Detrimental Actions of Chlorinated Nucleosides on the Function and Viability of Insulin-Producing Cells.

Neutrophils are innate immune cells that play a key role in pathogen clearance. They contribute to inflammatory diseases, including diabetes, by releasing pro-inflammatory cytokines, reactive oxygen species, and extracellular traps (NETs). NETs contain a DNA backbone and catalytically active myeloperoxidase (MPO), which produces hypochlorous acid (HOCl). Chlorination of the DNA nucleoside 8-chloro-deoxyguanosine has been reported as an early marker of inflammation in diabetes. In this study, we examined the reactivity of different chlorinated nucleosides, including 5-chloro-(deoxy)cytidine (5ClC, 5CldC), 8-chloro-(deoxy)adenosine (8ClA, 8CldA) and 8-chloro-(deoxy)guanosine (8ClG, 8CldG), with the INS-1E ß-cell line. Exposure of INS-1E cells to 5CldC, 8CldA, 8ClA, and 8CldG decreased metabolic activity and intracellular ATP, and, together with 8ClG, induced apoptotic cell death. Exposure to 8ClA, but not the other nucleosides, resulted in sustained endoplasmic reticulum stress, activation of the unfolded protein response, and increased expression of thioredoxin-interacting protein (TXNIP) and heme oxygenase 1 (HO-1). Exposure of INS-1E cells to 5CldC also increased TXNIP and NAD(P)H dehydrogenase quinone 1 (NQO1) expression. In addition, a significant increase in the mRNA expression of NQO1 and GPx4 was seen in INS-1E cells exposed to 8ClG and 8CldA, respectively. However, a significant decrease in intracellular thiols was only observed in INS-1E cells exposed to 8ClG and 8CldG. Finally, a significant decrease in the insulin stimulation index was observed in experiments with all the chlorinated nucleosides, except for 8ClA and 8ClG. Together, these results suggest that increased formation of chlorinated nucleosides during inflammation in diabetes could influence ß-cell function and may contribute to disease progression.

Ventricular septal hamartoma mimicking hypertrophic cardiomyopathy in a 41-year-old woman presenting with paroxysmal supraventricular tachycardia.

We report an unusual case of cardiac hamartoma involving the ventricular septum. The patient presented with palpitations and exertional chest pain. Echocardiography indicated a large homogeneous mass occupying the superior two-thirds of the ventricular septum. This report confirms the use of transthoracic echocardiography as a screening tool in the diagnosis and management of an uncommon case of a benign cardiac tumor.

The transition from an analog to a digital echocardiography laboratory: the Mayo experience.

Our echocardiography laboratory has completed the transition from an analog to a digital imaging laboratory. The process involved a thorough analysis of the practice and design of a complete digital solution. After an effective implementation of a robust reporting solution, the transition to digital imaging ensued. The implementation plan for digital imaging enabled the transition to be made without adversely affecting the practice, which has an average daily examination load of more than 200 patients. Full-load testing simulations were required on high-end image processing review workstations, high-speed local area network connections to each imaging suite, and new clustered imaging servers. We had to test the ability of approximately 100 ultrasound machines with 3 idiosyncratic ultrasound platforms to allow digital image transfer to the new imaging servers over the local area network. Our sonographer, allied health, and physician staff of more than 250 persons had to be trained to adapt to important changes that the digital echocardiographic image acquisition and review platform would have on their specific roles in the laboratory. The efficiency of the implementation, reporting, and imaging resulted in improved staff resource allocation. The lessons learned may benefit laboratories with a similar interest in making the transition to a digital imaging laboratory with minimal effect on patient scheduling and staff satisfaction. The effect of the transition to a completely digital laboratory on operating expenses, imaging, and reviewing systems and the impact on the clinical practice of echocardiography at our institution are presented, with emphasis on the particular aspects of transitioning to digital imaging.

Diastolic function: a sonographer's approach to the essential echocardiographic measurements of left ventricular diastolic function.

Noninvasive assessment of left ventricular filling pressures by echocardiography has been validated by invasive hemodynamic studies and correlated with clinical findings. A comprehensive echocardiographic examination based on the referral diagnosis and patient symptomatology routinely includes efforts to measure specific parameters of left ventricular diastolic function. We provide a step-by-step approach to goal-directed echocardiographic assessment of diastolic function.

