RESUMEN
OBJECTIVE: To evaluate the efficiency of radioguided occult lesion localising in non-palpable breast lesions (NPBL) compared to the surgical wire technique. METHOD: A prospective study was conducted on 161 women with NPBL, of whom 80 marked with the wire (group 1), whereas 81 women were marked with an intratumour injection of 99mTc-nanocoloid (group 2). The NPBL were located by ultrasound or stereotactic guidance. The lumpectomies were performed following the wire direction in group 1, and with the aid of a gamma-probe in group 2. Surgical margins were then checked, determining the need of extension if the margin was less than 5mm in the intra-surgical study, and less than 2mm in the deferred study. Data were collected on the mean number detected by surgery, surgical margins, number of extensions, presence of residual tumour in the extension, second surgeries, lumpectomy volume, as well as total resected volume, volume/tumour ratio, and complications. RESULTS: No significant differences were observed between the two groups in the mean number detected, surgical margins, number of extensions, presence of residual tumour in the extension, second surgeries, lumpectomy volume, total resected volume, volume/tumour ratio or complications. The multivariate analysis showed the determining factors of the resected volume were the radiological guidance technique, as well as the surgeon. CONCLUSIONS: The radioguided occult lesion localising technique helps in the detection and resection of NPBL with the same efficiency as the surgical wire, and adds the possibility of sentinel node detection in the same surgery. The determining factors of the resected volume were the radiological guidance technique and the surgeon.
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Enfermedades de la Mama/cirugía , Neoplasias de la Mama/cirugía , Mastectomía Segmentaria/métodos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Palpación , Estudios Prospectivos , Radiofármacos , Cirugía Asistida por Computador , Agregado de Albúmina Marcado con Tecnecio Tc 99mRESUMEN
A rapid in situ biosynthesis of gold nanoparticles (AuNPs) is proposed in which a geranium (Pelargonium zonale) leaf extract was used as a non-toxic reducing and stabilizing agent in a sonocatalysis process based on high-power ultrasound. The synthesis process took only 3.5 min in aqueous solution under ambient conditions. The stability of the nanoparticles was studied by UV-Vis absorption spectroscopy with reference to the surface plasmon resonance (SPR) band. AuNPs have an average lifetime of about 8 weeks at 4 °C in the absence of light. The morphology and crystalline phase of the gold nanoparticles were characterized by transmission electron microscopy (TEM). The composition of the nanoparticles was evaluated by electron diffraction and X-ray energy dispersive spectroscopy (EDS). A total of 80% of the gold nanoparticles obtained in this way have a diameter in the range 8-20 nm, with an average size of 12±3 nm. Fourier transform infrared spectroscopy (FTIR) indicated the presence of biomolecules that could be responsible for reducing and capping the biosynthesized gold nanoparticles. A hypothesis concerning the type of organic molecules involved in this process is also given. Experimental design linked to the simplex method was used to optimize the experimental conditions for this green synthesis route. To the best of our knowledge, this is the first time that a high-power ultrasound-based sonocatalytic process and experimental design coupled to a simplex optimization process has been used in the biosynthesis of AuNPs.
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Geranium/química , Oro/química , Nanopartículas del Metal/química , Extractos Vegetales/química , Hojas de la Planta/química , Sonicación/métodos , Catálisis , Técnicas de Química Sintética , Sonicación/instrumentaciónRESUMEN
BACKGROUND: In experimental models of glioblastoma multiforme (GBM), irradiation (IR) induces local expression of the chemokine CXCL12/SDF-1, which promotes tumour recurrence. The role of CXCR7, the high-affinity receptor for CXCL12, in the tumour's response to IR has not been addressed. METHODS: We tested CXCR7 inhibitors for their effects on tumour growth and/or animal survival post IR in three rodent GBM models. We used immunohistochemistry to determine where CXCR7 protein is expressed in the tumours and in human GBM samples. We used neurosphere formation assays with human GBM xenografts to determine whether CXCR7 is required for cancer stem cell (CSC) activity in vitro. RESULTS: CXCR7 was detected on tumour cells and/or tumour-associated vasculature in the rodent models and in human GBM. In human GBM, CXCR7 expression increased with glioma grade and was spatially associated with CXCL12 and CXCL11/I-TAC. In the rodent GBM models, pharmacological inhibition of CXCR7 post IR caused tumour regression, blocked tumour recurrence, and/or substantially prolonged survival. CXCR7 expression levels on human GBM xenograft cells correlated with neurosphere-forming activity, and a CXCR7 inhibitor blocked sphere formation by sorted CSCs. CONCLUSIONS: These results indicate that CXCR7 inhibitors could block GBM tumour recurrence after IR, perhaps by interfering with CSCs.
