Nagesh Ragavendra

Dysfunctional Proinflammatory High-Density Lipoproteins Confer Increased Risk of Atherosclerosis in Women With Systemic Lupus Erythematosus

OBJECTIVE Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at-risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high-density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE. METHODS Carotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima-media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low-density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A-I, were also measured. RESULTS Among the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P<0.001). Patients with piHDL also had a higher IMT (P<0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P<0.001), older age (OR 1.2, P<0.001), hypertension (OR 3.0, P=0.04), dyslipidemia (OR 3.4, P=0.04), and mixed racial background (OR 8.3, P=0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P=0.02), older age (OR 1.1, P<0.001), a higher body mass index (OR 1.07, P=0.04), a cumulative lifetime prednisone dose>or=20 gm (OR 2.9, P=0.04), and African American race (OR 8.3, P=0.001). CONCLUSION Dysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis.

High plasma leptin levels confer increased risk of atherosclerosis in women with systemic lupus erythematosus, and are associated with inflammatory oxidised lipids

Background Patients with systemic lupus erythematosus (SLE) are at increased risk of atherosclerosis, even after accounting for traditional risk factors. High levels of leptin and low levels of adiponectin are associated with both atherosclerosis and immunomodulatory functions in the general population. Objective To examine the association between these adipokines and subclinical atherosclerosis in SLE, and also with other known inflammatory biomarkers of atherosclerosis. Methods Carotid ultrasonography was performed in 250 women with SLE and 122 controls. Plasma leptin and adiponectin levels were measured. Lipoprotein a (Lp(a)), oxidised phospholipids on apoB100 (OxPL/apoB100), paraoxonase, apoA-1 and inflammatory high-density lipoprotein (HDL) function were also assessed. Results Leptin levels were significantly higher in patients with SLE than in controls (23.7±28.0 vs 13.3±12.9 ng/ml, p<0.001). Leptin was also higher in the 43 patients with SLE with plaque than without plaque (36.4±32.3 vs 20.9±26.4 ng/ml, p=0.002). After multivariate analysis, the only significant factors associated with plaque in SLE were leptin levels in the highest quartile (≥29.5 ng/ml) (OR=2.8, p=0.03), proinflammatory HDL (piHDL) (OR=12.8, p<0.001), age (OR=1.1, p<0.001), tobacco use (OR=7.7, p=0.03) and hypertension (OR=3.0, p=0.01). Adiponectin levels were not significantly associated with plaque in our cohort. A significant correlation between leptin and piHDL function (p<0.001), Lp(a) (p=0.01) and OxPL/apoB100 (p=0.02) was also present. Conclusions High leptin levels greatly increase the risk of subclinical atherosclerosis in SLE, and are also associated with an increase in inflammatory biomarkers of atherosclerosis such as piHDL, Lp(a) and OxPL/apoB100. High leptin levels may help to identify patients with SLE at risk of atherosclerosis.

Low Physical Activity is Associated with Proinflammatory High Density Lipoprotein and Increased Subclinical Atherosclerosis in Women with Systemic Lupus Erythematosus

To investigate the association between physical activity, functional activity of high‐density lipoprotein (HDL), and subclinical cardiovascular disease in patients with systemic lupus erythematosus (SLE).

A Panel of Biomarkers Is Associated With Increased Risk of the Presence and Progression of Atherosclerosis in Women With Systemic Lupus Erythematosus

An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well‐documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high‐density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH.

