Acute Effects Of Triiodothyronine T. (T3) Replacement Therapy in Patients with Chronic Heart Failure and Low-T3 Syndrome: A Randomized, Placebo-Controlled Study

Context: Low-T3 syndrome is a predictor of poor outcome in patients with cardiac dysfunction. The study aimed to assess the short-term effects of synthetic L-T3 replacement therapy in patients with low-T3 syndrome and ischemic or nonischemic dilated cardiomyopathy (DC). Design:Atotal of 20 clinically stable patients with ischemic (n12) or nonischemic (n8) DC were enrolled. There were 10 patients (average age 72 yr, range 66–77; median, 25–75th percentile) who underwent 3-d synthetic L-T3 infusion (study group); the other 10 patients (average age 68 yr, range 64–71) underwent placebo infusion (control group). Clinical examination, electrocardiography, cardiac magnetic resonance, and bio-humoral profile (free thyroid hormones, TSH, plasma renin activity, aldosterone, noradrenaline, N-terminal-pro-B-Type natriuretic peptide, and IL-6) were assessed at baseline and after 3-d synthetic L-T3 (initial dose: 20 g/m2 body surfaced) or placebo infusion. Results: After T3 administration, free T3 concentrations increased until reaching a plateau at 24–48 h (3.43, 3.20–3.84 vs. 1.74, 1.62–1.93 pg/ml; P 0.03) without side effects. Heart rate decreased significantly after T3 infusion (63, 60–66 vs. 69, 60–76 beats per minute; P 0.008). Plasma noradrenaline (347; 270–740 vs. 717, 413–808 pg/ml; P 0.009), N-terminal pro-B-Type natriuretic peptide (3000, 438-4005 vs. 3940, 528-5628 pg/ml; P0.02), and aldosterone (175, 152–229 vs. 231, 154–324 pg/ml; P 0.047) significantly decreased after T3 administration. Neurohormonal profile did not change after placebo infusion in the control group. After synthetic L-T3 administration, left-ventricular end-diastolic volume (142, 132–161 vs. 133, 114–158 ml/m2 body surface; P 0.02) and stroke volume (40, 34–44 vs. 35, 28–39 ml/m2 body surface; P 0.01) increased, whereas external and intracardiac workload did not change. Conclusions: In DC patients, short-term synthetic L-T3 replacement therapy significantly improved neuroendocrine profile and ventricular performance. These data encourage further controlled trials with more patients and longer periods of synthetic L-T3 administration

A review of tertiary BIM education for advanced engineering communication with visualization

SPECT with Tc-99m-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasoclilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. Methods: N-13-Ammonia PET was used to quantitatively assess blood flow, and F-18-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent N-13-ammonia PET at rest and after nitrate administration. Results: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P <0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. Conclusion: N-13-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability

The Role of TiO2 Doping on RuO2-Coated Electrodes for the Water Oxidation Reaction

Electrochemical water splitting into H2 and O2 presents a significant and challenging energy loss due to the high overpotential required at the anode. Today, in industrially relevant applications, dimensionally stable anodes (DSA) based on the electrocatalytic active RuO2 are conventionally utilized. To enhance the resistance against corrosion, incorporation of TiO2 in the RuO2-coated electrodes is widely employed. In the present work we have used scanning electrochemical microscopy (SECM) to demonstrate that TiO2-doped RuO2-coated electrodes, in addition to being more durable, also show an electrocatalytic activity that is, on average, 13% higher as compared to the pure RuO2-coated electrodes. We also demonstrate that cracks in the pure RuO2 coating are the most active zones, probably because Ti from the Ti support has diffused into the first applied layer of the RuO2 coating. To reveal the nature of this enhanced activity for water oxidation displayed on TiO2-doped RuO2 electrodes, we have employed X-ray photoelectron spectroscopy (XPS) for material characterization. The results show that the electrocatalytic activity enhancement displayed on the mixed (Ru1–x:Tix)O2 coating is promoted through a charge transfer from the RuO2 to the TiO2, which provides new and more reactive sites designated as activated RuO2δ+.This study has partly been carried out in the framework of the European Commission FP7 Initial Training Network “ELCAT”, Grant Agreement No. 214936-2. Portions of this research were performed at SPring-8 with the approval of Japan Synchrotron Radiation Research Institute as Nanotechnology Support Project of the Ministry of Education, Culture, Sports, Science and Technology (Proposal No. 2007A2005 and 2008A1671/BL-47XU)

Extracellular volume quantification in isolated hypertension - changes at the detectable limits?

