RESUMEN
OBJECTIVE: To identify acute predictors of generic and specific health-related quality of life (HRQoL) six and 12 months after stroke in individuals from a middle-income country. MATERIAL AND METHODS: This was a prospective study. The dependent outcomes assessed during six and 12 months after stroke included both generic and specific HRQoL (Short Form Health Survey-36 [SF-36] and stroke-specific quality of life [SSQOL]). The predictors were age, sex, education level, length of hospital stay, current living arrangement, stroke severity, functional independence, and motor impairment. RESULTS: 122 (59.9±14 years) and 103 (59.8±14.71 years) individuals were evaluated six and 12 months after stroke, respectively. Functional independence and sex were significant acute predictors of both generic and specific HRQoL. Functional independence was the strongest predictor (0.149≤R2≤0.262; 20.01≤F≤43.96, p<0.001), except for generic HRQoL at 12 months, where sex was the strongest predictor (R2=0.14; F=17.97, p<0.001). CONCLUSION: Generic and specific HRQoL in chronic individuals six and 12 months after stroke, from a middle-income country, can be predicted based on functional independence, the strongest predictor, assessed in the acute phase, except for generic HRQoL at 12 months. Functional independence can be modified by rehabilitation strategies and thus should be considered for HRQoL prognoses at chronic phase.
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Estado Funcional , Calidad de Vida , Recuperación de la Función , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Anciano , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/fisiopatología , Factores de Tiempo , Rehabilitación de Accidente Cerebrovascular , Evaluación de la Discapacidad , Resultado del Tratamiento , Factores Sexuales , Adulto , Estado de Salud , Índice de Severidad de la EnfermedadRESUMEN
El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.
Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.
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Humanos , Masculino , Adolescente , Priapismo/complicaciones , Priapismo/etiología , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Enfermedad CrónicaRESUMEN
Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.
El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Priapismo , Masculino , Humanos , Adolescente , Priapismo/etiología , Priapismo/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Enfermedad CrónicaRESUMEN
P21 is an immunomodulatory protein expressed throughout the life cycle of Trypanosoma cruzi, the etiologic agent of Chagas disease. In vitro and in vivo studies have shown that P21 plays an important role in the invasion of mammalian host cells and establishment of infection in a murine model. P21 functions as a signal transducer, triggering intracellular cascades in host cells and resulting in the remodeling of the actin cytoskeleton and parasite internalization. Furthermore, in vivo studies have shown that P21 inhibits angiogenesis, induces inflammation and fibrosis, and regulates intracellular amastigote replication. In this study, we used the CRISPR/Cas9 system for P21 gene knockout and investigated whether the ablation of P21 results in changes in the phenotypes associated with this protein. Ablation of P21 gene resulted in a lower growth rate of epimastigotes and delayed cell cycle progression, accompanied by accumulation of parasites in G1 phase. However, P21 knockout epimastigotes were viable and able to differentiate into metacyclic trypomastigotes, which are infective to mammalian cells. In comparison with wild-type parasites, P21 knockout cells showed a reduced cell invasion rate, demonstrating the role of this protein in host cell invasion. However, there was a higher number of intracellular amastigotes per cell, suggesting that P21 is a negative regulator of amastigote proliferation in mammalian cells. Here, for the first time, we demonstrated the direct correlation between P21 and the replication of intracellular amastigotes, which underlies the chronicity of T. cruzi infection.
