Screening for familial hypercholesterolaemia in primary care: Time for general practice to play its part

Fifty per cent of first-degree relatives of index cases with familial hypercholesterolemia (FH) inherit the disorder. Despite cascade screening being the most cost-effective method for detecting new cases, only a minority of individuals with FH are currently identified. Primary care is a key target area to increase identification of new index cases and initiate cascade screening, thereby finding close relatives of all probands. Increasing public and health professional awareness about FH is essential. In the United Kingdom and in Australia, most of the population are reviewed by a General Practitioner (GP) at least once over a three-year period, offering opportunities to check for FH as part of routine clinical consultations. Such opportunistic approaches can be supplemented by systematically searching electronic health records with information technology tools that identify high risk patients. GPs can help investigate and implement results of this data retrieval. Current evidence suggests that early detection of FH and cascade testing meet most of the criteria for a worthwhile screening program. Among heterozygous patients the long latent period before the expected onset of coronary artery disease provides an opportunity for initiating effective drug and lifestyle changes. The greatest challenge for primary care is to implement an efficacious model of care that incorporates sustainable identification and management pathways

Relationship between Sustained Reductions in Plasma Lipid and Lipoprotein Concentrations with Apheresis and Plasma Levels and mRNA Expression of PTX3 and Plasma Levels of hsCRP in Patients with HyperLp(a)lipoproteinemia

The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 ± 9.3 years (mean ± SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R(2) = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins

High-Q-factor Al [subscript 2]O[subscript 3] micro-trench cavities integrated with silicon nitride waveguides on silicon

We report on the design and performance of high-Q integrated optical micro-trench cavities on silicon. The microcavities are co-integrated with silicon nitride bus waveguides and fabricated using wafer-scale silicon-photonics-compatible processing steps. The amorphous aluminum oxide resonator material is deposited via sputtering in a single straightforward post-processing step. We examine the theoretical and experimental optical properties of the aluminum oxide micro-trench cavities for different bend radii, film thicknesses and near-infrared wavelengths and demonstrate experimental Q factors of > 10[superscript 6]. We propose that this high-Q micro-trench cavity design can be applied to incorporate a wide variety of novel microcavity materials, including rare-earth-doped films for microlasers, into wafer-scale silicon photonics platforms

Familial hypercholesterolaemia: challenges in primary care

Familial hypercholesterolaemia remains largely unrecognised and undertreated in Australian primary care. A new approach involving increased awareness, early detection, lifelong treatment and cascade testing of relatives is essential to improve outcomes of patients with this disorder. Key Points Familial hypercholesterolaemia (FH) is a relatively common inherited disorder of high cholesterol levels. FH can lead to atherosclerosis, premature coronary artery disease and early death if left untreated. Cascade testing of relatives of patients with FH is cost- effective and necessary as one in two will have the condition. Innovations in primary care can improve FH detection in the community. An integrated approach to FH detection involving GPs, specialists and pathology laboratories is recommended. Primary care teams are well positioned to provide a sustainable approach to FH diagnosis and management but greater awareness of this condition is needed

Treating patients with low high-density lipoprotein cholesterol: choices, issues and opportunities

Three clinical trials have recently focused on the benefits of lipid-regulating therapy in populations with normocholesterolaemia and low high-density lipoprotein (HDL)-cholesterol. Two secondary prevention studies (Veterans Affairs HDL-Cholesterol Intervention Trial [VA-HIT] and Bezafibrate Infarction Prevention [BIP] trial) testified to the efficacy of fibrates in decreasing cardiovascular events, particularly in patients with coexisting risk factors, including hypertriglyceridaemia. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) demonstrated that a statin could decrease acute coronary events in patients with isolated low HDL-cholesterol in a primary prevention setting. The absolute risk reduction in coronary events in the VA-HIT study compares favourably with those reported from the statin-based Cholesterol and Recurrent Events (CARE) and Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) trials. The absolute risk reduction in AFCAPS-TexCAPS is similar to that in West of Scotland Coronary Pravastatin Study (WOSCOPS). Recommendations are given concerning lifestyle and pharmacological management of low HDL-cholesterol. Optimal management also requires review of current treatment targets for HDL-cholesterol and triglycerides levels

Mouse mast cell tryptase mMCP-6 is a critical link between adaptive and innate immunity in the chronic phase of Trichinella spiralis infection

Although the innate immune function of mast cells in the acute phase of parasitic and bacterial infections is well established, their participation in chronic immune responses to indolent infection remains incompletely understood. In parasitic infection with Trichinella spiralis, the immune response incorporates both lymphocyte and mast cell-dependent effector functions for pathogen eradication. Among the mechanistic insights still unresolved in the reaction to T. spiralis are the means by which mast cells respond to parasites and the mast cell effector functions that contribute to the immunologic response to this pathogen. We hypothesized that mast cell elaboration of tryptase may comprise an important effector component in this response. Indeed, we find that mice deficient in the tryptase mouse mast cell protease-6 (mMCP-6) display a significant difference in their response to T. spiralis larvae in chronically infected skeletal muscle tissue. Mechanistically, this is associated with a profound inability to recruit eosinophils to larvae in mMCP-6-deficient mice. Analysis of IgE-deficient mice demonstrates an identical defect in eosinophil recruitment. These findings establish that mast cell secretion of the tryptase mMCP-6, a function directed by the activity of the adaptive immune system, contributes to eosinophil recruitment to the site of larval infection, thereby comprising an integral link in the chronic immune response to parasitic infection

Shared and distinct transcriptional programs underlie the hybrid nature of iNKT cells

Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled iNKT cell gene expression during ontogeny and in peripheral subsets as part of the Immunological Genome Project (ImmGen). High-resolution comparative transcriptional analyses defined developmental and subset-specific iNKT cell gene expression programs. In addition, iNKT cells were found to share an extensive transcriptional program with natural killer (NK) cells, similar in magnitude to that shared with major histocompatibility complex (MHC)-restricted T cells. Strikingly, the NK- iNKT program also operated constitutively in γδT cells and in adaptive T cells following activation. Together, our findings highlight a core effector program regulated distinctly in innate and adaptive lymphocytes

Economic development, human development, and the pursuit of happiness, April 1, 2, and 3, 2004

This repository item contains a single issue of the Pardee Conference Series, a publication series that began publishing in 2006 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. This was the Center's spring conference, which took place during April 1, 2, and 3, 2004.The conference asks the questions, how can we make sure that the benefits of economic growth flow into health, education, welfare, and other aspects of human development; and what is the relationship between human development and economic development? Speakers and participants discuss the role that culture, legal and political institutions, the UN Developmental Goals, the level of decision-making, and ethics, play in development

Challenges in the care of familial hypercholesterolemia: a community care perspective

Familial hyperchoelsterolaemia (FH) remains under-diagnosed and under-treated in the community setting. Earlier evidence suggested prevalence of 1:500 worldwide but newer evidence suggests it is more common. Less than 15% of FH patients are ever diagnosed with children and young adults rarely tested despite having most to gain given their lifetime exposure. Increasing awareness among primary care teams is critical to improve detection profile for FH. Cascade testing in the community setting needs a sustainable approach to be developed to facilitate family tracing of index cases. The use of the Dutch Lipid Clinic Network Criteria score to facilitate a phenotypic diagnosis is the preferred approach adopted in Australia and eliminates the need to undertake genetic testing for all suspected FH cases