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1.
RSC Adv ; 10(18): 10646-10660, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35492913

RESUMO

A controlled synthesis of methotrexate (MTX) silver nanoparticles (AgNPs-MTX) using borohydride and citrate as reduction and reduction/capping agents, respectively, was performed in order to obtain AgNPs-MTX conjugates with a narrow size distribution. Their characterization showed polydispersed spherical shape nanoparticles with a mean size around 13 nm and distribution range between 7-21 nm. The presence of MTX was confirmed by FTIR and EDX analysis. Spectroscopic determinations suggest the chemisorption of MTX through a carboxylic group (-COOH) onto AgNPs via the exchange with a citrate molecule. Drug loading capacities calculated for AgNPs synthesized using different amounts of MTX were 28, 31 and 40%. In vitro drug release tests depicted similar release profiles for all conjugated amounts releasing between 77 to 85% of the initial MTX loaded into the AgNPs. With respect to free MTX, the addition of the nanocarrier delayed its release and also changed its pharmacokinetics. Free MTX is released after 3 hours following a first order kinetic model, whereas in the presence of AgNPs, a fast initial release is observed during the first 5 hours, followed by a plateau after 24 hours. In this case, AgNPs-MTX fitted a Higuchi model, where its solubilization is controlled by a diffusion process. Results obtained from flow cytometry of different cell lines treated with AgNPs-MTX demonstrated the combined anticancer effect of both reagents, decreasing the percentage of living cells in a colon cancer cell line (HTC-116) down to 40% after 48 hours of exposure. This effect was weaker but still significant for a lung cancer cell line (A-549). Finally, a zebrafish assay with AgNPs-MTX did not show any significant cytotoxic effect, confirming thereby the reduction of systemic drug toxicity achieved by coupling MTX to AgNPs. This observed toxicity reduction in the zebrafish model implies also a probable improvement of the usage of AgNPs-MTX in chemotherapy against human cancers.

2.
J Environ Manage ; 257: 109973, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31868639

RESUMO

The objective of this study was to analyse the effectiveness of advanced oxidation processes (AOPs) with Solar and UV radiation (UV/H2O2, UV/K2S2O8) for the degradation of hydrochlorothiazide (HCTZ), a widely used diuretic drug, in aqueous solution focusing on the influence of four experimental parameters: initial concentration of HCTZ, solution pH, nature of the water matrix, and initial concentration of radicals. The obtained results showed that using both kinds of direct photolysis (UV and Solar), the percentage of degraded HCTZ was low, but there was a decrease in the degradation rate favored by the increase of the initial concentration of this pollutant. In addition, the degradation rates were higher at acid pHs. With regard to the nature of water, the degradation rate varied in the order: ultrapure > superficial > tap water. This is due to the presence of organic and inorganic matter (bicarbonates, nitrates, and chlorides) in surface and tap water, that react with the radicals generated, which reduces the availability of radical species, generating competitive kinetics. The presence of radical-promoter species increased the degradation rate of the pollutant, reaching a degradation of 100% of HCTZ after 20 min of treatment. The results obtained point out that the degradation rate was higher in the presence of HO radicals. This behavior was attributed to the higher oxidation power of HO versus radicals. The determination of the degradation by-products led to structures very similar to the parent compound. For example, the corresponding hydroxylated dechlorinated derivative of HCTZ was found in all the systems used. The cytotoxicity test showed that these byproducts have a lower toxicity than the original product. Finally, the economic viability study confirmed that the UV/K2S2O8 system has the lowest cost.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Diuréticos , Hidroclorotiazida , Peróxido de Hidrogênio , Cinética , Oxirredução , Fotólise , Raios Ultravioleta
3.
Science ; 366(6469): 1143-1149, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31780560

RESUMO

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.