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Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Glioblastoma/tratamiento farmacológico , Glioblastoma/radioterapia , Receptores CXCR/antagonistas & inhibidores , Animales , Neoplasias Encefálicas/patología , Quimiocina CXCL11/metabolismo , Quimiocina CXCL12/metabolismo , Glioblastoma/patología , Humanos , Ratones , Ratones Desnudos , Recurrencia Local de Neoplasia/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores CXCR/metabolismoRESUMEN
PURPOSE: The objective of this study is to evaluate the tolerability and outcome of craniospinal irradiation (CSI) with helical tomotherapy (HT) in the treatment of medulloblastoma. METHODS: We evaluated 19 consecutive patients with primary medulloblastoma who were treated with HT from 2007 through 2010. HT regimens to the neuroaxis included: 23.4 Gy at 1.8 Gy/fraction (N = 10), 36 Gy at 1.8 Gy/fraction (N = 7), and 39 Gy bid at 1.3 Gy/fraction (N = 2). The tumor bed received 54-60 Gy. Potential associations between patient, treatment, and toxicity factors and overall survival (OS) were assessed in univariate analyses using the Cox proportional hazards model. Spearman's rank correlation coefficient was used to correlate potential risk factors with the grade of acute toxicity. RESULTS: The median age at diagnosis was 5 years (range 2-14) and the median follow-up for alive patients (N = 14) 40 months (range 10-62). Two- and three-year overall survival was 75 and 68 %, respectively. The most common acute toxicity was hematological (79 %), being grade 2 and grade 3 in 4 (21 %) and 11 (58 %) cases, respectively. No grade ≥2 late toxicities were observed. Higher grades of acute body toxicity were found in older children (P = 0.004). Longer time between diagnosis and radiation therapy was correlated with shorter OS (P = 0.03). In addition, higher grades of acute thrombocytopenia were associated with shorter OS (P = 0.03). CONCLUSIONS: CSI delivered with HT for medulloblastoma is well tolerated with low rates of severe acute toxicity. Further research is necessary to assess late toxicity with a longer follow-up (AU)
No disponible
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Irradiación Craneoespinal/efectos adversos , Meduloblastoma/radioterapia , Radioterapia de Intensidad Modulada/efectos adversos , Resultado del Tratamiento , Neoplasias Encefálicas/radioterapia , Irradiación Craneoespinal/métodosRESUMEN
PURPOSE: The objective of this study is to evaluate the tolerability and outcome of craniospinal irradiation (CSI) with helical tomotherapy (HT) in the treatment of medulloblastoma. METHODS: We evaluated 19 consecutive patients with primary medulloblastoma who were treated with HT from 2007 through 2010. HT regimens to the neuroaxis included: 23.4 Gy at 1.8 Gy/fraction (N = 10), 36 Gy at 1.8 Gy/fraction (N = 7), and 39 Gy bid at 1.3 Gy/fraction (N = 2). The tumor bed received 54-60 Gy. Potential associations between patient, treatment, and toxicity factors and overall survival (OS) were assessed in univariate analyses using the Cox proportional hazards model. Spearman's rank correlation coefficient was used to correlate potential risk factors with the grade of acute toxicity. RESULTS: The median age at diagnosis was 5 years (range 2-14) and the median follow-up for alive patients (N = 14) 40 months (range 10-62). Two- and three-year overall survival was 75 and 68 %, respectively. The most common acute toxicity was hematological (79 %), being grade 2 and grade 3 in 4 (21 %) and 11 (58 %) cases, respectively. No grade ≥2 late toxicities were observed. Higher grades of acute body toxicity were found in older children (P = 0.004). Longer time between diagnosis and radiation therapy was correlated with shorter OS (P = 0.03). In addition, higher grades of acute thrombocytopenia were associated with shorter OS (P = 0.03). CONCLUSIONS: CSI delivered with HT for medulloblastoma is well tolerated with low rates of severe acute toxicity. Further research is necessary to assess late toxicity with a longer follow-up.