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Enfermedad de Chagas , Trypanosoma cruzi , Citoesqueleto de Actina/fisiología , Animales , Enfermedad de Chagas/parasitología , Técnicas de Inactivación de Genes , Estadios del Ciclo de Vida/fisiología , Mamíferos/genética , Ratones , Trypanosoma cruzi/fisiologíaRESUMEN
Neospora caninum is a protozoan associated with abortions in ruminants and neuromuscular disease in dogs. Classically, the immune response against apicomplexan parasites is characterized by the production of proinflammatory cytokines, such as IL-12, IFN-γ and TNF. TNF is mainly produced during the acute phases of the infections and binds to TNF receptor 1 (CD120a, p55, TNFR1) activating a variety of cells, hence playing an important role in the induction of the inflammatory process against diverse pathogens. Thus, in this study, we aimed to evaluate the role of TNF in cellular and humoral immune responses during N. caninum infection. For this purpose, we used a mouse model of infection based on wildtype (WT) and genetically deficient C57BL/6 mice in TNFR1 (Tnfr1-/-). We observed that Tnfr1-/- mice presented higher mortality associated with inflammatory lesions and increased parasite burden in the brain after the infection with N. caninum tachyzoites. Moreover, Tnfr1-/- mice showed a reduction in nitric oxide (NO) levels in vivo. We also observed that Tnfr1-/- mice showed enhanced serum concentration of antigen-specific IgG2 subclass, while IgG1 production was significantly reduced compared to WT mice, suggesting that TNFR1 is required for regular IgG subclass production and antigen recognition. Based on our results, we conclude that the TNF-TNFR1 complex is crucial for mediating host resistance during the infection by N. caninum.
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Coccidiosis , Neospora , Receptores Tipo I de Factores de Necrosis Tumoral , Factor de Necrosis Tumoral alfa/inmunología , Animales , Coccidiosis/inmunología , Citocinas , Femenino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Embarazo , Receptores Tipo I de Factores de Necrosis Tumoral/inmunologíaRESUMEN
BACKGROUND: Chagas disease or American trypanosomiasis is caused by the protozoan Trypanosoma cruzi and is endemic of the Americas. The control of the disease is restricted to toxic and potentially teratogenic drugs, which limit the use during pregnancy. The use of food supplementation offers a safe and low-cost form to alleviate Chagas disease symptoms, mostly in areas with alimentary risk. For example, zinc demonstrates positive effects in immune response, including in Chagas disease during pregnancy. PURPOSE: This study describes the innate response in pregnant rats chronically infected with T. cruzi and supplemented with zinc. METHODS: Pregnant female Wistar rats, infected with T. cruzi, were treated with 20 mg/kg/day zinc sulfate and euthanized on the 18th day. Samples (plasma, splenocytes, and peritoneal exudate) were collected and several immune parameters (nitric oxide, RT1B, CD80/CD86, MCP-1, CD11b/c, NK/NKT, IL-2, IL-10, INF-cc, and apoptosis) evaluated. RESULTS: Under Zinc supplementation and/or T. cruzi infection, the gestation developed normally. Several innate immune parameters such as RT1B, CD80/CD86, MCP-1 expressing lymphocytes, IL-2, and IL-17 were positively altered, whereas nitric oxide, CD11b/c, NK/NKT, apoptosis, INF-γ, and corticosterone demonstrated a pro-pregnancy pattern. CONCLUSION: Our results indicated that zinc has diverse effects on immune response during pregnancy. An anti-T. cruzi immunity, as well as a pro-gestation response, were observed after zinc supplementation. The complete comprehension of zinc supplementation in pregnancy will base an adequate strategy to alleviate Chagas disease symptoms and propagation, especially for populations from endemic areas.
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Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/inmunología , Suplementos Dietéticos , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Trypanosoma cruzi/efectos de los fármacos , Zinc/uso terapéutico , Animales , Enfermedad Crónica , Femenino , Embarazo , Complicaciones Infecciosas del Embarazo/parasitología , Ratas , Ratas WistarRESUMEN
Chagas disease remains neglected, and current chemotherapeutics present severe limitations. Lychnopholide (LYC) at low doses loaded in polymeric poly(d,l-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules (LYC-PLA-PEG-NC) exhibits anti-Trypanosoma cruzi efficacy in mice infected with a partially drug-resistant strain. This study reports the efficacy of LYC-PLA-PEG-NC at higher doses in mice infected with a T. cruzi strain resistant to benznidazole (BZ) and nifurtimox (NF) treated at both the acute phase (AP) and the chronic phase (CP) of infection by the oral route. Mice infected with the T. cruzi VL-10 strain were treated by the oral route with free LYC (12 mg/kg of body weight/day), LYC-PLA-PEG-NC (8 or 12 mg/kg/day), or BZ at 100 mg/kg/day or were not treated (controls). Treatment efficacy was assessed by hemoculture (HC), PCR, enzyme-linked immunosorbent assay (ELISA), heart tissue quantitative PCR (qPCR), and histopathology. According to classical cure criteria, treatment with LYC-PLA-PEG-NC at 12 mg/kg/day cured 75% (AP) and 88% (CP) of the animals, while at a dose of 8 mg/kg/day, 43% (AP) and 43% (CP) were cured, showing dose-dependent efficacy. The negative qPCR results for heart tissue and the absence of inflammation/fibrosis agreed with the negative results obtained by HC and PCR. Thus, the mice treated with the highest dose could be considered 100% cured, in spite of a low ELISA reactivity in some animals. No cure was observed in animals treated with free LYC or BZ or the controls. These results are exceptional in terms of experimental Chagas disease chemotherapy and provide evidence of the outstanding contribution of nanotechnology in mice infected with a T. cruzi strain totally resistant to BZ and NF at both phases of infection. Therefore, LYC-PLA-PEG-NC has great potential as a new treatment for Chagas disease and deserves further investigations in clinical trials.
