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Resumen Introducción y objetivos: La Insuficiencia Cardíaca (IC) es un síndrome frecuente en la población adulta. Sacubitril / Valsartán (S/V) es un tratamiento novedoso para esta patología. El presente estudio pretende analizar el efecto de este medicamento sobre las variables clínicas, de laboratorio y ecocardiográficas en pacientes con IC con FEVIr. Metodología: Se realizó un estudio observacional retrospectivo de los expedientes de los pacientes del PIC que tuvieran prescrito S/V. De estos, se recopilaron datos basales y de seguimiento de los principales parámetros de relevancia pronóstica, para estos pacientes. Luego se cuantificaron los cambios generados en el tiempo una vez establecido el tratamiento y se hicieron análisis estadísticos para validar si los cambios fueron significativos. Resultados: De la totalidad de pacientes del PIC, 27 cumplieron los criterios de inclusión, con una edad promedio de 70 años y en donde 37.0% se encontraron en la dosis meta después de un seguimiento promedio de 16.4 meses. A través del estudio fue posible encontrar una diferencia estadísticamente significativa para el cambio en la FEVI para 17 pacientes (p=0.016). En los pacientes en los que se pudo recopilar la información se observó que el NT-proBNP mejoró en un 68.75%, por su parte la caminata de 6 minutos mejoró en un 77.8%. Además, solamente 7.4% de los pacientes empeoraron en su escala funcional NYHA, 7.4% fallecieron y 3.7% sufrieron hospitalización durante el estudio. Conclusiones: Basados en los parámetros estudiados y a través de los cambios generados durante el tiempo de seguimiento, fue posible definir una mejoría en los pacientes tras el uso de S/V, asociado también a una baja mortalidad e incidencia de hospitalizaciones.
Abstract Effect of Sacubitril / Valsartan on the clinical, laboratory and echocardiographic variables used for the control of heart failure with reduced left ventricular ejection fraction (LVEFr) in active patients of the Heart Failure Program (HFP) of the Hospital Clínica Bíblica Introduction and objectives: Heart failure (HF) is a common syndrome in the adult population. Sacubitril /Valsartan (S/V) is a novel treatment for this pathology. This study aims to analyze the effect of this medication on clinical, laboratory and echocardiographic variables in patients with HF and left ventricular eyección fracción reduced (LVEFr). Methodology: A retrospective observational study was conducted on patients records who are enrolled in the Heart Failure Program (HFP) and have been prescribed with S/V. For these patients, baseline and follow-up data was collected for relevant parameters. Changes over time were then quantified once the treatment with S/V was initiated, and a statistical analysis was conducted to validate whether the changes were significant. Results: Of all HFP patients, 27 met the inclusion criteria, with an average age of 70 years and where 37.0% of them were at the target dose after an average follow- up of 16.4 months. Through the study it was possible to find a statistically significant difference in a change for the ejection fraction in 17 patients (p.0.016). In patients with available clinical data, it was observed that NT-proBNP improved by 68.75%, meanwhile the 6-minute walk improved by 77.8%. In addition, only 7.4% of patients worsened their NYHA functional scale, 3.7% were hospitalized and 7.4% died during the time. Conclusions: Based on the studied parameters and throughout all the clinical changes during the follow-up time, it was possible to establish an improvement in patients after the S/V therapy, which is also associated with a low hospitalization incidence and a low mortality rate.