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Neoplasias Cerebelosas/radioterapia , Irradiación Craneoespinal/métodos , Meduloblastoma/radioterapia , Radioterapia de Intensidad Modulada , Adolescente , Niño , Preescolar , Irradiación Craneoespinal/efectos adversos , Femenino , Humanos , Masculino , Radioterapia de Intensidad Modulada/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS (AU)
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Humanos , Masculino , Femenino , Radiocirugia/mortalidad , Radiocirugia/métodos , Radiocirugia , Pulmón/anomalías , Hígado/química , Corteza Suprarrenal/anomalíasRESUMEN
Objetivo: Realizar un análisis biomecánico del equilibrio y la marcha en pacientes con fibromialgia para establecer una correlación con el estado funcional percibido. Material y método: Estudio transversal con 42 pacientes diagnosticados de fibromialgia (40 mujeres y 2 hombres). Se excluyeron personas con patologías concomitantes que alterasen la marcha y equilibrio. Se compararon los resultados del estado funcional medido mediante el Cuestionario de Impacto de la Fibromialgia (FIQ), con sus valoraciones biomecánicas del equilibrio medido con la aplicación NedSVE/IBV y cinética de la marcha con el sistema NedAMH/IBV. Resultados: Un 43% de los sujetos presentaba alteración en la valoración global de la prueba de Romberg Ojos Cerrados (ROC). Se encontró una correlación significativa entre el FIQ y la estabilidad medio lateral en la prueba de ROC (p=0,020). La valoración cinética de la marcha de todos los sujetos obtuvo parámetros dentro de la normalidad. No se encontraron correlaciones entre las variables del análisis cinético de la marcha y el resultado de la FIQ. Conclusión: Los hallazgos indican una buena correlación entre la FIQ con fibromialgia y su equilibrio postural medido con posturografía, pero no con los del análisis cinético de la marcha (AU)
Objective: To perform a biomechanical analysis of balance and gait in patients with fibromyalgia to establish a correlation with perceived functional status. Material and methods: A cross-sectional study of 42 patients diagnosed with fibromyalgia (40 women and 2 men). Subjects with concomitant conditions affecting balance and gait were excluded. Functional status results measured by the Fibromyalgia Impact Questionnaire (FIQ) were compared with the biomechanical assessments of balance measured with the NedSVE/IBV application and gait kinetics with the NedAMH/IBV system. Results: Forty-three percent of subjects had abnormalities on the overall assessment of the Romberg eyes closed (REC) test. A significant correlation was found between FIQ and lateral medial stability on the REC test (p=0.020). Gait kinetics assessment of all subjects obtained parameters within the normal range. No correlations were found between variables in the gait kinetics analysis and the FIQ result. Conclusion: Our findings indicate a good correlation of the FIQ with fibromyalgia and postural balance measured with posturography, but not with the results of gait kinetics analysis (AU)
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Humanos , Masculino , Femenino , Fibromialgia/complicaciones , Fibromialgia/diagnóstico , Fenómenos Biomecánicos/inmunología , Fenómenos Biomecánicos/fisiología , Fibromialgia/fisiopatología , Estudios Transversales/métodos , Estudios Transversales/tendencias , Estudios Transversales , Encuestas y Cuestionarios , Cinética , Curva ROCRESUMEN
BACKGROUND: The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer. MATERIALS AND METHODS: We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. RESULTS: Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49-87) and the median follow-up 11 months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively). CONCLUSION: Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control (AU)
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Humanos , Masculino , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/cirugía , Control de la Radiación/efectos adversos , Control de la Radiación/métodosRESUMEN
BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia , Selección de Paciente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Femenino , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Curva ROC , Factores de RiesgoRESUMEN
PURPOSE: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. METHODS: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. RESULTS: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. CONCLUSIONS: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.
