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1.  Minor Isolated Q Waves and Cardiovascular Events in the MESA Study 
The American journal of medicine  2013;126(5):450.e9-450.e16.
The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown.
To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA).
This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events.
During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P = .030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity.
The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.
PMCID: PMC3741651  PMID: 23582938
Electrocardiography; MESA; Minor isolated Q waves; Race/ethnicity
2.  Relations of the Mediterranean dietary pattern with insulin resistance and diabetes incidence in the Multi-Ethnic Study of Atherosclerosis (MESA) 
The British journal of nutrition  2012;109(8):1490-1497.
Type 2 diabetes is a highly prevalent but preventable disorder. We assessed the association between an a priori Mediterranean diet score (MeDiet) and fasting glucose and insulin at baseline and incident type 2 diabetes after 6-year follow-up in MESA. Dietary intake was measured at baseline by a 127-item food frequency questionnaire in 5,390 men and women aged 45-84 years free of prevalent diabetes and clinical CVD. A MeDiet score was created based on intake of 10 food components: vegetables, whole grains, nuts, legumes, fruits, ratio of monounsaturated to saturated fat, red and processed meat, dairy, fish and alcohol. Multivariable linear and proportional hazard models were used to estimate the association of MeDiet, categorized in quintiles, with baseline insulin and glucose, and incident diabetes, respectively. Models adjusted for demographic, physiologic and behavioral characteristics. After multivariable adjustment, individuals with a higher MeDiet score had lower baseline mean (95% CI) insulin levels [mean Q1: = 5.8 (5.6-6.0) umol/l; mean Q5: = 4.8 (4.6-5.0) umol/l; p-trend= <0.0001]. A higher MeDiet score was also associated with significantly lower glucose levels after basic adjustment, but was attenuated after adjustment for waist circumference. During follow-up, 412 incident diabetes events accrued. MeDiet was not significantly related to risk of incident diabetes (p-trend=0.64). In summary, greater consistency with a Mediterranean-style diet, reflected by a higher a priori Mediterranean diet score, was cross-sectionally associated with lower insulin levels among non-diabetics, and lower blood glucose prior to adjustment for obesity, but not with lower incidence of diabetes.
PMCID: PMC4002212  PMID: 22932232
3.  Psychosocial Risks: Is Risk Management Strategic Enough in Business and Policy Making? 
Safety and Health at Work  2013;4(2):87-94.
In times of continuous change and volatile markets, organizations are increasingly characterized by downsizing, work intensification, and resource rationalization. This has resulted in diversification, and the emergence of new risks within the field of occupational health and safety, with an important impact. This paper focuses on one such type of risk in the modern workplace—psychosocial risks. The current study aimed to explore stakeholder perspectives, regarding the extent to which psychosocial risks are incorporated into strategic risk management practices, at both the business and policy level.
Semi-structured interviews were conducted with 14 professionals, representing employer, expert, policy maker, and trade union stakeholder perspectives.
It was found that the majority of organizations do not sufficiently, if at all, understand and incorporate psychosocial risks into strategic decision making, whereby the key barrier related to practical difficulties of not knowing how to manage psychosocial risks adequately.
The study found that there is a need to close the gap between policy and practice on a number of levels. Future recommendations comprise a policy framework and infrastructure underpinned by educational initiatives, partnerships, and networks to drive a shift in attitudes toward recognizing the duality of the concept of risk (including both potential negative and positive outcomes) and moving beyond simple regulatory compliance.
PMCID: PMC3732138  PMID: 23961331
organizations; policy making; psychosocial risk; strategy
4.  Right Ventricular Morphology and the Onset of Dyspnea: The MESA-Right Ventricle Study 
PLoS ONE  2013;8(2):e56826.
