Serological and genetic complement alterations in infection-induced and complement-mediated hemolytic uremic syndrome

Background: The role of complement in the atypical form of hemolytic uremic syndrome (aHUS) has been investigated extensively in recent years. As the HUS-associated bacteria Shiga-toxin-producing Escherichia coli (STEC) can evade the complement system, we hypothesized that complement dysregulation is also important in infection-induced HUS. Methods: Serological profiles (C3, FH, FI, AP activity, C3d, C3bBbP, C3b/c, TCC, αFH) and genetic profiles (CFH, CFI, CD46, CFB, C3) of the alternative complement pathway were prospectively determined in the acute and convalescent phase of disease in children newly diagnosed with STEC-HUS or aHUS. Serological profiles were compared with those of 90 age-matched controls. Results: Thirty-seven patients were studied (26 STEC-HUS, 11 aHUS). In 39 % of them, including 28 % of STEC-HUS patients, we identified a genetic and/or acquired complement abnormality. In all patient groups, the levels of investigated alternative pathway (AP) activation markers were elevated in the acute phase and normalized in remission. The levels were significantly higher in aHUS than in STEC-HUS patients. Conclusions: In both infection-induced HUS and aHUS patients, complement is activated in the acute phase of the disease but not during remission. The C3d/C3 ratio displayed the best discrepancy between acute and convalescent phase and between STEC-HUS and aHUS and might therefore be used as a biomarker in disease diagnosis and monitoring. The presence of aberrations in the alternative complement pathway in STEC-HUS patients was remarkable, as well

Inflammation in atherosclerosis: Imaging, biomarkers and novel therapeutic opportunities

The vast majority of cardiovascular-related morbidity and mortality is caused by atherosclerosis. Although many patients with atherosclerosis never develop any symptoms, clinical manifestations can vary between acute life-threatening situations to chronic minor complaints. Over the past decades, inflammatory pathways have emerged as important drivers of atherosclerosis as well as plaque disruption and thrombosis. These relatively novel insights expand the scope of treatment of atherosclerosis beyond the traditional focus on reducing cholesterol levels and arterial stenoses. However, targeting the inflammatory process of atherosclerosis carries the risk of severe complications arising from prolonged immunosuppression since atherosclerotic lesions typically form over the course of years. Therefore, there is a need to identify patients with prone-to-rupture atherosclerotic plaques, who can benefit from relatively short-term anti-inflammatory interventions. This thesis contributes to this effort by investigating existing and novel imaging strategies to quantify and qualify the atherosclerotic plaque (part I) and by investigating circulating biomarkers to estimate the risk for cardiovascular events (part II). Furthermore, selectively increasing the local concentration of immunosuppressive agents in the atherosclerotic plaque could potentially overcome the side-effects of systemic immune depression. Part III of this thesis describes several clinical trials testing anti-inflammatory strategies in patients with CVD. One of those studies tested the feasibility of using liposomal nanoparticles to deliver an anti-inflammatory agent to the atherosclerotic plaque. Given the global research efforts currently being made in this field, the challenge of developing anti-inflammatory treatment strategies for patients with cardiovascular disease will hopefully be fulfilled in the coming decades

Lipid measures and cardiovascular disease prediction

Traditional lipid measures are the cornerstone of risk assessment and treatment goals in cardiovascular prevention. Whereas the association between total, LDL-, HDL-cholesterol and cardiovascular disease risk has been generally acknowledged, the rather poor capacity to distinguish between patients who will and those who will not develop cardiovascular disease has prompted the search for further refinement of these traditional measures. A thorough understanding of lipid metabolism is mandatory to understand recent developments in this area. After a brief overview of lipid metabolism we will discuss the epidemiological data of total, LDL- and HDL-cholesterol and focus on recent advances in measurements of these lipoproteins. In addition we will discuss the role of triglycerides and the apolipoprotein B-A-I ratio on the incidence of cardiovascular diseas

INCREASING SPATIAL RESOLUTION ALTERS MEASUREMENT VARIABILITY OF CAROTID PLAQUES

Cardiovascular Aspects of Radiolog

Repeatability of in vivo quantification of atherosclerotic carotid artery plaque components by supervised multispectral classification

Cardiovascular Aspects of Radiolog

Ambulatory blood pressure monitoring is recommended in the clinical management of children with a solitary functioning kidney

Item does not contain fulltextBACKGROUND: Children with a solitary functioning kidney are at increased risk of developing chronic kidney disease. Hypertension may be an early indicator of renal dysfunction in these patients. We determined blood pressure (BP) profiles of children with a solitary functioning kidney by using ambulatory BP monitoring (ABPM). METHODS: To assess the occurrence with (pre)hypertension, we compared ABPM to office BP measurement in 47 children with a solitary functioning kidney. None of the subjects used antihypertensive agents or had been hypertensive during previous clinical visits. RESULTS: Mean age of study subjects was 12.7 (+/-3.3) years. Hypertension was identified in ten (21 %) subjects with ABPM, whereas only two (4 %) children were hypertensive during office BP measurement (p /=90th percentile versus six (13 %) subjects based on office BP measurement (p = 0.051). Although 24-h ABPM SD scores were higher in the congenital type than in the acquired type of solitary functioning kidney (p </= 0.01), the proportions of subjects with 24-h ABPM hypertension were similar between groups (congenital 25 % versus acquired 16 %; p = NS). CONCLUSIONS: Based on ABPM, one in five children with a solitary functioning kidney has hypertension. As the majority of these subjects were not hypertensive during office BP measurements, ABPM should be considered in the clinical management of solitary functioning kidney patients