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Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/cirugía , Neoplasias/cirugía , Radiocirugia , Radioterapia de Intensidad Modulada , Cirugía Asistida por Computador , Adolescente , Neoplasias de las Glándulas Suprarrenales/mortalidad , Neoplasias de las Glándulas Suprarrenales/secundario , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasias/mortalidad , Neoplasias/patología , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
There is a critical need for improved methane-oxidation catalysts to both reduce emissions of methane, a greenhouse gas, and improve the performance of gas turbines. However, materials that are currently available either have low activity below 400°C or are unstable at higher temperatures. Here, we describe a supramolecular approach in which single units composed of a palladium (Pd) core and a ceria (CeO(2)) shell are preorganized in solution and then homogeneously deposited onto a modified hydrophobic alumina. Electron microscopy and other structural methods revealed that the Pd cores remained isolated even after heating the catalyst to 850°C. Enhanced metal-support interactions led to exceptionally high methane oxidation, with complete conversion below 400°C and outstanding thermal stability under demanding conditions.
RESUMEN
The safety and pharmacokinetic (PK)/pharmacodynamic (PD) profile of the novel CCR1 antagonist CCX354 was evaluated in double-blind, placebo-controlled, single- and multiple-dose phase I studies (1-300 mg/day oral doses). CCX354 was well tolerated and displayed a linear dose-exposure profile, with half-life approaching 7 h at the 300-mg dose. The extent of CCR1 receptor blockade on blood monocytes, which correlated well with plasma concentrations of the drug, was assessed using fluorescently labeled CCL3 binding in whole blood from phase I subjects. High levels of receptor coverage at the 12-h time point were achieved after a single dose of 100 mg CCX354. Preclinical studies indicate that effective blockade of inflammatory cell infiltration into tissues requires ≥90% CCR1 inhibition on blood leukocytes at all times. The comparison of the properties of CCX354 with those published for other CCR1 antagonists has informed the dose selection for ongoing clinical development of CCX354 in rheumatoid arthritis (RA).
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Mediadores de Inflamación/farmacología , Mediadores de Inflamación/farmacocinética , Quinoxalinas/farmacología , Quinoxalinas/farmacocinética , Receptores CCR1/antagonistas & inhibidores , Adulto , Animales , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Mediadores de Inflamación/administración & dosificación , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Monocitos/patología , Unión Proteica/fisiología , Quinoxalinas/administración & dosificación , Conejos , Ratas , Ratas Wistar , Receptores CCR1/metabolismo , Adulto JovenRESUMEN
A novel series of imidazolylpyrimidines were found to possess inhibitory activity against the human CMV UL70 primase. Extensive SAR studies on an HTS lead led to potent, orally bioavailable compounds with anti-CMV IC(50) values of 150 nM in both viral yield and viral DNA replication assays and with a much reduced cytotoxicity compared to marketed treatments ganciclovir and cidofovir.
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Antivirales/química , Citomegalovirus/efectos de los fármacos , ADN Primasa/antagonistas & inhibidores , Pirimidinas/farmacología , Administración Oral , Animales , Antivirales/farmacología , Disponibilidad Biológica , Citomegalovirus/enzimología , Replicación del ADN , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Concentración 50 Inhibidora , Pirimidinas/química , Pirimidinas/toxicidad , Ratas , Relación Estructura-Actividad , Carga ViralRESUMEN
Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles.
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Citomegalovirus/efectos de los fármacos , Citomegalovirus/enzimología , ADN Primasa/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Antivirales/síntesis química , Antivirales/química , Antivirales/farmacología , Médula Ósea/efectos de los fármacos , Línea Celular , ADN Primasa/metabolismo , Inhibidores Enzimáticos/química , Humanos , Estructura Molecular , Pirimidinas/química , Relación Estructura-ActividadRESUMEN
INTRODUCTION: Studies examining the relationship between stress secondary to adverse life events (ALE) and inflammatory bowel disease (IBD) have produced controversial data. The aim of this study was to explore the subjective perception of this relationship in IBD patients. PATIENTS AND METHODS: Seventy consecutive patients suffering from IBD (40 Crohn's disease, 30 ulcerative colitis) were assessed using a self-rating questionnaire related to demographic variables, clinical characteristics, subjective perception of the influence of ALE on the course of IBD, psychiatric background, and the HAD scale. The results of this scale were compared with a group of 25 relatives. RESULTS: Forty-two patients (60%) perceived that there was relationship between ALE and the onset of their disease, forty-nine (70%) between ALE and the increasing IBD symptoms severity, and fifty-one patients (72.9%) with disease activity. Sixteen of the patients (22.9%) had been visited by a psychiatrist during relapses of IBD. Twenty-five patients (42.4%) reached a score of 11 or higher on the depression or anxiety subscales of the HAD, indicating a probable psychological disorder. CONCLUSIONS: IBD patients perceive a strong relationship between ALE and the course of IBD. We have found a high prevalence of anxiety and depression symptoms in these patients. If this observation is confirmed with objective measurements, it will be important to consider psychiatric intervention for these patients.