Increased mitral regurgitation during the valsalva maneuver in a patient with pheochromocytoma, uncontrolled hypertension, cardiac hypertrophy, and dynamic outflow tract obstruction.

Dynamic left ventricular outflow tract obstruction is a common feature of hypertrophic cardiomyopathy, but it can also be demonstrated in other conditions that result in increased thickness of the left ventricular septal wall. Severe uncontrolled hypertension may lead to severe hypertrophy of the left ventricle and produce systolic anterior motion of the mitral valve and an outflow gradient. We report a case of pheochromocytoma with echocardiographic demonstration of markedly increased mitral regurgitation during the Valsalva maneuver in a patient with left ventricular hypertrophy and a dynamic outflow tract obstruction.

Isolated supravalvular pulmonary artery ridge in a 70-year-old man.

Transthoracic echocardiography allows noninvasive assessment of the structure and function of the great vessels of the heart. We report a case of a 70-year-old man who had an isolated, mildly obstructive, supravalvular pulmonary artery ridge that was detected incidentally with transthoracic echocardiography. This report confirms the utility of transthoracic echocardiography in the detection of this condition and discusses quantification of this rare anomaly.

An echocardiographic left ventricular wall area index for functional detection of myocardial injury in hemodynamically unloaded hearts.

Functional assessment of the left ventricle is affected by loading conditions. Detection of rejection-mediated myocardial injury in a heterotopic heart transplant model is a challenge for the echocardiographer because the heart is in an unloaded state. We examined the relationship of a novel left ventricular (LV) wall area index (LVWAI) and serum cardiac troponin T (cTnT) levels. The LVWAI, based on prior methods of determining LV mass, was defined as the difference between epicardial and endocardial areas divided by the epicardial area. The biphasic morphometric response of LVWAI reflected changes in the cTnT levels and allowed echocardiographic detection of myocardial injury in hemodynamically unloaded hearts.

Biphasic Doppler pattern of the descending thoracic aorta: a new echocardiographic finding in patients with aortic valve stenosis.

A total of 59 patients (> or = 65 years of age) with normal left ventricular function (ejection fraction > 50%) and varying degrees of aortic valve structure and hemodynamics (normal to severely stenotic) were screened; 50 were subsequently enrolled. Continuous wave Doppler echocardiography in the descending thoracic aorta showed two general patterns: (1) in aortic stenosis, the pattern consisted of two peak systolic velocity components (S1 and S2); and (2) in normal aortic valve function, the pattern was a uniphasic signal with a single peak systolic velocity component. The new Doppler pattern yielded 95% sensitivity and 90% specificity in the detection of clinically significant aortic valve stenosis, and 92% sensitivity and 70% specificity in the detection of severe aortic valve stenosis. Sensitivity was 96% in uniphasic signals during normal aortic valve function by conventional 2-dimensional and Doppler criteria. This article introduces characteristics of this Doppler velocity profile as a new diagnostic finding of aortic valve stenosis.

Doppler echocardiographic evaluation of pulmonary regurgitation facilitates the diagnosis of constrictive pericarditis.

Diagnosing constrictive pericarditis (CP) remains a clinical challenge. Ventricular interdependence and dissociation of intrathoracic and intracardiac pressures are hallmark features that are readily recognized by invasive and noninvasive hemodynamics. The Doppler echocardiographic signal from pulmonic valve regurgitation depends on the relationship between pulmonary artery (intrathoracic) and right ventricular (intracardiac) pressure. Respiration-associated changes in this signal may aid in the evaluation of pericardial constriction. We demonstrate here that early diastolic cessation with inspiration can indicate a CP process. Early diastolic cessation with inspiration was shown to have correctly diagnosed CP in 70% of the patients in this study, with a sensitivity of 77%, specificity of 64%, positive predictive value of 67%, and negative predictive value of 75%. This noninvasive insight into dissociation of intracardiac and intrathoracic pressures, although not sufficient on its own, may be a valuable tool for aiding in the diagnosis of CP.