The association of right ventricular (RV) structure and function with symptoms in individuals without cardiopulmonary disease is unknown. We hypothesized that greater RV mass and RV end-diastolic volume (RVEDV), smaller RV stroke volume (RVSV), and lower RV ejection fraction (RVEF) measured by cardiac magnetic resonance imaging (MRI) in participants free of clinical cardiovascular disease at baseline would be associated with a greater risk of self-reported dyspnea.
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRIs on participants without clinical cardiovascular disease between 2000 and 2002. We excluded subjects who reported “prevalent” dyspnea at the first assessment (24 months). The presence of dyspnea was assessed at 24 months, 42 months, and 60 months from baseline. Cox proportional hazards models were used to examine the relationship between RV measures and incident dyspnea.
In the final study sample (N = 2763), there were significant interactions between RV measures and sex in terms of the risk of dyspnea (p<0.05). Among men (N = 1453), lower RV mass (p = 0.003), smaller RVEDV (p<0.001), smaller RV end-systolic volume (RVESV) (p = 0.03) and decreased RVSV (p<0.001) were associated with an increased risk of developing dyspnea after adjusting for covariates. Associations remained after adjusting for left ventricular function and lung function. However, there were no significant associations between RV measures and the risk of dyspnea in women.
Lower RV mass and smaller RV volumes were associated with an increased risk of dyspnea in men, but not in women.
PMCID: PMC3574101  PMID: 23457622
5.  Myocardial Structure, Function and Scar in Patients with Type 1 Diabetes 
Circulation  2011;124(16):1737-1746.
We report relationships of cardiovascular disease (CVD) risk factors with myocardial structure, function and scar in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.
Cardiac magnetic resonance (CMR) was obtained in 1017 patients with type 1 diabetes. Gadolinium CMR was also obtained in 741 patients. The mean age was 49 ± 7 years, 52% were men, and mean diabetes duration was 28± 5 years. Associations of CVD risk factors with CMR parameters were examined using linear and logistic regression models. History of macroalbuminuria was positively associated with LV mass (by +14.8 g) leading to a significantly higher LV mass/EDV ratio (by 8%). Mean hemoglobin A1c (HbA1c) levels over the preceding 22 years were inversely associated with end-diastolic volume (−3.0 ml per unit mean HbA1c %) and stroke volume (−2.3 ml per unit mean HbA1c %) and positively related to elevated LV mass/EDV ratio (0.02 g/ml per unit). The overall prevalence of myocardial scar was 4.3% by CMR and 1.4% by clinical adjudication of myocardial infarction. Both mean HbA1c (Odds ratio (O.R.) 1.5 [1.0–2.2] per unit) and macroalbuminuria (OR 3.5 [1.2–9.9]) were significantly associated with myocardial scar as well as traditional CVD risk factors.
In addition to traditional CVD risk factors, elevated mean HbA1c and macroalbuminuria were significantly associated with alterations in LV structure and function. The prevalence of myocardial scar was 4.3% in this subcohort of DCCT/EDIC participants with relatively preserved renal function.
PMCID: PMC3215589  PMID: 21947298
Myocardial function; myocardial scar; type 1 diabetes; delayed enhancement; CMR
6.  Sex and Race Differences in Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
Circulation  2011;123(22):2542-2551.
Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease, however determinants of RV anatomy have not been well-studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease.
Methods and Results
The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging (MRI) on 5098 participants. RV volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived using an allometric approach. The study sample (N = 4123) was 61.5 ± 10.1 years old and 47.5% male. Older age was associated with lower RV mass (~5% lower mass per decade) with larger age-related decrements in men than in women (p for interaction < 0.05). Older age was also associated with higher RV ejection fraction (RVEF), an association which differed between races/ethnicities (p for interaction ≤ 0.01). Overall, men had greater RV mass (~8%) and larger RV volumes than women, but had lower RVEF (4% in absolute terms) (p < 0.001). African Americans had lower RV mass than Caucasians (p ≤ 0.002), whereas Hispanics had higher RV mass (p ≤ 0.02). Using the derived normative equations, 7.3% (95%CI, 6.5–8.1%) met criteria for RV hypertrophy and 5.9% (95%CI, 5.2–6.6%) had RV dysfunction.