Assuntos
Enterococcus/crescimento & desenvolvimento , Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/microbiologia , Transplante de Células-Tronco Hematopoéticas , Lactose/metabolismo , Idoso , Animais , Disbiose , Enterococcus/genética , Enterococcus/metabolismo , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Intestinos/microbiologia , Masculino , Camundongos , Microbiota , Pessoa de Meia-Idade , RNA Ribossômico 16S , Análise de Sequência de RNA , Transplante Homólogo
4.
Int J Cardiol ; 258: 249-256, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29544939

RESUMO

BACKGROUND: Cardiogenic shock (CS) is the leading cause of death in patients admitted for acute myocardial infarction (MI). Despite the recent advances in reperfusion and medical treatment mortality remains unacceptably high. Whether cells of the blood compartment in CS-patients are activated and release microparticles (cMPs) that may be both messengers and biomarkers of cell damage is not known. We aimed to investigate the cMP subtypes and parental activated cells of ST-elevation MI (STEMI)-patients complicated by CS and that of non-CS STEMI-patients (non-CS) in order to identify a cMP signature that could aid CS patient's risk stratification. METHODS: Clinically-characterized STEMI-patients with and without CS (36/group) were included. Treatment was delivered according to guidelines and included primary percutaneous coronary intervention. cMPs were characterized by triple-labeling flow cytometry using Annexin V and cell surface-specific monoclonal antibodies. RESULTS: Increased levels of leukocyte-derived (neutrophil and granulocyte origin) and platelet-derived cMPs were detected in CS compared to non-CS patients. A signature of cMPs derived from platelets, leukocytes, and endothelium discriminated CS-patients (AUC of 0.743±0.059 [95% CI: 0.628-0.859], P<0.0001) and predicted mortality in CS (AUC of 0.869±0.06 [95% CI: 0.750-0.988], P<0.0001). In CS-patients, a higher number of platelet- and monocyte-cMPs and of tissue factor-rich cMPs associated to worse myocardial blush grade and thrombolysis in myocardial infarction flow. CONCLUSIONS: cMPs derived from proinflammatory and prothrombotic cells were found to be elevated in CS-patients. In treated as per guidelines CS patients, granulocytes and neutrophils remained activated and actively shed cMPs. These cMPs were biomarkers of adverse prognosis in CS. TRANSLATIONAL ASPECT: Increased levels of leukocyte and platelet-derived circulating microparticles (cMPs) are found in cardiogenic shock (CS) patients as compared to non-CS patients. In CS-patients, a higher number of platelet- and monocyte-cMPs and a higher number of tissue factor-rich cMPs were associated to worse myocardial reperfusion. A specific prothrombotic and proinflammatory cMPs signature in cardiogenic shock (CS) patients is a potential discriminator and survival prognostic biomarker for CS, which could aid management and improve clinical outcomes.


Assuntos
Micropartículas Derivadas de Células/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Índice de Gravidade de Doença , Choque Cardiogênico/sangue , Choque Cardiogênico/epidemiologia , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Choque Cardiogênico/diagnóstico
6.
Bone Marrow Transplant ; 52(12): 1629-1636, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28991247

RESUMO

CD34+ cell selection significantly improves GvHD-free survival in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, specific information regarding long-term prognosis and risk factors for late mortality after CD34+ cell-selected allo-HSCT is lacking. We conducted a single-center landmark analysis in 276 patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT for AML (n=164), ALL (n=33) or myelodysplastic syndrome (n=79). At 5 years' follow-up after the 1-year landmark (range 0.03-13 years), estimated relapse-free survival (RFS) was 73% and overall survival (OS) 76%. The 5-year cumulative incidence of relapse and non-relapse mortality (NRM) were 11% and 16%, respectively. In multivariate analysis, Hematopoietic Cell Transplantation Comorbidity Index score⩾3 correlated with marginally worse RFS (hazard ratio (HR) 1.78, 95% confidence interval (CI) 0.97-3.28, P=0.06) and significantly worse OS (HR 2.53, 95% CI 1.26-5.08, P=0.004). Despite only 24% of patients with acute GvHD within 1 year, this also significantly correlated with worse RFS and OS, with increasing grades of acute GvHD associating with increasingly poorer survival on multivariate analysis (P<0.0001). Of 63 deaths after the landmark, GvHD accounted for 27% of deaths and was the most common cause of late mortality, followed by relapse and infection. Although prognosis is excellent for patients alive without relapse 1 year after CD34+ cell-selected allo-HSCT, risks of late relapse and NRM persist, particularly due to GvHD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Antígenos CD34 , Comorbidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Fatores de Risco , Análise de Sobrevida , Sobreviventes , Transplante Homólogo , Adulto Jovem
8.
Bone Marrow Transplant ; 51(12): 1579-1583, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27643868

