Combined use of chemical and biological compounds to control hookworm.

The aim of this study was to evaluate the combined use of different chemical (albendazole, ivermectin, glycerine and Vaseline) and biological (Monacrosporium thaumasium) compounds in the control of Ancylostoma caninum. Infective larvae of A. caninum were obtained from coprocultures of positive faeces from naturally infected dogs. We used 1% ivermectin, 1% albendazole, 100% glycerine, 100% Vaseline and an isolate of the nematophagous fungus M. thaumasium (NF34), alone or in combinations. Next, an experimental test was set up with 16 groups in microtubes, with a 24-h interaction. The groups (G1 to G15) that contained any chemical or biological compound (NF34) and/or their combined use (chemical + biological) showed a difference in relation to the control group, except G5 - Vaseline 100% without combinations. It was concluded that, even on an experimental basis, the combined use of anthelmintic drugs with biological control was efficient; however, more studies must be carried out in order to elucidate the synergistic action between chemical and biological compounds to be used in the effective control of hookworms in the future.

Cardiometabolic disease in South Asians: A global health concern in an expanding population.

Cardiovascular disease (CVD) is one of the main causes of mortality and morbidity worldwide. As an emerging population, South Asians (SAs) bear a disproportionately high burden of CVD relative to underlying classical risk factors, partly attributable to a greater prevalence of insulin resistance and diabetes and distinct genetic and epigenetic influences. While the phenotypic distinctions between SAs and other ethnicities in CVD risk are becoming increasingly clear, the biology of these conditions remains an area of active investigation, with emerging studies involving metabolism, genetic variation and epigenetic modifiers (e.g., extracellular RNA). In this review, we describe the current literature on prevalence, prognosis and CVD risk in SAs, and provide a landscape of translational research in this field toward ameliorating CVD risk in SAs.

Abdominal fat radiodensity, quantity and cardiometabolic risk: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Fat radiodensity, as measured by fat attenuation on computed tomography (CT), has emerged as a potential biomarker of "fat quality." We sought to characterize the relationship between fat radiodensity and quantity in subcutaneous, visceral, and intermuscular fat depots, and its role in inflammation, insulin resistance, and metabolic syndrome (MetS). METHODS AND RESULTS: We studied 1511 individuals from the Multi-Ethnic Study of Atherosclerosis who underwent CT for measurement of regional fat distribution and radiodensity, along with biomarker assessments and adjudication of incident metabolic syndrome (MetS). Linear, logistic and Cox regression analyses were used to measure association between fat radiodensity and (1) fat quantity, (2) biomarkers of cardiometabolic dysfunction, and (3) both prevalent and incident MetS. In each fat depot, radiodensity was strongly and inversely associated with quantity (e.g., visceral fat radiodensity vs. quantity: ρ = -0.82, P < 0.01). After adjustment for age, sex and race, lower visceral fat radiodensity was associated with greater C-reactive protein, leptin and insulin, but lower adiponectin (P < 0.01 for all). After full adjustment for cardiovascular disease risk factors, visceral (but not subcutaneous or intermuscular) fat radiodensity was associated with prevalent MetS (OR = 0.96, 95% CI = 0.93-0.99, P = 0.01). Moreover, lower visceral fat radiodensity was associated with incident MetS after the same adjustment (HR = 0.95, 95% CI 0.93-0.98, P < 0.01). However, this association became non-significant after further adjustment for visceral fat quantity. CONCLUSION: Fat radiodensity is strongly correlated with fat quantity and relevant inflammatory biomarkers. Fat radiodensity (especially for visceral fat) may be a complementary, easily assessed marker of cardiometabolic risk.

Diet and adipose tissue distributions: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Dietary quality affects cardiometabolic risk, yet its pathways of influence on regional adipose tissue depots involved in metabolic and diabetes risk are not well established. We aimed to investigate the relationship between dietary quality and regional adiposity. METHODS AND RESULTS: We investigated 5079 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) who had food-frequency questionnaires and measurement of pericardial fat and hepatic attenuation at the baseline study visit in MESA, as well as a subgroup with imaging for visceral and subcutaneous fat (N = 1390). A dietary quality score (DietQuality) was constructed to include established food group constituents of a Mediterranean-type diet. Linear models estimated associations of dietary score as well as its constituents with regional adiposity. Baseline mean age was 61 (± 10) years, and approximately half of the participants (47%) were male. Those with a higher DietQuality score were generally older, female, with a lower body mass index, C-reactive protein, and markers of insulin resistance. After adjustment, a higher DietQuality score was associated with lower visceral fat (lowest vs. highest dietary score quartile: 523.6 vs. 460.5 cm(2)/m; P < 0.01 for trend), pericardial fat (47.5 vs. 41.3 cm(3)/m; P < 0.01 for trend), lesser hepatic steatosis (by hepatic attenuation; 58.6 vs. 60.7 Hounsfield units; P < 0.01 for trend), but not subcutaneous fat (P = 0.39). Greater fruits, vegetables, whole grains, seeds/nuts and yogurt intake were associated with decreased adiposity, while red/processed meats were associated with greater regional adiposity. CONCLUSION: A higher quality diet pattern is associated with less regional adiposity, suggesting a potential mechanism of beneficial dietary effects on diabetes, metabolic, and cardiovascular risk.

