Early high-dosage atorvastatin treatment improved serum immune-inflammatory markers and functional outcome in acute ischemic strokes classified as large artery atherosclerotic stroke: A randomized trial

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-a, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile

Genetics and gene therapy of anderson-fabry disease

Fabry's disease is a genetic disorder of X-linked inheritance caused by mutations in the alpha galactosidase A gene resulting in deficiency of this lysosomal enzyme. The progressive accumulation of glycosphingolipids, caused by the inadequate enzymatic activity, is responsible of organ dysfunction and thus of clinical manifestations. In the presence of a high clinical suspicion, a careful physical examination and specific laboratory tests are required, finally diagnosis of Fabry’s disease is confirmed by the demonstration of absence or reduced alpha-galactosidase A enzyme activity in hemizygous men and gene typing in heterozygous females; in fact the performance of enzymatic activity assay alone in women is inconclusive. Measurement of the biomarkers Gb3 and Lyso Gb3 in biological specimens may facilitate diagnosis. Because of its multisystemic involvement Fabry’s disease may present a large spectrum of clinical manifestations as acroparesthesias, hypohidrosis, angiokeratomas, signs and symptoms of cardiac, renal, cerebrovascular involvement (renal insufficiency, proteinuria, left ventricular hypertrophy, strokes). Enzyme replacement therapy with recombinant α-galactosidase A is actually the specific therapy for Fabry disease. Early beginning of this treatment has shown beneficial effects in particular in cardiac and renal disease, a less efficacy it has been reported in central nervous system involvement. ERT has shown to be associated to a significant reduction of Gb3 accumulation in several tissues, in particular heart and kidney; moreover it improves pain related quality of life. Next generation lysosomal storage disorder treatment is based on new strategic approaches as stem cell based therapy, pharmacological chaperones, viral gene therapy; concerning Fabry’s disease, it has been recently addressed to great interest this last innovative method, that is to say viral gene therapy, for delivering recombination enzyme into main involved tissues; promising results have been reported in animal models. Great efforts have been made and are still required in this field in order to make available a more effective, safer, advantageous therapeutic strategy for patients with Fabry’s disease

Autonomic dysfunction in a group of lower extremities arterial disease outpatients

Background: The understanding of the specific role of sympathetic neural control and dysregulation in lower extremities arterial disease (LEAD) is still very limited. Aim of our study was to investigate the autonomic profile in LEAD patients and to evaluate if the eventual autonomic alterations were more severe in patients with advanced disease. Methods: We enrolled all consecutive outpatients with LEAD referred to our Departments between July 2012 and September 2014. They were compared to a group of matched outpatients without LEAD. All patients underwent Holter ECG monitoring. Time-domain analysis of heart rate variability (HRV) was evaluated. Results: Compared to controls, patients with LEAD had a lower SDNN (P=0.007) and SDANN (P=0.003). Patients with clinically advanced LEAD had a lower SDNN (P=0.006) and SDANN (P=0.004) compared to LEAD patients with less severe disease and to those without disease. Conclusions: LEAD patients had a reduced SDNN and SDANN than patients without LEAD. Autonomic dysfunction was more significant in clinically advanced stages of disease. This association did not relate to ABI value but to clinical stage of disease

A family with various symptomatology suggestive of Anderson-Fabry disease and a genetic polymorphism of alpha galactosidase A gene