The funding source (British Heart Foundation and UK National Institute for Health Research) provided salaries for research training (FZ, TT, DS, SW), but had no role in study design, collection, analysis, interpretation, writing, or decisions with regard to publication. This work was undertaken at University College London Hospital, which received a proportion of funding from the UK Department of Health National Institute for Health Research Biomedical Research Centres funding scheme. We are grateful to King’s College London Laboratories for processing the collagen biomarker panel

Microstructure and bending properties of die-casting alloys at various chromium contents

A study of the effects of chromium addition on AlSi9Cu3(Fe) alloy was carried out. Die cast EN AC-46000 alloyplates for microstructural investigation and bend testing were produced using a multispecimen die in a highpressure, cold chamber machine. The Cr ranged within the tolerance limits of the EN AC-46000 type alloys,according to the EN 1706 standard. The investigations allowed evaluation of modifications to microstructuraland bending properties produced by Cr additions. In particular, the microstructural analysis revealed that themorphology of primary sludge compounds was mainly cubic-type, such as polyhedral, star-like and blocky,while proeutectic ?-Alx(Fe,Mn,Cr)ySiz intermetallics showed blocky or polyhedral morphology at any Cr level.Increasing the Cr content, the whole area fraction of these particles increased and the primary intermetalliccompounds segregated in the central region of the cross section of the castings. This was associated to amechanism similar to that suggested for the ESCs entrapment. The increase of brittle Fe-rich particles affectedthe fracture load and the displacement to fracture of the alloy at the highest Cr level

T1 mapping in cardiac MRI

Quantitative myocardial and blood T1 have recently achieved clinical utility in numerous pathologies, as they provide non-invasive tissue characterization with the potential to replace invasive biopsy. Native T1 time (no contrast agent), changes with myocardial extracellular water (edema, focal or diffuse fibrosis), fat, iron, and amyloid protein content. After contrast, the extracellular volume fraction (ECV) estimates the size of the extracellular space and identifies interstitial disease. Spatially resolved quantification of these biomarkers (so-called T1 mapping and ECV mapping) are steadily becoming diagnostic and prognostically useful tests for several heart muscle diseases, influencing clinical decision-making with a pending second consensus statement due mid-2017. This review outlines the physics involved in estimating T1 times and summarizes the disease-specific clinical and research impacts of T1 and ECV to date. We conclude by highlighting some of the remaining challenges such as their community-wide delivery, quality control, and standardization for clinical practice

[risk Factors Associated With The Acquisition Of Multiresistant Bacteria In A Pediatric Nursery]

OBJECTIVE: To identify the risk factors in patients who had a multiresistant bacteria during their staying in a Pediatric Intensive Care Unit and in a pediatric nursery of a tertiary teaching hospital.METHODS: Chart review of the patients who stayed in the units from January, 1995 to July, 1997 and had a multiresistant microorganism isolated (both infection and colonization). A case-control study was done using McNemar test for group comparison and using stepwise logistic regression to select independent risk factors. The following risk factors were tested: prior hospital staying, underlying disease, intensive care unit admission, surgical procedure, urinary catheter, central venous line, ventilator, prior antibiotic therapy and skin lesion.RESULTS: Among 52 patients, 66 multiresistant bacteria were identified (among them, 33 were gram-negative bacilli and 33 were methicillin-resistant S. aureus). The logistic regression analysis of the case-control study identified 2 risk factors: prior antibiotic therapy and skin lesion. A single risk factor was indicated for patients with gram-negative bacilli. Nevertheless, for patients with methicillin-resistant S. aureus, central venous lines and skin lesion were significant.CONCLUSION: Prior antibiotic therapy and skin lesion were the factors associated with the acquisition of multiresistant bacteria. Besides skin lesion, for oxacilin-resistant S. aureus colonized patients, central venous catheter use was a risk factor. The strategies employed to limit the spread of those bacteria in the hospital should consider these three factors.76275-8

Systematic comparison of single-chain Fv antibody-fusion toxin constructs containing Pseudomonas Exotoxin A or saporin produced in different microbial expression systems