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Humanos , Anciano , Anciano de 80 o más Años , Valsartán/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , AncianoRESUMEN
PURPOSE: Lung cancer (LC) has a significant impact on patients' health-related quality of life (HRQoL). We investigate the correlations between pre-radiation therapy HRQoL and survival. MATERIALS AND METHODS: A prospective, intention-to-treat, multicentre study of 437 patients with LC recruited at the radiation oncology departments of three different institutions was conducted between 2012 and 2016. QoL was assessed using the EORTC-QLQ-C30 (v3.0) and EORTC-QLQ-LC13 questionnaires. Global health status (GHS), physical (PF), role functioning (RF), emotional (EF), cognitive (CF), and social functioning (SF) as well as symptoms scores were evaluated in univariate and multivariate analyses. RESULTS: The cohort consisted of 376 men (86%) and 61 women, with a median age of 66 years (range 31-88). Histology was: 72% (n = 315) non-small cell lung cancer and 28% small cell lung cancer. The most common stage was III (80%) and the median follow-up for alive patients was 30 months (range 7-76). Multivariate analysis showed that RF was associated with a lower risk of mortality (HR: 0.693; p = 0.008) and recurrence (HR: 0.737; p = 0.040). Additionally, lower scores on EF and PF were associated with higher mortality (HR: 0.696; p = 0.003 and HR: 0.765; p = 0.044, respectively). Appetite loss, constipation, and dysphagia were associated with a higher risk of mortality (HR: 1.985; p < 0.001, HR: 1.373; p = 0.036, and HR: 1.659; p = 0.002, respectively), while appetite loss was the only symptom associated with a higher risk of recurrence (HR: 1.525; p = 0.014). CONCLUSIONS: Pre-radiation therapy scores on RF, EF, and PF and symptoms like appetite loss, dysphagia, and constipation were associated with the risk of mortality. This information could be added to other prognostic factors to guide our treatment decisions.
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Carcinoma de Pulmón de Células no Pequeñas/psicología , Neoplasias Pulmonares/psicología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Femenino , Estado de Salud , Humanos , Análisis de Intención de Tratar , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Calidad de Vida , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.
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Ensayos Clínicos como Asunto/estadística & datos numéricos , Cooperación Internacional , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Estudios Observacionales como Asunto/estadística & datos numéricos , Objetivos Organizacionales , Sociedades Médicas/organización & administración , Adolescente , Supervivientes de Cáncer , Niño , Neoplasias Hematológicas/terapia , Hematología/organización & administración , Humanos , Oncología Médica/organización & administración , Neoplasias/terapia , Pediatría/organización & administración , EspañaRESUMEN
PURPOSE: Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3-60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12-70]); and 50 (15%) patients underwent surgery. RESULTS: Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31-88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025). CONCLUSIONS: HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.
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Adenocarcinoma/mortalidad , Carcinoma de Células Grandes/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Células Escamosas/mortalidad , Enfermedades Cardiovasculares/mortalidad , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Grandes/complicaciones , Carcinoma de Células Grandes/patología , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
PURPOSE: The present work aims at evaluating intensity-modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) in squamous cell carcinomas (SCC) of the larynx and hypopharynx. METHODS/PATIENTS: We performed a single institutional retrospective analysis on 116 pharyngo (29%)-laryngeal (71%) SCC patients (93% male) treated with IMRT-SIB to 66-69.96 Gy in 33 fractions between 2008 and 2016. Those who underwent surgery (54%) received adjuvant radiation of 66 Gy at 2 Gy/fraction to the surgical bed. 16 patients (14%) were treated for a local recurrence after prior surgery. High-risk lymph node regions received 59.4 Gy at 1.8 Gy/fraction and low risk regions 54.12 Gy at 1.64 Gy/fraction. The median age was 60 years and 95% of patients had an ECOG performance status 0-2. Most had advanced stage disease (III 22%, IV 74%). Chemotherapy was delivered in 74% of cases. RESULTS: Median follow-up was 32 months. Two and three-year overall survival for all patients was 87% and 82%, respectively. There were 28 (24%) locoregional recurrences and 19 (16%) distant failures. Grade 3 mucositis, dermatitis, and xerostomy were observed in 12%, 10%, and 3%, respectively. A longer IMRT-SIB overall treatment time was associated with a higher risk of mortality (HR 1.09, CI 1.01-1.17, P = 0.02). Postoperative IMRT-SIB associated with a significantly lower risk of any recurrence (HR 0.34, CI 0.18-0.64, P = 0.001) and higher local control (HR 0.06, CI 0.01-0.24, P < 0.01). Additionally, it associated with a lower risk of mucositis (P = 0.029) compared with definitive radio (chemo) therapy. CONCLUSIONS: IMRT-SIB is a safe and feasible radiation treatment technique for pharyngo-laryngeal SCC patients with a tolerable acute toxicity profile.