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Enfermedad de Chagas/tratamiento farmacológico , Portadores de Fármacos/química , Lactonas/uso terapéutico , Sesquiterpenos/uso terapéutico , Tripanocidas/uso terapéutico , Trypanosoma cruzi/efectos de los fármacos , Animales , Femenino , Ratones , Nanocápsulas/uso terapéutico , Poliésteres/química , Polietilenglicoles/químicaRESUMEN
Chronic myeloid leukemia (CML) is a stem cell derived malignant disorder result of translocation t(9;22)(q34;q11) called Philadelphia chromosome (Ph+). microRNAS (miRNAs) are involved in several biological processes, altering the progression of various pathologies, including CML. This study evaluated whether circulating miRNAs display differential expression profiles in peripheral blood of CML-Chronic Phase (CML-CP) patients newly diagnosed in comparison with CML-CP treated with imatinib. We obtained peripheral blood samples from CML-CP Ph+ patients divided among group 1 (untreated newly diagnosed) and group 2 (treated with imatinib). A pool of total leukocytes from healthy donors was considered as control group. Expression analyses were performed for 768 miRNAs by RT-qPCR array. Bioinformatic tools were used to identify significant pathways and interaction networks. We found 80 deregulated miRNAs between the groups and, according to bioinformatic analysis, they are involved in different pathways, including molecular mechanisms of cancer. The study allows better understanding of disease molecular behavior, and it is useful for possible monitoring CML treatment and prognostic biomarkers identification.
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Biomarcadores de Tumor , MicroARN Circulante , Mesilato de Imatinib/uso terapéutico , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Transcriptoma , Biología Computacional/métodos , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Humanos , Mesilato de Imatinib/administración & dosificación , Mesilato de Imatinib/efectos adversos , Leucemia Mieloide de Fase Crónica/sangre , Leucemia Mieloide de Fase Crónica/diagnóstico , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
Hydroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug effective in vivo during acute infections, and it has less hepatotoxicity effect than the standard drug benznidazole (BZN) which has been used during short- and long-term treatment. In the present study, we induced the indeterminate form of Chagas disease in mice with a Y strain of Trypanosoma cruzi and analysed the histopathological data about the effects of NFOH and BZN on different tissues, including the heart, skeletal muscle, liver, kidney, colon, spleen and brain. After infection, BALB/c mice were treated with NFOH (150 mg/kg) and BZN (60 mg/kg) for 60 days and then submitted to immunosuppression using dexamethasone (5 mg/kg) for 14 days. Two trained analysts, as part of a blind evaluation, examined the results using serial sections of 3 mm diameter in two different moments. The results showed reactivation of the disease only in the infected nontreated group (POS). After treatment, amastigote nests were found in the heart, colon, liver and skeletal muscle in the POS group and in the heart and liver of the BZN group. Interestingly, amastigote nests were not found in the NFOH and NEG groups. The histopathological analysis showed fewer tissue lesions and parasite infiltrates in the NFOH group when compared with the BZN and POS groups. We have not observed any increase in the levels of hepatocellular injury biomarkers (AST/ALT) in the NFOH group. These in vivo studies show the potential for NFOH as an effective and safe compound useful as an anti-T. cruzi agent.
