Importance of the right ventricle in valvular heart disease

The importance of the right ventricle as a determinant of clinical symptoms, exercise capacity, peri-operative survival and postoperative outcome has been underestimated for a long time. Right ventricular ejection fraction has been used as a measure of right ventricular function but has been found to be dependent on loading conditions, ventricular interaction as well as on myocardial structure. Altered left ventricular function in patients with valvular disease influences right ventricular performance mainly by changes in afterload but also by ventricular interaction. Right ventricular function and regional wall motion can be determined with right ventricular angiography, radionuclide ventriculography, two-dimensional echocardiography or magnetic resonance imaging. However, the complex structure of the right ventricle and its pronounced translational movements render quantification difficult. True regional wall motion analysis is, however, possible with myocardial tagging based on magnetic resonance techniques. With this technique a baso-apical shear motion of the right ventricle was observed which was enhanced in patients with aortic stenosi

Cytotoxic drug sensitivity of Epstein-Barr virus transformed lymphoblastoid B-cells.

BACKGROUND: Epstein-Barr virus (EBV) is the causative agent of immunosuppression associated lymphoproliferations such as post-transplant lymphoproliferative disorder (PTLD), AIDS related immunoblastic lymphomas (ARL) and immunoblastic lymphomas in X-linked lymphoproliferative syndrome (XLP). The reported overall mortality for PTLD often exceeds 50%. Reducing the immunosuppression in recipients of solid organ transplants (SOT) or using highly active antiretroviral therapy in AIDS patients leads to complete remission in 23-50% of the PTLD/ARL cases but will not suffice for recipients of bone marrow grafts. An additional therapeutic alternative is the treatment with anti-CD20 antibodies (Rituximab) or EBV-specific cytotoxic T-cells. Chemotherapy is used for the non-responding cases only as the second or third line of treatment. The most frequently used chemotherapy regimens originate from the non-Hodgkin lymphoma protocols and there are no cytotoxic drugs that have been specifically selected against EBV induced lymphoproliferative disorders. METHODS: As lymphoblastoid cell lines (LCLs) are well established in vitro models for PTLD, we have assessed 17 LCLs for cytotoxic drug sensitivity. After three days of incubation, live and dead cells were differentially stained using fluorescent dyes. The precise numbers of live and dead cells were determined using a custom designed automated laser confocal fluorescent microscope. RESULTS: Independently of their origin, LCLs showed very similar drug sensitivity patterns against 29 frequently used cytostatic drugs. LCLs were highly sensitive for vincristine, methotrexate, epirubicin and paclitaxel. CONCLUSION: Our data shows that the inclusion of epirubicin and paclitaxel into chemotherapy protocols against PTLD may be justified

Single breath-hold slice-following CSPAMM myocardial tagging

Myocardial tagging has shown to be a useful magnetic resonance modality for the assessment and quantification of local myocardial function. Many myocardial tagging techniques suffer from a rapid fading of the tags, restricting their application mainly to systolic phases of the cardiac cycle. However, left ventricular diastolic dysfunction has been increasingly appreciated as a major cause of heart failure. Subtraction based slice-following CSPAMM myocardial tagging has shown to overcome limitations such as fading of the tags. Remaining impediments, to this technique, however, are extensive scanning times (∼10 min), the requirement of repeated breath-holds using a coached breathing pattern, and the enhanced sensitivity of artifacts related to poor patient compliance or inconsistent depths of end-expiratory breath-holds. We therefore propose a combination of slice-following CSPAMM myocardial tagging with a segmented EPI imaging sequence. Together with an optimized RF excitation scheme, this enables to acquire as many as 20 systolic and diastolic grid-tagged images per cardiac cycle with a high tagging contrast during a short period of sustained respiratio

Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease.

Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease (CKD), but whether renal oxygenation predicts renal function decline in humans has not been proven. Therefore, we performed a prospective study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD, 47 with hypertension without CKD, and 24 healthy control individuals. Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2* value of each layer (a high R2* corresponds to low oxygenation), along with the change in R2* between layers called the R2* slope. Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate (MDRD eGFR). Follow up was three years. The change in eGFR in CKD, hypertensive and control individuals was -2.0, 0.5 and -0.2 ml/min/1.73m <sup>2</sup> /year, respectively. In multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers, eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2* value of the cortical layers, and positively with the R2* slope, but not with the other covariates. Patients with CKD and high outer R2* or a flat R2* slope were three times more likely to develop an adverse renal outcome (renal replacement therapy or over a 30% increase in serum creatinine). Thus, low cortical oxygenation is an independent predictor of renal function decline. This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression

Myocardial tagging for the analysis left ventricular function

8. Conclusions: Based on our measurements following observations were made: (1) The left ventricle performs a systolic wringing motion which occurs mainly during isovolumic contraction. (2) Diastolic untwisting is found predominantly during isovolumic relaxation and occurs opposite to systolic rotation. (3) After myocardial infarction regional shortening is reduced in infarcted and remote regions. Predominantly diastolic untwisting is delayed and prolonged. (4) In patients with aortic stenosis apical rotation is enhanced, whereas diastolic untwisting is significantly inhibited, which explains the diastolic dysfunction in these patients. Myocardial tagging makes an accurate regional wall motion analysis and the assessment of cardiac rotation possible and, thus, allow new insight into the mechanical function of the hear

Design and Commissioning of the ISAC Control System at TRIUMF

The control system for the initial stage of the ISAC radioactive beam facility at TRIUMF was recently commissioned and the facility delivered the first radioactive beam to users in December of 1998. The control system is based on the EPICS toolkit. VME based Motorola MVME162 CPUs serve as input/output Controllers, SUN workstations as application servers, and PCs are used with X-terminal software as operator interface stations. Modicon PLCs control the vacuum system and ion sources. A network of CAN-bus based controllers is used for the beam guidance system. Custom VME modules were developed for beam diagnostics. 1 ISAC ISAC, an Online Isotope Separator and ACcelerator, is being built at TRIUMF and provided the first beams of short-lived radioactive isotopes to experiments in December of 1998. At present, ISAC is the world’s most intense source of low energy radioactive beams. By the end of next year it will also deliver the world’s most energetic radioactive beams (1.5 MeV/u). A 500 MeV proton beam of up to 10 µA from the TRIUMF cyclotron produces short-lived radioactive species in a hot (2000 °C) production target. They are extracted and accelerated to 60 keV in a target-ion-source and pass through a magnetic pre-separator before being isotopically separated in a high-resolution mass separator. This radioactive beam can either feed the low-energy experimental area or be further accelerated in a 19-ring radio-frequency quadrupole (RFQ) followed by a five-tank drift tube linac (DTL). For tuning purposes, an off-line ion source provides non-radioactive beams

Understanding Social Class in Place: Responding to Supergentrification in Aspen, Colorado

Existing research portrays elite places as prone to exclusion, welcoming of upscaling, and focused on protecting their economic self-interests. This paper provides nuance to this research by exploring how stakeholders understand and respond to supergentrification. During the fall of 2016, a group of citizen activists in the exclusive community of Aspen, Colorado, initiated an ordinance seeking to limit the expansion of luxury chain stores. Drawing on qualitative data related to this case, we show that how communities respond to supergentrification depends on locally specific understandings of place and social class, and how class interests have been institutionalized in local policies. In Aspen, residents opposed luxury chain stores by marshaling narratives that foreground the community\u27s history of class mixing and the significance of working locals. Elected officials responded by taking account of the political power of local residents as well as the city\u27s dependence on tax revenues from affluent visitors and second homeowners. Our findings extend and complicate understandings of how power works in elite places, highlighting both the potential for, and limitations of, efforts to thwart supergentrification and associated dislocation