In conclusion, age, sex, and race are associated with significant differences in RV mass, RV volumes and RVEF, potentially explaining distinct responses of the RV to cardiopulmonary disease.
PMCID: PMC3111939  PMID: 21646505
right ventricle; pulmonary heart disease; magnetic resonance imaging; pulmonary hypertension
7.  Selective Serotonin Reuptake Inhibitor Use Is Associated with Right Ventricular Structure and Function: The MESA-Right Ventricle Study 
PLoS ONE  2012;7(2):e30480.
Serotonin and the serotonin transporter have been implicated in the development of pulmonary hypertension (PH). Selective serotonin reuptake inhibitors (SSRIs) may have a role in PH treatment, but the effects of SSRI use on right ventricular (RV) structure and function are unknown. We hypothesized that SSRI use would be associated with RV morphology in a large cohort without cardiovascular disease (N = 4114).
SSRI use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were assessed via cardiac magnetic resonance imaging. The cross-sectional relationship between SSRI use and each RV measure was assessed using multivariable linear regression; analyses for RV mass and end-diastolic volume (RVEDV) were stratified by sex.
After adjustment for multiple covariates including depression and left ventricular measures, SSRI use was associated with larger RV stroke volume (RVSV) (2.75 mL, 95% confidence interval [CI] 0.48–5.02 mL, p = 0.02). Among men only, SSRI use was associated with greater RV mass (1.08 g, 95% CI 0.19–1.97 g, p = 0.02) and larger RVEDV (7.71 mL, 95% 3.02–12.40 mL, p = 0.001). SSRI use may have been associated with larger RVEDV among women and larger RV end-systolic volume in both sexes.
SSRI use was associated with higher RVSV in cardiovascular disease-free individuals and, among men, greater RV mass and larger RVEDV. The effects of SSRI use in patients with (or at risk for) RV dysfunction and the role of sex in modifying this relationship warrant further study.
PMCID: PMC3281845  PMID: 22363441
8.  Physical Activity and Right Ventricular Structure and Function 
Rationale: Intense exercise in elite athletes is associated with increased left ventricular (LV) and right ventricular (RV) mass and volumes. However, the effect of physical activity on the RV in an older community-based population is unknown.
Objectives: We studied the association between levels of physical activity in adults and RV mass and volumes.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on community-based participants without clinical cardiovascular disease. RV volumes were determined from manually contoured endocardial margins. RV mass was determined from the difference between epicardial and endocardial volumes multiplied by the specific gravity of myocardium. Metabolic equivalent–minutes/day were calculated from the self-reported frequency, duration, and intensity of physical activity.
Measurements and Main Results: The study sample (n = 1,867) was aged 61.8 ± 10 years, 48% male, 44% white, 27% African American, 20% Hispanic, and 9% Chinese. Higher levels of moderate and vigorous physical activity were linearly associated with higher RV mass (P = 0.02) after adjusting for demographics, anthropometrics, smoking, cholesterol, diabetes mellitus, hypertension, and LV mass. Higher levels of intentional exercise (physical activity done for the sole purpose of conditioning or fitness) were nonlinearly associated with RV mass independent of LV mass (P = 0.03). There were similar associations between higher levels of physical activity and larger RV volumes.
Conclusions: Higher levels of physical activity in adults were associated with greater RV mass independent of the associations with LV mass; similar results were found for RV volumes. Exercise-associated RV remodeling may have important clinical implications.
PMCID: PMC3056232  PMID: 20813888
exercise; pulmonary heart disease; pulmonary hypertension; magnetic resonance imaging
9.  Cardiovascular Imaging for Assessing Cardiovascular Risk in Asymptomatic Men Versus Women 
Coronary artery calcium (CAC), carotid intima-media thickness, and left ventricular (LV) mass and geometry offer the potential to characterize incident cardiovascular disease (CVD) risk in clinically asymptomatic individuals. The objective of the study was to compare these cardiovascular imaging measures for their overall and sex-specific ability to predict CVD.