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Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/psicología , Estrés Fisiológico , Actividades Cotidianas , Adulto , Ansiedad/complicaciones , Ansiedad/epidemiología , Depresión/complicaciones , Depresión/epidemiología , Femenino , Humanos , Enfermedades Inflamatorias del Intestino/epidemiología , Masculino , Prevalencia , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
La finalidad de este estudio fue evaluar la tasa de respuesta sostenida, a los 6, 12 meses y al acabar el seguimiento (46,39 ñ 9,74 meses, extremos 6 y 60 meses), en pacientes con hepatitis crónica C retratados con interferón-a-2b (IFN-a) más ribavirina durante 6 meses (grupo A) o 12 meses (grupo B), en pacientes con recaída o no respondedores a la monoterapia previa con IFN-a, así como evaluar los cambios de la lesión histológica hepática. Se incluyeron 104 pacientes (100 con genotipo 1 y cuatro con genotipo no 1), 44 en recaída y 60 no respondedores, de los cuales el 20,2 por ciento se excluyeron por los efectos adversos. El 50 por ciento de los pacientes en recaída con genotipo 1 mostraron una respuesta sostenida, siendo mayor esta tasa (65 por ciento vs. 31,2; p <0.09) y menor la tasa de recidiva en el grupo B que en el A (7,2 por ciento vs. 61,5 por ciento; p <0.009), mientras que el 9,3 por ciento de los no respondedores mostraron una respuesta sostenida (A/B: 2/2). Los pacientes no respondedores con genotipo no 1 mostraron respuesta sostenida. La tasa de respuesta a los seis meses de seguimiento se mantiene constante excepto en los pacientes con recaída del grupo A (recidiva tardía 28,6 por ciento). La carga viral no se relacionó con la respuesta. El grado y el estadio de la lesión histológica mejoraron en los pacientes con respuesta sostenida (n=20; p <0.0001 y p <0.0001) y en un tercio de los no respondedores (n=45). El tratamiento combinado fue más eficaz con 12 que con 6 meses de tratamiento en los pacientes con recaída con genotipo 1, siendo baja la eficacia en los no respondedores. La evaluación de la respuesta a los 6 meses es fiable, excepto en los pacientes no respondedores con 6 meses de tratamiento. La lesión histológica mejoró sensiblemente con el tratamiento combinado, particularmente en los pacientes con respuesta sostenida. (AU)
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Adulto , Masculino , Femenino , Humanos , Ribavirina , Factores de Tiempo , Interferón-alfa , Hepatitis C Crónica , Recurrencia , Estudios Prospectivos , Antivirales , Quimioterapia Combinada , Genotipo , Estudios de SeguimientoRESUMEN
The aims of this study were twofold: i) to evaluate the sustained response rate at 6 months, at 12 months and at the end of the follow-up [(46.39 +/- 9.74 months) (range: 6-60 months)] in patients with chronic hepatitis C retreated with interferon-a (IFN-a) plus ribavirin for 6 months (group A), 12 months (group B), in patients with relapse and those with no response to a previous course of monotherapy with IFN-a; and ii) to evaluate changes in the histological liver lesion. One hundred and four patients (100 with genotype 1 and four without), 44 with relapse and 60 non-responders, were included. A total of 20.2% of the patients were excluded because of side effects. Fifty percent of the relapsing patients with genotype 1 showed a sustained response. The sustained response rate was higher in group B than in group A, whereas the rate for the relapsing patients was lower in group B than in group A (13/20 vs. 5/16; 7.2% vs. 61.5%; p <0.09 and p <0.009, respectively). However, 9.3% of the non-responding patients showed a sustained response (A/B: 2/2). The relapsing patients who had a genotype other than 1 showed a sustained response. The sustained response rate was constant throughout the follow-up, except in relapsing patients from group A (the late relapse rate was 28.6%). The viral load was not related to the response. The grade and stage of the histological lesion improved in patients with sustained response (n=20) and in one-third of the non-responding patients (n=45) (p <0.0001 and p <0.0001). IFN in combination with ribavirin was more effective in relapsing patients with genotype 1 at 12 months than in those at 6 months of treatment, whereas the effectiveness in non-responding patients was low. The sustained response evaluation at 6 months was reliable, except in relapsing patients with 6 months of treatment. The histological lesion improved significantly with combination antiviral therapy.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Hepatitis C Crónica/genética , Humanos , Interferón alfa-2 , Masculino , Estudios Prospectivos , Proteínas Recombinantes , Recurrencia , Factores de TiempoRESUMEN
