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1.
Hum Brain Mapp ; 45(11): e26754, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39046031

ABSTRACT

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.


Subject(s)
Brain , Magnetic Resonance Imaging , Sex Characteristics , Humans , Adolescent , Male , Child , Female , Child, Preschool , Infant , Brain/diagnostic imaging , Brain/growth & development , Brain/anatomy & histology , Age Factors , Child Development/physiology , Functional Laterality/physiology , Adolescent Development/physiology
2.
Nat Commun ; 14(1): 2973, 2023 05 23.
Article in English | MEDLINE | ID: mdl-37221181

ABSTRACT

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.


Subject(s)
Carcinoid Tumor , Neuroendocrine Tumors , Humans , B7-H1 Antigen , Lung
3.
ESMO Open ; 6(5): 100270, 2021 10.
Article in English | MEDLINE | ID: mdl-34547581

ABSTRACT

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.


Subject(s)
Colorectal Neoplasms , Trifluridine , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/therapeutic use , Colorectal Neoplasms/drug therapy , Humans , Nivolumab/therapeutic use , Oxaliplatin/therapeutic use , Pyrrolidines , Thymine , Trifluridine/therapeutic use
4.
Clin. transl. oncol. (Print) ; 23(6): 1054-1066, jun. 2021. ilus, tab
Article in English | IBECS | ID: ibc-221326

ABSTRACT

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 (AU)


Subject(s)
Humans , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/therapy , Patient Care Team , Practice Guidelines as Topic , Consensus
5.
Clin Transl Oncol ; 23(6): 1054-1066, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33191439

ABSTRACT

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.


Subject(s)
Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/therapy , Female , Humans , Practice Guidelines as Topic , Pregnancy
6.
Clin Transl Oncol ; 22(9): 1499-1505, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31974820

ABSTRACT

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.


Subject(s)
Pancreatectomy/methods , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Prospective Studies , Survival Rate , Treatment Outcome
7.
Semergen ; 44(8): 557-561, 2018.
Article in Spanish | MEDLINE | ID: mdl-30290992

ABSTRACT

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.


Subject(s)
Activities of Daily Living , Cerebral Palsy/epidemiology , Disability Evaluation , Adult , Age Factors , Aged , Cerebral Palsy/physiopathology , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Life Expectancy , Male , Middle Aged
8.
Clin Pharmacol Ther ; 102(6): 997-1005, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28445610

ABSTRACT

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.


Subject(s)
Camptothecin/analogs & derivatives , Liposomes/adverse effects , Liposomes/pharmacokinetics , Neoplasms/metabolism , Adult , Aged , Camptothecin/adverse effects , Camptothecin/blood , Camptothecin/pharmacokinetics , Clinical Trials as Topic , Diarrhea/chemically induced , Female , Humans , Irinotecan , Liposomes/blood , Male , Middle Aged , Neoplasms/blood , Neoplasms/drug therapy , Neutropenia/chemically induced
9.
J Comp Physiol B ; 185(8): 859-68, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26391594

ABSTRACT

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.


Subject(s)
Muscle Development , Muscle, Skeletal/growth & development , Sea Bream/growth & development , Swimming , Age Factors , Animal Feed , Animals , Energy Metabolism , Growth Hormone/blood , Insulin-Like Growth Factor I/metabolism , Mitochondria, Muscle/metabolism , Muscle, Skeletal/metabolism , Nutritional Status , Phenotype , Sea Bream/blood
10.
Psychol Med ; 45(5): 965-76, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25229248

ABSTRACT

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.


Subject(s)
Attention Deficit Disorder with Hyperactivity/pathology , Autism Spectrum Disorder/pathology , Cerebellum/pathology , Gray Matter/pathology , Temporal Lobe/pathology , White Matter/pathology , Adolescent , Case-Control Studies , Child , Humans , Male , Organ Size
12.
Psychol Med ; 44(3): 633-46, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23597077

ABSTRACT

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.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Frontal Lobe/drug effects , Memory, Short-Term/drug effects , Methylphenidate/pharmacology , Neurotransmitter Uptake Inhibitors/pharmacology , Propylamines/pharmacology , Adolescent , Analysis of Variance , Atomoxetine Hydrochloride , Attention Deficit Disorder with Hyperactivity/physiopathology , Basal Ganglia/drug effects , Basal Ganglia/physiopathology , Brain Mapping , Child , Cross-Over Studies , Double-Blind Method , Frontal Lobe/physiopathology , Functional Laterality , Humans , Magnetic Resonance Imaging/methods , Male , Methylphenidate/administration & dosage , Methylphenidate/therapeutic use , Neuropsychological Tests , Neurotransmitter Uptake Inhibitors/administration & dosage , Neurotransmitter Uptake Inhibitors/therapeutic use , Placebos , Prefrontal Cortex/drug effects , Prefrontal Cortex/physiopathology , Propylamines/administration & dosage , Propylamines/therapeutic use
13.
Br J Cancer ; 109(4): 926-33, 2013 Aug 20.
Article in English | MEDLINE | ID: mdl-23907428

