Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
1.
Hum Brain Mapp ; 45(11): e26754, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39046031

RESUMEN

Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética , Caracteres Sexuales , Humanos , Adolescente , Masculino , Niño , Femenino , Preescolar , Lactante , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Encéfalo/anatomía & histología , Factores de Edad , Desarrollo Infantil/fisiología , Lateralidad Funcional/fisiología , Desarrollo del Adolescente/fisiología
2.
Nat Commun ; 14(1): 2973, 2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37221181

RESUMEN

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.


Asunto(s)
Tumor Carcinoide , Tumores Neuroendocrinos , Humanos , Antígeno B7-H1 , Pulmón
3.
ESMO Open ; 6(5): 100270, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34547581

RESUMEN

BACKGROUND: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. PATIENTS AND METHODS: In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. RESULTS: In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. CONCLUSION: FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.


Asunto(s)
Neoplasias Colorrectales , Trifluridina , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Nivolumab/uso terapéutico , Oxaliplatino/uso terapéutico , Pirrolidinas , Timina , Trifluridina/uso terapéutico
4.
Clin Transl Oncol ; 23(6): 1054-1066, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33191439

RESUMEN

Cancer during pregnancy is a challenge for multi- and interdisciplinary collaboration due to the diagnostic, prognostic and therapeutic implications, the need for an integrated harmonization of medical action for the pregnant patient and the embryo or foetus and the characteristics of each gestational period, which will determine the protocol to be proposed and its limitations. For this reason, a group of experts appointed by participating scientific societies, which includes the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM), the Spanish Association of Surgeons (Asociación Española de Cirujanos-AEC), the Spanish Society of Gynaecology and Obstetrics (Sociedad Española de Ginecología y Obstetricia-SEGO), the Spanish Society of Nuclear Medicine and Molecular Imaging (Sociedad Española de Medicina Nuclear e Imagen Molecular-SEMNIM), the Spanish Society of Oncological Radiotherapy (Sociedad Española de Oncología Radioterápica-SEOR) and the Spanish Society of Medical Radiology (Sociedad Española de Radiología Médica-SERAM), have worked together to establish consensus recommendations that allow the harmonization of management and ultimately the optimization of the healthcare of pregnant patients with cancer. When cancer is detected in a pregnant woman, the week of gestation in which the diagnosis is made must be considered, as well as the characteristics of the tumour. It is strongly recommended that a multidisciplinary team assesses the situation and guides the patient and her family during the informing, diagnosis and treatment process. Likewise, the foetus should be monitored and managed by specialized obstetricians who are part of a multidisciplinary cancer committee.


Asunto(s)
Complicaciones Neoplásicas del Embarazo/diagnóstico , Complicaciones Neoplásicas del Embarazo/terapia , Femenino , Humanos , Guías de Práctica Clínica como Asunto , Embarazo
5.
Clin Transl Oncol ; 22(9): 1499-1505, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31974820

RESUMEN

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.


Asunto(s)
Pancreatectomía/métodos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Radiocirugia/métodos , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Resultado del Tratamiento
6.
Semergen ; 44(8): 557-561, 2018.
Artículo en Español | MEDLINE | ID: mdl-30290992

RESUMEN

INTRODUCTION: As the life expectancy has increased in individuals with cerebral palsy, this has led to being able to assess the changes in the bio-psycho-social dimensions of their health. OBJECTIVE: The aim of the study is to describe the characteristics of individuals with cerebral palsy and to evaluate their functional situation. METHODS: Cross-sectional descriptive study conducted on a sample of 26 individuals between 27 and 65 years old with cerebral palsy. Data was collected during a semi-structured interview. The Cross Motor Function Classification System (GMFCS), the Manual Ability Classification System (MACS), and the Communication Function Classification System (CFCS), were used to evaluate the functional situation. RESULTS: The profile of the adult seen in the Cerebral Palsy Association of Burgos, Spain, is male, over 40 years old, single, illiterate, with no professional qualification, lives in a residence, receives social benefit, and with great functional disability. CONCLUSIONS: The functional capacity of people with cerebral palsy who are in adult care centres is low. It emphasises the low cultural level and the lack of professional qualification and all of them have a disability that limits their ability to perform daily activities, possibly related to the high mean age.


