74 research outputs found
Repeatability of fractional flow reserve despite variations in systemic and coronary hemodynamics
Objectives
This study classified and quantified the variation in fractional flow reserve (FFR) due to fluctuations in systemic and coronary hemodynamics during intravenous adenosine infusion.
Background
Although FFR has become a key invasive tool to guide treatment, questions remain regarding its repeatability and stability during intravenous adenosine infusion because of systemic effects that can alter driving pressure and heart rate.
Methods
We reanalyzed data from the VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice) study, which enrolled consecutive patients who were infused with intravenous adenosine at 140 ÎŒg/kg/min and measured FFR twice. Raw phasic pressure tracings from the aorta (Pa) and distal coronary artery (Pd) were transformed into moving averages of Pd/Pa. Visual analysis grouped Pd/Pa curves into patterns of similar response. Quantitative analysis of the Pd/Pa curves identified the âsmart minimumâ FFR using a novel algorithm, which was compared with human core laboratory analysis.
Results
A total of 190 complete pairs came from 206 patients after exclusions. Visual analysis revealed 3 Pd/Pa patterns: âclassicâ (sigmoid) in 57%, âhumpedâ (sigmoid with superimposed bumps of varying height) in 39%, and âunusualâ (no pattern) in 4%. The Pd/Pa pattern repeated itself in 67% of patient pairs. Despite variability of Pd/Pa during the hyperemic period, the âsmart minimumâ FFR demonstrated excellent repeatability (bias â0.001, SD 0.018, paired p = 0.93, r2 = 98.2%, coefficient of variation = 2.5%). Our algorithm produced FFR values not significantly different from human core laboratory analysis (paired p = 0.43 vs. VERIFY; p = 0.34 vs. RESOLVE).
Conclusions
Intravenous adenosine produced 3 general patterns of Pd/Pa response, with associated variability in aortic and coronary pressure and heart rate during the hyperemic period. Nevertheless, FFR â when chosen appropriately â proved to be a highly reproducible value. Therefore, operators can confidently select the âsmart minimumâ FFR for patient care. Our results suggest that this selection process can be automated, yet comparable to human core laboratory analysis
Expression analysis of three immune genes Interferon-gamma, Mx and Interferon regulatory factor-1 of Japanese flounder ( Paralichthys olivaceus )
Classification of current anticancer immunotherapies
During the past decades, anticancer immunotherapy has evolved from a promising
therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are
now approved by the US Food and Drug Administration and the European Medicines
Agency for use in cancer patients, and many others are being investigated as standalone
therapeutic interventions or combined with conventional treatments in clinical
studies. Immunotherapies may be subdivided into âpassiveâ and âactiveâ based on
their ability to engage the host immune system against cancer. Since the anticancer
activity of most passive immunotherapeutics (including tumor-targeting monoclonal
antibodies) also relies on the host immune system, this classification does not properly
reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer
immunotherapeutics can be classified according to their antigen specificity. While some
immunotherapies specifically target one (or a few) defined tumor-associated antigen(s),
others operate in a relatively non-specific manner and boost natural or therapy-elicited
anticancer immune responses of unknown and often broad specificity. Here, we propose
a critical, integrated classification of anticancer immunotherapies and discuss the clinical
relevance of these approaches
Roles of stromal cells in the immune system
Stromal cells were typically defined as passive organizers of an organ, producing extracellular matrix and basement membrane proteins. While stromal cells do provide important structural support for most organs, their role in coordinating the local microenvironment in the steady state and during inflammation is becoming increasingly better known. In this article we will review the many roles of stromal cells in regulating immune responses in their local tissue environment, including both lymphoid tissue and inflammatory lesions
Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8+ T cells
Fibroblastic reticular cells (FRCs), through their expression of CC chemokine ligand (CCL)19 and CCL21, attract and retain T cells in lymph nodes (LNs), but whether this function applies to both resting and activated T cells has not been examined. Here we describe a model for conditionally depleting FRCs from LNs based on their expression of the diphtheria toxin receptor (DTR) directed by the gene encoding fibroblast activation protein-α (FAP). As expected, depleting FAP+ FRCs causes the loss of naïve T cells, B cells, and dendritic cells from LNs, and this loss decreases the magnitude of the B- and T-cell responses to a subsequent infection with influenza A virus. In contrast, depleting FAP+ FRCs during an ongoing influenza infection does not diminish the number or continued response of activated T and B cells in the draining LNs, despite still resulting in the loss of naïve T cells. Therefore, different rules govern the LN trafficking of resting and activated T cells; once a T cell is engaged in antigen-specific clonal expansion, its retention no longer depends on FRCs or their chemokines, CCL19 and CCL21. Our findings suggest that activated T cells remain in the LN because they down-regulate the expression of the sphingosine-1 phosphate receptor-1, which mediates the exit of lymphocytes from secondary lymphoid organs. Therefore, LN retention of naïve lymphocytes and the initiation of an immune response depend on FRCs, but is an FRC independent and possibly cell-autonomous response of activated T cells, which allows the magnitude of clonal expansion to determine LN egress
The role of immunoglobulin and complement in enhancing the respiratory burst of neutrophils against Trichomonas vaginalis
Influence of whole body protein turnover rate on resting energy expenditure in patients with cancer
Whole body protein turnover and resting energy expenditure are measured simultaneously in weight stable and weight losing patients with lung (n = 22) or colorectal cancer (n = 38). These results were compared with those from weight stable and weight losing non-cancer controls (n = 22). Rates of whole body protein turnover were calculated from the plateau isotopic enrichment of urinary ammonia and urea following a primed, continuous, 24-h infusion of [15N]glycine. Resting energy expenditure was measured by indirect calorimetry. All groups of cancer patients had significantly elevated rates of whole body protein turnover (P less than 0.05) and synthesized, on average, 1.9 g/kg/day more protein compared with weight stable non-cancer controls. In contrast, the resting energy expenditure of cancer patients and controls was similar. Moreover, there was no correlation between individual rates of whole body protein turnover. Thus, although cancer patients had rates of whole body protein turnover which were 50-70% greater than controls, this did not result in a measurable increase in resting energy expenditure. The assumption that elevation of whole body protein turnover or resting energy expenditure causes weight loss in cancer patients must be an oversimplification. An acute phase protein response was observed in the majority of cancer patients. Although the presence of such an inflammatory response did not correlate with the rate of whole body protein turnover, the role of inflammatory mediators in the pathogenesis of disturbed protein metabolism in cancer patients merits further investigation
Characterization of a Monoclonal Antibody Against P57, The C3/C3b-Cleaving Proteinase Expressed in Human Erythrocyte Membranes
Human platelets after their contact with influenza virus activate the complement system in autologous serum
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