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Enfermedad de Chagas/tratamiento farmacológico , Nitrofurazona/análogos & derivados , Trypanosoma cruzi/efectos de los fármacos , Animales , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/patología , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Inflamación/parasitología , Inflamación/patología , Riñón/efectos de los fármacos , Riñón/patología , Hígado/parasitología , Hígado/patología , Masculino , Ratones , Músculo Esquelético/patología , Nitrofurazona/química , Nitrofurazona/farmacología , Nitroimidazoles/uso terapéuticoRESUMEN
Abstract Chagas disease is a protozoan infection that was identified over a century ago. No drugs are available to treat the indeterminate and determinate chronic phases of the disease. Success of a drug design is dependent on correct biological evaluation. Concerning new drug designs for Chagas disease, it is essential to first identify the most effective, existing, experimental chronic protocols that can be used for comparison purposes. Here, we present a literature review regarding experimental models with chronic Chagas disease to evaluate the efficacy of benznidazole (BZN). We searched literature published in PubMed and Web of Science databases, using these keywords: animal model, BZN, Chagas disease, T. cruzi, and chronic phase, with no timeframe limitations. We excluded articles involving acute phase animal models and/or those without BZN treatment. The selected studies were conducted using different BZN concentrations (10mg-100mg) involving several different periods (5-70 days). Concentrations and durations of use are directly related to side effects, but do not prevent chronic tissue lesions. BZN use during the late/chronic phases of Chagas disease is unable to eliminate amastigote forms present in infected tissues. This study suggests the administration of a lower BZN concentration (<100mg/kg/day) during the chronic phase of the animal model, as this had been reported to result in fewer side effects.
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Animales , Tripanocidas/administración & dosificación , Enfermedad de Chagas/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Nitroimidazoles/administración & dosificación , Enfermedad Crónica , Modelos Animales de Enfermedad , RatonesRESUMEN
PURPOSE: The fusion gene BCR-ABL has an important role to the progression of chronic myeloid leukemia (CML) and several signaling pathways have been characterized as responsible for the terminal blastic phase (BP). However, the initial phase, the chronic phase (CP), is long lasting and there is much yet to be understood about the critical role of BCR-ABL in this phase. This study aims to evaluate transcriptional deregulation in CD34+ hematopoietic cells (CD34+ cells) from patients with untreated newly diagnosed CML compared with CD34+HC from healthy controls. METHODS: Gene expression profiling in CML-CD34 cells and CD34 cells from healthy controls were used for this purpose with emphasis on five main pathways important for enhanced proliferation/survival, enhanced self-renewal and block of myeloid differentiation. RESULTS: We found 835 genes with changed expression levels (fold change ≥ ±2) in CML-CD34 cells compared with CD34 cells. These include genes belonging to PI3K/AKT, WNT/b-catenin, SHH, NOTCH and MAPK signaling pathways. Four of these pathways converge to MYC activation. We also identified five transcripts upregulated in CD34-CML patients named OSBPL9, MEK2, p90RSK, TCF4 and FZD7 that can be potential biomarkers in CD34-CML-CP. CONCLUSION: We show several mRNAs up- or downregulated in CD34-CML during the chronic phase.
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Biomarcadores de Tumor/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Transducción de Señal/genética , Transcriptoma , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD34 , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Células Madre Hematopoyéticas/patología , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Vía de Señalización Wnt/genética , Adulto JovenRESUMEN
In 2015 in Colombia, 60 pregnant women were hospitalized with chikungunya virus infections confirmed by reverse transcription PCR. Nine of these women required admission to the intensive care unit because of sepsis with hypoperfusion and organ dysfunction; these women met the criteria for severe acute maternal morbidity. No deaths occurred. Fifteen women delivered during acute infection; some received tocolytics to delay delivery until after the febrile episode and prevent possible vertical transmission. As recommended by a pediatric neonatologist, 12 neonates were hospitalized to rule out vertical transmission; no clinical findings suggestive of neonatal chikungunya virus infection were observed. With 36 women (60%), follow-up was performed 1 year after acute viremia; 13 patients had arthralgia in >2 joints (a relapse of infection). Despite disease severity, pregnant women with chikungunya should be treated in high-complexity obstetric units to rule out adverse outcomes. These women should also be followed up to treat potential relapses.
