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Barttfeld P.,CONICET | Barttfeld P.,University of Buenos Aires | Wicker B.,CONICET | Wicker B.,Aix - Marseille University | And 5 more authors.
Neuropsychologia | Year: 2012

Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that functional connectivity changes in opposite ways in ASD and typicals as attention shifts from external world towards one's body generated information. Furthermore, ASD subject alter more markedly than typicals their connectivity across cognitive states. Using differences in brain connectivity across conditions, we ranked brain regions according to their classification power. Anterior insula and dorsal-anterior cingulate cortex were the regions that better characterize ASD differences with typical subjects across conditions, and this effect was modulated by ASD severity. These results pave the path for diagnosis of mental pathologies based on functional brain networks obtained from a library of mental states. © 2012 Elsevier Ltd.

Arazi H.C.,FLENI | Badimon J.J.,FLENI
Current Pharmaceutical Design | Year: 2012

Atherosclerosis is considered an inflammatory disease. T-cells, macrophages, and mast cells infiltrate atherosclerotic plaques and platelets play an essential role releasing inflammatory mediators that stimulate plaque progression. This is important in acute coronary syndromes but it is also the mechanism involved in plaque progresion and endothelial dysfunction. Antiplatelet drugs exert their effects not only by inhibition of platelet aggregation but also through their antiinflammatory effect. Aspirin, thyenopiridines and GPIIb/IIIa inhibitors have antiinflammatory properties that involve different mechanisms of action, especially related to the blockade of platelet activation and platelet-leukocyte interactions. Testing platelet function in addition to assessing levels of inflammatory markers, and not only the risk of bleeding, could help in decision-making to balance the risk-benefit of anti-thrombotic treatment. Different clinical settings are associated with variable inflammatory states, and this could be, in part, responsible for variable response to treatment. © 2012 Bentham Science Publishers.

Giorgi M.A.,Austral University | Miguel L.S.,FLENI
Vascular Health and Risk Management | Year: 2012

Warfarin is the traditional therapeutic option available to manage thromboembolic risk in atrial fibrillation. The hemorrhagic risk with warfarin depends mainly on the international normalized ratio (INR). Data from randomized controlled trials show that patients have a therapeutic INR (2.00-3.00) only 61%-68% of the time while taking warfarin, and this target is sometimes hard to establish. Many compounds have been developed in order to optimize the profile of oral anticoagulants. We focus on one of them, rivaroxaban, comparing it with novel alternatives, ie, dabigatran and apixaban. The indication for rivaroxaban in nonvalvular atrial fibrillation was evaluated in ROCKET-AF (Rivaroxaban-once daily, Oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation). In this trial, rivaroxaban was associated with a 12% reduction in the incidence of the primary endpoint compared with warfarin (hazard ratio 0.88; 95% confidence interval [CI] 0.74-1.03; P, 0.001 for noninferiority and P = 0.12 for superiority). However, patients remained in the therapeutic range for INR only 55% of the time, which is less than that in RE-LY (the Randomized Evaluation of Long-Term Anticoagulation Therapy, 64%) and in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation, 66%). This shorter time spent in the therapeutic range has been one of the main criticisms of the ROCKET-AF trial, but could actually reflect what happens in real life. In addition, rivaroxaban exhibits good pharmacokinetic and pharmacoeconomic properties. Novel anticoagulants are a viable and commercially available alternative to vitamin K antagonists nowadays for the prevention of thromboembolic complications in atrial fibrillation. Rivaroxaban is an attractive alternative, but the true picture of this novel compound in atrial fibrillation will only become available with more widespread use. © 2012 Giorgi and Miguel, publisher and licensee Dove Medical Press Ltd.

