917-97 Decreased Resistance Against Oxidation of LDL from Patients with Homozigous Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) was the first genetic disorder recognized to cause myocardial infarction. Homozigotes (H) inherit two mutant genes at the low density lipoprotein (LDL) receptor locus, and as a result of the increased levels and prolonged residence time of LDL in plasma, there is a strong tendency toward accumulation of LDL in the arterial wall, causing early atherogenesis. It has been shown that LDL might undergo oxidation before it can be taken up by macrophages and it become foam cells. Thus, one additional explanation for atherogenesis in FH may be the extent to which LDL is susceptible to oxidation. We selected 8 homozigous FH pts (mean total-cholesterol 825±70mg/dl) matched with 8 healthy subjects to investigate the LDL oxidizability. Skin fibroblast cultures showed that one patient was receptor negative, while others were receptor-defective. LDL were isolated from serum by ultracentrifugations in KBr. Purified LDL was exposed to oxygen radicals generated by the xanthine/xanthine oxidase reaction (2mM and 100mU, respectively for 18hs at 37°C). Malonildihaldehyde (MDAI content was evaluated by the thiobarbiturate method. LDL analysis was carried on polyacrylamide (PAGE; 5 to 16% gradient) and agarose gel electrophoresis (0.8% in Tris-HCL buffer). No significant increase was observed in the basal concentration of MDA between LDL from H and controls (0.8±0.12 and 0.9±0.15nmoles of MDAlmg of protein, respectively). Instead, afteroxidation MDAwas 35.1±4.5* nmoles/mg of protein LDL from H, and 23.5±4.1 in controls (*p<0.05). PAGE confirmed the purity of LDL, present as an intact apolipoprotein B100(apo-B100). When oxidized LDL was run on PAGE an extensive apo-B100fragmentation, replaced by lower fragments ranging from 97.400 to 205.000 m.w., was only observed in LDL from H but not in controls in our experimental conditions. MDA content after oxidation of LDL correlated well with the loss of intact apo-B100. Finally, the relative LDL mobility on agarose gel was evaluated. This assay allows to detect changes in electric charge induced by oxidation. Basal LDL from H and controls migrated as homogeneous bands to 1.2±0.2 and 1.1±0.2cm from the origin. In contrast, oxidized LDL from H migrated to 2.1±0.3*cm from the origin while those of controls migrated to 1.5±0.2 (*p<0.05). Thus, in FH LDL appear to be more susceptible to oxidationin vitro; the indices for LDL oxidizability were all significantly different from those of controls. This phenomenon may be an important additional mechanism of atherogenesis in homozigous FH

Clinical conundrum. Three management strategies for three-vessel coronary artery disease?

Inspired by King’s word, the goal of optimal pharmacotherapy is optimizing patient outcomes in an appropriate and consistent fashion, integrating itself with other management strategies, when and as appropriate, but this goal cannot be achieved if such therapy is not implemented in a forceful and proactive fashion. Indeed, cardiovascular pharmacotherapy for ischemic heart disease due to coronary artery disease (CAD) represents a unique case study in this sense, given the complex interplay between societal and individual preventive strategies as well as clinical treatments aimed at secondary or tertiary prevention, which may apparently challenge immediate and thorough implementation

Rotational atherectomy for the treatment of isolated femoral artery traumatic lesion: a case report

We describe the case of a 50-year-old man with an isolated plaque of the left distal superficial femoral artery (SFA), probably not related to atherosclerosis, but rather to a traumatic event. He was admitted to our hospital because of intermittent claudication. The critical distal SFA stenosis was documented by angiography and the lesion was treated by rotational atherectomy without stent implantation. At 1-year follow up, Doppler Ultrasound scan demonstrated a normal flow pattern of the left SFA and downstream districts in the absence of any complication. Therefore, rotational atherectomy is a safe and effective technique particularly in cases of peripheral arterial disease wherein stent implantation is dangerous

Expression pattern of perilipins in human brain during aging and in Alzheimer's disease

Aims: Perilipins are conserved proteins that decorate intracellular lipid droplets and are essential for lipid metabolism. To date, there is limited knowledge on their expression in human brain or their involvement in brain aging and neurodegeneration. The aim of this study was to characterise the expression levels of perilipins (Plin1-Plin5) in different cerebral areas from subjects of different age, with or without signs of neurodegeneration. Methods: We performed real-time RT-PCR, western blotting, immunohistochemistry and confocal microscopy analyses in autoptic brain samples of frontal and temporal cortex, cerebellum and hippocampus from subjects ranging from 33 to 104 years of age, with or without histological signs of neurodegeneration. To test the possible relationship between Plins and inflammation, correlation analysis with IL-6 expression was also performed. Results: Plin2, Plin3 and Plin5, but not Plin1 and Plin4, are expressed in the considered brain areas with different intensities. Plin2 appears to be expressed more in grey matter, particularly in neurons in all the areas analysed, whereas Plin3 and Plin5 appear to be expressed more in white matter. Plin3 seems to be expressed more in astrocytes. Only Plin2 expression is higher in old subjects and patients with early tauopathy or Alzheimer's disease and is associated with IL-6 expression. Conclusions: Perilipins are expressed in human brain but only Plin2 appears to be modulated with age and neurodegeneration and linked to an inflammatory state. We propose that the accumulation of lipid droplets decorated with Plin2 occurs during brain aging and that this accumulation may be an early marker and initial step of inflammation and neurodegeneration