Background: Anderson/Fabry disease expresses a wide range of clinical variability in patients that it is possible to explain referring to a genetic variability with numerous mutations described in the literature (more than 600). Methods: We report some clinical cases of some members of a Sicilian family to express phenotypical variability of this disease in subjects with the same genetic mutation. Results: The first case was a 59-year-old female. Brain MRI revealed right frontal periventricular white matter of likely vascular-degenerative origin. The proband's alpha galactosidase A activity was 3.7. nmol/mL/h. Molecular genetics revealed a polymorphism: - 10 C. >. T; IVS 2-76_80del5; IVS4-16 A. >. G; IVS6-22 C. >. T. The second case was a 30. year-old male affected by acroparesthesias and hypoidrosis since he was an adolescent. Renal impairment was first detected at age 29; it began with high plasma levels of creatinine and microalbuminuria date. The third case was a 41. year-old daughter that presented with acroparesthesias, hypoidrosis since she was very young. The patient's alpha galactosidase A activity was 4.1. nmol/mL/h, in whole blood, which is compatible with heterozygote subject for Fabry's disease or healthy control. The fourth case was a male grandson of the proband, 9. year-old child. He had a classic gastrointestinal involvement. He complained of recurrent abdominal pain, post prandial bloating and pain. This child's enzyme activity was 1.65. nmol/mL/h. In cases 2, 3, and 4, molecular genetics revealed a polymorphism: - 10 C. >. T; IVS 2-76_80del5; IVS4-16 A. >. G; IVS6-22 C. <. T. Discussion: A recent study reported that IVS4. +. 68 A. >. G, IVS6-22C. >. T polymorphisms occurred in 8.9% and 3.7% of the subjects respectively, and the significance of this haplotype in FD pathology remains unknown but possibly suggestive of Anderson/Fabry disease

Mediterranean Diet Adherence and Congestive Heart Failure: Relationship With Clinical Severity and Ischemic Pathogenesis

Objectives: To our knowledge, no study has addressed the relationship between adherence to a Mediterranean diet style and severity of heart failure. The aim of this retrospective study was to evaluate the relationship between adherence to the Mediterranean diet assessed using the calculation of Mediterranean diet score and congestive heart failure (CHF), its severity, and pathogenesis. Methods: We analyzed charts and collected data of all consecutive patients with a diagnosis of CHF at admission to our Internal Medicine Ward from 2008 to 2014. Results: We analyzed 209 patients with CHF and 200 controls. Patients with CHF showed a significantly lower mean MeDi score than controls. At receiver operating characteristic curve analysis, we found a good sensitivity and specificity of mean MeDi score to predict CHF. We also observed a significant positive correlation between MeDi score and ischemic pathogenesis of CHF, a positive relationship between New York Heart Association (NYHA) class and ischemic heart disease, and a significant negative relationship between NYHA class and MeDi score. Conclusion: The beneficial effects of adherence to the Mediterranean diet suggest a possible answer to the question of the biochemical bases of our data, which should be seen as the direct consequence of the anti-inflammatory, antioxidant, and anti-remodeling effects linked to the diet

Mediterranean Diet in patients with acute ischemic stroke: Relationships between Mediterranean Diet score, diagnostic subtype, and stroke severity index

Background: Adherence to a Mediterranean Diet appears to reduce the risk of cardiovascular disease, cancer, Alzheimer's disease, and Parkinson's disease, as well as the risk of death due to cardiovascular disease. No study has addressed the association between diagnostic subtype of stroke and its severity and adherence to a Mediterranean Diet in subjects with acute ischemic stroke. Aim: To evaluate the association between Mediterranean Diet adherence, TOAST subtype, and stroke severity by means of a retrospective study. Methods: The type of acute ischemic stroke was classified according to the TOAST criteria. All patients admitted to our ward with acute ischemic stroke completed a 137-item validated food-frequency questionnaire adapted to the Sicilian population. A scale indicating the degree of adherence to the traditional Mediterranean Diet was used (Me-Di score: range 0-9). Results: 198 subjects with acute ischemic stroke and 100 control subjects without stroke. Stroke subjects had a lower mean Mediterranean Diet score compared to 100 controls without stroke. We observed a significant positive correlation between Me-Di score and SSS score, whereas we observed a negative relationship between Me-Di score and NIHSS and Rankin scores. Subjects with atherosclerotic (LAAS) stroke subtype had a lower mean Me-Di score compared to subjects with other subtypes. Multinomial logistic regression analysis in a simple model showed a negative relationship between MeDi score and LAAS subtype vs. lacunar subtype (and LAAS vs. cardio-embolic subtype). Conclusions: Patients with lower adherence to a Mediterranean Diet are more likely to have an atherosclerotic (LAAS) stroke, a worse clinical presentation of ischemic stroke at admission and a higher Rankin score at discharge

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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