Introduction. Misoprostol is commonly used in Argentina to attempt abortion, although a certain proportion of pregnancies is not interrupted. On the other hand, various reports showed an association between misoprostol and congenital anomalies. Objectives. To estimate the risk of major congenital anomalies in children prenatally exposed to misoprostol, and to know their way of consumption during pregnancy. Method. A cohort study compared the frequency of abortion and major congenital abnormalities in offspring of pregnant women exposed to misoprostol (94) and an unexposed group of pregnant women (401), both groups consulting to a teratology information service. Results. Among women exposed to misoprostol only the 8.2% purchased it on prescription, 81.5% heard about its abortifacient effect by friends, neighbors or relatives, the average dose was 1.439 mg which was used both orally and vaginally by the 77.2%; the mean gestational age was 48.5 days and 35.2% used an additional abortive agent. Women exposed to misoprostol had a significantly higher frequency of abortions (exposed: 17/94= 18.1%, unexposed, 29/401= 7.2%, RR= 2.27, 95%: 1,30-3,98), and offspring with major congenital abnormalities (exposed: 5/77= 6.49%, unexposed: 8/372= 2.15%, RR= 3.02, 95%: 1,02-8.98). The five malformed children prenatally exposed to misoprostol showed: 1) encephalocele and transverse limb defects; 2) porencephaly, 3) pulmonary adenomatous cystic malformation, 4) occipital encephalocele and, 5) intestinal malrotation. Conclusions. The study found a significant association between prenatal exposure to misoprostol and the occurrence of major congenital anomalies. © 2011 Sociedad Argentina de Pediatría.

Palma J.,Hospital Calvo Mackenna | Sasso D.F.,Instituto Argentino Of Diagnostico Y Tratamiento | Dufort G.,Hospital Calvo Mackenna | Koop K.,Hospital Calvo Mackenna | And 6 more authors.
Bone Marrow Transplantation | Year: 2012

High-dose chemotherapy (HDC) followed by autologous stem cell rescue (ASCR) is the only curative treatment for metastatic retinoblastoma, but its feasibility in developing countries is unknown. We report 11 consecutive children (six unilateral) treated in three South-American middle-income countries with HDC-ASCR. One patient had metastatic retinoblastoma at diagnosis and the remaining ones had a metastatic relapse. Metastatic sites included BM=6, bone=4, orbit=5 and central nervous system (CNS)=4. All patients received induction with conventional chemotherapy achieving CR at a median of 5.7 months from the diagnosis of metastasis. Conditioning regimens included carboplatin and etoposide with thiotepa in six or with CY in four or melphalan in one patient. All patients engrafted after G-CSF-mobilized peripheral blood ASCR and no toxic deaths occurred. Two children received post-ASCR CNS radiotherapy. Seven children have disease-free survival (median follow-up 39 months). CNS relapse, isolated (n=3) or with systemic relapse (n=1), occurring at a median of 7 months after ASCT was the most common event. In the same period, five children with metastatic retinoblastoma did not qualify for HDC-ASCR and died. We conclude that HDC-ASCR is a feasible and effective treatment for children with metastatic retinoblastoma in middle-income countries. © 2012 Macmillan Publishers Limited. All rights reserved.

Bronte-Stewart H.,Stanford University | Taira T.,Tokyo Women's Medical University | Merello M.,FLENI | Marks W.J.,University of California at San Francisco | And 3 more authors.
Movement Disorders | Year: 2011

When considering a patient with dystonia for deep brain stimulation (DBS) surgery several factors need to be considered. Level B evidence has shown that all motor features and associated pain in primary generalized and segmental dystonia are potentially responsive to globus pallidus internus (GPi) DBS. However, improvements in clinical series of ≥90% may reflect methods that need improvement, and larger prospective studies are needed to address these factors. Nevertheless, to date the selection criteria for DBS-specifically in terms of patient features (severity and nature of symptoms, age, time of evolution, or any other demographic or disease aspects)-have not been assessed in a systematic fashion. In general, dystonia patients are not considered for DBS unless medical therapies have been previously and extensively tested. The vast majority of reported patients have had DBS surgery when the disease was provoking important disability, with loss of independence and impaired quality of life. There does not appear to be an upper age limit or a minimum age limit, although there are no published data regarding the outcome of GPi DBS for dystonia in children younger than 7 years of age. There is currently no enough evidence to prove that subjects with primary-generalized dystonia who undergo DBS at an early age and sooner rather than later after disease onset may gain more benefit from DBS than those undergoing DBS after the development of fixed skeletal deformities. There is no enough evidence to refuse or support consideration of DBS in patients with previous ablative procedures. © 2011 Movement Disorder Society.

