Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice.

Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.     

Disentangling breast cancer patients' perceptions and experiences with regard to endocrine therapy: Nature and relevance for non-adherence

Background & study aimsAdjuvant endocrine therapy effectively prevents recurrence and progression of estrogen-receptor positive breast cancer. However, studies reveal substantial non-adherence. The objective was therefore to identify the nature of the experiences and beliefs of women treated with endocrine therapy in an attempt to find potential determinants of non-adherence.MethodOnline Focus Groups (OFGs) and individual interviews were conducted with 37 women who were treated with endocrine therapy. Sixty-three statements derived from the OFGs and 11 belief items from the Beliefs about Medicines Questionnaire (BMQ) were used in a Q-sorting task conducted with 14 of the women. The quantitative Q-sorting data were statistically analyzed with Hierarchical Cluster Analysis.ResultsA six cluster solution was revealed that included the clusters ‘information’, ‘efficacy’, ‘tenacity’, ‘coping’, ‘side effects’ and ‘usage’. Women's own experiences and perceptions were not clearly delineated from the beliefs measured with the BMQ. However, women judged their own experiences and perceptions with regard to endocrine therapy as more relevant for adherence than the BMQ beliefs.ConclusionIn order to understand and to improve women's adherence to endocrine therapy, women's own perceptions and experiences about endocrine therapy should be targeted in addition to common beliefs that apply to a wide range of medicines.     

Different circulating lymphocyte profiles in patients with different subtypes of juvenile idiopathic arthritis

OBJECTIVE: To determine the immunophenotypic profiles of circulating lymphocytes in patients with different disease types of Juvenile Idiopathic Arthritis (JIA). METHODS: Peripheral blood lymphocyte subsets from 19 patients with oligoarticular JIA (o-JIA), 10 patients with polyarticular JIA (p-JIA), 12 patients with systemic JIA (s-JlA) andfrom 41 age-matched healthy controls were characterized by two color immunofluorescence flow cytometry analysis. RESULTS: Patients with o-JIA and p-JIA had increased numbers of HLA-DR+ Tcells and Tcells co-expressing CD57 and CD16/56, indicating T cell activation and terminal differentiation of CD8+ T cells respectively. By contrast, in patients with s-JIA there was no increase in the activation or differentiation markers on T cells, but a profound decrease in circulating NK cells. All patients had hypergammaglobulinemia consistent with B cell hyperactivity, but increased numbers of CD5+ B cells were found only in o-JIA and p-JIA. CONCLUSION: Distinct immunophenotypic lymphocyte profiles in patients with o-JIA and p-JIA compared to patients with s-JIA as demonstrated in this study, are consistent with afundamental heterogeneity of the disease.     

Therapeutic options of caesarean scar pregnancy: Case series and literature review

We describe our experience with the treatment of 4 caesarean scar pregnancies and provide an overview of current literature. Four women diagnosed with a caesarean scar pregnancy in our hospital between 1996 and 2007 were treated with local or systemic methotrexate and had a steady decline of the serum β‐hCG level. The uterus was preserved in all women and 3 of them had an uneventful subsequent pregnancy and delivery. We suggest that transcervical needle aspiration of amniotic fluid followed by intra‐amniotic injection of methotrexate should be the treatment of choice, followed by surgical treatment only if methotrexate fails. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2010     

Clinical review: Practical recommendations on the management of perioperative heart failure in cardiac surgery

Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients, yet current acute heart failure (HF) classification is not applicable to this period. Indicators of major perioperative risk include unstable coronary syndromes, decompensated HF, significant arrhythmias and valvular disease. Clinical risk factors include history of heart disease, compensated HF, cerebrovascular disease, presence of diabetes mellitus, renal insufficiency and high-risk surgery. EuroSCORE reliably predicts perioperative cardiovascular alteration in patients aged less than 80 years. Preoperative B-type natriuretic peptide level is an additional risk stratification factor. Aggressively preserving heart function during cardiosurgery is a major goal. Volatile anaesthetics and levosimendan seem to be promising cardioprotective agents, but large trials are still needed to assess the best cardioprotective agent(s) and optimal protocol(s). The aim of monitoring is early detection and assessment of mechanisms of perioperative cardiovascular dysfunction. Ideally, volume status should be assessed by 'dynamic' measurement of haemodynamic parameters. Assess heart function first by echocardiography, then using a pulmonary artery catheter (especially in right heart dysfunction). If volaemia and heart function are in the normal range, cardiovascular dysfunction is very likely related to vascular dysfunction. In treating myocardial dysfunction, consider the following options, either alone or in combination: low-to-moderate doses of dobutamine and epinephrine, milrinone or levosimendan. In vasoplegia-induced hypotension, use norepinephrine to maintain adequate perfusion pressure. Exclude hypovolaemia in patients under vasopressors, through repeated volume assessments. Optimal perioperative use of inotropes/vasopressors in cardiosurgery remains controversial, and further large multinational studies are needed. Cardiosurgical perioperative classification of cardiac impairment should be based on time of occurrence (precardiotomy, failure to wean, postcardiotomy) and haemodynamic severity of the patient's condition (crash and burn, deteriorating fast, stable but inotrope dependent). In heart dysfunction with suspected coronary hypoperfusion, an intra-aortic balloon pump is highly recommended. A ventricular assist device should be considered before end organ dysfunction becomes evident. Extra-corporeal membrane oxygenation is an elegant solution as a bridge to recovery and/or decision making. This paper offers practical recommendations for management of perioperative HF in cardiosurgery based on European experts' opinion. It also emphasizes the need for large surveys and studies to assess the optimal way to manage perioperative HF in cardiac surgery.