Evidence-Based Assessment of the Role of Ultrasonography in the Management of Benign Thyroid Nodules

BackgroundAlthough ultrasonographic (US) evaluation is currently recommended for the workup of all palpable thyroid nodules, little guidance exists regarding the manner in which US data are to be used. Herein, we examine the available evidence and recommend how US can be used most effectively to predict malignancy. We discuss the role of US-guided fine needle aspiration (FNA) and other special topics regarding US evaluation and management of benign nodules.MethodsWe also present a systematic review of the literature using evidence-based criteria.ResultsUS features alone cannot predict malignancy or benignity, but techniques that combine US features and FNA cytology are most effective and most accurate for predicting malignancy (Level III and IV evidence). US features suggesting malignancy include a blurred or ill-defined margin, irregular shape, solid echo structure, hypoechogenicity, absent halo, fine calcifications, and intranodular vascular pattern. Most patients with malignancies have more than two US features characteristic of malignancy. US-guided FNA has nonsignificantly higher sensitivity, specificity, and accuracy than the palpation-guided technique (Level III and IV evidence). US guidance is particularly beneficial in patients with nonpalpable, multiple, or heterogeneous nodules for preferentially aspirating a specific segment of the nodule (large or partially cystic nodule) or when nodule palpation is difficult (patients with diffuse glandular disease or obesity).ConclusionsUS is an essential component of thyroid nodule evaluation and management. Techniques that combine US features and FNA cytology for thyroid nodule workup are more accurate than either technique alone. US-guided FNA can decrease the rate of nondiagnostic aspirates.

Association of paraoxonase 1 gene polymorphism and enzyme activity with carotid plaque in rheumatoid arthritis.

OBJECTIVE To investigate the relationship of genetic and biochemical determinants of paraoxonase 1 activity to carotid plaque as a surrogate marker of cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). METHODS The relationships between paraoxonase 1 activity, PON1 genotype (for the functional polymorphism at position 192), and carotid plaque presence were determined in 168 RA patients. After an overnight fast, blood was collected for lipoprotein analysis, and paraoxonase 1 activity was measured using paraoxon as the substrate. The PON1 Q192R genotype was determined for all patients. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease characteristics were assessed for all patients. RESULTS Paraoxonase 1 activity values in the RA patients were highest for the RR genotype, intermediate for the QR genotype, and lowest for the QQ genotype (P < 0.0001). Compared to patients with either the QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased risk of carotid plaque on multivariate analysis, controlling for traditional CV risk factors, high-sensitivity C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (P < 0.05). Additional multivariate logistic regression analysis controlling for the above factors also revealed a significant association of plasma paraoxonase 1 activity with carotid plaque in RA patients. Lower plasma paraoxonase 1 activity was associated with increased risk of carotid plaque (P < 0.05). CONCLUSION The current findings suggest a relationship of the genetic determinants and activity of paraoxonase 1 to CV risk in RA patients, as assessed by the presence or absence of carotid plaque. Further CV outcome studies are warranted to validate the utility of paraoxonase 1 as a biomarker of CV risk in patients with RA.

Fine Needle Elastography (FNE) device for biomechanically determining local variations of tissue mechanical properties.

Diseased tissues exhibit changes in mechanical properties and thus possess clinical diagnostic significance. We report the design and development of a Fine Needle Elastography (FNE) prototype device integrated with Fine Needle Aspiration Cytology (FNAC) needle that allows for quantitative and sensitive assessment of tissues and materials based on local variations in elastic, friction, and cutting forces on needle insertion. A piezoelectric force-sensor at the base of FNA needle measures the forces opposing needle penetration with micrometer scale resolution. Measurement precision (±5 μm) and axial resolution (~20 μm) of FNE device was tested using control mm size gelatin matrices and unripe pear in assessing needle penetration resistance, force heterogeneity and optimization of needle penetration velocity. Further, we demonstrated the usefulness of FNE in quantitative, biomechanical differentiation of simulated thyroid tumor nodules in an ultrasound neck phantom. Fluid or solid nodules were probed in the phantom study coupled with ultrasound guidance. Our data shows significantly higher force variations (1-D force heterogeneity; HF,a=6.5 mN, HF,q=8.25 mN and stiffness heterogeneity; HS,a=0.0274 kN/m, HS,q=0.0395 kN/m) in solid nodules compared either to fluid nodules or to regions corresponding to healthy thyroid tissue within the ultrasound phantom. The results suggest future applications of in vivo FNE biopsies based on force heterogeneity to diagnose thyroid tumors in areas where ultrasound instrumentation or access to a qualified pathologist for FNAC are unavailable, as well as an ancillary diagnostic tool in thyroid cancer management.