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Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/radioterapia , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Faríngeas/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Neoplasias Laríngeas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Neoplasias Faríngeas/patología , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Retrospectivos , Tasa de Supervivencia , Pruebas de Toxicidad , Resultado del TratamientoRESUMEN
BACKGROUND: Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature. PATIENTS AND METHODS: Patients with CSI GCTC were screened between January 2012 and December 2016. Patients had previously undergone inguinal orchidectomy as the primary treatment and chosen AS as their preferred management strategy after receiving information about all available strategies. RESULTS: Out of 91 patients screened, 82 patients selected AS as their preferred management strategy. Relapse rate in the overall population was 20% (95% CI 12-30) and median time to relapse was 11.5 months (range 1.0-35.0). In patients with seminomatous tumors, relapse rate decreased to 13% and median time to relapse was 13 months; whereas in patients with non-seminomatous tumors, relapse rate was 33% (IA) or 29% (IB) and median time to relapse was 12 months in stage IA and 4.5 months in stage IB patients. All relapses were rescued with three or four cycles of chemotherapy and two also required a retroperitoneal lymphadenectomy. All patients are currently alive and free of disease. CONCLUSIONS: The clinical outcomes of patients with CSI GCTC managed by AS in this series were excellent. This strategy limited the administration of active treatments specifically to the minority of patients who relapsed without compromising performance.
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Imagen Multimodal/métodos , Neoplasias de Células Germinales y Embrionarias/prevención & control , Orquiectomía/mortalidad , Vigilancia de la Población , Neoplasias Testiculares/prevención & control , Espera Vigilante/estadística & datos numéricos , Adolescente , Adulto , Anciano , Manejo de la Enfermedad , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/cirugía , Espera Vigilante/normas , Adulto JovenRESUMEN
PURPOSE: The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. RESULTS: The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). CONCLUSION: This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/efectos adversos , Enfermedades del Esófago/etiología , Recurrencia Local de Neoplasia/terapia , Radioterapia de Intensidad Modulada/efectos adversos , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Grandes/patología , Carcinoma de Células Grandes/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Enfermedades del Esófago/patología , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Adulticidal and oviposition- and hatching-altering activities of essential oil extracted from Mexican oregano leaves (Lippia graveolens H.B.K.) (OEO) were evaluated on engorged adult female Rhipicephalus microplus ticks using the adult immersion test bioassay. Twofold dilutions of OEO were tested from a starting dilution of 10% down to 1.25%. Results showed 100% adulticidal activity at 10% OEO concentration and oviposition inhibition of 65.8% and 40.9% at 5.0% and 2.5% OEO concentration, respectively. Egg hatching inhibition was achieved by 26.0% and 11.5% at 5.0% and 2.5% OEO concentration, respectively. These effects could be attributed to OEO major components: thymol, carvacrol and p-cymene, which together account for more than 60.0% of the OEO chemical composition. Mexican oregano could represent a potential source for development of alternative tick control agents.
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PURPOSE: Despite numerous advances, survival remains dismal for children and adolescents with poor prognosis cancers or those who relapse or are refractory to first line treatment. There is, therefore, a major unmet need for new drugs. Recent advances in the knowledge of molecular tumor biology open the door to more adapted therapies according to individual alterations. Promising results in the adult anticancer drug development have not yet been translated into clinical practice. We report the activity in early pediatric oncology trials in Spain. METHODS: All members of the Spanish Society of Pediatric Hematology Oncology (SEHOP) were contacted to obtain information about early trials open in each center. RESULTS: 22 phase I and II trials were open as of May 2015: 15 for solid tumors (68 %) and 7 for hematological malignancies (32 %). Fourteen (64 %) were industry sponsored. Since 2010, four centers have joined the Innovative Therapies For Children With Cancer, an international consortium whose aim is developing novel therapies for pediatric cancers. A substantial number of studies have opened in these 5 years, improving the portfolio of trials for children. Results of recently closed trials show the contribution of Spanish investigators, the introduction of molecularly targeted agents and their benefits. CONCLUSIONS: Clinical trials are the way to evaluate new drugs, avoiding the use of off-label drugs that carry significant risks. The Spanish pediatric oncology community through the SEHOP is committed to develop and participate in collaborative academic trials, to favor the advancement and optimization of existing therapies in pediatric cancer.