Asunto(s)
Actividades Cotidianas , Parálisis Cerebral/epidemiología , Evaluación de la Discapacidad , Adulto , Factores de Edad , Anciano , Parálisis Cerebral/fisiopatología , Estudios Transversales , Femenino , Humanos , Entrevistas como Asunto , Esperanza de Vida , Masculino , Persona de Mediana Edad
7.
Clin Pharmacol Ther ; 102(6): 997-1005, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28445610

RESUMEN

Nanoliposomal irinotecan (nal-IRI) is a liposomal formulation of irinotecan with a longer half-life (t1/2 ), higher plasma total irinotecan (tIRI), and lower SN-38 maximum concentration (Cmax ) compared with nonliposomal irinotecan. Population pharmacokinetic (PK) analysis of nal-IRI was performed for tIRI and total SN-38 (tSN38) using patient samples from six studies. PK-safety association was evaluated for neutropenia and diarrhea in 353 patients. PK-efficacy association was evaluated from a phase III study in pancreatic cancer NAPOLI1. Efficacy was associated with longer duration of unencapsulated SN-38 (uSN38) above a threshold and higher Cavg of tIRI, tSN38, and uSN38. Neutropenia was associated with uSN38 Cmax and diarrhea with tIRI Cmax . Baseline predictive factors were race, body surface area, and bilirubin. Analysis identified PK factors associated with efficacy, safety, and predictive baseline factors. The results support the benefit of nal-IRI dose of 70 mg/m2 (free-base; equivalent to 80 mg/m2 salt base) Q2W over 100 mg/m2 Q3W.


Asunto(s)
Camptotecina/análogos & derivados , Liposomas/efectos adversos , Liposomas/farmacocinética , Neoplasias/metabolismo , Adulto , Anciano , Camptotecina/efectos adversos , Camptotecina/sangre , Camptotecina/farmacocinética , Ensayos Clínicos como Asunto , Diarrea/inducido químicamente , Femenino , Humanos , Irinotecán , Liposomas/sangre , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Neutropenia/inducido químicamente
8.
J Comp Physiol B ; 185(8): 859-68, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26391594

RESUMEN

Fish growth is strongly influenced by environmental and nutritional factors and changing culture conditions can help optimize it. The importance of early-life experience on the muscle phenotype later in life is well known. Here, we study the effects of 5 weeks of moderate and sustained swimming activity (5 BL s(-1)) in gilthead sea bream during early development. We analysed growth and body indexes, plasma IGF-I and GH levels, feed conversion, composition [proximate and isotopic ((15)N/(13)C)] and metabolic key enzymes (COX, CS, LDH, HOAD, HK, ALAT, ASAT) of white muscle. Moderate and continuous exercise in fingerlings of gilthead sea bream increased plasma IGF-I, whereas it reduced plasma GH. Under these conditions, growth rate improved without any modification to feed intake through an increase in muscle mass and a reduction in mesenteric fat deposits. There were no changes in the content and turnover of muscle proteins and lipid reserves. Glycogen stores were maintained, but glycogen turnover was higher in white muscle of exercised fish. A lower LDH/CS ratio demonstrated an improvement in the aerobic capacity of white muscle, while a reduction in the COX/CS ratio possibly indicated a functional adaptation of mitochondria to adjust to the tissue-specific energy demand and metabolic fuel availability in exercised fish. We discuss the synergistic effects of dietary nutrients and sustained exercise on the different mitochondrial responses.


Asunto(s)
Desarrollo de Músculos , Músculo Esquelético/crecimiento & desarrollo , Dorada/crecimiento & desarrollo , Natación , Factores de Edad , Alimentación Animal , Animales , Metabolismo Energético , Hormona del Crecimiento/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Estado Nutricional , Fenotipo , Dorada/sangre
9.
Psychol Med ; 45(5): 965-76, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25229248

RESUMEN

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are two common childhood disorders that exhibit genetic and behavioural overlap and have abnormalities in similar brain systems, in particular in frontal and cerebellar regions. This study compared the two neurodevelopmental disorders to investigate shared and disorder-specific structural brain abnormalities. METHOD: Forty-four predominantly medication-naïve male adolescents with ADHD, 19 medication-naïve male adolescents with ASD and 33 age-matched healthy male controls were scanned using high-resolution T1-weighted volumetric imaging in a 3-T magnetic resonance imaging (MRI) scanner. Voxel-based morphometry (VBM) was used to test for group-level differences in structural grey matter (GM) and white matter (WM) volumes. RESULTS: There was a significant group difference in the GM of the right posterior cerebellum and left middle/superior temporal gyrus (MTG/STG). Post-hoc analyses revealed that this was due to ADHD boys having a significantly smaller right posterior cerebellar GM volume compared to healthy controls and ASD boys, who did not differ from each other. ASD boys had a larger left MTG/STG GM volume relative to healthy controls and at a more lenient threshold relative to ADHD boys. CONCLUSIONS: The study shows for the first time that the GM reduction in the cerebellum in ADHD is disorder specific relative to ASD whereas GM enlargement in the MTG/STG in ASD may be disorder specific relative to ADHD. This study is a first step towards elucidating disorder-specific structural biomarkers for these two related childhood disorders.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/patología , Trastorno del Espectro Autista/patología , Cerebelo/patología , Sustancia Gris/patología , Lóbulo Temporal/patología , Sustancia Blanca/patología , Adolescente , Estudios de Casos y Controles , Niño , Humanos , Masculino , Tamaño de los Órganos
11.
Psychol Med ; 44(3): 633-46, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23597077