Assessment of asynchronous transfer mode (ATM) networks for regional teleradiology

The purpose of this study was to assess the effect of ATM network capabilities on the clinical practice of regional teleradiology, by providing immediate interactive radiology consultations between subspecialists and general radiologists at affiliated academic institutions. PACS installed at three affiliated hospitals (UCLA Medical Center, West LA VAMC and UCLA Olive-View Medical Centers) were connected via an ATM network. Two commercial PACS (Agfa) systems, one at the VAMC and one in an ultrasound outpatient clinic at UCLA were connected via ATM switches (Newbridge, Inc.) and a Santa Monica GTE central office switch. We evaluated this initial system configuration and measured image transfer performance, including memory-to-memory, disk-to-disk, disk-to-archive with and without DICOM protocols. Although the memory-to-memory data rate was 25 Mbps, the average remote disk-to-disk image transfer performance, using DICOM 3.0 communications protocols on SUN SPARCstation 10 servers, was 3 to 5 Mbps. Using these capabilities, timely interactive subspecialty consultations between radiologists was successfully performed while both were at different physical locations. We present the use of ATM technology in a realistic clinical environment and evaluate its impact on patient care and clinical teaching within the radiology departments of 2 institutions. Image communications over a regional PACS using an ATM network can allow interactive consultations between different subspecialist and general radiologists or other specialized radiologist spread over three different medical centers.

A Primer on Imaging Anatomy and Physiology

An understanding of medical imaging informatics begins with knowledge of medical imaging and its application toward diagnostic and therapeutic clinical assessment. This chapter is divided into two sections: a review of current imaging modalities; and a primer on imaging anatomy and physiology. In the first half, we introduce the major imaging modalities that are in use today: projectional imaging, computed tomography, magnetic resonance, and ultrasound. The core physics concepts behind each modality; the parameters and algorithms driving image formation; and variants and newer advances in each of these areas are briefly covered to familiarize the reader with the capabilities of each technique. From this foundation, in the second half of the chapter we describe several anatomical and physiologic systems from the perspective of imaging. Three areas are covered in detail: 1) the respiratory system; 2) the brain; and 3) breast imaging. Additional coverage of musculoskeletal, cardiac, urinary, and upper gastrointestinal systems is included. Each anatomical section begins with a general description of the anatomy and physiology, discusses the use of different imaging modalities, and concludes with a description of common medical problems/conditions and their appearance on imaging. From this chapter, the utility of imaging and its complexities becomes apparent and will serve to ground discussion in future chapters.

Impact of ultrasound video transfer on the practice of ultrasound

Sonography can be highly dependent on real-time imaging and as such is highly physician intensive. Such situations arise mostly during complicated ultrasound radiology studies or echocardiology examinations. Under those circumstances it would be of benefit to transmit real-time images beyond the immediate area of the ultrasound laboratory when a physician is not on location. We undertook this study to determine if both static and dynamic image transfer to remote locations might be accomplished using an ultrafast ATM network and PACS. Image management of the local image files was performed by a commercial PACS from AGFA corporation. The local network was Ethernet based, and the global network was based on Asynchronous Transfer Mode (ATM, rates up to 100 Mbits/sec). Real-time image transfer involved two teaching hospitals, one of which had 2 separate ultrasound facilities. Radiologists consulted with technologists via telephone while the examinations were being performed. The applications of ATM network providing real time video for ultrasound imaging in a clinical environment and its potential impact on health delivery and clinical teaching. This technology increased technologist and physician productivity due to the elimination of commute time for physicians and waiting time for technologists and patients. Physician confidence in diagnosis increased compared to reviewing static images alone. This system provided instant access for radiologists to real-time scans from remote sites. Image quality and frame rate were equivalent to the original. The system increased productivity by allowing physicians to monitor studies at multiple sites simultaneously.