Background Antibodies raised against selected antigens over-expressed at the cell surface of malignant cells have been chemically conjugated to protein toxin domains to obtain immunotoxins (ITs) that are able to selectively kill cancer cells. Latest generation immunotoxins are composed of a toxic domain genetically fused to antibody fragment(s) which confer on the IT target selective specificity. In this study, we rescued from the hydridoma 4KB128, a recombinant single-chain variable fragment (scFv) targeting CD22, a marker antigen expressed by B-lineage leukaemias and lymphomas. We constructed several ITs using two enzymatic toxins both able to block protein translation, one of bacterial origin (a truncated version of Pseudomonas exotoxin A, PE40) endowed with EF-2 ADP-ribosylation activity, the other being the plant ribosome-inactivating protein saporin, able to specifically depurinate 23/26/28S ribosomal RNA. PE40 was selected because it has been widely used for the construction of recombinant ITs that have already undergone evaluation in clinical trials. Saporin has been also evaluated clinically and has recently been expressed successfully at high levels in a Pichia pastoris expression system. The aim of the present study was to evaluate optimal microbial expression of various IT formats. Results An anti-CD22 scFv termed 4KB was obtained which showed the expected binding activity which was also internalized by CD22+ target cells. Binding of this scFv was also competed for by the parental monoclonal CD22 antibody. Several fusion constructs were designed and expressed either in E. coli or in Pichia pastoris and the resulting fusion proteins affinity-purified. Protein synthesis inhibition assays were performed on CD22+ human Daudi cells and showed that the selected ITs were active, having IC50 (inhibitory concentration by 50%) in the nanomolar range. Conclusions The primary goal of this study was to undertake a systematic comparison between the performance of the different fusion constructs, with respect to yields from E. coli or P. pastoris expression systems and also with regard to each constructs specific killing efficacy. Overall our results confirm that E. coli is the system of choice for the expression of recombinant fusion toxins of bacterial origin whereas we further demonstrate that saporin-based ITs are best expressed and recovered from P. pastoris cultures after yeast codon-usage optimization

Prevalence and Correlates of Dilated and Non-Dilated Left Ventricular Cardiomyopathy in Transfusion-Dependent Thalassemia: Data from a National, Multicenter, Observational Registry

We investigated the prevalence, clinical characteristics, and prognostic role of dilated cardiomyopathy (DCM) and non-dilated left ventricular cardiomyopathy (NDLVC) in patients with transfusion-dependent beta-thalassemia (beta-TDT). We retrospectively included 415 beta-TDT patients who underwent cardiovascular magnetic resonance to quantify myocardial iron overload (MIO) and biventricular function parameters and to detect replacement myocardial fibrosis. Demographic and laboratory parameters were comparable among patients with no overt cardiomyopathy (NOCM; n = 294), DCM (n = 12), and NDLVC (n = 109), while cardiac size and systolic function were significantly different. Compared to NOCM patients, DCM and NDLVC patients had a higher prevalence of MIO and replacement myocardial fibrosis. During a mean follow-up of 57.03 +/- 18.01 months, cardiac complications occurred in 32 (7.7%) patients: 15 heart failures, 15 supraventricular arrhythmias, and 2 pulmonary hypertensions. Compared to the NOCM group, both the NDLVC and the DCM groups were associated with a significantly increased risk of cardiac complications (hazard ratio = 4.26 and 8.81, respectively). In the multivariate analysis, the independent predictive factors were age, MIO, and the presence of DCM and NDLVC versus the NOCM phenotype. In beta-TDT, the detection of NDLVC and DCM phenotypes may hold value in predicting cardiac outcomes

Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis

BACKGROUND: The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined. METHODS AND RESULTS: We included all patients diagnosed with amyloid light-chain (AL) or transthyretin cardiac amyloidosis at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular endomyocardial biopsy. Patients (n=37) were more often men (92%), with a median age of 72 years (interquartile range, 68–81). Lambda-positive AL was found in 14 of 19 AL cases (38%) and kappa-positive AL in 5 of 19 (14%), while transthyretin was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10%–30%), without significant differences between AL and transthyretin amyloidosis. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10%–23%; range, 5%–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between transthyretin amyloidosis and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance, the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (r=0.661, P=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (P=0.035) and N-terminal pro-B-type natriuretic peptide (P=0.002) serum levels. CONCLUSIONS: Extracellular spaces in cardiac amyloidosis are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased extracellular volume at cardiac magnetic resonance and circulating biomarkers than amyloid extent alone