RESUMEN

BACKGROUND: The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM). METHOD: A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys. RESULTS: Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects. CONCLUSIONS: The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Lóbulo Frontal/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Metilfenidato/farmacología , Inhibidores de la Captación de Neurotransmisores/farmacología , Propilaminas/farmacología , Adolescente , Análisis de Varianza , Clorhidrato de Atomoxetina , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Ganglios Basales/efectos de los fármacos , Ganglios Basales/fisiopatología , Mapeo Encefálico , Niño , Estudios Cruzados , Método Doble Ciego , Lóbulo Frontal/fisiopatología , Lateralidad Funcional , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Metilfenidato/administración & dosificación , Metilfenidato/uso terapéutico , Pruebas Neuropsicológicas , Inhibidores de la Captación de Neurotransmisores/administración & dosificación , Inhibidores de la Captación de Neurotransmisores/uso terapéutico , Placebos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Propilaminas/administración & dosificación , Propilaminas/uso terapéutico
12.
Br J Cancer ; 109(4): 926-33, 2013 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-23907428

RESUMEN

BACKGROUND: Nab-paclitaxel and gemcitabine have demonstrated a survival benefit over gemcitabine alone in advanced pancreatic cancer (PDA). This study aimed to investigate the clinical, biological, and imaging effects of the regimen in patients with operable PDA. METHODS: Patients with operable PDA received two cycles of nab-paclitaxel and gemcitabine before surgical resection. FDG-PET and CA19.9 tumour marker levels were used to measure clinical activity. Effects on tumour stroma were determined by endoscopic ultrasound (EUS) elastography. The collagen content and architecture as well as density of cancer-associated fibroblasts (CAFs) were determined in the resected surgical specimen and compared with a group of untreated and treated with conventional chemoradiation therapy controls. A co-clinical study in a mouse model of PDA was conducted to differentiate between the effects of nab-paclitaxel and gemcitabine. RESULTS: A total of 16 patients were enrolled. Treatment resulted in significant antitumour effects with 50% of patients achieving a >75% decrease in circulating CA19.9 tumour marker and a response by FDG-PET. There was also a significant decrement in tumour stiffness as measured by EUS elastography. Seven of 12 patients who completed treatment and were operated had major pathological regressions. Analysis of residual tumours showed a marked disorganised collagen with a very low density of CAF, which was not observed in the untreated or conventionally treated control groups. The preclinical co-clinical study showed that these effects were specific of nab-paclitaxel and not gemcitabine. CONCLUSION: These data suggest that nab-paclitaxel and gemcitabine decreases CAF content inducing a marked alteration in cancer stroma that results in tumour softening. This regimen should be studied in patients with operable PDA.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fibroblastos/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Albúminas/administración & dosificación , Albúminas/farmacología , Animales , Antígeno CA-19-9/sangre , Colágeno/efectos de los fármacos , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Modelos Animales de Enfermedad , Diagnóstico por Imagen de Elasticidad , Endosonografía , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Masculino , Ratones , Persona de Mediana Edad , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Tomografía de Emisión de Positrones , Gemcitabina
13.
Invest New Drugs ; 31(1): 14-9, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22669334