RESUMO

Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9-70 years) transplanted for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor (CNI)/mycophenolate mofetil. With a median 5.2-year (range 1.6-9.7 years) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10.4 months (range 5.8-24.5) post CBT for a 7% cumulative incidence 3 years after the day 100 landmark. Six patients presented with severe disease (hemoglobin ⩽6 g/dL and/or platelets <20 × 109/L). All AH patients were direct antiglobulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute GVHD. All 10 patients received rituximab 2-18 days after diagnosis, and corticosteroids combined with rituximab within <7 days was the most effective. No patient died of AH/ITP. AH/ITP occurs infrequently after CBT but may be life-threatening requiring emergency therapy. Rituximab combined with corticosteroids at diagnosis is warranted in patients with severe disease.


Assuntos
Anemia Hemolítica Autoimune/etiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Neoplasias Hematológicas/complicações , Púrpura Trombocitopênica Idiopática/etiologia , Rituximab/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Anemia Hemolítica Autoimune/tratamento farmacológico , Antineoplásicos Imunológicos/uso terapêutico , Criança , Pré-Escolar , Estado Terminal , Seguimentos , Neoplasias Hematológicas/terapia , Hemólise , Humanos , Terapia de Imunossupressão , Lactente , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto Jovem
11.
BJOG ; 123(2): 190-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26841002

RESUMO

OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i-WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis.


Assuntos
Cesárea/estatística & dados numéricos , Diabetes Gestacional/epidemiologia , Obesidade/prevenção & controle , Pré-Eclâmpsia/epidemiologia , Complicações na Gravidez/prevenção & controle , Gestantes , Nascimento Prematuro/etiologia , Adulto , Técnica Delphi , Diabetes Gestacional/etiologia , Dieta Redutora , Feminino , Humanos , Recém-Nascido , Estilo de Vida , Obesidade/complicações , Pré-Eclâmpsia/etiologia , Gravidez , Complicações na Gravidez/etiologia , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Aumento de Peso
12.
Bone Marrow Transplant ; 50(4): 493-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25621808

RESUMO

We compared outcomes of adult patients receiving T-cell-depleted (TCD) hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52), with those of patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5% vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and 9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3 years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Depleção Linfocítica , Modelos Biológicos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Linfócitos T , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Taxa de Sobrevida
13.
Bone Marrow Transplant ; 50(3): 438-43, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25599164

RESUMO

Antifungal prophylaxis with azoles is considered standard in allogeneic hematopoietic SCT (allo-HSCT). Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. We identified 67 patients with hematologic malignancies who underwent allo-HSCT with sirolimus, tacrolimus and low-dose MTX and received concomitant voriconazole prophylaxis from April 2008 to June 2011. All patients underwent a non-myeloablative or reduced-intensity conditioned allo-HSCT. Patients received sirolimus and voriconazole concurrently for a median of 113 days. The median daily dose reduction of sirolimus at the start of coadministration was 90%. The median serum sirolimus trough levels before and at steady state of coadministration were 5.8 ng/mL (range: 0-47.6) and 6.1 ng/mL (range: 1-14.2) (P=0.45), respectively. One patient with an average sirolimus level of 6 ng/mL developed sirolimus-related thrombotic microangiopathy that resolved after sirolimus discontinuation. No sinusoidal obstructive syndrome was reported. Seventeen patients (25%) prematurely discontinued voriconazole because of the adverse events. Only two patients (3%) presented with possible invasive fungal infections at day 100. We demonstrate that sirolimus and voriconazole coadministration with an empiric 90% sirolimus dose reduction and close monitoring of sirolimus trough levels is safe and well tolerated.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Sirolimo/administração & dosagem , Voriconazol/administração & dosagem , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antifúngicos/administração & dosagem , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sirolimo/efeitos adversos , Transplante Homólogo , Voriconazol/efeitos adversos , Adulto Jovem
14.
Eval Health Prof ; 38(1): 59-72, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24872442