Methods and Results
The study sample consisted of 4965 Multi-Ethnic Study of Atherosclerosis participants (48% men; mean age, 62±10 years). They were free of CVD at baseline and were followed for a median of 5.8 years. There were 297 CVD events, including 187 coronary heart disease (CHD) events, 65 strokes, and 91 heart failure (HF) events. CAC was most strongly associated with CHD (hazard ratio [HR], 2.3 per 1 SD; 95% CI, 1.9 to 2.8) and all CVD events (HR, 1.7; 95% CI, 1.5 to 1.9). Most strongly associated with stroke were LV mass (HR, 1.3; 95% CI, 1.1 to 1.7) and LV mass/volume ratio (HR, 1.3; 95% CI, 1.1 to 1.6). LV mass showed the strongest association with HF (HR, 1.8; 95% CI, 1.6 to 2.1). There were no significant interactions for imaging measures with sex and ethnicity for any CVD outcome. Compared with traditional risk factors alone, overall risk prediction (C statistic) for future CHD, HF, and all CVD was significantly improved by adding CAC, LV mass, and CAC, respectively (all P<0.05).
There was no evidence that imaging measures differed in association with incident CVD by sex. CAC was most strongly associated with CHD and CVD; LV mass and LV concentric remodeling best predicted stroke; and LV mass best predicted HF.
PMCID: PMC3037859  PMID: 21068189
imaging; cardiovascular diseases; sex
10.  Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: The MESA-RV Study 
Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45–84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p = 0.008 and p = 0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p = 0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.
PMCID: PMC3045574  PMID: 20923324
Inflammation; thrombosis; hypertension; pulmonary
11.  The Association of Chronic Kidney Disease and Metabolic Syndrome with Incident Cardiovascular Events: Multiethnic Study of Atherosclerosis 
Background. There is an association between chronic kidney disease (CKD) and metabolic syndrome (MetS). We examined the joint association of CKD and MetS with incident cardiovascular (CVD) events in the Multiethnic Study of Atherosclerosis (MESA) cohort. Methods. We analyzed 2,283 Caucasians, 363 Chinese, 1,449 African-Americans, and 1,068 Hispanics in the MESA cohort. CKD was defined by cystatin C estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2 and MetS was defined by NCEP criteria. Cox proportional regression adjusting for age, ethnicity, gender, study site, education, income, smoking, alcohol use, physical activity, and total and LDL cholesterol was performed to assess the joint association of CKD and MetS with incident CVD events. Participants were divided into four groups by presence of CKD and/or MetS and compared to the group without CKD and MetS (CKD−/MetS−). Tests for additive and multiplicative interactions between CKD and MetS and prediction of incident CVD were performed. Results. During follow-up period of 5.5 years, 283 participants developed CVD. Multivariate Cox regression analysis demonstrated that CKD and MetS were independent predictors of CVD (hazard ratio, 2.02 for CKD, and 2.55 for MetS). When participants were compared to the CKD−/MetS− group, adjusted HR for the CKD+/MetS+ group was 5.56 (95% CI 3.72–8.12). There was no multiplicative interaction between CKD and MetS (P = 0.2); however, there was presence of additive interaction. The relative excess risk for additive interaction (RERI) was 2.73, P = 0.2, and the attributable portion (AP) was 0.49 (0.24–0.74). Conclusion. Our findings illustrate that the combination of CKD and MetS is a strong predictor of incident clinical cardiovascular events due to presence of additive interaction between CKD and MetS.