Visceral adiposity and left ventricular remodeling: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Visceral fat (VF) is a source of pro-inflammatory adipokines implicated in cardiac remodeling. We sought to determine the impact of visceral fat and subcutaneous fat (SQ) depots on left ventricular (LV) structure, function, and geometry in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS AND RESULTS: We performed a post-hoc analysis on 1151 participants from MESA with cardiac magnetic resonance quantification of LV mass and LV mass-to-volume ratio (LVMV, an index of concentricity) and computed tomographic-derived SQ and VF area. Multivariable regression models to estimate association between height-indexed SQ and VF area (per cm(2)/m) with height-indexed LV mass (per height(2.7)) and LVMV were constructed, adjusted for clinical, biochemical, and demographic covariates. We found that both VF and SQ area were associated with height-indexed LV mass (ρ = 0.36 and 0.12, P < 0.0001, respectively), while only VF area was associated with LVMV (ρ = 0.28, P < 0.0001). Individuals with above-median VF had lower LV ejection fraction, greater indexed LV volumes and mass, and higher LVMV (all P < 0.001). In multivariable models adjusted for weight, VF (but not SQ) area was associated with LV concentricity and LV mass index, across both sexes. CONCLUSION: Visceral adiposity is independently associated with LV concentricity, a precursor to heart failure. Further study into the role of VF in LV remodeling as a potential therapeutic target is warranted.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

Noninvasive assessment of coronary stenosis.

Invasive coronary angiography (ICA) has been the gold standard in the diagnosis of coronary artery disease (CAD) for a long time and angiographic procedures performed annually in the United States have steadily increased during the last 25 years. The unmatched temporal and spatial imaging resolution, the high level contrast between the coronary lumen and the adjacent structures, and the ability to concurrently perform percutaneous coronary interventions (PCI) are the technical advantages of coronary angiography. However, the isolated intraluminal imaging, the relatively high financial cost of the procedure, and the risks associated with catheterization may be limitations to its use. Moreover, a better selection of patients really in need of ICA and PCI is necessary since many patients referred for ICA are found not to have significant CAD. Therefore, a remarkable technical progress has been achieved by both cardiac magnetic resonance and cardiac computed tomography in this regard for the noninvasive detection of coronary stenoses.

Differentiation of myocardial scar from potential pitfalls and artefacts in delayed enhancement MRI.

Delayed enhancement cardiac magnetic resonance (DE-CMR) imaging is used increasingly to identify and quantify focal myocardial scar. Our objective is to describe factors used in the interpretation of DE-CMR images and to highlight potential pitfalls and artefacts that mimic myocardial scar. Inversion recovery gradient recalled echo sequence is commonly accepted as the standard of reference for DE-CMR. There are also alternative sequences that can be performed in a single breath-hold or with free breathing. Radiologists need to be aware of factors affecting image quality, and potential pitfalls and artefacts that may generate focal hyperintense areas that mimic myocardial scar.

Endothelial dysfunction is associated with left ventricular mass (assessed using MRI) in an adult population (MESA).

Brachial flow-mediated dilation (FMD) is a measure of endothelial nitric oxide bioavailability. Endothelial nitric oxide controls vascular tone and is likely to modify the ventricular muscle coupling mechanism. The association between left ventricular mass and FMD is not well understood. We assessed the association between left ventricular mass index (LVMI) and FMD in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a population-based study of 6814 adults free of clinical cardiovascular disease at baseline who were recruited from six US clinics. LVMI (left ventricular mass per body surface area) and FMD were measured in 2447 subjects. Linear regression analysis was used to evaluate the association. The subjects had a mean age of 61.2±9.9 years, 51.2% females with 34.3% Caucasians, 21.6% Chinese, 19.4% African Americans and 24.7% Hispanics. The mean body mass index (BMI) was 27.4±4.8 kg m⁻², 9.4% had diabetes, 11% were current smokers and 38% hypertensives. The mean±s.d. LVMI was 78.1±15.9 g m⁻² and mean±s.d. FMD was 4.4%±2.8%. In univariate analysis, LVMI was inversely correlated with FMD (r= -0.20, P<0.0001). In the multivariable analysis, LVMI was associated with FMD (ß coefficient (se) = -0.50 (0.11), P<0.001 (0.5 g m⁻² reduction in LVMI per 1% increase in FMD)) after adjusting for age, gender, race/ethnicity, systolic blood pressure, diabetes mellitus, smoking, weight, statin use, antihypertensive medication use, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol. The association between brachial flow mediated dilation and LVMI maybe independent of traditional CV risk factors in population based adults.

