Quang T. Bui

Expanded Polyglutamine Protein Forms Nuclear Inclusions and Causes Neural Degeneration in Drosophila

Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human neurodegenerative diseases caused by glutamine-repeat expansion. We have recreated glutamine-repeat disease in Drosophila using a segment of the SCA3/MJD protein. Targeted expression of the protein with an expanded polyglutamine repeat led to nuclear inclusion (NI) formation and late-onset cell degeneration. Differential sensitivity to the mutant transgene was observed among different cell types, with neurons being particularly susceptible; NI formation alone was not sufficient for degeneration. The viral antiapoptotic gene P35 mitigated polyglutamine-induced degeneration in vivo. Our results demonstrate that cellular mechanisms of human glutamine-repeat disease are conserved in invertebrates. This fly model will aid in identifying additional factors that modulate neurodegeneration.

Atherosclerotic plaque development

Atherosclerosis is now recognized as an inflammatory/immunomodulatory reaction to the presence of oxidized low-density lipoproteins within the arterial wall, often times in the setting of such risk factors as family history, hypercholesterolemia, high blood pressure, diabetes mellitus and smoking. The progression to high-risk lesions such as thin-fibrous cap atheromas results in an increased risk of sudden death, acute myocardial infarction and ischemic stroke. The interplay of macrophages, T lymphocytes and mast cells play a central role in both the development but more importantly in the progression of coronary and carotid artery disease to high-risk phenotypes.

Therapeutic hypothermia for acute myocardial infarction and cardiac arrest.

This report focuses on cardioprotection and describes the advantages and disadvantages of various methods of inducing therapeutic hypothermia (TH) with regard to neuroprotection and cardioprotection for patients with cardiac arrest and ST-segment elevation myocardial infarction (STEMI). TH is recommended in cardiac arrest guidelines. For patients resuscitated after out-of-hospital cardiac arrest, improvements in survival and neurologic outcomes were observed with relatively slow induction of TH. More rapid induction of TH in patients with cardiac arrest might have a mild to modest incremental impact on neurologic outcomes. TH drastically reduces infarct size in animal models, but achievement of target temperature before reperfusion is essential. Rapid initiation of TH in patients with STEMI is challenging but attainable, and marked infarct size reductions are possible. To induce TH, a variety of devices have recently been developed that require additional study. Of particular interest is transcoronary induction of TH using a catheter or wire lumen, which enables hypothermic reperfusion in the absence of total-body hypothermia. At present, the main methods of inducing and maintaining TH are surface cooling, endovascular heat-exchange catheters, and intravenous infusion of cold fluids. Surface cooling or endovascular catheters may be sufficient for induction of TH in patients resuscitated after out-of-hospital cardiac arrest. For patients with STEMI, intravenous infusion of cold fluids achieves target temperature very rapidly but might worsen left ventricular function. More widespread use of TH would improve survival and quality of life for patients with out-of-hospital cardiac arrest; larger studies with more rapid induction of TH are needed in the STEMI population.

Intracoronary delivery of bone-marrow-derived stem cells

Ischemic heart disease is the single greatest killer of Americans and its complications are a major cause of congestive heart failure and ventricular arrhythmias while signifiicantly contributing to increased health care costs and reduced patient quality of life. Advances in medical therapy, although signifiicant over the past decade, are still inadequate in regards to targeting the prime underlying pathology, the irreversible loss of damaged or dead cardiomyocytes. Research into the use of cell transplantation therapy to treat cardiac diseases, with the goal of improving cardiac function, shows promise. The aim of this review will be to discuss the potential therapeutic effects of myocardial stem cell and progenitor cell therapy delivered by an intracoronary route with special reference to treatment of infarcted myocardium.

“Double wire” angio-seal closure technique after balloon aortic valvuloplasty†

Objectives: To report the feasibility of a collagen‐mediated closure device using a modified Angio‐Seal closure technique for access site management following percutaneous balloon aortic valvuloplasty (BAV). Background: With the advent of percutaneous aortic valve replacement therapies, there has been a resurgence of interest in BAV procedures. Vascular complications, including bleeding, are a common source of morbidity post procedure as a result of the requirement for large bore femoral artery access. The use of vascular closure devices may reduce bleeding complications. Methods: We describe a new technique for vascular closure in this setting. At the conclusion of the valvuloplasty procedure, two 0.035″ wires are inserted through the femoral artery sheath. A conventional collagen‐mediated closure device (8F Angio‐Seal) is deployed over the first wire and along side the second wire. If immediate hemostasis is not achieved, a second device is loaded onto the second wire and deployed to achieve hemostasis. Results: Percutaneous BAV was performed in 21 patients. Hemostasis was successfully achieved in all patients with either a single 8F Angio‐Seal closure device (18 patients) or after placement of a second device (three patients). Conclusions: The modified “Double Wire” Angio‐Seal technique is a feasible method for hemostasis following percutaneous BAV.

Previous Myocardial Infarction as a Risk Factor for In-Hospital Cardiovascular Outcomes (from the National Registry of Myocardial Infarction 4 and 5)

Patients with acute coronary syndromes have a substantial disease burden and are at continued risk of future cardiovascular events. In this setting, the relation between previous myocardial infarction (MI) and the risk of subsequent in-hospital adverse cardiovascular outcomes has not been definitively established. The data were analyzed from 427,778 hospitalized patients presenting with acute MI from July 2002 to December 2006, who were enrolled in the National Registry of Myocardial Infarction 4-5 study. Multivariate logistic regression models were developed to examine the association between a history of MI and in-hospital all-cause mortality, recurrent MI, and congestive heart failure/pulmonary edema. Covariate adjustments were made for demographic characteristics, co-morbidities, prearrival medications, and health status at presentation. Similarly, multivariate linear regression models were used to evaluate the length of stay. Of the 232,927 patients with acute MI included in the present study after exclusions, 24.7% reported a history of MI. In-hospital mortality was not significantly different between the patients with and without a history of MI (adjusted odds ratio 0.99, 95% confidence interval 0.95 to 1.04, p = 0.75). However, patients with a previous MI had a small increased risk of in-hospital recurrent MI (adjusted odds ratio 1.18, 95% confidence interval 1.08 to 1.29, p <0.001) and congestive heart failure/pulmonary edema (adjusted odds ratio 1.23, 95% confidence interval1.19 to 1.28, p <0.001) compared with patients with no history of MI. In conclusion, a history of MI did not significantly affect in-hospital mortality after admission for an acute MI.