RESUMO

Recent studies have estimated the prevalence of depression during pregnancy to be between 10% and 30%, which is higher than that in the postpartum period. Pharmacological treatment during pregnancy is difficult because of the possible side effects of antidepressants on the mother and the fetus. The aim of this study was to examine whether a supervised exercise program (EP) reduces depressive symptoms in pregnant women. A randomized controlled trial was designed. One hundred eighty four healthy pregnant women from Fuenlabrada Hospital were included (31.37 ± 3.62 years). Women from the exercise group (EG) participated in a supervised EP consisting of three, 55- to 60-min sessions per week throughout pregnancy. The main outcome measure was the patients' depression level assessed by means of the Center for Epidemiologic Studies Depression Scale (CES-D). A total of 167 pregnant women were analyzed; 90 were allocated to the EG and 77 to the control group (CG). Significant differences were found between groups at the end of the study in CES-D scores (EG: 7.67 ± 6.30 vs. CG: 11.34 ± 9.74, p = .005) and in percentages of pregnant women depressed (EG: n = 11/12.2% vs. CG: n = 19/24.7%, p = .04). Our results show that supervised physical exercise during pregnancy reduces the level of depression and its incidence in pregnant women.


Assuntos
Depressão/terapia , Terapia por Exercício/métodos , Complicações na Gravidez/terapia , Adulto , Índice de Apgar , Índice de Massa Corporal , Feminino , Humanos , Gravidez , Resultado da Gravidez , Espanha , Aumento de Peso
15.
Rev. chil. obstet. ginecol ; 80(1): 48-54, 2015. tab
Artigo em Espanhol | LILACS | ID: lil-743834

RESUMO

ANTECEDENTES: Las gestaciones en pacientes con daño medular representan un reto para la obstetricia. Las complicaciones más frecuentes son las infecciones de las vías respiratorias y de las vías urinarias, y la más grave la hiperreflexia autonómica. El parto vaginal es posible en lesiones por debajo de T5, pero por encima de ese nivel, la imposibilidad de percibir las contracciones, de identificar el trabajo de parto y realizar pujos lleva a la necesidad de una cesárea programada. OBJETIVO: Exponer nuestra experiencia y revisar el manejo más adecuado de la embarazada parapléjica. MÉTODOS: Estudio retrospectivo en el periodo 2003-2014. Hubo 10 pacientes con 24 gestaciones: 6 abortos espontáneos, un 1 aborto inducido, quedando para el análisis 17 gestaciones (1 embarazo gemelar). La evaluación es independiente a la etiología o localización de la lesión. Se analiza las complicaciones perinatales y maternas. Resultados: La edad media fue 33 años. La edad gestacional media al parto fue 37 semanas: 12 de término (70,59%), 4 de pretérmino (23,53%) y una desconocida (5,88%). Hubo 10 cesáreas (58,82%) y 7 partos vaginales (41,18%). Peso medio neonatal de 2940 g, ninguno con retraso de crecimiento intrauterino. CONCLUSIONES: Nuestra experiencia muestra una alta tasa de prematuridad y de cesáreas, pero con buenos resultados maternos y perinatales, que hace permisible que estas pacientes puedan cumplir su deseo genésico, superando su discapacidad.


