Computed Tomography of the Coronary Arteries

MSCT Coronary Angiography is a fast developing non-invasive diagnostic technique that can detect a coronary stenosis. The detection of a coronary stenosis is hampered by limited image quality and by motion artefacts and extensive calcifications. However, MSCT-coronary angiography is highly reliable to rule out coronary stenosis. The role of MSCT-coronary angiography in the diagnostic work-up of coronary artery disease needs further research

A scale-down mimic for mapping the process performance of centrifugation, depth and sterile filtration

In the production of biopharmaceuticals disk-stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot-scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale-down approach based upon the use of a shear device and a bench-top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large-scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited

Diagnostic accuracy of computed tomography coronary angiography in patients with a zero calcium score

To evaluate the diagnostic accuracy of 64-slice CT coronary angiography (CT-CA) for the detection of significant coronary artery stenosis in patients with zero on the Agatston Calcium Score (CACS). We enrolled 279 consecutive patients (96 male, mean age 48±12 years) with suspected coronary artery disease. Patients were symptomatic (n=208) or asymptomatic (n=71), and underwent conventional coronary angiography (CAG). For CT-CA we administered an IV bolus of 100 ml of iodinated contrast material. CT-CA was compared to CAG using a threshold for significant stenosis of ≤50%. The prevalence of disease demonstrated at CAG was 15% (1.4% in asymptomatic). The population at CAG showed no or non-significant disease in 85% (238/279), single vessel disease in 9% (25/279), and multi-vessel disease in 6% (16/279). Sensitivity, specificity, and positive and negative predictive values of CT-CA vs. CAG on the patient level were 100%, 95%, 76%, and 100% in the overall population and 100%, 100%, 100%, and 100% in asymptomatic patients, respectively. CT-CA proves high diagnostic performance in patients with or without symptoms and with zero CACS. The prevalence of significant disease detected by CT-CA was not negligible in asymptomatic patients. The role of CT-CA in asymptomatic patients remains uncertain

The last frontier: Catch records of white sharks (carcharodon carcharias) in the northwest pacific ocean

White sharks are highly migratory apex predators, globally distributed in temperate, sub-tropical, and tropical waters. Knowledge of white shark biology and ecology has increased recently based on research at known aggregation sites in the Indian, Atlantic, and Northeast Pacific Oceans; however, few data are available for the Northwest Pacific Ocean. This study provides a meta-analysis of 240 observations of white sharks from the Northwest Pacific Ocean between 1951 and 2012. Records comprise reports of bycatch in commercial fisheries, media accounts, personal communications, and documentation of shark-human interactions from Russia (n = 8), Republic of Korea (22), Japan (129), China (32), Taiwan (45), Philippines (1) and Vietnam (3). Observations occurred in all months, excluding October-January in the north (Russia and Republic of Korea) and July-August in the south (China, Taiwan, Philippines, and Vietnam). Population trend analysis indicated that the relative abundance of white sharks in the region has remained relatively stable, but parameterization of a 75% increase in observer effort found evidence of a minor decline since 2002. Reliably measured sharks ranged from 126–602 cm total length (TL) and 16–2530 kg total weight. The largest shark in this study (602 cm TL) represents the largest measured shark on record worldwide. For all countries combined the sex ratio was non-significantly biased towards females (1∶1.1; n = 113). Of 60 females examined, 11 were confirmed pregnant ranging from the beginning stages of pregnancy (egg cases) to near term (140 cm TL embryos). On average, 6.0±2.2 embryos were found per litter (maximum of 10) and gestation period was estimated to be 20 months. These observations confirm that white sharks are present in the Northwest Pacific Ocean year-round. While acknowledging the difficulties of studying little known populations of a naturally low abundance species, these results highlight the need for dedicated research to inform regional conservation and management planning

Endothelial Cell Processing and Alternatively Spliced Transcripts of Factor VIII: Potential Implications for Coagulation Cascades and Pulmonary Hypertension

Background: Coagulation factor VIII (FVIII) deficiency leads to haemophilia A. Conversely, elevated plasma levels are a strong predictor of recurrent venous thromboemboli and pulmonary hypertension phenotypes in which in situ thromboses are implicated. Extrahepatic sources of plasma FVIII are implicated, but have remained elusive. Methodology/Principal Findings: Immunohistochemistry of normal human lung tissue, and confocal microscopy, flow cytometry, and ELISA quantification of conditioned media from normal primary endothelial cells were used to examine endothelial expression of FVIII and coexpression with von Willebrand Factor (vWF), which protects secreted FVIII heavy chain from rapid proteloysis. FVIII transcripts predicted from database mining were identified by rt-PCR and sequencing. FVIII mAb-reactive material was demonstrated in CD31+ endothelial cells in normal human lung tissue, and in primary pulmonary artery, pulmonary microvascular, and dermal microvascular endothelial cells. In pulmonary endothelial cells, this protein occasionally colocalized with vWF, centered on Weibel Palade bodies. Pulmonary artery and pulmonary microvascular endothelial cells secreted low levels of FVIII and vWF to conditioned media, and demonstrated cell surface expression of FVIII and vWF Ab–reacting proteins compared to an isotype control. Four endothelial splice isoforms were identified. Two utilize transcription start sites in alternate 59 exons within the int22h-1 repeat responsible for intron 2