RESUMEN

A high throughput screening for anticancer activity of FDA approved drugs identified mycophenolic acid (MPA), an inhibitor of inositol monophosphate dehydrogenase (IMPDH) as an active agent with an antiangiogenesis mode of action. Exposure of pancreatic cancer cell lines to MPA resulted in growth inhibition and reduced the expression of VEGF that was reversed by supplementing the media with guanosine supporting and IMPDH-dependant mechanism. In preclinical in vivo study, MPA showed a moderate inhibition of tumor growth in a panel of 6 human derived pancreatic cancer xenografts but reduced the expression of VEGF. To investigate the effects of MPA in human pancreatic cancer, a total of 12 patients with resectable pancreatic cancer (PDA) received increasing doses of mycophenolate mofetil (MMF) in cohorts of 6 patients each from 5-15 days prior to surgical resection. Treatment was well tolerated with one episode of grade 1 muscle pain, one episode of grade 2 lymphopenia (2 gr/day dose) and one episode of grade 2 elevantion in LFT (all in the 2 gr./day dose). Patients recovered from surgery uneventfully with no increased post-operative complications. Assessment of CD31, VEGF, and TUNEL in resected specimens compared to a non treated control of 6 patients showed no significant variations in any of the study endpoints. In conclusion, this study shows the feasibility of translating a preclinical observation to the clinical setting and to explore a drug mechanism of action in patients. MPA, however, did not show any hints of antiangiogenesis of anticancer clinical activity questioning if this agent should be further developed in PDA.


Asunto(s)
Carcinoma Ductal Pancreático/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Anciano , Animales , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Femenino , Guanosina Trifosfato/metabolismo , Humanos , Inmunosupresores/sangre , Inmunosupresores/farmacología , Masculino , Ratones , Persona de Mediana Edad , Ácido Micofenólico/sangre , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéutico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Mol Psychiatry ; 18(2): 236-44, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22290121

RESUMEN

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato-thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto-striato-parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto-striato-cerebellar dysregulation in ASD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/patología , Atención/fisiología , Trastorno Autístico/patología , Corteza Cerebral/patología , Análisis de Varianza , Mapeo Encefálico , Estudios de Casos y Controles , Corteza Cerebral/irrigación sanguínea , Niño , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Movimiento/fisiología , Pruebas Neuropsicológicas , Oxígeno/sangre , Estimulación Luminosa , Desempeño Psicomotor , Tiempo de Reacción/fisiología , Encuestas y Cuestionarios
15.
Nanotechnology ; 20(50): 505701, 2009 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-19907067

RESUMEN

A low melting point soda-lime glass powder containing copper nanoparticles with high antibacterial (against gram-positive and gram-negative bacteria) and antifungal activity has been obtained. Sepiolite fibres containing monodispersed copper nanoparticles (d(50) approximately 30 +/- 5 nm) were used as the source of the copper nanoparticles. The observed high activity of the obtained glass powder, particularly against yeast, has been explained by considering the inhibitory synergistic effect of the Ca(2+) lixiviated from the glass on the growth of the colonies.


Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Compuestos de Calcio/química , Cobre/farmacología , Vidrio/química , Nanopartículas/química , Óxidos/química , Hidróxido de Sodio/química , Escherichia coli/efectos de los fármacos , Escherichia coli/ultraestructura , Pruebas de Sensibilidad Microbiana , Nanopartículas/ultraestructura , Tamaño de la Partícula , Espectrofotometría Ultravioleta , Difracción de Rayos X
16.
Nanotechnology ; 20(8): 085103, 2009 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-19417439

RESUMEN

The antibacterial and antifungal activity of a low melting point soda-lime glass powder containing silver nanoparticles has been studied. Nano-Ag sepiolite fibres containing monodispersed silver nanoparticles (d(50) approximately 11 +/- 9 nm) were used as the source of silver. This powder presents a high antibacterial (against gram-positive and gram-negative bacteria) as well as antifungal (against I. orientalis) activity. The observed high activity against yeast has been explained by considering the inhibitory effect of the Ca(2+) lixiviated from the glass on the growth of the yeast colonies.


Asunto(s)
Antibacterianos/administración & dosificación , Antifúngicos/administración & dosificación , Ascomicetos/efectos de los fármacos , Compuestos de Calcio/química , Escherichia coli/efectos de los fármacos , Micrococcus luteus/efectos de los fármacos , Nanopartículas/administración & dosificación , Óxidos/química , Plata/administración & dosificación , Hidróxido de Sodio/química , Ascomicetos/citología , Escherichia coli/citología , Vidrio/química , Ensayo de Materiales , Micrococcus luteus/citología
17.
Nanotechnology ; 19(21): 215605, 2008 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-21730578

RESUMEN

Isolated tungsten nanoparticles (α-W and ß-W phase) were synthesized and epitaxially grown on alumina and spinel particle surfaces with an average tungsten size of ≤20 nm for a low tungsten content (of ≤1.5 vol%). Using tungsten (VI) ethoxide alcoholic solutions, tungsten trioxide hydrated precursors were attached to a ceramic grains surface as a nanoparticle coating. High-resolution transmission electron microscopy (HRTEM) micrographs showed epitaxial interfaces between alumina, spinel and metallic tungsten. This epitaxial growth is assumed to be due to the effect of water vapour on the sublimation of ortho-tungstic acid during the reduction process in a hydrogen atmosphere. The planes involved in the epitaxy were found to be [Formula: see text] and [Formula: see text].