BACKGROUND: The pregnancies in patients with spinal cord injury represent a challenge for obstetrics. The most common complications are infections of the respiratory and urinary tract, and the most severe is the autonomic hyperreflexia. Vaginal delivery is possible in lesions below T5, but above that level the inability to perceive contractions, to identify labor and perform straining leads to the need for a scheduled cesarean. OBJECTIVE: To describe our experience and review the most appropriate management of paraplegic pregnant. Methods: Retrospective study in the period 2003-2014. There were 10 patients with 24 pregnancies: 6 spontaneous abortions, 1 induced abortion, leaving 17 for analysis pregnancies (one twin pregnancy). The evaluation is independent of the etiology or location of the lesion. Perinatal and maternal complications were analyzed. RESULTS: The mean age was 33 years. The mean gestational age at delivery was 37 weeks: 12 to term (70.59%), 4 preterm deliveries (23.53%) and one unknow. There were 10 cesarean sections (58.82%) and 7 vaginal deliveries (41.18%). Average birth weight of 2940 g, none with intrauterine growth restriction. CONCLUSIONS: Our experience shows a high rate of prematurity and cesarean section, but with good maternal and perinatal outcomes, which makes it permissible for these patients can fulfill their procreative desire, overcoming his disability.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Adulto Jovem , Paraplegia/complicações , Complicações na Gravidez/etiologia , Complicações na Gravidez/terapia , Traumatismos da Medula Espinal/complicações , Complicações na Gravidez/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Urinárias/epidemiologia , Resultado da Gravidez , Cesárea , Estudos Retrospectivos , Complicações do Trabalho de Parto , Trabalho de Parto Prematuro
16.
Nefrologia ; 33(4): 515-23, 2013.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-23897183

RESUMO

UNLABELLED: Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains. Acute renal failure can be a symptom of MM, and it is sometimes its form of presentation. Circulating free light chains (FLC) could lead to renal failure due to their intratubular precipitation, causing a cast nephropathy. The treatment of myeloma, adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease. Several apheresis techniques have been attempted for the removal of FLC, with long haemodialysis sessions with filters for the removal of these light chains (high cut-off filters) being proposed as the most effective treatment for myeloma nephropathy. METHODS: We report 5 cases of myeloma nephropathy: three had cast nephropathy (CN) diagnosed by renal biopsy and the other two had a high probability of CN (FLC levels >500 mg/l). They were treated with long haemodialysis sessions with a high cut-off membrane. All patients had suffered acute renal failure; four required renal replacement therapy and one patient had advanced renal failure. In all patients, FLC levels were very high. They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of <500 mg/l. RESULTS: Four of the five patients recovered renal function, and became independent of dialysis. The progression time for myeloma from the time the first symptoms appeared varied (1-6 months). The number of treatment sessions ranged from 8-16. The patient with the longest progression time required more sessions and did not recover renal function. CONCLUSIONS: Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy. The early initiation of treatment could be a determining factor for the response.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Mieloma Múltiplo/complicações , Diálise Renal/instrumentação , Diálise Renal/métodos , Injúria Renal Aguda/sangue , Idoso , Feminino , Filtração/instrumentação , Humanos , Cadeias Leves de Imunoglobulina/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Resultado do Tratamento
17.
Biol Blood Marrow Transplant ; 19(6): 904-11, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23416854

RESUMO

Manifestations of and risk factors for graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age, 37 years) who underwent transplantation for hematologic malignancies with myeloablative or nonmyeloablative conditioning and calcineurin inhibitor/mycophenolate mofetil immunosuppression. Incidence of day 180 grades II to IV and III to IV acute GVHD (aGVHD) were 53% (95% confidence interval, 44 to 62) and 23% (95% confidence interval, 15 to 31), respectively, with a median onset of 40 days (range, 14 to 169). Eighty percent of patients with grades II to IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD, with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome. Late GVHD in the form of classic chronic GVHD was uncommon. Notably, grades III to IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A, -B, -DRB1 allele match was >4/6 to the recipient (hazard ratio, 0.385; P = .031), whereas engrafting unit infused nucleated cell dose and unit-to-unit HLA match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, and had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Trato Gastrointestinal/imunologia , Doença Enxerto-Hospedeiro/terapia , Antígenos HLA/imunologia , Neoplasias Hematológicas/terapia , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Budesonida/uso terapêutico , Calcineurina/metabolismo , Inibidores de Calcineurina , Criança , Pré-Escolar , Inibidores Enzimáticos/uso terapêutico , Feminino , Trato Gastrointestinal/patologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Índice de Gravidade de Doença , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
18.
Bone Marrow Transplant ; 48(1): 99-104, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22750997