The novel anticancer compound T138067 is an irreversible inhibitor of tubulin polymerization. Amides 3-6 were synthesized using standard methodologies and determined to be significantly less lipophilic than T138067 based on logP calculations. Tubulin polymerization and [(3)H]-T138067 competition assays revealed that these amides are pro-drugs for parent aniline 2. Amides 3-5 showed no detectable signs of crossing the blood brain barrier, while amide 6 was found in extremely small amounts (12 ng/g of brain tissue). Aniline 2, which was formed in vivo from these amides, was found in significantly smaller amounts (approximately 20 to >5000 times) in the brain than when 2 was administered directly. The in vivo efficacy of amide 6 approached that of T138067 and was better tolerated when administered to athymic nude mice bearing MX-1 human mammary tumor xenografts.
Asunto(s)
Compuestos de Anilina/síntesis química , Antineoplásicos/síntesis química , Barrera Hematoencefálica , Sulfonamidas/química , Compuestos de Anilina/química , Compuestos de Anilina/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Encéfalo/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Masculino , Ratones , Ratones Desnudos , Polímeros , Relación Estructura-Actividad , Trasplante Heterólogo , Tubulina (Proteína)/química , Células Tumorales CultivadasRESUMEN
The five muscarinic receptor subtypes (M1-M5) are characterized by seven helices that define a transmembrane cavity which serves as the binding pocket for agonists and antagonists. The five cavities appear to be topographically different enough to permit subtype selectivity among antagonists but not among classical agonists which tend to be smaller in size than antagonists. It was reasoned that synthesis of muscarinic agonists longer/larger than their classical counterparts might result in subtype selectivity. M1 subtype selectivity was found in a class of 1-azabicyclo[2.2.1]heptan-3-one, O-(3-aryl-2-propynyl) oximes. One of these, CI-1017, improved spatial memory of hippocampally deficient mice and nbM-lesioned rats at doses of 1.0-3.2 and 0.1-0.3 mg/kg, respectively, while producing parasympathetic side effects only at very high doses (100-178 mg/kg). Additionally, CI-1017 inhibited production of amyloidogenic A beta and increased secretion of soluble APP. Thus, CI-1017, besides treating AD symptomatically, may also retard its progression. CI-1017 has recently completed phase I clinical trials.
Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Agonistas Muscarínicos/síntesis química , Agonistas Muscarínicos/farmacología , Oximas/síntesis química , Oximas/farmacología , Receptores Muscarínicos/efectos de los fármacos , Animales , Clonación Molecular , Humanos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratas , Receptor Muscarínico M1 , Receptores Muscarínicos/metabolismo , Sistemas de Mensajero Secundario/efectos de los fármacosRESUMEN
Meningiomas are the most frequent benign intracranial tumor. Up to 20% of these neoplasms may eventually extend beyond the skull, particularly when tumor spread affects the temporal bone. We report a clinicopathological observation of an extracranial meningothelial meningioma that was diagnosed morphologically using immunohistochemical techniques. The tumor presented as polyp in the ear canal of a 70-year-old woman who had a history of ear disease and seizures and was under medical treatment. The growth was associated with a right temporal lobe tumor involving the petrosal bone that had been detected 6 years earlier on computed axial tomography.