Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy.

Patients having Duchenne muscular dystrophy (DMD) are currently being treated with corticosteroids, which slow down disease progression at the expense of serious adverse effects. Tamoxifen is a pro-drug some of whose metabolites interact with the nuclear estrogen receptor, leading to anti-fibrotic and muscle-protective effects as has been demonstrated in a murine model of DMD. Here we report the results from a monocentric single arm prospective study in 13 ambulant boys aged 6-14 years with genetically confirmed DMD, aimed to assess the safety of tamoxifen and its impact on disease progression.

Molecular genetics of familial hypercholesterolemia in Israel-revisited.

Background And Aims: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the genes for LDL receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type9 (PCSK9). The purpose of the current investigation was to define the current spectrum of mutations causing FH in Israel.

Methods: New families were collected through the MEDPED (Make Early Diagnosis Prevent Early Death) FH program.

One year experience with a low density lipoprotein apheresis system.

Background: Low density lipoprotein apheresis is used as a complementary method for treating hypercholesterolemic patients who cannot reach target LDL-cholesterol levels on conventional dietary and drug treatment. The DALI system (direct absorption of lipoproteins) is the only extracorporeal LDL-removing system compatible with whole blood.

Objective: To describe our one year experience using the DALI system.

A cholesterol-lowering gene maps to chromosome 13q.

A cholesterol-lowering gene has been postulated from familial hypercholesterolemia (FH) families having heterozygous persons with normal LDL levels and homozygous individuals with LDL levels similar to those in persons with heterozygous FH. We studied such a family with FH that also had members without FH and with lower-than-normal LDL levels. We performed linkage analyses and identified a locus at 13q, defined by markers D13S156 and D13S158.

Molecular genetics of familial hypercholesterolemia in Israel.

Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by a multitude of low density lipoprotein receptor (LDL-R) mutations. The purpose of the current investigation was to define the spectrum of mutations causing FH in Israel and determine their relative distribution among diverse origin groups. A total of 193 FH families were recruited in Israel, 54 of them through the MED PED (Make Early Diagnosis Prevent Early Death) FH program.

Efficacy and safety of triple therapy (fluvastatin-bezafibrate-cholestyramine) for severe familial hypercholesterolemia.

Familial hypercholesterolemia carries a markedly increased risk of coronary artery disease. Reduction of plasma low density lipoprotein cholesterol (LDL-C) levels to the normal range may prevent premature atherosclerosis and usually requires a combination of cholesterol-lowering drugs such as 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors plus resins or fibrates. The current, 60-week, open-label investigation involved 22 patients whose plasma LDL-C had not reached the target level for prevention of coronary artery disease in 3 previous studies using fluvastatin alone and in combination with other cholesterol-lowering medications.

High-dose fluvastatin and bezafibrate combination treatment for heterozygous familial hypercholesterolemia.

This study assessed the long-term use of fluvastatin, alone or in combination with bezafibrate, in patients with severe familial hypercholesterolemia who, in a previous study, did not achieve target levels (European Atherosclerosis Society) of low density lipoprotein cholesterol (LDL-C) with fluvastatin at 60 mg/day plus bezafibrate 200 mg/day, with or without cholestyramine (CME) at 8 g/day. This open-label study comprised 3 periods: period I, 6 weeks of fluvastatin at 40 mg twice daily (at breakfast and at bedtime); period II, fluvastatin at 80 mg/day (40 mg at breakfast, 40 mg at bedtime), and bezafibrate at 200 mg/day (at lunchtime) for 6 weeks in patients not achieving LDL-C target levels; and period III, force-titration of fluvastatin to 800 mg/day (as in period II) and bezafibrate at 400 mg/day (slow release) in patients receiving combination treatment. Patients were excluded if, during the previous study, they had experienced a serious drug-related adverse event or deterioration in liver or kidney function (liver enzymes > 3 times upper limit of normal).

Efficacy and safety of a combination fluvastatin-bezafibrate treatment for familial hypercholesterolemia: comparative analysis with a fluvastatin-cholestyramine combination.

Purpose: Familial hypercholesterolemia (FH) carries a markedly increased risk for coronary artery disease (CAD). Reduction of plasma low-density lipoprotein cholesterol (LDL-C) levels to the normal range may prevent premature atherosclerosis and usually requires a combination of cholesterol-lowering drugs. The major objective of this study is to compare two different drug combinations for the treatment of heterozygous FH.

Genetic determinants of responsiveness to the HMG-CoA reductase inhibitor fluvastatin in patients with molecularly defined heterozygous familial hypercholesterolemia.

Background: In familial hypercholesterolemia, plasma lipoproteins can be modulated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, although the underlying response mechanisms are still unknown.

Methods And Results: A single-blind study with fluvastatin, an HMG-CoA reductase inhibitor, was conducted in 64 familial hypercholesterolemia patients who had defined apolipoprotein E (apo E) and apolipoprotein(a) [apo(a)] isoforms. Plasma lipids and lipoproteins were analyzed throughout the study.

Efficacy and safety of high dose fluvastatin in patients with familial hypercholesterolaemia.

The efficacy and safety of the HMG CoA reductase inhibitor fluvastatin have been evaluated in a double blind study in 52 patients with familial hypercholesterolaemia. A standard AHA Phase II lipid lowering diet was prescribed throughout the study. After 6 weeks of a single blind dosage stabilisation period, in which patients received fluvastatin 40 mg qPM, patients were randomly allocated to one of two double blind treatment groups: group A (n = 24) received fluvastatin 20 mg b.