Emax * C)/(C + EC50)] was the best-fit PK/PD modeling for FTY720 dose (Emax = 87.8 ± 5.3% and ED50 = 0.48 ± 0.08 mg, r² = 0.94) or concentration (Emax = 78.3 ± 2.9% and EC50 = 0.59 ± 0.09 ng/ml, r² = 0.89) vs effect (% reduction in peripheral lymphocytes). FTY720 PK/PD is dose dependent and follows an Emax model (EC50 = 0.5 mg or 0.6 ng/ml). Using lymphopenia as an FTY720 PD surrogate marker, high % reductions (~80%) in peripheral lymphocytes are required to achieve best efficacy to prevent acute allograft rejection.
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    Preservation of graft function in low-risk living kidney transplant recipients treated with a combination of sirolimus and cyclosporine
    (Associação Brasileira de Divulgação Científica, 2004-09-01) Machado, Paula Goulart Pinheiro [UNIFESP]; Felipe, Claudia Rosso [UNIFESP]; Park, Sung In [UNIFESP]; Garcia, Riberto [UNIFESP]; Moreira, Silvia Regina Silva [UNIFESP]; Casarini, Dulce Elena [UNIFESP]; Franco, Marcello Fabiano de [UNIFESP]; Alfieri, F.; Tedesco-Silva Junior, Hélio [UNIFESP]; Pestana, Jose Osmar Medina [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Laboratórios Wyeth-Ayerst do Brasil
    The use of sirolimus (SRL) in combination with full doses of cyclosporin A (CsA) results in reduced one-year kidney allograft function, which is associated with shorter long-term allograft survival. We determined the effect of reduced CsA exposure on graft function in patients receiving SRL and prednisone. Ninety recipients of living kidney transplants receiving SRL (2 mg/day, po) were compared to 35 recipients receiving azathioprine (AZA, 2 mg kg-1 day-1, po). All patients also received CsA (8-10 mg kg-1 day-1, po) and prednisone (0.5 mg kg-1 day-1). Efficacy end-point was a composite of biopsy-confirmed acute rejection, graft loss, or death at one year. Graft function was measured by creatinine, creatinine clearance, and graft function deterioration between 3 and 12 months (delta1/Cr). CsA concentrations in patients receiving SRL were 26% lower. No differences in one-year composite efficacy end-point were observed comparing SRL and AZA groups (18 vs 20%) or in the incidence of biopsy-proven acute rejection (14.4 and 14.3%). There were no differences in mean ± SD creatinine (1.65 ± 0.46 vs 1.60 ± 0.43 mg/dl, P = 0.48) or calculated creatinine clearances (61 ± 15 vs 62 ± 13 ml/min, P = 0.58) at one year. Mean ± SD delta1/Cr (-11 ± 17 vs -14 ± 15%, P = 0.7) or the percentage of patients with >20% (26 vs 31%, P = 0.6) or >30% delta1/Cr (19 vs 17%, P = 1) did not differ between the two groups. The use of 2-mg fixed oral doses of SRL and reduced CsA exposure was effective in preventing acute rejection and preserving allograft function.