RESUMO

Palifermin, a recombinant human keratinocyte growth factor, is commonly given to prevent mucositis following autologous transplantation. In the allogeneic hematopoietic stem cell transplant (allo-HSCT) setting, safety and efficacy data are limited. We conducted a retrospective study in 251 patients undergoing allo-HSCT, 154 of whom received peritransplant palifermin. In all patients, palifermin significantly decreased the mean number of days of total parenteral nutrition (TPN, 13 vs 16 days, P=0.006) and patient-controlled analgesia (PCA, 6 vs 10 days, P=0.023), as well as the length of initial hospital stay (LOS, 32 vs 37 days, P=0.014). However, the effect of palifermin was only significant in patients who received a TBI- but not BU-based chemotherapy conditioning regimen. In TBI recipients, palifermin decreased the mean number of days of TPN (13 vs 17 days, P<0.001) and PCA (7 vs 12 days, P=0.033), and the length of stay (32 vs 38 days, P=0.001). Palifermin did not affect GVHD, graft failure or relapse. Therefore, in the largest analysis with this patient population to date, we demonstrate that palifermin is safe in allo-HSCT patients, decreases TPN and PCA use and decreases LOS following TBI-based but not chemotherapy-based allo-HSCT.


Assuntos
Fator 7 de Crescimento de Fibroblastos/uso terapêutico , Trato Gastrointestinal/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mucosite/prevenção & controle , Substâncias Protetoras/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Estudos de Coortes , Feminino , Fator 7 de Crescimento de Fibroblastos/efeitos adversos , Fator 7 de Crescimento de Fibroblastos/genética , Seguimentos , Trato Gastrointestinal/fisiopatologia , Trato Gastrointestinal/efeitos da radiação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mucosite/epidemiologia , Mucosite/etiologia , Mucosite/fisiopatologia , Cidade de Nova Iorque/epidemiologia , Substâncias Protetoras/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto Jovem
19.
Nefrologia ; 31(4): 471-83, 2011.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-21738250

RESUMO

INTRODUCTION: Hospitalizations are frequent in hemodialysis patients and is often accompanied by nutritional deterioration showed by a loss of weight and a reduction of albumin serum levels. This phenomenon is related with length of stay having its origin in a complex interplay of factors. Our aim in this study was to analyze if changes in body weight and other nutritional parameters are influenced by the illnesses presented during hospitalization. PATIENTS AND METHODS: Over a period of three years, we retrospectively chose chronic haemodialysis patients that were admitted for more than four days, excluding those cases that died in the hospital. We randomly chose one admission episode per patient so as to avoid excessive weighing of repeated admissions. We took data concerning weight changes, pre-admission and post-discharge analytical results, analytical results following first week of hospital stay, disorders causing hospital admission and those that developed during the hospital stay. We created a point score system to record the total of illnesses presented. RESULTS: The study included 77 patients, aged 67±12 years and having undergone haemodialysis for 31±34 months. Hospital stay was 17.8±12.6 days (median, 12 days). We observed that many patients admitted for digestive and osteoarticular disorders, heart failure or coronary syndrome lost more weight during their hospital stay, although no significant differences were reached. The total number of disorders suffered during the hospital stay was independent of the cause of hospitalisation. Anaemia,heart arrhythmias and signs of heart failure were associated with longer hospital stays, however it was only anaemia that was significantly related to greater weight loss. Weight loss was not related to surgery or infections. Albumin levels during the first week of hospital stay were different depending on the disorder upon admission. It was lower when the patients were admitted for digestive disorders (ANOVA, P=.05). Changes in albumin and creatinine levels before and after the hospital stay did not differ among disorders. We observed a relationship between having presented with more disorders during the stay and a longer stay, lower initial albumin and greater weight loss following discharge. In the multivariate analysis, we found the following weight loss predictors: stay, anaemia, and sepsis. We also found the following hospital stay predictors:Charlson's comorbidity index, heart arrhythmias, anaemia, sepsis and surgery. CONCLUSIONS: Malnutrition during the hospital stay depends on the duration and the number of disorders that develop during this time, the cause of admission having less impact on this. Albumin levels decrease earlier in patients that are going to develop more disorders during hospital stay.