PMCID: PMC3154776  PMID: 21860804
12.  Relation of Cardiovascular Risk Factors to Right Ventricular Structure and Function as Determined by Magnetic Resonance Imaging (Results from the Multi-Ethnic Study of Atherosclerosis) 
The American journal of cardiology  2010;106(1):110-116.
The impact of cardiovascular risk factors on the left ventricle is well known but their impact on right ventricle has not been studied using advanced imaging techniques. The purpose of this study was to determine the relation between cardiovascular risk factors and right ventricular (RV) structure and function and its interaction with the left ventricle. Cardiac magnetic resonance images were analyzed in 4204 participants free of clinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression models were used to study the cross sectional association between individual RV parameters and risk factors. All RV parameters except ejection fraction decreased with age (p<0.0001). RV mass was positively associated with systolic blood pressure (+0.4g, p<0.0001) and high density lipoprotein (HDL) cholesterol (+0.2g, p<0.0001); inversely with diastolic blood pressure (−0.3g, p<0.0001) and total cholesterol (−0.2g, p<0.01). RV end diastolic volume was positively associated with systolic blood pressure (+1.6ml, p<0.01) and HDL cholesterol (+1.8ml, p<0.0001); and inversely with diastolic blood pressure (−2.2 ml, p<0.0001), total cholesterol (−1.4ml, p<0.0001), current smoking (−2.7ml, p<0.05) and diabetes mellitus (−3.1ml, p<0.01). RV ejection fraction was positively related with systolic blood pressure (+1.0%, p<0.0001), HDL cholesterol (+0.4%, p<0.0001) and inversely with diastolic blood pressure (−0.7%, p<0.0001). In conclusion, the mass and volumes of the right ventricle decrease with age. Cardiovascular risk factors, especially blood pressure and HDL cholesterol are associated with subclinical changes in RV mass and volumes.
PMCID: PMC2901248  PMID: 20609657
13.  High prevalence of Left Ventricular Regional Dysfunction in Arrhythmogenic Right Ventricular Dysplasia: a tagged MRI study 
Although arrhythmogenic right ventricular dysplasia (ARVD) is characterized by predominantly right sided morphologic changes, genetic/histological and molecular changes are biventricular. Alterations in regional left ventricular (LV) strain in patients referred for suspicion of ARVD have not previously been determined.
Methods and Results
The study population included 21 patients with suspected ARVD who underwent evaluation with MRI including tagging. Eleven healthy volunteers served as controls. Global RV and LV function were studied by MRI and peak regional systolic circumferential strain (Ecc, %) was calculated by harmonic phase from tagged MRI based on a 16-segment model. Patients who met ARVD Task Force criteria were classified as definite ARVD, whereas patients with a positive family history who had one additional minor criterion and patients without a family history with at least 1 major or 2 minor criteria were classified as probable ARVD.
Of the 21 ARVD subjects, 11 had definite ARVD (63.6% males, mean age 41.2 ± 14.2 years) and, 10 had probable ARVD (30% males, 34.9 ± 12.1 years). Compared with controls (58.9 ± 6.2%), probable ARVD patients (53.6 ± 7.6%) had similar global RV ejection fraction (RVEF) (p> 0.05), but definite ARVD patients (45.2 ± 6.0%) had significantly reduced RVEF (p< 0.0001). Global LVEF was normal in all three groups (p>0.05). Compared to controls, mean LV circumferential strain (Ecc) was significantly reduced in 7/16 (44%) segments in definite ARVD, and 3/16 segments (19%) in probable ARVD (p< 0.05 for all).
There was a high prevalence of regional LV dysfunction in patients with definite ARVD, with less dysfunction in those with probable ARVD. Further, the extent of regional LV dysfunction appeared to parallel RV dysfunction, whereas global LV function was normal. Similar to the RV abnormalities, our findings suggest ARVD results in regional alterations of LV dysfunction prior to global abnormalities.
