Apheresis-inducible cytokine pattern change in severe, genetic dyslipidemias.

OBJECTIVE: The effects of direct adsorption of lipids LDL-apheresis (DALILDL-a) on plasma cytokines in two Homozygous and heterozygous familial hypercholesterolemic (HozFH, HtzFH) and in four HyperLp(a)lipoproteinemic [HyperLp(a)] patients, were evaluated. METHODS: Plasma, macrophage inflammatory proteins 1α (MIP-1α), macrophage inflammatory proteins 1ß (MIP-1ß), monocyte chemoattractant protein-1 (MCP-1), RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted), granulocyte-colony stimulating factor (GCSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-1α (IL-1α), interleukin-1ß (IL-1ß), interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), concentrations, were measured before and after LDL-a on three consecutive sessions for each patient. RESULTS: MIP-1α was significantly reduced (P=0.05), while MIP-1ß was significantly increased (P=0.05). Plasma MCP-1 was reduced, although not significantly, while RANTES was significantly increased (P=0.05). GCSF and GM-CSF were both significantly reduced (GM-CSF: P=0.05, GCSF: P=0.05, respectively). IL-1α level was significantly reduced (P=0.001). IL-1ß, IL-6, and IFN-γ levels were significantly reduced in plasma after apheresis (IL-1ß: P=0.001, IL-6: T1 P=0.001; T2 P=0.05, respectively, IFN-γ: P=0.001). IL-2 level in plasma was significantly reduced at T0, and T2, (P=0.001). However, IL-2 level showed a statistically significant increase at T1 (P=0.001). A significant correlation between IL-1α and IFN-γ was found: r=0.882 (P=0.001). CONCLUSIONS: In this study LDL-a induced profound changes in several circulating cytokines and promoted anti-inflammatory and anti-atherogenic cytokine profile in plasma of patients with severe dyslipidemia, with pre-existing angiographically demonstrated Coronary heart disease (CHD), and aortic valvular disease (#=1) (AVD).

Immunoadsorption apheresis and immunosuppressive drug therapy in the treatment of complicated HCV-related cryoglobulinemia.

The immunosuppressive drug therapy (IDT) is not always effective to avoid the development of complications in hepatitis C virus-related cryoglobulinemia (HCV-Cr). Removal of cryoglobulins by therapeutic plasmapheresis is currently accepted. In this randomized, parallel group study, 17 male and female patients aged 43-79 years, with complicated HCV-Cr, were submitted for 12 weeks (initial immunosuppressive therapy) to IDT (alpha-interferon, pegylated-interferon alpha-2a, cyclophosphamide, methylprednisolone, prednisone, cyclosporine, ribavirin, and melphalan). Then, they were randomly assigned to two parallel groups: A # 9 patients treated by immunoadsorption apheresis (Selesorb((R))) (IA) plus IDT, and B # 8 patients submitted to IDT only, for further 12 weeks. # 187 IA aphereses were performed. No adverse reactions or complications were observed. A Clinical Score (CS) was adapted from a pre-existing scoring model to evaluate signs and symptoms inherent to the underlying immunologic disorder. The CS was calculated at baseline (CS0), after the initial immunosuppressive therapy (CS1 = 12 weeks) when patients were treated only with IDT, and at the end of the study (24 weeks) in the group A (CSA; IA plus IDT) and B (CSB; IDT only). The score did not change significantly from CS0 to CS1. However, statistically significant differences were observed between CS1 and CSA (P < 0.001), and CSA versus CSB (P = 0.03), respectively. The changes observed were favorable to the patients assigned to the IA plus IDT group (A): in most case relief of symptoms and complications have been obtained.

Combined treatment with Dif1stat and diet reduce plasma lipid indicators of moderate hypercholesterolemia more effectively than diet alone: a randomized trial in parallel groups.