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Ensayos Clínicos como Asunto , Oncología Médica/tendencias , Neoplasias/terapia , Pediatría/tendencias , Adolescente , Niño , Femenino , Humanos , Masculino , Oncología Médica/métodos , Pediatría/métodos , EspañaRESUMEN
PURPOSE: We assessed therapeutic outcomes of reirradiation with helical tomotherapy (HT) for locoregional recurrent nasopharyngeal carcinoma (LRNPC) patients. METHODS AND MATERIALS: Treatment outcomes were evaluated retrospectively in 17 consecutive LRNPC patients receiving HT between 2006 and 2012. Median age was 57 years and most patients (n = 13) were male. Simultaneous systemic therapy was applied in 5 patients. Initial treatment covered the gross tumor volume with a median dose of 70 Gy (60-81.6 Gy). Reirradiation was confined to the local relapse region with a median dose of 63 Gy (50-70.2 Gy), resulting in a median cumulative dose of 134 Gy (122-148.2 Gy). The median time interval between initial and subsequent treatment was 42 months (11-126). RESULTS: The median follow-up for the entire cohort was 23 and 35 months for survivors. Three patients (18 %) developed both local and distant recurrences and only one patient (6 %) suffered from isolated local recurrence. Two-year actuarial DFS and LC rates were 74 and 82 %, respectively. Two-year OS rate was 79 %. Acute and late grade 2 toxicities were observed in 8 patients (47 %). No patient experienced late grade ≥3 toxicity. Late toxicity included fibrosis of skin, hypoacusia, dysphagia, and xerostomia. Patients with higher Karnofsky performance status scores associated with a lower risk of mortality (HR 0.85, p = 0.015). CONCLUSION: Reirradiation with HT in patients with LRNPC is feasible and yields encouraging results in terms of local control and overall survival with acceptable toxicity.
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Neoplasias Nasofaríngeas/radioterapia , Recurrencia Local de Neoplasia/radioterapia , Radioterapia de Intensidad Modulada/métodos , Adulto , Anciano , Carcinoma , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada/efectos adversos , Estudios RetrospectivosRESUMEN
The carbon dioxide Raman spectrum is simulated within an algebraic approach based on curvilinear coordinates in a local representation. The two main advantages of the present algebraic approach are a possible connection with configuration space and the correct description of systems with either local or normal mode character. The system Hamiltonian and polarizability tensor are expanded in terms of curvilinear coordinates. The curvilinear coordinates are in turn expanded into normal coordinates, obtaining an algebraic representation in terms of normal bosonic operators. A canonical transformation maps the operators into a local algebraic representation. The final step is an anharmonization procedure to local operators. The Raman spectrum of CO2 has been simulated, obtaining results close to experimental accuracy, and polarizability transition moments for the Raman spectral lines between 1150 cm(-1) and 1500 cm(-1) are reported. The comparison between experimental and simulated spectra has provided six new CO2 experimental vibrational terms.
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Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.
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Metabolismo de los Hidratos de Carbono , Genotipo , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Madres , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/metabolismo , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Homocisteína/sangre , Humanos , Incidencia , Defectos del Tubo Neural/epidemiología , Embarazo , Factores de Riesgo , Disrafia Espinal/epidemiología , Disrafia Espinal/genética , Disrafia Espinal/metabolismo , Adulto JovenRESUMEN
Upon oxygen shift-down, Mycobacterium tuberculosis complex bacteria can induce a genetic program characterized by halted duplication, which is called Non-replicating persistence (NRP). During this phase, at least 48 genes, collectively named Dormancy survival regulator (DosR) regulon, are important for the long-term survival of bacilli under a non-respiring state, a condition that bacilli encounter inside granulomatous lesions. It remains unclear whether expression of NRP genes occurs within the tissue of Mycobacterium bovis naturally infected cattle. In order to start dissecting this question, total RNA from bovine lymph node tissues of sacrificed tuberculin reacting animals was isolated and transcription of genes required for in vivo duplication (esxB and fbpB) and in vitro NRP (hspX, pfkB, and mb2660c) were analyzed by RT-PCR approaches. Detection of transcripts was positive in bovine tissue samples for genes hspX, pfkB, and mb2660c in 84, 32, and 21%, respectively. NRP genes were upregulated even in animals with a negative IFN-γ in vitro test, and the expression of NRP genes occurred more often than expression of the esxB gene.