Quantification of lumen stenoses with known dimensions by conventional angiography and computed tomography: implications of using conventional angiography as gold standard.

BACKGROUND: Quantitative coronary angiography (QCA) has inherent limitations for displaying complex vascular anatomy, yet it remains the gold standard for stenosis quantification. OBJECTIVE: To investigate the accuracy of stenosis assessment by multi-detector computed tomography (MDCT) and QCA compared to known dimensions. METHODS: Nineteen acrylic coronary vessel phantoms with precisely drilled stenoses of mild (25%), moderate (50%) and severe (75%) grade were studied with 64-slice MDCT and digital flat panel angiography. Fifty-seven stenoses of circular and non-circular shape were imaged with simulated cardiac motion (60 bpm). Image acquisition was optimised for both imaging modalities, and stenoses were quantified by blinded expert readers using electronic callipers (for MDCT) or lumen contour detection software (for QCA). RESULTS: Average difference between true and measured per cent diameter stenosis for QCA was similar compared to MDCT: 7 (+/-6)% vs 7 (+/-5)% (p=0.78). While QCA performed better than MDCT in stenoses with circular lumen (mean error 4 (+/-3)% vs 7 (+/-6)%, p<0.01), MDCT was superior to QCA for evaluating stenoses with non-circular geometry (mean error 10 (+/-7)% vs 7 (+/-5)%, p<0.05). In such lesions, QCA underestimated the true diameter stenosis by >20% in 9 of 27 (33%) vs 1 of 29 (3%) in lumen with circular geometry. CONCLUSIONS: QCA often underestimates diameter stenoses in lumen with non-circular geometry. Compared to QCA, MDCT yields mildly greater measurement errors in perfectly circular lumen but performs better in non-circular lesions. These findings have implications for using QCA as the gold standard for stenosis quantification by MDCT.

Physical activity and physiological cardiac remodelling in a community setting: the Multi-Ethnic Study of Atherosclerosis (MESA).

OBJECTIVE: To evaluate the association of physical activity with left ventricular structure and function in the general population in a community setting. DESIGN: Cross-sectional study. SETTING: The Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical atherosclerosis. PARTICIPANTS: A multiethnic sample of 4992 participants (aged 45-84 years; 52% female) free of clinically apparent cardiovascular disease. INTERVENTIONS: Physical activity induces beneficial physiological cardiac remodelling in a cross-sectional study of non-athlete individuals. MAIN OUTCOME MEASURES: Left ventricular mass, volumes and function were assessed by cardiac magnetic resonance imaging. Physical activity, defined as intentional exercise and total moderate and vigorous physical activity, was assessed by a standard semiquantitative questionnaire. RESULTS: Left ventricular mass and end-diastolic volume were positively associated with physical activity (eg, 1.4 g/m(2) (women) and 3.1 g/m(2) (men) greater left ventricular mass in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p = 0.05 and p<0.001, respectively). Relationships were non-linear, with stronger positive associations at lower levels of physical activity (test for non-linearity; p = 0.02 and p = 0.03, respectively). Cardiac output and ejection fraction were unchanged with increased physical activity levels. Resting heart rate was lower in women and men with higher physical activity levels (eg, -2.6 beats/minute lower resting heart rate in the highest category of intentional exercise compared with individuals reporting no intentional exercise; p<0.001). CONCLUSIONS: In a community-based population free of clinically apparent cardiovascular disease, higher physical activity levels were associated with proportionally greater left ventricular mass and end-diastolic volume and lower resting heart rate.

Is magnetic resonance imaging the 'reference standard' for cardiac functional assessment? Factors influencing measurement of left ventricular mass and volumes.

