Comparison of Particle Image Velocimetry and Laser Doppler Anemometry Measurements in Turbulent Fluid Flow

PAC00: 8763Lk, 4262Be, 8719Uv, 8719Hh, 8780-y     

Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait

Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss.     

Antibody drug conjugates - Trojan horses in the war on cancer

Antibody drug conjugates (ADCs) consist of an antibody attached to a cytotoxic drug by means of a linker. ADCs provide a way to couple the specificity of a monoclonal antibody (mAb) to the cytotoxicity of a small-molecule drug and, therefore, are promising new therapies for cancer. ADCs are prodrugs that are inactive in circulation but exert their cytotoxicity upon binding to the target cancer cell. Earlier unsuccessful attempts to generate ADCs with therapeutic value have emphasized the important role each component plays in determining the efficacy and safety of the final ADC. Scientific advances in engineering antibodies for maximum efficacy as anticancer agents, identification of highly cytotoxic molecules, and generation of linkers with increased stability in circulation have all contributed to the development of the many ADCs that are currently in clinical trials. This review discusses parameters that guide the selection of the components of an ADC to increase its therapeutic window, provides a brief look at ADCs currently in clinical trials, and discusses future challenges in this field.     

Inclusion of Compliance and Persistence in Economic Models

Economic models are developed to provide decision makers with information related to the real-world effectiveness of therapeutics, screening and diagnostic regimens. Although compliance with these regimens often has a significant impact on real-world clinical outcomes and costs, compliance and persistence have historically been addressed in a relatively superficial fashion in economic models. In this review, we present a discussion of the current state of economic modelling as it relates to the consideration of compliance and persistence. We discuss the challenges associated with the inclusion of compliance and persistence in economic models and provide an in-depth review of recent modelling literature that considers compliance or persistence, including a brief summary of previous reviews on this topic and a survey of published models from 2005 to 2012. We review the recent literature in detail, providing a therapeutic-area-specific discussion of the approaches and conclusions drawn from the inclusion of compliance or persistence in economic models. In virtually all publications, variation of model parameters related to compliance and persistence was shown to have a significant impact on predictions of economic outcomes. Growing recognition of the importance of compliance and persistence in the context of economic evaluations has led to an increasing number of economic models that consider these factors, as well as the use of more sophisticated modelling techniques such as individual simulations that provide an avenue for more rigorous consideration of compliance and persistence than is possible with more traditional methods. However, we note areas of continuing concern cited by previous reviews, including inconsistent definitions, documentation and tenuous assumptions required to estimate the effect of compliance and persistence. Finally, we discuss potential means to surmount these challenges via more focused efforts to collect compliance and persistence data.     

Cardiac-specific overexpression of phospholamban alters calcium kinetics and resultant cardiomyocyte mechanics in transgenic mice.

Phospholamban is the regulator of the cardiac sarcoplasmic reticulum (SR) Ca(2+)-ATPase activity and an important modulator of basal contractility in the heart. To determine whether all the SR Ca(2+)-ATPase enzymes are subject to regulation by phospholamban in vivo, transgenic mice were generated which overexpressed phospholamban in the heart, driven by the cardiac-specific alpha-myosin heavy chain promoter. Quantitative immunoblotting revealed a twofold increase in the phospholamban protein levels in transgenic hearts compared to wild type littermate hearts. The transgenic mice showed no phenotypic alterations and no changes in heart/body weight, heart/lung weight, and cardiomyocyte size. Isolated unloaded cardiac myocytes from transgenic mice exhibited diminished shortening fraction (63%) and decreased rates of shortening (64%) and relengthening (55%) compared to wild type (100%) cardiomyocytes. The decreases in contractile parameters of transgenic cardiomyocytes reflected decreases in the amplitude (83%) of the Ca2+ signal and prolongation (131%) in the time for decay of the Ca2+ signal, which was associated with a decrease in the apparent affinity of the SR Ca(2+)-ATPase for Ca2+ (56%), compared to wild type (100%) cardiomyocytes. In vivo analysis of left ventricular systolic function using M mode and pulsed-wave Doppler echocardiography revealed decreases in fractional shortening (79%) and the normalized mean velocity of circumferential shortening (67%) in transgenic mice compared to wild type (100%) mice. The differences in contractile parameters and Ca2+ kinetics in transgenic cardiomyocytes and the depressed left ventricular systolic function in transgenic mice were abolished upon isoproterenol stimulation. These findings indicate that a fraction of the Ca(2+)-ATPases in native SR is not under regulation by phospholamban. Expression of additional phospholamban molecules results in: (a) inhibition of SR Ca2+ transport; (b) decreases in systolic Ca2+ levels and contractile parameters in ventricular myocytes; and (c) depression of basal left ventricular systolic function in vivo.     

Functional integrity of lacrimal drainage apparatus by radionuclide dacryocystography

30 patients with epiphora and related complaints were investigated by Radionuclide Dacrocystography. It was possible to do this procedure easily in all age groups. The site of block in the lacrimal system could be accurately determined by this non-invasive technique.     

Babesiosis as a cause of acute respiratory distress syndrome: a series of eight cases

Objectives: The characteristics of patients with Acute Respiratory Distress Syndrome (ARDS) as a complication of Babesia microti infection have not been systematically described.

Methods: Adult patients admitted to the medical intensive care unit (MICU) of a tertiary care hospital in the Lower Hudson Valley of New York from 1/1/2008 to 8/1/2016 were evaluated for ARDS complicating babesiosis.

Results: Of 22 patients with babesiosis in the MICU, eight (36.4%; 95% CI: 19.7–57.0%) had ARDS. Six patients (75%) developed ARDS following initiation of anti-babesia drug therapy; however, the mean duration of symptoms in these patients exceeded that of patients who developed ARDS prior to initiation of treatment (7.50 ± 3.83d vs. 4.50 ± 0.71d, p = 0.34). Three patients (37.5%; 95% CI: 13.7–69.4%) expired without recovery from ARDS. In comparison, the mortality rate for the 14 MICU babesiosis patients without ARDS was 14.3% (p = 0.31). There was a trend toward younger age in survivors relative to non-survivors (mean age 54.6 ± 13.8y vs. 74.0 ± 6.24y, p = 0.07). Three of the five survivors did not require mechanical ventilation. The mean sequential organ failure assessment score of non-survivors was significantly higher than that of survivors (12.3 ± 1.15 vs. 6.0 ± 1.4, p = 0.0006).

Conclusion: Among 22 critically ill adult patients with B. microti infection, ARDS developed in eight (35.4%), and three (37.5%) expired without resolution of the ARDS. ARDS often followed the initiation of anti-babesia drug therapy, raising the question of whether the death of the parasite per se contributed to its development. However, this observation was confounded by the longer duration of symptoms preceding initiation of drug therapy.     

Elucidating the associations between sleep disturbance and depression,fatigue, and pain in older adults with cancer

Objectives

Sleep disturbance is prevalent and often coexists with depression, fatigue, and pain in the cancer population. The aim of this study was to describe the prevalence of sleep disturbance with co-existing depression, fatigue, and pain in older patients with cancer. We also examined the associations of several socio-demographic and clinical variables with sleep disturbance.