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    Prevalence and correlates of non-adherence to immunosuppressants and to health behaviours in patients after kidney transplantation in Brazil - the ADHERE BRAZIL multicentre study: a cross-sectional study protocol
    (Biomed Central Ltd, 2018) Sanders-Pinheiro, Helady; Basile Colugnati, Fernando Antonio; Marsicano, Elisa Oliveira; De Geest, Sabina; Pestana Medina, Jose Osmar [UNIFESP]
    Background: Non-adherence to immunosuppressive therapy is a prevalent risk factor for poor clinical and after kidney transplantation (KT), and has contributed to the lack of improvement in long-term graft survival over the past decade. Understanding the multilevel correlates and risk factors of non-adherence is crucial to determine the optimal level for planning interventions, namely at the patient, health care provider, KT centre, and health care system level. Brazil, having the largest public transplantation program in the world and with regional differences regarding access to health services and service implementation, is in a unique position to study this multilevel approach. Therefore, the Adhere Brazil Study (ADHERE BRAZIL) was designed to assess the prevalence and variability of non-adherence to immunosuppressants and to health behaviours among adult KT recipients in Brazil, and to assess the multilevel correlates of non-adherence to immunosuppressive medication. We describe the rationale, design, and methodology of the ADHERE BRAZIL study. Methods/Design: This is an observational, cross-sectional, multicentre study that includes 20 Brazilian KT centres. A stratified sampling approach is used, based on strata, with the following characteristics considered: geographical region and transplant activity (number of KTs per year). A random sample of patients (proportional to the size of the centre within each stratum) is selected from each centre. The prevalence of different health behaviours is assessed through self-report. The assessment of multilevel correlates of non-adherence is guided by the ecological model that considers factors at the level of the patient, health-care professional, and transplant centre, using established instruments or instruments developed for this study. Data will be collected over an 18-month period, with information obtained during the regular follow-up visits to the transplant outpatient clinic and directly entered into the Research Electronic Data Capture (RedCap) system. Data entry is performed by a trained professional who is part of the transplant team. The data collection began in December 2015. Discussion: This multicentre study is the first to evaluate multilevel correlates of non-adherence in KT patients and will provide a reliable estimate of non-adherence in Brazilian KT patients.
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    Prevalência de doença por citomegalovírus em pacientes transplantados renais com suspeita clínica desse diagnóstico
    (Universidade Federal de São Paulo (UNIFESP), 2017-04-28) Santos, Sanmya Danielle Rodrigues dos [UNIFESP]; Machado, Flavia Ribeiro [UNIFESP]; http://lattes.cnpq.br/1160079071166685; http://lattes.cnpq.br/0726019358724781; Universidade Federal de São Paulo (UNIFESP)
    Objectives - Cytomegalovirus (CMV) disease is one of the most frequent complications after kidney transplantation. Our objectives were to determine the prevalence of CMV disease among kidney transplant patients in the ICU who had a clinical suspicion of this complication, to identify its predisposing factors, and to analyze whether CMV disease impacts on the clinical evolution of these patients. Methods - In this retrospective observational study, we included all kidney transplant patients over 18 years of age, hospitalized for any reason in an intensive care unit (ICU), with at least one sampling of antigenemia or polymerase chain reaction (PCR) for CMV during the ICU stay. Patients who had graft loss more than 6 months ago, or those diagnosed with CMV at admission were excluded. CMV disease was defined as positive antigenemia at any level or a PCR above 500 log in the presence of symptoms. Results – We included 99 patients with a mean age of 53.4 ± 12.8 years being 71.6% male. All patients were using immunosuppression, but only 26 (26.3%) had received pulse therapy in the last six months, 32 (32.2%) had received thymoglobulin sometime in the past and 18 (18,2%) received thymoglobulin in the last year. Respiratory symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal symptoms (14%) were the main reasons for CMV laboratory sampling. CMV disease was diagnosed in 39 patients (39.4%), of whom 20 (51.2%) had positive antigenemia in the first sampling, four (10.3%) had positive antigenemia in the second sampling, and 15 (38.5% %) were diagnosed by PCR. Time since transplantation was shorter in those diagnosed with CMV disease than in those without this diagnosis (6.5 months and 31.2 months, p = 0.001). Both the use of pulse therapy in the last six months (41% and 16,9%, p = 0.008) as the previous use of thymoglobulin in the prior 12 months before admission (35.9% and 6.8%, p <0.001) were more frequent among those with CMV disease. In the logistic regression model, only the time since transplantation less than 6 months [OR 4.755 (95% CI -1.497 to 12.785, p = 0.007]) and thymoglobulin use in the last 12 months [OR 4.855 (CI 95% -1.334 to 17.530), p = 0.016] were associated with a higher frequency of CMV disease. There was no difference in the clinical evolution between patients with and without CMV disease. Conclusion: The prevalence of CMV disease in kidney transplant patients admitted to the ICU, in whom there is a clinical suspicion of this disease, is high. The predisposing factors independently associated with increased risk of CMV disease in this population were time since transplantation less than six months and thymoglobulin use in the prior year before admission. Patients with CMV disease did not have worse clinical outcomes as compared with patients without CMV.
