Craig S. McLachlan

Staged endovascular treatment for complicated type B aortic dissection

Background A 40-year-old man presented with acute chest and back pain, hypertension and anuria. Two years previously he had been diagnosed with acute uncomplicated type B aortic dissection. Following conservative management, with aggressive antihypertensive therapy and analgesia, he was monitored with 6-monthly surveillance CT scans. These demonstrated a complicated type B dissection with renal and iliac malperfusion.Investigations Multislice CT, transthoracic and transesophageal echocardiography, digital subtraction aortography.Diagnosis Acute-on-chronic type B aortic dissection, complicated by aneurysmal dilatation of the thoracic aorta and visceral malperfusion.Management Antihypertensive therapy; staged thoracoabdominal and branch vessel endoluminal repair (STABLE procedure), with stabilization of the dissection and rescue of renal function; CT imaging surveillance to monitor for any further complications.

Prevalence of Hypertension in Member Countries of South Asian Association for Regional Cooperation (SAARC): Systematic Review and Meta-Analysis

AbstractHypertension is a leading attributable risk factor for mortality in South Asia. However, a systematic review on prevalence and risk factors for hypertension in the region of the South Asian Association for Regional Cooperation (SAARC) has not carried out before.The study was conducted according to the Meta-Analysis of Observational Studies in Epidemiology Guideline. A literature search was performed with a combination of medical subject headings terms, “hypertension” and “Epidemiology/EP”. The search was supplemented by cross-references. Thirty-three publications that met the inclusion criteria were included in the synthesis and meta-analyses. Hypertension is defined when an individual had a systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg, was taking antihypertensive drugs, or had previously been diagnosed as hypertensive by health care professionals. Prehypertension is defined as SBP 120–139 mm Hg and DBP 80–89 mm Hg.The overall prevalence of hypertension and prehypertension from the studies was found to be 27% and 29.6%, respectively. Hypertension varied between the studies, which ranged from 13.6% to 47.9% and was found to be higher in the studies conducted in urban areas than in rural areas. The prevalence of hypertension from the latest studies was: Bangladesh: 17.9%; Bhutan: 23.9%; India: 31.4%; Maldives: 31.5%; Nepal: 33.8%; Pakistan: 25%; and Sri Lanka: 20.9%. Eight out of 19 studies with information about prevalence of hypertension in both sexes showed that the prevalence was higher among women than men. Meta-analyses showed that sex (men: odds ratio [OR] 1.19; 95% confidence interval [CI]: 1.02, 1.37), obesity (OR 2.33; 95% CI: 1.87, 2.78), and central obesity (OR 2.16; 95% CI: 1.37, 2.95) were associated with hypertension.Our study found a variable prevalence of hypertension across SAARC countries, with a number of countries with blood pressure above the global average. We also noted that studies are not consistent in their data collection about hypertension and related modifiable risk factors.

Apoptosis of vascular smooth muscle cells induced by cholesterol and its oxides in vitro and in vivo

The ability of cholesterol and its oxides to induce apoptosis in vascular smooth muscle cells in tissue culture and in a rabbit model of atherosclerosis was evaluated. Apoptosis was detected using DNA laddering and in situ end-labelling of fragmented DNA. Cholesterol oxides, but not cholesterol, were found to inhibit proliferation and induce apoptosis of vascular smooth muscle cells in tissue culture. 7-ketocholesterol was found to be the most potent inhibitor of proliferation, while 25-hydroxycholesterol was found to be the most potent inducer of apoptosis. These data suggest that the inhibition of proliferation and the induction of apoptosis by cholesterol oxides within vascular smooth muscle cells use different pathways, suggesting a differential role for these cholesterol oxides within the arterial wall. Cholesterol feeding after balloon injury in a rabbit model of atherosclerosis is known to result in the accumulation of cholesterol oxides. However, we found that cholesterol feeding had no effect on the level of apoptosis in the rabbit aortic wall after balloon injury, suggesting that the major factor determining apoptosis in our model was the balloon injury.

P2X (purinergic) receptor redistribution in rabbit aorta following injury to endothelial cells and cholesterol feeding

The redistribution of purinergic P2X receptor subunits (P2X1 to P2X7) within the rabbit aorta wall three weeks after endothelial balloon injury/cholesterol feeding was examined. P2X1 receptor cluster density was elevated in the media following balloon injury/cholesterol feeding by about 30% and these clusters appeared on smooth muscle cells throughout the greatly expanded neointima but they did not change significantly on the endothelial cells following balloon injury. P2X4 clusters were found in high density throughout the media and in very high density in the enlarged neointima following balloon injury, particularly on the endothelial cells where the density increased about 10-fold after balloon injury. P2X5 clusters were found in high density in the media of normal aorta but with little change following balloon injury. P2X3, P2X6 and P2X7 cluster density was low in normal aorta and remained unchanged following balloon injury. All receptor subunits were found on endothelial cells. It is suggested that the release of ATP from damaged endothelial cells and from smooth muscle cells sufficient to activate P2X4 receptors may contribute to neointimal proliferation.

Reduced cardiac output is associated with decreased mitochondrial efficiency in the non-ischemic ventricular wall of the acute myocardial-infarcted dog.

Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction (MI). Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending (LAD) coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements of hemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 (UCP3) expression were determined over 24 h period. Hemodynamic measurements revealed a > 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid (PA). GTP inhibition of (PA)-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance (EPR) methods showed an increase in reactive oxygen species (ROS) over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.

Is modern external beam radiotherapy with androgen deprivation therapy still a viable alternative for prostate cancer in an era of robotic surgery and brachytherapy: A comparison of Australian series

We compare the results of modern external‐beam radiotherapy (EBRT), using combined androgen deprivation and dose‐escalated intensity‐modulated radiotherapy with MRI‐CT fusion and daily image guidance with fiducial markers (DE‐IG‐IMRT), with recently published Australian series of brachytherapy and surgery.

Direct template matching reveals a host subcellular membrane gyroid cubic structure that is associated with SARS virus

Abstract Viral infection can result in alterations to the host subcellular membrane. This is often reported when using transmission electron microscopy (TEM), resulting in a description of tubuloreticular membrane subcellular ultrastructure rather than a definition based on 3-D morphology. 2-D TEM micrographs depicting subcellular membrane changes are associated with subcellular SARS virion particles [Goldsmith CS, Tatti KM, Ksiazek TG et al. Ultra-structural characterization of SARS coronavirus. Emerg Infect Dis 2004; 10: 320–326]. In the present study, we have defined the 2-D membrane pattern and shape associated with the SARS virus infection. This is by using a direct template matching method to determine what the 3-D structure of the SARS virus associated host membrane change would be. The TEM image for our purposes is defined on 2-D information, such as the membrane having undergone proliferation and from pattern recognition suggesting that the membrane-described pattern is possibly a gyroid type of membrane. Features of the membrane were used to compute and match the gyroid structure with an existing 2-D TEM micrograph, where it was revealed that the membrane structure was indeed a gyroid-based cubic membrane. The 2-D gyroid computer-simulated image that was used to match the electron micrograph of interest was derived from a mathematically well-defined 3-D structure, and it is from this 3-D derivative that allows us to make inferences about the 3-D structure of this membrane. In conclusion, we demonstrate that a 3-D structure can be defined from a 2-D membrane patterned image and that a SARS viral associated membrane change has been identified as cubic membrane morphology. Possible mechanisms for this cubic membrane change are discussed with respect to viral severity, persistence and free radical production.

Increased total heart rate variability and enhanced cardiac vagal autonomic activity in healthy humans with sinus bradycardia

Sinus bradycardia can be defined as a sinus rhythm with a resting heart rate of 60 beats per minute or less. While it is assumed that increased autonomic parasympathetic activity is associated with sinus bradycardia, such an association has yet to be proven. The aims of this study were to compute a number of heart rate variability (HRV) parameters in healthy individuals with sinus bradycardia and determine whether there was a significant vagal component to sinus bradycardia. Forty-three healthy adults with normal sinus rhythm and 25 healthy adults with sinus bradycardia had an electrocardiogram recorded for 20 minutes, from which HRV indices were calculated. Results showed significant increases in SDNN (standard deviation of NN intervals) (P< 0.05), RMSDD (square root of the mean squared differences of successive NN intervals) (P< 0.05), and DFA32 (detrended fluctuation analysis) (P< 0.05) in bradycardic subjects compared with subjects with normal sinus rhythm. There were no significant differences in sympathetic frequency domain indices between the two groups. In conclusion, there were significant increases in total heart variability and increased parasympathetic drive in subjects with bradycardia. Clinically, bradycardia is likely to be cardioprotective in aging populations based upon these HRV findings.

Planning magnetic resonance imaging for prostate cancer intensity-modulated radiation therapy: Impact on target volumes, radiotherapy dose and androgen deprivation administration.

Magnetic resonance imaging (MRI) scans are increasingly utilized for radiotherapy planning to contour the primary tumors of patients undergoing intensity‐modulated radiation therapy (IMRT). These scans may also demonstrate cancer extent and may affect the treatment plan. We assessed the impact of planning MRI detection of extracapsular extension, seminal vesicle invasion, or adjacent organ invasion on the staging, target volume delineation, doses, and hormonal therapy of patients with prostate cancer undergoing IMRT.

Growth arrest-specific gene 6 expression in proliferating rabbit vascular smooth muscle cells in vitro and in vivo.

Proliferation and migration of vascular smooth muscle cells (VSMCs) are involved in the processes of atherosclerosis and restenosis. The protein product of the growth arrest‐specific gene 6 (Gas‐6) has recently been identified as a ligand for the Axl/Rse/Mer tyrosine kinase receptor family, which may be involved in proliferation and migration of VSMCs. Here we show that Gas‐6 gene expression is increased in proliferating VSMCs in tissue culture (2.5‐fold increase by Northern blot) and following neointimal proliferation in a rabbit balloon‐injury model (3‐fold increase by Western blot). Neither platelet‐derived growth factor (PDGF) nor thrombin stimulate the expression of Gas‐6 in cultured VSMCs despite the ability of the PDGF, but not thrombin, to stimulate proliferation in growth‐arrested cells. These data suggest a role for the Gas‐6 regulatory system in VSMC proliferation, which may be a target for therapeutic interventions in the atherosclerotic process and restenosis after angioplasty.