PURPOSE: MRI is considered reference standard for the assessment of left ventricular (LV) volume and mass measurements. There are few accepted guidelines for uniform assessment of cardiac function with MRI. We sought to investigate different confounding factors influencing LV measurement results. MATERIAL AND METHODS: In 60 diabetic type-II patients (group A) we compared intra-/inter-reader variability of MRI for cardiac function measured twice at a 3 month interval by one MRI trained reader and one untrained. In 20 patients (group B) two different techniques were compared for determining the epicardial and endocardial LV-borders. RESULTS: Bland Altman analysis showed excellent intra-observer measurement agreement for the trained reader 1 for EDM (mean = -2.3 (-23.6-19)), EDV (2.9(-9.2-15.0)), ESV (3.3(-5.8-12.4)) and EF (1.2(-3.3-5.7)). Untrained reader 2 measurement agreement was considerably less appropriate for EDM (mean = -8.2 (-25.8-9.5)), EDV (7.8(-5.1-20.7)), ESV (5.3(-8.0-18.6)). Only for EF (0.8 (-6.5-8.1)) results were comparable to reader 1. Inter-observer measurement in the beginning was poor for EDM (-13.5(-55.6-28.6)) and EDV (7.3(-61.9-76.6)), whereas agreement for ESV (2.1(-29.9-34.2)) and EF (-0.9(-11.6-9.9)) was good. After 3 months, measurement agreement for EDM (-5.3 (-46.4-35.8)) was considerably improved, for EDV (0.4(-67.0-66.2)) was excellent, whereas agreement for ESV (3.1(-34.4-28.1)) and EF (-1.7(-13.0-9.6)) was similar. Using different techniques for determining the epicardial and endocardial borders, only end-diastolic volume was unchanged whereas all other parameters were significantly different using the two methods (p < or = 0.03). CONCLUSION: Intra- and inter-reader variability, analyst experience as well as different techniques for determining the boundaries of the left ventricle significantly affect MRI parameters for cardiac function. These results suggest a need for developing commonly accepted standards for cardiac MRI evaluation.

Left insular stroke is associated with adverse cardiac outcome.

BACKGROUND: After stroke, 10% of patients have adverse cardiac outcomes. Left insular damage may contribute to this by impairing sympathovagal balance (associated with cardiac structural damage and arrhythmias). METHODS: The authors conducted a prospective study of 32 patients with left insular stroke (Group 1) and 84 patients with non-insular stroke/TIA (Group 2). Adverse cardiac outcomes (cardiac death, myocardial infarction, angina, and heart failure) were assessed over 1 year. Myocardial wall motion was investigated with transesophageal echocardiography. RESULTS: Group 1's cardiac outcome relative risk (RR) compared with Group 2 was 1.75 (95% CI: 1.02, 3.00, p = 0.05). Left insular stroke remained an independent predictor of cardiac outcome in multivariate analyses. Sensitivity analysis excluding TIA and angina showed similar results. For Group 1 patients without symptomatic coronary artery disease (SCAD), cardiac outcome RR = 4.06 (95% CI: 1.83, 9.01, p = 0.002). For Group 1 with SCAD, RR = 0.36 (95% CI: 0.06, 2.13, p = 0.14). Cardiac wall motion impairment was also associated with left insular stroke independent of CAD or nonischemic heart disease. Right insular stroke was not associated with adverse cardiac outcomes or cardiac wall motion impairment. CONCLUSIONS: Left insular stroke is associated with an increased risk of adverse cardiac outcome and decreased cardiac wall motion compared to stroke in other locations and TIA. This was particularly marked in patients without symptomatic coronary artery disease (SCAD). In patients with SCAD, the cardioprotective effect of medications, especially beta-blockers alone or combined with ischemic preconditioning, may explain the lack of association in this subgroup.

Non-invasive half millimetre 32 detector row computed tomography angiography accurately excludes significant stenoses in patients with advanced coronary artery disease and high calcium scores.

OBJECTIVE: To show an overall diagnostic accuracy > or = 90% for detection of > or = 50% stenoses by coronary half millimetre 32 detector row computed tomography angiography (32 x 0.5-MDCTA) in patients with advanced coronary artery disease (CAD) and a high likelihood of raised calcium scores. METHODS: ECG gated 32 x 0.5-MDCTA (32 x 0.5 mm cross sections, 0.35 x 0.35 x 0.35 mm3 isotropic voxels, 400 ms rotation) was performed after injection of iodixanol (120 ml, 320 mg/ml) in 30 consecutive patients (25 men, mean (SD) age 59 (13) years, body mass index 26.2 (4.9) kg/m2). Native arteries, including > or = 1.5 mm branches, and bypass grafts were screened for > or = 50% stenoses. Stents were excluded. Conventional coronary angiography (performed 18 (12) days before 32 x 0.5-MDCTA) was analysed by quantitative coronary angiography. RESULTS: Median Agatston calcium score was 510 (range 3-5066). Sensitivity, specificity, and positive and negative predictive values for detection of > or = 50% stenoses in native arteries were 76% (29 of 38), 94% (190 of 202), 71% (29 of 41), and 96% (190 of 199), respectively. Overall diagnostic accuracy was 91% (219 of 240). Due to the following artefacts 20% (69 of 352) of the vessels were excluded: motion, noise, and low contrast enhancement isolated or in combination (45 of 69 (65%)); image distortion by implantable cardioverter-defibrillator or pacemaker leads (18 of 69 (26%)); and blooming secondary to severe calcification (6 of 69 (9%)). CONCLUSIONS: Coronary 32 x 0.5-MDCTA accurately excludes > or = 50% stenoses in patients with advanced CAD and high calcium scores with an overall diagnostic accuracy of 91%.