ABSTRACT

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.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fibroblasts/pathology , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Albumins/administration & dosage , Albumins/pharmacology , Animals , CA-19-9 Antigen/blood , Collagen/drug effects , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Disease Models, Animal , Elasticity Imaging Techniques , Endosonography , Female , Fibroblasts/drug effects , Humans , Male , Mice , Middle Aged , Neoadjuvant Therapy , Paclitaxel/administration & dosage , Paclitaxel/pharmacology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Positron-Emission Tomography , Gemcitabine
14.
Mol Psychiatry ; 18(2): 236-44, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22290121

ABSTRACT

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.


Subject(s)
Attention Deficit Disorder with Hyperactivity/pathology , Attention/physiology , Autistic Disorder/pathology , Cerebral Cortex/pathology , Analysis of Variance , Brain Mapping , Case-Control Studies , Cerebral Cortex/blood supply , Child , Functional Laterality , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Movement/physiology , Neuropsychological Tests , Oxygen/blood , Photic Stimulation , Psychomotor Performance , Reaction Time/physiology , Surveys and Questionnaires
15.
Invest New Drugs ; 31(1): 14-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22669334

ABSTRACT

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.


Subject(s)
Carcinoma, Pancreatic Ductal/drug therapy , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Aged , Animals , Carcinoma, Pancreatic Ductal/metabolism , Carcinoma, Pancreatic Ductal/pathology , Cell Line, Tumor , Female , Guanosine Triphosphate/metabolism , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/pharmacology , Male , Mice , Middle Aged , Mycophenolic Acid/blood , Mycophenolic Acid/pharmacology , Mycophenolic Acid/therapeutic use , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Treatment Outcome , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
16.
Med. prev ; 18(1): 18-23, ene.-mar. 2012. tab, ilus
Article in Spanish | IBECS | ID: ibc-110260

ABSTRACT

OBJETIVO: El objetivo del estudio es medir la prevalencia de agregación de tres de los principales factores de riesgo cardiovascular: hipertensión, hipercolesterolemia y diabetes mellitusen la población mayor o igual a 14 años atendida en las consultas de Atención Primaria de un Área Sanitaria de Madrid y estudiar su distribución por sexo y edades. MÉTODOS: Se realizó un estudio transversal. Mediante un muestreo aleatorio proporcional al número de pacientes adscritos por tarjeta sanitaria a los Centros de Salud del Área 2 de Madrid, se seleccionaron 1.733 historias de pacientes mayores o iguales a 14 años. Se midieron los datos de registro de hipertensión arterial, diabetes e hipercolesterolemia, de forma individual y agregada. RESULTADOS: La prevalencia de hipertensión e hipercolesterolemia fue mayor en mujeres que en hombres. La proporción de pacientes con hipertensión y diabetes fue de 1,9% sin diferencias por sexos. La proporción de pacientes con hipercolesterolemia y diabetes fue más frecuente en hombres que en mujeres. La asociación de los tres factores de riesgo cardiovascular estudiados fue más frecuente en mujeres y más alta en el grupo de edad de mayor o igual a 76 años. CONCLUSIONES: La prevalencia de asociación de dos o más factores deriesgo cardiovascular en nuestra población es importante, siendo la asociación más frecuente la hipertensión e hipercolesterolemia, seguida de hipertensión y diabetes


OBJECTIVE: To measure the prevalence of aggregation of three major cardiovascular risk factors: hypertension, hypercholesterolemia and diabetes mellitus in a population greater than or equal to 14 years in a Health Area of Madrid and study their distribution by sex and age. METHODS: We conducted a cross-sectional study by random sampling proportional to the number of patients assigned by health card to the Health Centers in the Area 2 of Madrid. 1733 records of patients greater than or equal to 14 years were finally selected. Were measured data of hypertension, diabetes and hypercholesterolemia, individually and aggregated. RESULTS: The prevalence of hypertension and hypercholesterolemiawas higher in women than in men. The proportion of patients with hypertension and diabetes mellitus was 1.9% with no differences by sex. The proportion of patients with hypercholesterolemia and diabetes mellitus was more frequent in men than in women. The combination of the three cardiovascular risk factors studied was more frequent in women and highest in the age group greater than or equal to 76 years CONCLUSIONS: The prevalence of association of two or more cardiovascular risk factors in our population is important, being the most frequent the association of hypertension and hypercholesterolemia, followed by hypertension and diabetes mellitus


Subject(s)
Humans , Cardiovascular Diseases/epidemiology , Hypertension/epidemiology , Hypercholesterolemia/epidemiology , Risk Factors , Primary Health Care/statistics & numerical data , Practice Patterns, Physicians' , Diabetes Mellitus/epidemiology
17.
Clin. transl. oncol. (Print) ; 12(2): 148-149, feb. 2010. ilus
Article in English | IBECS | ID: ibc-123897