An open-labeled randomized trial with parallel groups was carried out to study the effects of Dif1stat (Monascus purpureus-Linear aliphatic alcohols-Niacin) in the treatment of primary moderate hypercholesterolemia. The trial lasted 8 months. The patients, males and females, were assigned to two groups: A (#130), treated with diet, and B (#110) submitted to diet + Dif1stat. After 4 months, group A did not show significant changes in Total cholesterol (TC), LDL-cholesterol (LDLC), HDL-cholesterol (HDLC) or non-HDL-cholesterol (non-HDLC). The same group, showed a reduction in TC (-22%), LDLC (-30%) and non-HDLC (-27%) after 8 months (P < or = 0.001). After 4 months, TC (-21.3%), LDLC (-29%), and non-HDLC (-26%) were significantly lowered in group B (P < or = 0.001). In group B, TC, LDLC and non-HDLC showed a further reduction after 8 months: -29.4, -38 and -37%, respectively (P < or = 0.001). Even triglycerides (TG) decreased significantly (-33%) (P < or = 0.001). After 8 months, group B showed a significant reduction of TG (-33%) (P < or = 0.001), when compared to group A. Some safety parameters were significantly reduced in both groups: AST and gamma-GT in group A after 4 and 8 months, as well as ALT, AST and gamma-GT in group B after 8 months (P < or = 0.001). Dif1stat, given with a suitable diet, was well tolerated in the long-term and induced an anti-atherogenic plasma lipid and lipoprotein profile, in patients with moderate hypercholesterolemia.

Aorta and coronary angiographic follow-up of children with severe hypercholesterolemia treated with low-density lipoprotein apheresis.

BACKGROUND: In this single-center, nonrandomized, prospective study, 11 children with severe genetic hypercholesterolemia, without previous cardiovascular disease events, were treated with low-density lipoprotein apheresis (LDLa). STUDY DESIGN AND METHODS: LDLa was given every 1 or 2 weeks for 2 to 17 years. Clinical cardiovascular events and coronary revascularization, as well as aortic and coronary angiographic findings and ejection fractions, were serially evaluated for 2 to 17 years. RESULTS: Total cholesterol (TC) and LDL cholesterol levels at baseline were 826.1 +/- 183.3 and 767.8 +/- 181.9 mg/dL, respectively. After LDLa, these levels decreased to 122.6 +/- 24.4 and 79.1 +/- 20.7 mg/dL, respectively (both differences, p < or = 0.001). There were no cardiac deaths, and 6 children were free from any coronary lesions. Nonfatal myocardial infarction was not observed, and coronary revascularization was not required in any patient. Regression of coronary stenosis in children with existing angiographically established lesions after treatment with LDLa was prospectively demonstrated. The statistical analysis applicable to a scoring model (overall atherogenic index [OAI]) highlighted a significant relation between values of 0 to 4 years relevant to the score (p < or = 0.018) and a weaker significant statistic for the value of OAI between 0 and 2 years (p < or = 0.03). The OAI score at baseline was significantly related to the basal values of TC (p = 0.015), LDL cholesterol (p = 0.015), and triglycerides (p = 0.01), but not of high-density lipoprotein cholesterol (p = 0.075) as demonstrated by the logistic regression analysis (Cox and Snell pseudo-R(2) of 0.67). CONCLUSION: LDLa interrupted the development of new aortic and coronary lesions in the native arteries and prevented cardiac events and the need for coronary revascularization in children without previous cardiovascular disease events.

Therapeutic plasma exchange in patients with severe hypertriglyceridemia: a multicenter study.

Extremely high plasma triglyceride (TG) concentration is a recognized risk factor for acute pancreatitis (AP). In order to evaluate the therapeutic efficacy of plasma-exchange plasmapheresis in treating patients with severe hypertriglyceridemia (sHTG), 17 patients who had not responded to conventional medical therapy (fat-free diet plus pharmaceutical interventions) were referred for therapeutic plasma exchange (TPE) in a multicenter frame case series study. Two hundred seventeen TPE sessions were performed, and therapy is ongoing for five (30%) of the patients. After treatment, the mean plasma TG and total cholesterol concentrations were significantly reduced from 1929 and 510 mg/dL, to 762 and 227 mg/dL, respectively (P < or = 0.001 in both cases). In most cases, the interval between treatments was related to the clinical presentation and individual circumstances. The removal of TG-rich lipoproteins prevented relapses of AP. In this case series, TPE is confirmed as a safe and reliable method for treating patients with refractory sHTG when a severe complication, such as AP, is clinically demonstrated or can be actively prevented. Therefore, in cases where standard medical approaches fail to promote the clearance of TGs from plasma and a high risk of first or second hypertriglyceridemic pancreatitis persists, TPE provides a therapeutic option for preventing life-threatening sHTG.

