The most severe forms of hypercholesterolaemia scarcely respond to diet and conventional drugs administration and. need, therefore, alternative treatments. Terapeutic Plasma. Exchange demonstrated an improved survival of subjects with Familial Hypercholesterolaemia (FH) in spite of its limitations.Semi-selective and selective techniques have been developed in order to remove LDL cholesterol alone.We studied the efficiency in LDL removal both, of membrane filtration as of dextrane sulphate adsorption on 14 FH patients, performing 302 procedures.Cholesterol extraction with, the different methods was in the range of 40-65%. Mean cholesterol level was reduced from 7% to 64% depending on the protocol used.The procedures were all performed on an outpatient basis. Side effects occurred rarely and were always of not serious degree. The short and the middle term clinical effects of LDL-Apheresis are then evaluated.
Peripheral blood eosinophilia (PBE) may be associated with the development of thrombosis and this holds true also for transient PBE though in the latter case the likely hood of thrombosis may not be as high as for long standing PBE. The co-existence of transient PBE with other pro-coagulant factors may precipitate thrombosis in some patients. We report a young gentleman with PBE of unknown cause who developed thrombosis at the peak of his transient PBE and was later found to have antiphospholipid antibodies. We performed a systematic review to evaluate how often the two conditions co-existed, their clinical expression and their management.
A low platelet count is one of the most sensitive tests for cirrhosis detection in patients with hepatitis C virus (HCV) infection. We evaluated whether the human platelet antigen (HPA) genotype could predict platelet count in HCV-positive patients.We genotyped the HPA 1, 2, 3, 5 and 15 polymorphisms in consecutive patients with HCV infection.Out of the 56 patients enrolled, 56.1% had liver cirrhosis. The mean platelet count was significantly lower in those with HPA1aa genotype than in those with HPA1ab/bb genotype. Platelet count did not differ among the other HPA polymorphisms. However, at logistic regression analysis, only the HPA3aa genotype and liver cirrhosis were independent predictors of a low platelet count.HPA3aa is an independent factor for a low platelet count in this cohort of patients with HCV chronic infection regardless of disease stage.
Homozygous familial hypercholesterolemia (HFH) results from a mutation affecting both the structure and function of a cell surface receptor that removes low density lipoproteins (LDL) from plasma. The disorder is characterized by autosomal dominant inheritance, a lifelong elevation in the concentration of LDL-bound cholesterol in blood and by cholesterol deposits that form xanthomas and early coronary artery disease. HFH patients, as a result of the increased levels and prolonged residence time of LDL in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall causing premature atherosclerosis. Selective LDL-apheresis (LA) on dextran/sulphate cellulose columns is the best therapy reducing mortality of these patients. We previously showed that prolonged lifelong enhanced LDL oxidation in HFH. LDL undergo oxidation before being taken up by macrophages then transformed into foam cells. At the present time, the relevance of the in vitro macrophages studies to the accumulation of cholesterol esters in scavenger cells of HFH patients is not yet established. The aim of this study was to investigate LDL oxidation, induced by xanthine (2 mM)+xanthine oxidase (100 mU), and cholesterol esterification in macrophages, in 8 HFH patients before and after LA. LDL peroxidation by conjugated-diene absorbance showed an increased resistance against oxidation after LA: lag time 129 +/- 25 vs 112 +/- 27 min, p < 0.05; diene production 9.1 +/- 2.1 vs 13.9 +/- 2.5 nM/min/mg LDL, p < 0.01. Peroxidation was also evaluated from lipid peroxides (158 +/- 34 vs 57 +/- 18 nM/mg protein after LA, p < 0.05) and malonyldialdehyde (38 +/- 12 vs 27 +/- 8 nM/mg protein after LA, p < 0.05) content. When oxidized LDL was run on polyacrylamide gel extensive apo-B100 fragmentation was observed in LDL before LA, vs a less fragmentation after LA. A similar reduction was obtained in LDL agarose mobility after LA (1.7 +/- 0.2 vs 2.5 +/- 0.2, p < 0.05). Cholesterol esterification in mouse peritoneal macrophages was also decreased after LA (8.5 +/- 1.8 vs 14.6 +/- 2.7 nM/mg cell protein/12 hours, p < 0.05). Vitamin E content of LDL (mg/g protein) was increased after LA (4.44 +/- 1.0 vs 3.9 +/- 1.2, p < 0.05). Thus, selective LA, not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation and decreased high cholesterol esterification in macrophages. The prevention of these mechanisms by LA contributes actively to retard atherogenesis in HFH patients.