ABSTRACT

Spermatic cord sarcomas (SCS) are very infrequent and sometimes misdiagnosed malignancies. Moreover, their optimal management remains undefined with ongoing controversy about the indications for adjuvant therapy. Histologically, liposarcomas are the most common type. Osteosarcoma is rarely observed in this location and combined tumours with this component have not been described. We present a case of SCS with mixed differentiation with both liposarcoma and osteosarcoma elements (AU)


Subject(s)
Humans , Male , Middle Aged , Liposarcoma/diagnosis , Neoplasms, Complex and Mixed/diagnosis , Osteosarcoma/diagnosis , Liposarcoma/complications , Neoplasms, Complex and Mixed/pathology , Osteosarcoma/complications , Spermatic Cord/pathology , Testis/pathology
18.
Nanotechnology ; 20(50): 505701, 2009 Dec 16.
Article in English | MEDLINE | ID: mdl-19907067

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Calcium Compounds/chemistry , Copper/pharmacology , Glass/chemistry , Nanoparticles/chemistry , Oxides/chemistry , Sodium Hydroxide/chemistry , Escherichia coli/drug effects , Escherichia coli/ultrastructure , Microbial Sensitivity Tests , Nanoparticles/ultrastructure , Particle Size , Spectrophotometry, Ultraviolet , X-Ray Diffraction
19.
Nanotechnology ; 20(8): 085103, 2009 Feb 25.
Article in English | MEDLINE | ID: mdl-19417439

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Antifungal Agents/administration & dosage , Ascomycota/drug effects , Calcium Compounds/chemistry , Escherichia coli/drug effects , Micrococcus luteus/drug effects , Nanoparticles/administration & dosage , Oxides/chemistry , Silver/administration & dosage , Sodium Hydroxide/chemistry , Ascomycota/cytology , Escherichia coli/cytology , Glass/chemistry , Materials Testing , Micrococcus luteus/cytology
20.
Rev. Med. Univ. Navarra ; 52(4): 19-22, oct.-dic. 2008. ilus, tab
Article in Spanish | IBECS | ID: ibc-62113

ABSTRACT

El puente epifi sario longitudinal es un trastorno congénito infrecuentede la osifi cación encondral que afecta a pacientes esqueléticamenteinmaduros. Se presenta la revisión retrospectiva de los resultados deltratamiento quirúrgico en 4 pacientes (6 pies) entre los años 1999-2004. El puente epifi sario longitudinal, se localizó de forma bilateralen las falanges proximales del primer dedo del pie en 2 pacientes (4pies) y unilateralmente en los primeros metatarsianos de 2 pacientes(2 pies). El objetivo fue analizar los resultados obtenidos en nuestrocentro tras el tratamiento quirúrgico de esta patología. La técnicaquirúrgica, consistió en resección de la región central del puente deforma aislada en 1 caso y resección central de la lesión asociada aosteotomía en cuña de adición correctora de la deformidad angular ydel acortamiento óseo en los 5 casos restantes. El seguimiento mediofue de 6 años (4-8 años). Los resultados se valoraron en función dela mejoría postoperatoria de la desviación angular en varo del primerdedo y el aumento postoperatorio del crecimiento longitudinal delhueso. Todos los pacientes presentaron una evolución satisfactoria yno se registraron compliciones secundarias a la cirugía realizada. Eltratamiento del puente epifi sario longitudinal es siempre quirúrgico yla técnica ha de individualizarse para cada paciente(AU)


The longitudinal epiphyseal bracket is a rare ossifi cation defect in immaturepatients. We report our results in the surgical treatment of 4 patients(6 feet) from 1999 to 2004. The longitudinal epiphyseal bracket wasbilateral in the proximal phalanx of the toe in 2 patients (4 feet) andunilateral in the fi rst metatarsal in 2 patients (2 feet).The aim was toconsider the results of surgical treatment for this deformity. The surgicaltechnique consisted of excision of the central area of the longitudinalepiphyseal bracket in one case and central physiolysis associated withcorrective addition osteotomy of angular and shortening deformity in theother 5 cases. The average follow-up was 6 years (range 4-8 years).The results were assessed considering correction of angular deviationof the toe and increase in longitudinal bone growth. All patients presentsatisfactory evolution with no complications of surgical treatmentreported. Surgical treatment is always indicated in such cases, and theapproach should be individualized(AU)


Subject(s)
Humans , Male , Female , Child , Metatarsal Bones/abnormalities , Metatarsal Bones/surgery , Toe Phalanges/abnormalities , Toe Phalanges/surgery , Osteotomy/methods , Osteotomy/trends , Diagnostic Imaging/methods , Retrospective Studies , Growth Plate/pathology , Osteotomy/instrumentation , Musculoskeletal Abnormalities/complications , Musculoskeletal Abnormalities/surgery
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