Effects of low-dose atorvastatin and rosuvastatin on plasma lipid profiles: a long-term, randomized, open-label study in patients with primary hypercholesterolemia.

BACKGROUND AND OBJECTIVE: Despite the favorable effects of reduction of low-density lipoprotein-cholesterol (LDL-C) levels in decreasing the risk of coronary heart disease, many patients treated with lipid-lowering HMG-CoA reductase inhibitors (statins) do not achieve goal LDL-C levels. This may be due to high doses of statins prescribed that could potentially induce adverse effects and compromise patient safety and compliance with considerable expense in the long-term. We compared the actions of rosuvastatin and atorvastatin, administered at the low dosages of 10 and 20 mg/day, respectively, in reducing plasma LDL-C levels and their effects on other components of the atherogenic lipid profile in patients with primary hypercholesterolemia. METHODS: In this randomized, parallel group, open-label clinical study, 106 patients with LDL-C >200 mg/dL were treated with rosuvastatin 10 mg/day (group A; n = 52), or atorvastatin 20 mg/day (group B; n = 54) for 48 weeks. RESULTS: At 48 weeks, rosuvastatin 10 mg/day was associated with a significantly greater reduction in plasma LDL-C levels compared with atorvastatin 20 mg/day (-44.32% vs -30%; p < 0.005). Compared with atorvastatin, rosuvastatin also produced a greater reduction in plasma total cholesterol, triglycerides, and non-high-density lipoprotein-cholesterol (non-HDL-C) levels (p < 0.005). Plasma HDL-C levels were not affected significantly, independent of the drug used. CONCLUSION: In high-risk patients with primary hypercholesterolemia, rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels, enabling goal LDL-C levels to be achieved and improving other lipid parameters. Both treatments were well tolerated over 48 weeks.

Cyclophosphamide and immunoadsorption apheresis treatment of lupus nephritis nonresponsive to drug therapy alone.

In this report we present a 28-year-old male patient with systemic lupus erythematosus (SLE) that was treated with immunoadsorption apheresis (IA) and cyclophosphamide for lupus nephritis (proliferative glomerulonephritis, class IV-B) after proving nonresponsive to drug therapy alone. Before starting the therapeutic cycle with IA, the patient was administered prednisone 25 mg/d, hydroxychloroquine 200mg twice/d, ACE inhibitors 5 mg/d, aspirin 100 mg/d, furosemide 50 mg/d, and intravenous (IV) albumin (20%) 50 mL. Deteriorating clinical conditions necessitated a renal biopsy, and thereafter an increase in medication. The patient was given a bolus of IV cyclophosphamide 1 g/d for 1 day and IV methylprednisone 500 mg/d for 3 days. This was not followed by any improvement and the renal functions worsened. Thus, 3 weeks after the more aggressive pharmacologic treatment with cyclophosphamide, which had been prescribed to improve renal function, and given the young age of the patient, the decision was made to administer IA (Selesorb). IA selectively removes IgG and IgM immune complexes from the plasma, thereby reducing the complications induced by the pathogenic autoimmune reaction. The treatment was administrated twice a week for the first 15 days, once a week for a further 5 weeks, and biweekly in the last month with a bolus of cyclophosphamide (average 250-100 mg) after each session. After twelve sessions of IA over 3 months, renal function was completely restored and the patient discharged. Although it is not proven, the concomitant use of cyclophosphamide could presumably improve the final clinical outcome.