AngioJet® rheolytic thrombectomy for acute superficial femoral artery stent or femoropopliteal by-pass thrombosis

Thrombosis of superficial femoral artery (SFA) nitinol stents or polytetrafluoroethylene (PTFE) femoropopliteal bypass grafts after discontinuation of antiplatelet therapy is an emergent clinical challenge of acute limb ischemia (ALI), requiring immediate percutaneous intervention. Currently, there is no evidence-based approach for the management of such complications. We describe the cases of two patients presenting with ALI due to nitinol stent thrombosis after discontinuation of antiplatelet therapy and the case of a patient presenting with ALI due to PTFE femoropopliteal graft thrombosis in which limb salvage was obtained by AngioJet® rheolytic thrombectomy and re-stenting. In both cases, the thrombus was successfully removed using the Possis AngioJet® mechanical thrombectomy catheter and percutaneous transluminal angioplasty (PTA) was performed to recanalize two femoropopliteal nitinol stents and a femoropopliteal PTFE graft. In both cases, optimal angiographic result was obtained. To the best of our knowledge, these are the first three cases reporting the use of the AngioJet rheolytic thrombectomy in ALI due to stent or graft thrombosis. Taken together, these cases suggest that AngioJet® rheolytic thrombectomy might represent a novel effective strategy in the percutaneous treatment of stent or graft thrombosis determining ALI

AngioJet® rheolytic thrombectomy for acute superficial femoral artery stent or femoropopliteal by-pass thrombosis

Thrombosis of superficial femoral artery (SFA) nitinol stents or polytetrafluoroethylene (PTFE) femoropopliteal bypass grafts after discontinuation of antiplatelet therapy is an emergent clinical challenge of acute limb ischemia (ALI), requiring immediate percutaneous intervention. Currently, there is no evidence-based approach for the management of such complications. We describe the cases of two patients presenting with ALI due to nitinol stent thrombosis after discontinuation of antiplatelet therapy and the case of a patient presenting with ALI due to PTFE femoropopliteal graft thrombosis in which limb salvage was obtained by AngioJet® rheolytic thrombectomy and re-stenting. In both cases, the thrombus was successfully removed using the Possis AngioJet® mechanical thrombectomy catheter and percutaneous transluminal angioplasty (PTA) was performed to recanalize two femoropopliteal nitinol stents and a femoropopliteal PTFE graft. In both cases, optimal angiographic result was obtained. To the best of our knowledge, these are the first three cases reporting the use of the AngioJet rheolytic thrombectomy in ALI due to stent or graft thrombosis. Taken together, these cases suggest that AngioJet® rheolytic thrombectomy might represent a novel effective strategy in the percutaneous treatment of stent or graft thrombosis determining ALI

Mortality in Peripheral Arterial Disease: A Comparison of Patients Managed by Vascular Specialists and General Practitioners

BACKGROUND: Peripheral arterial disease (PAD) is undertreated by general practitioners (GPs). However, the impact of the suboptimal clinical management is unknown. OBJECTIVE: To assess the mortality rate of PAD patients in relation to the type of physician who provides their care (GP or vascular specialist). DESIGN: Prospective study. SETTING: Primary care practice and academic vascular laboratory. PARTICIPANTS: GP patients (n = 60) were those of the Peripheral Arteriopathy and Cardiovascular Events study (PACE). Patients managed by specialists (n = 82) were consecutive subjects with established PAD who were referred to our vascular laboratory during the enrolment period of the PACE study. MEASUREMENTS: All-cause and cardiovascular mortality. RESULTS: After 32 months of follow-up, specialist management was associated with a lower rate of all-cause mortality (RR = 0.04; 95% CI 0.01–0.34; p = .003) and cardiovascular mortality (RR = 0.07; 95% CI 0.01–0.65; p = .020), after adjustment for patients’ characteristics. Specialists were more likely to use antiplatelet agents (93% vs 73%, p < .001), statins (62% vs 25%, p < .001) and beta blockers (28% vs 3%, p < .001). Survival differences between specialists and GPs disappeared once the use of pharmacotherapies was added to the proportional hazard model. The fully adjusted model showed that the use of statins was significantly associated with a reduced risk of all-cause mortality (RR = 0.02; 95% CI 0.01–0.73, p = .034) and cardiovascular mortality (RR = 0.02; 95% CI 0.01–0.71, p = .033). CONCLUSIONS: Specialist management of patients with symptomatic PAD resulted in better survival than generalist management. This effect appears to be mainly caused by the more frequent use of effective medicines by specialists

Reduction of serum IGF-I levels in patients affected with Monoclonal Gammopathies of undetermined significance or Multiple Myeloma. Comparison with bFGF, VEGF and K-ras gene mutation

<p>Abstract</p> <p>Background</p> <p>Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-<it>ras </it>mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added.</p> <p>Methods</p> <p>Cytokine determinations were performed by commercially available ELISA kits, while K12-<it>ras </it>mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay.</p> <p>Results</p> <p>Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-<it>ras </it>mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels.</p> <p>Conclusion</p> <p>IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.</p