18.
Rev Neurol ; 43(11): 678-84, 2006.
Artículo en Español | MEDLINE | ID: mdl-17133329

RESUMEN

INTRODUCTION: Several different follow-up studies have shown that attention deficit hyperactivity disorder (ADHD) can persist into adulthood. AIM: To review the findings in adults with ADHD related to alterations in the executive functions. DEVELOPMENT: Research conducted among children with ADHD has revealed the existence of alterations in different tasks that evaluate the executive functions, such as the planning test, sustained attention tasks, cognitive flexibility, verbal fluency and working memory tasks, as well as several inhibition response tasks. In adults with ADHD, despite the lower number of reports in the literature and the methodological shortcomings that exist in some studies, analogous results have also been described with respect to executive functioning, namely, disorders affecting inhibition response, the capacity for planning, difficulties in cognitive flexibility and verbal fluency, and problems with working memory, which include aspects of spatial working memory, logical or visual memory. CONCLUSIONS: The findings we have available at present enable us to confirm the persistence of executive dysfunctions in adult patients with ADHD that are similar to those observed in children with ADHD.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Actividad Nerviosa Superior/fisiología , Adulto , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Toma de Decisiones , Trastornos Disruptivos, del Control de Impulso y de la Conducta/etiología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/fisiopatología , Humanos , Inhibición Psicológica , Trastornos de la Memoria/etiología , Trastornos de la Memoria/fisiopatología , Pruebas Neuropsicológicas , Trastornos del Habla/etiología , Trastornos del Habla/fisiopatología
20.
Am J Clin Oncol ; 24(2): 192-7, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11319297

RESUMEN

The purpose of this study was to evaluate cisplatin nephrotoxicity in patients 70 years and older and to identify factors influencing nephrotoxicity occurrence. Forty-nine (N = 49) patients older than 70 years were studied retrospectively. All patients received treatment with cisplatin. Variables under study were as follows: prechemotherapy serum creatinine levels (Crb), maximum serum creatinine level during treatment (Crmax), steady serum creatinine level 3 months after treatment completion (Crstb), as well as their corresponding creatinine clearance values (CrbC, CrmaxC, CrstbC) as calculated by the Cockroft and Gault formula. Maximum creatinine increment (Imax = Crmax - Crb), stable creatinine increment (Istb = Crstb - Crb) and the corresponding clearance decrements (Dmax and Dstb) were calculated as well. The potential relationship of the above variables to cisplatin dose intensity and accumulated dose as well as to different prognostic factors were also considered. Assessment of associated conditions was carried out by means of Charlson comorbidity index. The patients' mean age was 73 years (range: 70-79 years). There were 43 men (88%) and 6 women (12%). Mean cisplatin dose intensity was 27 mg/m2/wk. A total of 157 chemotherapy courses were administered with a mean of 3.2 per patient. Mean Crb was 1.02 mg/dl (95% CI = 1.02-1.12), mean Crmax was 1.45 (95% CI = 1.34-1.46), and mean Crstb was 1.24 (95% CI = 1.16-1.32). Imax was equal to 0 in 13 patients (26%) and more than 0.4 mg/dl in 21 patients (43%). Istb was equal to 0 or negative in 22 (45%) and more than 0.4 in only 9 patients (18.3%). No significant relationship of serum creatinine levels, creatinine clearance levels, or of their increments or decrements to cisplatin dose intensity or accumulated dose were found. These levels also did not correlate with age, sex, comorbidity or Eastern Cooperative Oncology Group score. In 85% of patients, Crmax was reached between chemotherapy initiation and the third chemotherapy course, and thereafter renal function began to recover despite continued administration of cisplatin. Cisplatin is well tolerated by patients 70 years and older and dose intensity does not seem to influence renal function deterioration. Therefore, we failed to find reasons to encourage modification or limitation of cisplatin treatment in the elderly population.


Asunto(s)
Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Enfermedades Renales/inducido químicamente , Anciano , Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Comorbilidad , Creatinina/sangre , Femenino , Humanos , Enfermedades Renales/diagnóstico , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Estudios Retrospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA