Prandial inhaled insulin plus basal insulin glargine versus twice daily biaspart insulin for type 2 diabetes: a multicentre randomised trial.

Background: Insulin therapy is often a delayed strategy in patients with type 2 diabetes mellitus because it is associated with weight gain, hypoglycaemia, and the need for subcutaneous injections. We aimed to assess the efficacy and safety of prandial Technosphere inhaled insulin compared with twice daily biaspart insulin.

Methods: In this randomised, open-label, parallel-group study, adult patients with type 2 diabetes mellitus and poor glycaemic control despite insulin therapy, with or without oral antidiabetes drugs, were enrolled from ten countries between Feb 23, 2006, and Aug 8, 2007.

Central venous sampling for intraoperative parathyroid hormone monitoring: are peripheral guidelines applicable?

Intraoperative parathyroid hormone (PTH) monitoring has become an integral adjunct to minimally invasive parathyroidectomy. Guidelines for predicting therapeutic excision of all hyperactive parathyroid tissue have been routinely based on peripheral blood samples drawn at various time intervals. Whether these same guidelines can be used to predict success based on central blood draws has not been established.

Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial.

Aims: In high risk patients with non-ST elevation acute coronary syndromes (ACS), enoxaparin is generally preferred to unfractionated heparin (UFH). However, less is known about the relative merits of these two forms of heparin in patients receiving concomitant glycoprotein IIb/IIIa inhibitors.

Methods And Results: The A phase of the A-to-Z trial was an open label non-inferiority trial in which 3987 patients with non-ST elevation ACS were randomised to receive either enoxaparin or UFH in combination with aspirin and tirofiban.

Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial.

Context: Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome (ACS) event affect clinical outcome.

Objective: To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS.

Design, Setting, And Participants: International, randomized, double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter (n = 2265) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin (n = 2232), who were enrolled in phase Z of the A to Z trial between December 29, 1999, and January 6, 2003.

Efficacy and safety of simvastatin in Asian and non-Asian coronary heart disease patients: a comparison of the GOALLS and STATT studies.

Background: Asians are thought to be more responsive to the lipid-lowering effects of statins than non-Asians although there are no head-to-head trials that examine this perception.

Objective: To compare the results of the GOALLS and STATT studies that used similar titrate-to-goal protocols with 20 mg up to 80 mg simvastatin in Asian and non-Asian coronary heart disease (CHD) patients.

Methods: GOALLS (N = 198; included non-Asians and Asians) and STATT (N = 133; included Asians only) were both multi-center, open-label 14-week studies in CHD patients with serum low density lipoprotein cholesterol (LDL-C) levels 115 mg/dL-180 mg/dL and triglycerides (TG) levels < or = 400 mg/dL.

Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.

Context: Enoxaparin or the combination of glycoprotein IIb/IIIa inhibitor tirofiban with unfractionated heparin independently have shown superior efficacy over unfractionated heparin alone in patients with non-ST-elevation acute coronary syndromes (ACS). It is not clear if combining enoxaparin with glycoprotein IIb/IIIa inhibitors is as safe or as effective as the current standard combination of unfractionated heparin with glycoprotein IIb/IIIa inhibitors.

Objective: To assess efficacy and safety of the combination of enoxaparin and tirofiban compared with unfractionated heparin and tirofiban in patients with non-ST-elevation ACS.

The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy.

Background: The A-to-Z Trial is an ongoing international, multicenter, randomized study designed to investigate 2 issues concerning contemporary care of patients with acute coronary syndromes (ACS). The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affects outcomes and safety when used as a therapy adjunctive to baseline treatment with tirofiban and aspirin in patients with non-ST-elevation (nSTE) ACS. The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based "accepted care" regimen of a lower-dose statin started 3 to 6 months after an acute event.

Insulin stimulates receptor-mediated uptake of apoE-enriched lipoproteins and activated alpha 2-macroglobulin in adipocytes.

The low density lipoprotein receptor-related protein (LRP) is a cell surface receptor that binds and internalizes several macromolecules including apolipoprotein E-enriched remnant lipoproteins and protease/antiprotease complexes such as activated alpha 2-macroglobulin. Its function has been studied primarily in cultured fibroblasts and in liver. In the current studies, we provide evidence that LRP is present on the surface of primary adipocytes isolated from rat epididymal fat pads.

Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group.

A subgroup of patients with familial hypercholesterolemia (FH) respond inadequately to standard diet and drug therapy, and are therefore at high risk for the premature development or progression of coronary artery disease. This study evaluated low-density lipoprotein (LDL) cholesterol and lipoprotein (a) removal in a multicenter, controlled trial with a new LDL apheresis procedure (Liposorber LA-15 System). The study comprised patients with FH who had not responded adequately to diet and maximal drug therapy.

Treatment of children with homozygous familial hypercholesterolemia: safety and efficacy of low-density lipoprotein apheresis.

We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p less than 0.

Clinical considerations regarding treatment of hypercholesterolemia in the elderly.

Therapy for hypercholesterolemia has been shown to reduce the risk for coronary heart disease in middle-aged men. Current guidelines for detecting and treating hypercholesterolemia in adults render large numbers of elderly patients eligible for medical intervention. The elderly are a heterogeneous group of individuals who differ widely in their ability to function physically, behaviorally, cognitively and emotionally.

The low density lipoprotein receptor in Xenopus laevis. II. Feedback repression mediated by conserved sterol regulatory element.

The 5'-flanking regions of the two low density lipoprotein (LDL) receptor genes in Xenopus laevis contain three repeat sequences that are virtually identical to the repeats that mediate sterol-regulated transcription of the human LDL receptor gene. Like their human counterparts, Xenopus repeats 1 and 3, but not repeat 2, bind the transcription factor Sp1 and thus probably function as positive transcription elements. Xenopus repeat 2, like human repeat 2, contains all of the nucleotides that are required for sterol regulation.

Pathobiology of human familial hypercholesterolaemia and a related animal model, the Watanabe heritable hyperlipidaemic rabbit.

Defective expression of low density lipoprotein (LDL) receptors is the basic genetic defect in human familial hypercholesterolaemia (FH) and its animal counterpart, the Watanabe heritable hyperlipidaemic (WHHL) rabbit. The pathologic manifestations of human FH were evaluated based on the study of material from six subjects with homozygous FH and a review of the literature. This analysis indicated that homozygous FH is characterized by accelerated atherosclerosis and prominent lipid accumulation in macrophages and other stromal cells of the aortic and mitral valves, skin, tendon, and, variably, in other extravascular sites.

Long-term clinical tolerance of lovastatin and simvastatin.

3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors are gaining widespread use in the treatment of hypercholesterolemia. Clinical experience with lovastatin, which is approaching 4 years in many patients, indicates that it is well tolerated. Short-term adverse effects have usually been self-limited and have included abdominal pain, cramps, bloating, and flatus in 4-6% of cases.

Cholesterol education implications for clinical practice.

It is well established that an elevated plasma cholesterol level is a major risk factor for coronary heart disease (CHD). Furthermore, results from several clinical trials indicate that therapeutic reduction of high-risk plasma cholesterol levels is followed by a reduction in CHD risk. The National Cholesterol Education Program (NCEP) was launched to enhance the detection of individuals with increased risk for CHD due to elevated plasma cholesterol levels, and to provide guidelines to clinicians for the detection, evaluation and treatment of these high-risk individuals.

Portacaval shunt and liver transplantation in treatment of familial hypercholesterolemia.

Portacaval shunt surgery and liver transplantation have been used to treat patients with severe familial hypercholesterolemia (FH). These operations have usually been performed on patients with homozygous FH, but portacaval shunt surgery has also been used in several patients with the heterozygous form of the disease. Portacaval shunt surgery lowers the low density lipoprotein (LDL) cholesterol level by 25% or more in about 80% of patients.

Therapeutic control of hyperlipidemia in the prevention of coronary atherosclerosis: a review of results from recent clinical trials.

The link between elevated plasma cholesterol levels and coronary atherosclerosis is now well established. During the past decade, results from therapeutic trials indicate that control of hypercholesterolemia does result in lower cardiovascular risk. Many of these results were obtained in hypercholesterolemic, middle-aged men.

Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentrations or turnover.

To determine whether at least part of the fall in low density lipoprotein (LDL) levels during lovastatin therapy might be the result of a reduced secretion of lipoproteins by the liver, three children 6 to 9 years of age with receptor-negative homozygous familial hypercholesterolemia underwent treatment with lovastatin. These patients have no capacity to synthesize LDL receptors. During lovastatin therapy, at a dose of 2 mg/kg/day, there was no decrease in LDL-cholesterol levels, nor was the turnover rate of LDL affected by the drug.

Combination drug therapy for familial combined hyperlipidemia.

Study Objective: To compare the efficacy of gemfibrozil and colestipol with gemfibrozil and lovastatin in patients with familial combined hyperlipidemia.

Design: A prospective, randomized trial.

Setting: An outpatient clinical research center in a tertiary care center.

Uptake of cholesterol-rich remnant lipoproteins by human monocyte-derived macrophages is mediated by low density lipoprotein receptors.

The uptake and degradation of cholesterol-rich remnant lipoproteins, referred to as beta-VLDL, are shown in the present study to be mediated by LDL receptors (apoB,E(LDL) receptors), not by unique beta-VLDL receptors. Human blood monocytes cultured for 5-7 d bound apoB- and/or apoE-containing lipoproteins from different species with affinities equivalent to those demonstrated for the receptors on cultured human fibroblasts. Low density lipoproteins competed effectively and completely with 125I-beta-VLDL for binding to and degradation by monocyte-derived macrophages.