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    Response to immunization in children born to renal transplant recipients using immunosuppressive drugs during gestation
    (Elsevier Sci Ltd, 2016) Dinelli, Maria Isabel Saraiva [UNIFESP]; Ono, Erika [UNIFESP]; Viana, Patricia Oliveira [UNIFESP]; Spina, Fernanda Garcia [UNIFESP]; Weckx, Lily Yin [UNIFESP]; Nunes dos Santos, Amelia Miyashiro [UNIFESP]; de Moraes-Pinto, Maria Isabel [UNIFESP]
    The use of immunosuppressive drugs can impair vaccination responses. When used during pregnancy, they may interfere with the development of the fetus's immune system. However, little is known regarding their influence on infant's response to vaccinations. Twenty-seven children born to renal transplant mothers (Tx) taking immunosuppressive drugs and 31 healthy children had the humoral immune response and reactogenicity to tetanus, Haemophilus influenzae type b (Hib) and 7 pneumococcal serotypes evaluated. The evolution of BCG vaccine scar was also registered. Antibodies were measured by ELISA. Lymphocyte immunophenotyping was performed on cord blood and at 7-8 months of age. Among Tx neonates, 82.4% had low B lymphocyte numbers at birth, and 29.4% had also low numbers of other lymphocyte subpopulations. Nevertheless, all children developed protective antibodies with similar antibody concentrations to the control group. Vaccine reactogenicity was similar in both groups and BCG healing was uneventful. (C) 2015 Elsevier Ltd. All rights reserved.
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    Response to immunization in children born to renal transplant recipients using immunosuppressive drugs during gestation
    (Elsevier Sci Ltd, 2016) Dinelli, Maria Isabel Saraiva [UNIFESP]; Ono, Erika [UNIFESP]; Viana, Patricia Oliveira [UNIFESP]; Spina, Fernanda Garcia [UNIFESP]; Weckx, Lily Yin [UNIFESP]; Nunes dos Santos, Amelia Miyashiro [UNIFESP]; de Moraes-Pinto, Maria Isabel [UNIFESP]
    The use of immunosuppressive drugs can impair vaccination responses. When used during pregnancy, they may interfere with the development of the fetus's immune system. However, little is known regarding their influence on infant's response to vaccinations. Twenty-seven children born to renal transplant mothers (Tx) taking immunosuppressive drugs and 31 healthy children had the humoral immune response and reactogenicity to tetanus, Haemophilus influenzae type b (Hib) and 7 pneumococcal serotypes evaluated. The evolution of BCG vaccine scar was also registered. Antibodies were measured by ELISA. Lymphocyte immunophenotyping was performed on cord blood and at 7-8 months of age. Among Tx neonates, 82.4% had low B lymphocyte numbers at birth, and 29.4% had also low numbers of other lymphocyte subpopulations. Nevertheless, all children developed protective antibodies with similar antibody concentrations to the control group. Vaccine reactogenicity was similar in both groups and BCG healing was uneventful. (C) 2015 Elsevier Ltd. All rights reserved.
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    Sepsis in Solid-Organ Transplant Patients
    (Lippincott Williams & Wilkins, 2017) Bafi, Antonio Tonete [UNIFESP]; Tomotani, Daniere Yurie Vieira [UNIFESP]; Freitas, Flavio Geraldo Rezende [UNIFESP]
    The growing population of solid organ transplant (SOT) recipients is at a significantly increased risk for developing infections. In some patients, the infection can lead to a dysregulated systemic inflammatory response with acute organ dysfunction. SOT recipients with sepsis tend to have less fever and leukocytosis instances. Moreover, they have diminished symptoms and attenuated clinical and radiologic findings. The current management of sepsis is similar to general patients. It relies mainly on early recognition and treatment, including appropriate administration of antibiotics and resuscitation with intravenous fluids and vasoactive drugs when needed. The infusion of fluids should be closely monitored because elevated central venous pressure levels and fluid overload can be particularly harmful. There is no consensus on how to manage immunosuppressive therapies during sepsis, although dose reduction or withdrawal is suggested to improve the host immunological response. There is compelling evidence suggesting that infections are associated with reduced allograft and patient survival. However, the traditional belief that SOT patients who develop sepsis have worse outcomes than non-transplanted patients has been challenged.