Giorgi M.A.,FLENI | Giorgi M.A.,Austral University | Caroli C.,FLENI | Arazi H.C.,FLENI | And 2 more authors.
Expert Opinion on Pharmacotherapy | Year: 2011

Introduction: The use of genomics to predict adverse drug reactions (ADRs) has been the subject of much research over the last decade. Concerns about the muscular safety of statins, a highly prescribed group of drugs, are partially related to their high exposure. Many studies have identified a variety of genetic markers related to statin-induced myopathy. However, only polymorphisms in the SLCO1B1 gene (which encodes the carrier responsible for the hepatic uptake of statins, which, in turn, contributes to the regulation of plasma levels of SLCO1B1) were strongly associated with statin-induced muscular adverse effects. These was found to be most prominent for simvastatin. The strength of these findings relies on the use of modern genetic approaches, such as well-designed, case-controlled and genome-wide association studies. Nevertheless, the clinical use of this information is far from known at present and needs to be evaluated. Areas covered: The links between genetic polymorphisms (i.e., SLCO1B1 gene) and statin-induced muscle ADRs and the methodological issues involved in the establishment of such an association are explored. Expert opinion: Despite there being a statingene association for myopathy, in the case of some statins the usefulness of this information still needs to be proven. © Informa UK, Ltd.

Poggio R.,Heart Failure and Heart Transplant Program | Grancelli H.O.,FLENI | Miriuka S.G.,Heart Failure and Heart Transplant Program | Miriuka S.G.,CONICET
Postgraduate Medical Journal | Year: 2010

The risk of hyperkalaemia in patients with heart failure has increased in the past few years together with the evolution of pharmacological treatment for these patients. This significant change has been associated with the introduction of angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and aldosterone antagonists. High potassium concentrations in heart failure could lead to life threatening events, and therefore should be taken seriously. In this review we summarise the information about potassium homeostasis in heart failure and the current risk of developing potentially serious hyperkalaemia, particularly in association with the use of aldosterone antagonists.

Riudavets M.A.,FLENI | Bartoloni L.,Hospital Zubizarreta | Troncoso J.C.,Johns Hopkins University | Pletnikova O.,Johns Hopkins University | And 4 more authors.
Brain Pathology | Year: 2013

Most of the mutations in the presenilin-1 gene (PS-1) are associated with familial Alzheimer's disease (AD). However, certain examples can be associated with frontotemporal dementia (FTD). We performed a clinical evaluation of individuals belonging to a family with the FTD phenotype, and additional molecular studies and neuropathological assessment of the proband. The PS-1 M146V mutation was found in the 50-year-old subject (the proband) with family history of early-onset FTD. Neuropathological examination showed abundant amyloid plaques, widespread neurofibrillary pathology, Pick bodies in the hippocampus and cortex, cortical globose tangles and ubiquitin-positive nuclear inclusions in white matter oligodendrocytes. We report a kindred with clinical features of FTD, whose proband bore the PS-1 M146V mutation and showed diffuse Alzheimer's type pathology and Pick bodies on post-mortem neuropathological examination. As with other mutations within the same codon, this substitution may predispose to both diseases by affecting APP and/or tau processing. © 2013 International Society of Neuropathology.

Rachow T.,University Hospital Jena | Berger S.,University Hospital Jena | Boettger M.K.,University Hospital Jena | Schulz S.,Jena University of Applied Sciences | And 4 more authors.
Psychophysiology | Year: 2011

We investigated to what degree tonic skin conductance levels (SCL) and cardiac autonomic dysfunction are interrelated in schizophrenia. Heart rate variability (HRV) and SCL were simultaneously assessed in 18 unmedicated patients and 18 controls matched for age, sex, weight, and smoking habits. For comparison to prior studies, phasic sympathetic skin responses (SPR) were also recorded. Compared to controls, patients had prolonged SPR latency and reduced SPR amplitude with a right-greater-than-left asymmetry, which was inversely correlated with positive symptoms. An autonomic imbalance was reflected in linear and nonlinear measures of HRV and increased SCL. Patients showed a stronger nonlinear association between SCL and heart rate than controls. HRV and SCL findings were strongly affected by group differences in breathing rate. Stronger HRV-SCL coupling in patients may suggest augmented sympathetic modulation in schizophrenia. © 2011 Society for Psychophysiological Research.

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