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Fiebre Chikungunya/fisiopatología , Complicaciones Infecciosas del Embarazo/fisiopatología , Adulto , Fiebre Chikungunya/mortalidad , Fiebre Chikungunya/terapia , Estudios de Cohortes , Colombia , Cuidados Críticos , Femenino , Hospitalización , Humanos , Recién Nacido , Embarazo , Complicaciones Infecciosas del Embarazo/mortalidad , Complicaciones Infecciosas del Embarazo/terapia , Complicaciones Infecciosas del Embarazo/virología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
CONTEXT AND OBJECTIVES: Chronic myeloid leukemia (CML) requires strict daily compliance with oral medication and regular blood and bone marrow control tests. The objective was to evaluate CML patients' perceptions about the disease, their access to information regarding the diagnosis, monitoring and treatment, adverse effects and associations of these variables with patients' demographics, region and healthcare access. DESIGN AND SETTING: Prospective cross-sectional study among CML patients registered with the Brazilian Lymphoma and Leukemia Association (ABRALE). METHODS: CML patients receiving treatment through the public healthcare system were interviewed by telephone. RESULTS: Among 1,102 patients interviewed, the symptoms most frequently leading them to seek medical care were weakness or fatigue. One third were diagnosed by means of routine tests. The time that elapsed between first symptoms and seeking medical care was 42.28 ± 154.21 days. Most patients had been tested at least once for Philadelphia chromosome, but 43.2% did not know the results. 64.8% had had polymerase chain reaction testing for the BCR/ABL gene every three months. 47% believed that CML could be controlled, but 33.1% believed that there was no treatment. About 24% reported occasionally stopping their medication. Imatinib was associated with nausea, cramps and muscle pain. Self-reported treatment adherence was significantly associated with normalized blood count, and positively associated with imatinib. CONCLUSIONS: There is a lack of information or understanding about disease monitoring tools among Brazilian CML patients; they are diagnosed quickly and have good access to treatment. Correct comprehension of CML control tools is impaired in Brazilian patients.
CONTEXTO E OBJETIVOS: Leucemia mieloide crônica (CML) exige estrita adesão à medicação oral e ao monitoramento do sangue e da medula. O objetivo foi avaliar percepções de pacientes com leucemia mieloide crônica (LMC) sobre a doença, seu acesso à informação sobre diagnóstico, monitoramento e tratamento, efeitos adversos e a associação destes com dados demográficos, geográficos e de acesso a tratamento. DESENHO E LOCAL: Estudo prospectivo transversal realizado com pacientes de LMC cadastrados na Associação Brasileira de Leucemia e Linfoma (Abrale). MÉTODOS: Pacientes com LMC recebendo tratamento do sistema público de saúde foram entrevistados por telefone. RESULTADOS: Entre os 1.102 pacientes entrevistados, os sintomas mais frequentemente levando à busca de consulta foram fraqueza e fadiga. Um terço foi diagnosticado por exames de rotina. O tempo entre sintoma inicial e procura por ajuda foi de 42,28 ± 154,21 dias. A maioria foi testada pelo menos uma vez para o cromossomo Filadélfia, mas 43,2% não sabiam os resultados. 64,8% fizeram exame de reação em cadeia da polimerase para o gene BCR/ABL a cada três meses. 47% acreditavam que LMC pode ser controlada, mas 33,1% acham que não há tratamento. Cerca de 24% disseram que ocasionalmente interrompem o tratamento. Imatinibe associou-se com náusea, câimbra e dor muscular. Aderência auto-reportada associou-se significativamente com hemograma normal e positivamente com uso de imatinibe. CONCLUSÕES: Falta informação ou compreensão sobre monitoramento entre pacientes com LMC; eles recebem diagnóstico rapidamente e têm bom acesso ao tratamento. A correta compreensão das ferramentas de controle em LMC está prejudicada entre eles.