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Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Ganglios Linfáticos/microbiología , Mycobacterium bovis/crecimiento & desarrollo , Regulación hacia Arriba , Animales , Proteínas Bacterianas/genética , Bovinos , Interferón gamma/biosíntesis , Ensayos de Liberación de Interferón gamma , Mycobacterium bovis/genética , Mycobacterium bovis/metabolismo , Mycobacterium bovis/patogenicidad , Regulón , Pruebas Cutáneas , Prueba de Tuberculina , Tuberculosis Bovina/microbiologíaRESUMEN
This communication describes the general biochemical properties and some immunological characteristics of the venom from the Peruvian scorpion Hadruroides lunatus, which is the most medically relevant species in Peru. The soluble venom of this scorpion is toxic to mice, the LD50 determined was 0.1 mg/kg and 21.55 mg/kg when the venom was injected intracranial or intraperitoneally, respectively. The soluble venom displayed proteolytic, hyaluronidasic, phospholipasic and cardiotoxic activities. High performance liquid chromatography of the soluble venom resulted in the separation of 20 fractions. Two peptides with phospholipasic activity were isolated to homogeneity and their molecular masses determined by mass spectrometry (MALDI TOF). Anti-H. lunatus venom sera were produced in rabbits. Western blotting analysis showed that most of the protein content of this venom is immunogenic. H. lunatus anti-venom displayed consistent cross-reactivity with venom antigens from the new World-scorpions Tityus serrulatus and Centruroides sculpturatus venoms; however, a weaker reactivity was observed against the venom antigens from the old World-scorpion Androctonus australis Hector.
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Venenos de Escorpión/química , Venenos de Escorpión/inmunología , Venenos de Escorpión/envenenamiento , Animales , Western Blotting , Fraccionamiento Químico , Cromatografía Líquida de Alta Presión , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Hialuronoglucosaminidasa/metabolismo , Sueros Inmunes/inmunología , Dosificación Letal Mediana , Ratones , Ratones Endogámicos C57BL , Perú , Fosfolipasas A2/metabolismo , Proteolisis , Conejos , Ratas , Ratas Wistar , Especificidad de la Especie , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
BACKGROUND: The purpose of this study is to assess the outcome of patients with Ewing sarcoma (EWS) of the bone and to identify prognostic factors. MATERIALS AND METHODS: Seventy-seven patients younger than 18 years old, diagnosed with EWS of the bone between 1979 and 2009, were analysed retrospectively. Four different protocols of chemotherapy were used successively. Local treatment consisted of surgery (N=32), radiotherapy (N=20) and a combination of both (N=19). RESULTS: The median age at diagnosis was 10 years old (range, 2-17) and the median follow-up for survivors 8.6 years (range, 1-18.8). Thirty-two relapses occurred (21 distant, 5 local and 6 both). The 2- and 5-year overall survival rates were 70% and 51%, respectively. Multivariate analysis showed four significant independent predictors for death: age ≥14 years old (HR: 5.06; p=0.019), lack of complete response (HR: 8.04; p<0.001), tumour volume ≥150 ml (HR: 2.21; p=0.045) and distant recurrences (HR: 1.45; p=0.001). CONCLUSIONS: Outcome of EWS of bone is influenced by many clinical and treatment-correlated variables. Criteria to stratify patients should include all the variables that have shown prognostic significance. The development of novel therapies should target these high-risk groups.