PMCID: PMC3036009  PMID: 20197508
ARVD; LV involvement; tagging; regional strain
14.  Diagnostic and Prognostic Utility of ECG for Left Ventricular Hypertrophy Defined by MRI in Relationship to Ethnicity: The Multi-Ethnic Study of Atherosclerosis (MESA) 
American heart journal  2010;159(4):652-658.
Left ventricular (LV) mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for LV mass measurement. Ethnicity is believed to affect ECG performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity.
Methods and Results
Data were analyzed from 4967 participants (48% males, mean age 62 ± 10 years; 39% Caucasian, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 yearsfor incident CVD. Thirteen traditional ECG-LVH criteria were assessed and showed overall and ethnicity-specific low sensitivity (10–26%) and high specificity (88–99%) in diagnosing MRI-defined LVH. 10 out of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared to Caucasians (p=0.02–0.001). The sum of amplitudes of S wave in V1, S wave in V2 and R wave in V5 (a MESA specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared to prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (ROC area=0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product and Framingham-adjusted Cornell voltage predicted increased CVD risk (p<0.05).
ECG has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared to other ethnic groups.
PMCID: PMC2856691  PMID: 20362725
16.  Th2 but Not Th1 Immune Bias Results in Altered Lung Functions in a Murine Model of Pulmonary Cryptococcus neoformans Infection▿  
Infection and Immunity  2009;77(12):5389-5399.
Changes in airway dynamics have been reported in the rat model of pulmonary cryptococcosis. However, it is not known if Cryptococcus neoformans-induced changes in lung functions are related to the immunophenotype that develops in response to cryptococcal infection in the lungs. In this study we performed a parallel analysis of the immunophenotype and airway resistance (standard resistance of the airways [SRAW]) in BALB/c mice infected with highly virulent C. neoformans strain H99 and moderately virulent strain 52D. H99 infection evoked a Th2 response and was associated with increased SRAW, while the SRAW for 52D infection, which resulted in a predominantly Th1-skewed response, did not differ from the SRAW for uninfected mice. We found that an altered SRAW in mice did not positively or negatively correlate with the pulmonary fungal burden, the magnitude of inflammatory response, the numbers of T cells, eosinophils or eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by lung leukocytes. However, the level of a systemic Th2 marker, serum immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the changes in lung functions were proportional to the level of Th2 skewing in this model. These data also imply that IgE may contribute to the altered SRAW observed in H99-infected mice. Lung histological analysis revealed severe allergic bronchopulmonary mycosis pathology in H99-infected mice and evidence of protective responses in 52D-infected mice with well-marginalized lesions. Taken together, the data show that C. neoformans can significantly affect airflow physiology, particularly in the context of a Th2 immune response with possible involvement of IgE as an important factor.
PMCID: PMC2786439  PMID: 19752036
17.  Role of cardiovascular magnetic resonance imaging in arrhythmogenic right ventricular dysplasia 
Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic cardiomyopathy characterized clinically by ventricular arrhythmias and progressive right ventricular (RV) dysfunction. The histopathologic hallmark is fibro-fatty replacement of RV myocardium. It is inherited in an autosomal pattern with variable penetrance. ARVD is unique in that it most commonly presents in young, otherwise healthy and highly athletic individuals. The cause of ARVD is not well-known but recent evidence suggests strongly that it is a disease of desmosomal dysfunction. The disease involvement is not limited only to the RV as left ventricle (LV) has also been reportedly affected. Diagnosis of ARVD is challenging and is currently based upon a multi-disciplinary work-up of the patient as defined by the Task Force. Currently, implanted cardioverter defibrillators (ICD) are routinely used to prevent sudden death in patients with ARVD. Cardiovascular MR is an important non-invasive diagnostic modality that allows both qualitative and quantitative evaluation of RV. This article reviews the genetics of ARVD, current status and role of CMR in the diagnosis of ARVD and LV involvement in ARVD.
PMCID: PMC2483704  PMID: 18570661

Results 1-17 (17)