Asunto(s)
Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Conocimientos, Actitudes y Práctica en Salud , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Antineoplásicos/uso terapéutico , Brasil , Estudios Transversales , Accesibilidad a los Servicios de Salud , Mesilato de Imatinib/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Cumplimiento de la Medicación , Percepción , Cromosoma Filadelfia , Estudios Prospectivos , Factores Socioeconómicos , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
Tyrosine kinase inhibitors (TKIs), imatinib, nilotinib and dasatinib, are the current treatment of chronic myeloid leukemia (CML). BCR-ABL1 point mutations are the principal cause of resistance to treatment; however other mechanisms could be involved in failure to TKI therapy. LYN is a src kinase protein that regulates survival and responsiveness of tumor cells by a BCR-ABL1 independent mechanism. PTEN tumor suppressor gene is downregulated by BCR-ABL1 in CML stem cells and its deletion is associated with acceleration of disease. In this study we evaluated the expression of LYN, PTEN and the ratio of both genes in 40 healthy donors (HD) and in 139 CML patients; 88 of them resistant to TKI in different phases of disease and 51 in chronic phase classified as optimal responders (OR) to TKI [40 treated with imatinib or nilotinib (OR-IN) and 11 treated with dasatinib (OR-D) therapy]. When we analyzed the gene expression values of LYN, an increase was observed only in advanced stages of the disease, however, when we analyzed the ratio between LYN and PTEN genes, the group of resistant patients in chronic phase in imatinib or nilotinib treatment (CP-IN) also showed a significant increase. Resistant patients treated with dasatinib, a src kinase inhibitor, presented a similar ratio to the observed in HD. In addition, the LYN/PTEN ratio and the LYN expression showed a direct significant correlation with BCR-ABL1 transcript levels in unmutated resistant patients treated with non-src kinase inhibitors. We were able to identify 8/35 (23%) of cases in CP-IN and 4/12 (33%) in accelerated phase and blast phase (AP/BC-IN), in which resistance could be associated with an increase in the ratio of the LYN/PTEN. Our data suggest that the LYN/PTEN expression ratio may be a sensitive monitor of disease progression in unmutated CML patients under imatinib or nilotinib treatment. This ratio could detect cases when resistance is related to altered LYN expression, suggesting that the treatment change to a src kinase inhibitor would be most suitable to overcome resistance.
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Regulación Leucémica de la Expresión Génica , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Fosfohidrolasa PTEN/genética , Familia-src Quinasas/genética , Resistencia a Antineoplásicos/genética , Proteínas de Fusión bcr-abl/genética , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Mutación , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
The pathogenesis and evolutive pattern of Chagas disease suggests that the chronic phase should be more widely treated in order to (i) eliminate Trypanosoma cruzi and prevent new inflammatory foci and the extension of tissue lesions, (ii) promote tissue regeneration to prevent fibrosis, (iii) reverse existing fibrosis, (iv) prevent cardiomyopathy, megaoesophagus and megacolon and (v) reduce or eliminate cardiac block and arrhythmia. All cases of the indeterminate chronic form of Chagas disease without contraindications due to other concomitant diseases or pregnancy should be treated and not only cases involving children or recently infected cases. Patients with chronic Chagas cardiomyopathy grade II of the New York Heart Association classification should be treated with specific chemotherapy and grade III can be treated according to medical-patient decisions. We are proposing the following new strategies for chemotherapeutic treatment of the chronic phase of Chagas disease: (i) repeated short-term treatments for 30 consecutive days and interval of 30-60 days for six months to one year and (ii) combinations of drugs with different mechanisms of action, such as benznidazole + nifurtimox, benznidazole or nifurtimox + allopurinol or triazole antifungal agents, inhibition of sterol synthesis.