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Neoplasias Óseas/diagnóstico , Neoplasias Óseas/mortalidad , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/mortalidad , Adolescente , Niño , Preescolar , Terapia Combinada/métodos , Femenino , Humanos , Masculino , Oncología Médica/métodos , Análisis Multivariante , Pronóstico , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Acaricidal effects of three essential oils extracted from Mexican oregano leaves (Lippia graveolens Kunth), rosemary leaves (Rosmarinus officinalis L.), and garlic bulbs (Allium sativum L.) on 10-d-old Rhipicephalus (Boophilus) microplus (Canestrini) tick larvae were evaluated by using the larval packet test bioassay. Serial dilutions of the three essential oils were tested from a starting concentration of 20 to 1.25%. Results showed that both Mexican oregano and garlic essential oils had very similar activity, producing high mortality (90-100%) in all tested concentrations on 10-d-old R. microplus tick larvae. Rosemary essential oil produced >85% larval mortality at the higher concentrations (10 and 20%), but the effect decreased noticeably to 40% at an oil concentration of 5%, and mortality was absent at 2.5 and 1.25% of the essential oil concentration. Chemical composition of the essential oils was elucidated by gas chromatography-mass spectrometry analyses. Mexican oregano essential oil included thymol (24.59%), carvacrol (24.54%), p-cymene (13.6%), and y-terpinene (7.43%) as its main compounds, whereas rosemary essential oil was rich in a-pinene (31.07%), verbenone (15.26%), and 1,8-cineol (14.2%), and garlic essential oil was rich in diallyl trisulfide (33.57%), diallyl disulfide (30.93%), and methyl allyl trisulfide (11.28%). These results suggest that Mexican oregano and garlic essential oils merit further investigation as components of alternative approaches for R. microplus tick control.
Asunto(s)
Acaricidas/farmacología , Ajo/química , Ixodidae/efectos de los fármacos , Lippia/química , Rhipicephalus/efectos de los fármacos , Rosmarinus/química , Acaricidas/química , Animales , Cromatografía de Gases y Espectrometría de Masas , Ixodidae/crecimiento & desarrollo , Larva/efectos de los fármacos , México , Aceites Volátiles/química , Aceites Volátiles/farmacología , Aceites de Plantas/química , Aceites de Plantas/farmacologíaRESUMEN
INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) constitutes a heterogeneous group of diseases. We summarize the experience of our hospital, one of Spain's largest series of renal (294), liver (47) and allogeneic stem cell transplants (67), where four cases of PTLD have developed related to complex viral infections. METHODS: Case 1 was a 24-month-old boy diagnosed with acute lymphoblastic leukemia who underwent allogeneic stem-cell transplantation (SCT). He was seropositive for Epstein-Barr virus (EBV) and developed an aggressive Bcell non-Hodgkin's lymphoma (B-NHL) related to EBV reactivation and human herpesvirus 6 (HHV-6) infection. Cases 2, 3, and 4 developed after kidney transplantation and were all EBV seronegative. Case 2 had associated cytomegalovirus (CMV) and EBV infection. Cases 3 and 4 only revealed EBV viral load. Cases 1, 3, and 4 progressed rapidly, with fatal outcome. Global incidence of PTLD in our series is 1.1%. CONCLUSION: PTLD is a rare but life-threatening condition. Although EBV plays a clear role in its pathogenesis, other associated viral infections could trigger this situation. Current therapies include rituximab, decreasing immunosuppressive drugs. and conventional chemotherapy.
Asunto(s)
Trastornos Linfoproliferativos/virología , Complicaciones Posoperatorias/virología , Infecciones Tumorales por Virus/virología , Virosis/complicaciones , Niño , Preescolar , Citomegalovirus , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/epidemiología , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4 , Humanos , Lactante , Recién Nacido , Trasplante de Riñón/efectos adversos , Masculino , Trasplante de Células Madre/efectos adversos , Infecciones Tumorales por Virus/complicaciones , Infecciones Tumorales por Virus/epidemiología , Carga Viral , Virosis/epidemiologíaRESUMEN
A case of an 8 year-old boy with history of nephroblastoma (Wilms' tumor) three years prior, which was managed with nephrectomy, chemotherapy and radiotherapy, is presented. During a routine follow up, a three month old rapidly growing mass on the left side of the face was detected. The roentgenogram showed a lytic lesion in the body and ascending ramus of the left jaw. Re-evaluation of the previous renal tumor was interpreted as a clear cell sarcoma of the kidney. Biopsy of the lesion of the left jaw showed similar histology, therefore, the diagnosis of clear cell sarcoma of the kidney metastatic to the left jaw was rendered. This is a rare case and to our knowledge is the first in the world's literature. We emphasize the diagnostic challenge of both the primary neoplasm and the metastasis and discuss the differential diagnosis of primary and metastatic sarcomas.