Assuntos
Hospitalização , Falência Renal Crônica/complicações , Desnutrição/etiologia , Diálise Renal , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Anemia/epidemiologia , Peso Corporal , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Comorbidade , Doenças do Sistema Digestório/complicações , Doenças do Sistema Digestório/epidemiologia , Feminino , Humanos , Hipoalbuminemia/etiologia , Infecções/complicações , Infecções/epidemiologia , Artropatias/complicações , Artropatias/epidemiologia , Falência Renal Crônica/terapia , Tempo de Internação/estatística & dados numéricos , Masculino , Desnutrição/sangue , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Amostragem , Índice de Gravidade de Doença
20.
Nefrologia ; 30(5): 557-66, 2010.
Artigo em Espanhol | MEDLINE | ID: mdl-20882095

RESUMO

BACKGROUND: It is frequent to observe that hemodialysis patients suffer important loss of weight during hospital stay. This issue has not been investigated previously. Our aim in this study was to analyze factors associated with this loss of weight and what changes occur after admission in biochemical parameters with nutritional interest. PATIENTS AND METHODS: We retrospectively selected patients undergoing chronic hemodialysis who were admitted at hospital for acute or chronic pathologies, with a minimum length of stay of 4 days, taking only one episode of admission per patient. We chose loss of weight observed at hospital discharge, at 2 and 4 weeks later and we also collected routine laboratory data and adequacy parameters before and after the hospital admission and basic biochemical parameters in the first week of hospital stay. RESULTS: We included 77 patients, with 67±12 years and 30±34 months in dialysis. Forty (51.9%) were female (51.9%) and 22 diabetics (28.6%). Length of stay was 17.8±12.6 days (median 12). There were 70.4% patients who suffered a loss of weight at discharge and 81.4% at 4 weeks, without differences in sex or diabetes. Weight decreased significantly with a mean of -1.09 kg (95%CI -0.73 to -1.44). After 2 weeks the loss of weight was -1.64 kg (95%CI -1.21 a -2.07 kg) and after 4 weeks was -1.94 kg (95%CI -1.47 a -2.42 kg). Comparing parameters before and after admission, we observed a significantly decrease in serum urea levels (before 134±40 vs after 119±36 mg/dl; p= 0.001), creatinine (before 8.1±2.6 vs after 7.5±2.6 mg/dl; p < 0.001), phosphate (before 5.2±1.7 vs after 4.3±1.5 mg/dl; p < 0.001) and albumin (before 3.70±0.48 vs after 3.56±0.58 g/dl; p=0.05), without changes in adequacy parameters. Greater loss of weight at 4 weeks from discharge was correlated with larger length of stay (r= 0.41; p < 0.001), greater body mass index at admission (r= -0.23; p=0.05) and lower serum albumin at admission (r= 0.39; p= 0.012). It was also correlated with a lower serum albumin (r= 0.27; p=0.05), lower creatinine (r= 0.30; p= 0.02) and lower protein intake (nPNA) (r= 0.47; p= 0.002) after discharge. Lower serum albumin levels at admission were correlated with greater decreases of creatinine after discharge (r= 0.42; p= 0.009) and larger length of stay (r= -0.61; p < 0.001). Employing multivariate analysis we found that loss of weight was associated to length of stay and serum potassium levels before admission. CONCLUSIONS: Hospitalization of hemodialysis patients have a negative nutritional impact causing a significant loss of weight, probably reflecting a reduction of muscle mass. We found that length of stay in hospital is a basic factor associated with this nutritional impairment. The pathologies promoting hospitalization could influence this derangement through inflammation but this hypothesis should be investigated.


Assuntos
Hospitalização , Inflamação/complicações , Falência Renal Crônica/terapia , Diálise Renal , Redução de Peso , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Creatinina/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/complicações , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Fósforo/sangue , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise , Ureia/sangue
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