Influence of intracoronary attenuation on coronary plaque measurements using multislice computed tomography: Observations in an ex vivo model of coronary computed tomography angiography

Assessment of attenuation (measured in Hounsfield units, HU) of human coronary plaques was performed using multislice computed tomography (MSCT) in an ex vivo model. In three ex vivo specimens of left coronary arteries in oil, MSCT was performed after intracoronary injection of four solutions of contrast material (400 mgI/ml iomeprol). The four solutions were diluted as follows: 1/∞, 1/200, 1/80, and 1/20. All scans were performe

Small coronary calcifications are not detectable by 64-slice contrast enhanced computed tomography

Recently, small calcifications have been associated with unstable plaques. Plaque calcifications are both in intravascular ultrasound (IVUS) and multi-slice computed tomography (MSCT) easily recognized. However, smaller calcifications might be missed on MSCT due to its lower resolution. Because it is unknown to which extent calcifications can be detected with MSCT, we compared calcification detection on contrast enhanced MSCT with IVUS. The coronary arteries of patients with myocardial infarction or unstable angina were imaged by 64-slice MSCT angiography and IVUS. The IVUS and MSCT images were registered and the arteries were inspected on the presence of calcifications on both modalities independently. We measured the length and the maximum circumferential angle of each calcification on IVUS. In 31 arteries, we found 99 calcifications on IVUS, of which only 47 were also detected on MSCT. The calcifications missed on MSCT (n = 52) were significantly smaller in angle (27° ± 16° vs. 59° ± 31°) and length (1.4 ± 0.8 vs. 3.7 ± 2.2 mm) than those detected on MSCT. Calcifications could only be detected reliably on MSCT if they were larger than 2.1 mm in length or 36° in angle. Half of the calcifications seen on the IVUS images cannot be detected on contrast enhanced 64-slice MSCT angiography images because of their size. The limited resolution of MSCT is the main reason for missing small calcifications

Is there a gender difference in noninvasive coronary imaging? Multislice computed tomography for noninvasive detection of coronary stenoses

<p>Abstract</p> <p>Background</p> <p>Multislice computed tomography (MSCT) coronary angiography is the foremost alternative to invasive coronary angiography.</p> <p>Methods</p> <p>We sought to compare the diagnostic accuracy of MSCT in female and male patients with suspected coronary disease. Altogether 50 women and 95 men underwent MSCT with 0.5 mm detector collimation. Coronary artery stenoses of at least 50% on conventional coronary angiography were considered significant.</p> <p>Results</p> <p>The coronary vessel diameters of all four main coronary artery branches were significantly larger in men than in women. The diagnostic accuracy of MSCT in identifying patients with coronary artery disease was significantly lower for women (72%) compared with men (89%, <it>p </it>< 0.05). Also sensitivity (70% vs. 95%), positive predictive value (64% vs. 93%), and the rate of nondiagnostic examinations (14% vs. 4%, all: <it>p </it>< 0.05) were significantly worse for women. The effective radiation dose of MSCT coronary angiography was significantly higher in the examination of women (13.7 ± 1.2 mSv) than of men (11.7 ± 0.9 mSv, <it>p </it>< 0.001), mainly as a result of the fact that the radiosensitive female breast (contributing 24.5% of the dose in women) is in the x-ray path.</p> <p>Conclusion</p> <p>Noninvasive coronary angiography with MSCT might be less accurate and sensitive for women than men. Also, women are exposed to a significantly higher effective radiation dose than men.</p

Over-expression of adenosine deaminase in mouse podocytes does not reverse puromycin aminonucleoside resistance

<p>Abstract</p> <p>Background</p> <p>Edema in nephrotic syndrome results from renal retention of sodium and alteration of the permeability properties of capillaries. Nephrotic syndrome induced by puromycin aminonucleoside (PAN) in rats reproduces the biological and clinical signs of the human disease, and has been widely used to identify the cellular mechanisms of sodium retention. Unfortunately, mice do not develop nephrotic syndrome in response to PAN, and we still lack a good mouse model of the disease in which the genetic tools necessary for further characterizing the pathophysiological pathway could be used. Mouse resistance to PAN has been attributed to a defect in glomerular adenosine deaminase (ADA), which metabolizes PAN. We therefore attempted to develop a mouse line sensitive to PAN through induction of normal adenosine metabolism in their podocytes.</p> <p>Methods</p> <p>A mouse line expressing functional ADA under the control of the podocyte-specific podocin promoter was generated by transgenesis. The effect of PAN on urinary excretion of sodium and proteins was compared in rats and in mice over-expressing ADA and in littermates.</p> <p>Results</p> <p>We confirmed that expression of ADA mRNAs was much lower in wild type mouse than in rat glomerulus. Transgenic mice expressed ADA specifically in the glomerulus, and their ADA activity was of the same order of magnitude as in rats. Nonetheless, ADA transgenic mice remained insensitive to PAN treatment in terms of both proteinuria and sodium retention.</p> <p>Conclusions</p> <p>Along with previous results, this study shows that adenosine deaminase is necessary but not sufficient to confer PAN sensitivity to podocytes. ADA transgenic mice could be used as a background strain for further transgenesis.</p