Asunto(s)
Animales , Femenino , Humanos , Embarazo , Enfermedad de Chagas/tratamiento farmacológico , Tripanocidas/administración & dosificación , Enfermedad Crónica , Enfermedad de Chagas/complicaciones , Enfermedad de Chagas/patología , Progresión de la Enfermedad , Esquema de Medicación , Quimioterapia CombinadaRESUMEN
En el presente artículo original se describen y comentan los datos aportados por un grupo de oncohematólogos, acerca del uso actual de los recursos sanitarios para el tratamiento de la leucemia mieloide crónica y de los eventos adversos relacionados con ésta, en Perú. Mediante la técnica de consenso Mini Delphi, los panelistas lograron elevado grado de acuerdo sobre los temas de interés. A modo de síntesis, se observó distribución de los recursos generales disponibles acorde con las necesidades de cada fase de la leucemia y en adhesión a las pautas terapéuticas internacionales, aunque se detectaron algunas instancias que podrían optimizarse. Resultó evidente la notable disminución de la realización de trasplantes de médula ósea, en Perú. Esta información puede constituir un punto de partida para futuros estudios adicionales en el contexto de la práctica clínica en Latinoamérica. Además, aplicada a modelos farmacoeconómicos apropiados, los datos podrían agilizar la toma de decisiones acorde a la realidad local, por parte de los distintos responsables de los sistemas de salud, para permitir a los enfermos con LMC acceder a las opciones terapéuticas más ventajosas y, aún más trascendente, mejorar su calidad de vida y supervivencia.
This original article details and discusses the information provided by a group of hematologists, about the current use of health resourcesin the management of chronic myeloid leukemia and its treatment related adverse events in Peru. By applying the Mini Delphi consensus technique, a high degree of agreement about the issues of interest was reached among the faculty. To summarize, although it was noticed that the allocation of health resources matches the requirement for each phase in the management of leukemia and it adheres to international guidelines, some topics that could be optimized were identified. A remarkable reduction of bone marrow transplant procedures was evident. These data may represent a starting point for further studies in the clinical practice setting in Latin America. Moreover, using appropriate pharmacoeconomic models, the information obtained may speed up the decision making process according to the local circumstances by those responsible for sanitary assistance, allowing patients with CML to reach the most convenient therapeutic options and, more importantly, improving their quality of life and survival.
Asunto(s)
Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Recursos en Salud , Perú , Técnica DelphiRESUMEN
This study investigated whether a long-term high-fat diet has an effect on the outcome of chronic murine schistosomiasis mansoni compared to a standard diet. Swiss Webster female mice (3 weeks old) were fed each diet for up to six months and were then infected with 50 Schistosoma mansoni cercariae. Their nutritional status was assessed by monitoring total serum cholesterol and body mass. Infected mice were examined 6-17 weeks post infection to estimate the number of eggs in faeces. Mice were euthanised the next day. Total serum cholesterol was lower in infected mice in comparison to uninfected controls (p = 0.0055). In contrast, body mass (p = 0.003), liver volume (p = 0.0405), spleen volume (p = 0.0124), lung volume (p = 0.0033) and faecal (p = 0.0064) and tissue egg density (p = 0.0002) were significantly higher for infected mice fed a high-fat diet. From these findings, it is suggested that a high-fat diet has a prominent effect on the course of chronic schistosomiasis mansoni in mice.
Asunto(s)
Animales , Femenino , Ratones , Colesterol/sangre , Grasas de la Dieta/metabolismo , Esquistosomiasis mansoni/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Índice de Masa Corporal , Enfermedad Crónica , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/sangre , Heces/parasitología , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/sangreRESUMEN
Pacientes na fase crônica da doença de Chagas foram tratados com corticóide em virtude de afecções associadas e, a fim de tentar coibir reativação da infecção pelo Trypanosoma cruzi, houve uso concomitante do nifurtimox. Levando em conta o verificado em pesquisa anterior, quando corticóide de fato promoveu aumento da parasitemia detectada pelo xenodiagnóstico, pôde ser notado que o nifurtimox mostrou-se apto a evitar a citada acentuação parasitária, podendo tal constatação ser útil em procedimentos assistenciais, quando circunstancialmente estiverem presentes doença de Chagas e imunodepressão.
Patients in the chronic phase of Chagas' disease and receiving corticoid because of concommitant diseases were treated with nifurtimox. We proved in another paper that in the chronic phase of Chagas' disease corticoid use is associated with increased parasitemia, as evaluated by xenodiagnosis. In this study nifurtimox use prevented this increase, and we suggest that in immunocompromised patients with chronic Chagas' disease the use of this drug could be useful.