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Search Results for all work with filters:

  • 2012
  • fluid

Work 1-10 of 11

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Article

Association of Coronary Wall Shear Stress With Atherosclerotic Plaque Burden, Composition, and Distribution in Patients With Coronary Artery Disease

by Parham Eshtehardi; Michael C McDaniel; Jin Suo; Saurabh Dhawan; Lucas Timmins; Jose N Binongo; Lucas J Golub; Michel T Corban; Aloke Finn; John Oshinski; Arshed Ali Quyyumi; Don P Giddens; Habib Samady

2012

Subjects
  • Engineering, Biomedical
  • Biology, Biostatistics
  • Health Sciences, Public Health
  • File Download
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Abstract:Close

BACKGROUND: Extremes of wall shear stress (WSS) have been associated with plaque progression and transformation, which has raised interest in the clinical assessment of WSS. We hypothesized that calculated coronary WSS is predicted only partially by luminal geometry and that WSS is related to plaque composition. METHODS AND RESULTS: Twenty-seven patients with coronary artery disease underwent virtual histology intravascular ultrasound and Doppler velocity measurement for computational fluid dynamics modeling for WSS calculation in each virtual histology intravascular ultrasound segment (N=3581 segments). We assessed the association of WSS with plaque burden and distribution and with plaque composition. WSS remained relatively constant across the lower 3 quartiles of plaque burden (P=0.08) but increased in the highest quartile of plaque burden (P<0.001). Segments distal to lesions or within bifurcations were more likely to have low WSS (P<0.001). However, the majority of segments distal to lesions (80%) and within bifurcations (89%) did not exhibit low WSS. After adjustment for plaque burden, there was a negative association between WSS and percent necrotic core and calcium. For every 10 dynes/cm(2) increase in WSS, percent necrotic core decreased by 17% (P=0.01), and percent dense calcium decreased by 17% (P<0.001). There was no significant association between WSS and percent of fibrous or fibrofatty plaque components (P=NS). CONCLUSIONS: IN PATIENTS WITH CORONARY ARTERY DISEASE: (1) Luminal geometry predicts calculated WSS only partially, which suggests that detailed computational techniques must be used to calculate WSS. (2) Low WSS is associated with plaque necrotic core and calcium, independent of plaque burden, which suggests a link between WSS and coronary plaque phenotype. (J Am Heart Assoc. 2012;1:e002543 doi: 10.1161/JAHA.112.002543.).

Article

Nematode sperm maturation triggered by protease involves sperm-secreted serine protease inhibitor (Serpin)

by Yanmei Zhao; Wei Sun; Pan Zhang; Hao Chi; Mei-Jun Zhang; Chun-Qing Song; Xuan Ma; Yunlong Shang; Bin Wang; Youqiao Hu; Zhiqi Hao; Andreas F. Huehmer; Fanxia Meng; Steven L'Hernault; Si-Min He; Meng-Qiu Dong; Long Miao

2012

Subjects
  • Biology, General
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Abstract:Close

Spermiogenesis is a series of poorly understood morphological, physiological and biochemical processes that occur during the transition of immotile spermatids into motile, fertilization-competent spermatozoa. Here, we identified a Serpin (serine protease inhibitor) family protein (As-SRP-1) that is secreted from spermatids during nematode Ascaris suum spermiogenesis (also called sperm activation) and we showed that As-SRP-1 has two major functions. First, As-SRP-1 functions in cis to supportmajor spermprotein (MSP)- based cytoskeletal assembly in the spermatid that releases it, thereby facilitating sperm motility acquisition. Second, As-SRP-1 released froman activated sperminhibits, in trans, the activation of surrounding spermatids by inhibiting vas deferens-derived As-TRY-5, a trypsin- like serine protease necessary for sperm activation. Because vesicular exocytosis is necessary to create fertilization-competent sperm in many animal species, components released during this process might be more important modulators of the physiology and behavior of surrounding sperm than was previously appreciated.

Article

Inpatient management of sickle cell pain: A snapshot of current practice

by Scott T. Miller; Hae-Young Kim; Debra Weiner; Carrie G. Wager; Dianne Gallagher; Lori Styles; Carlton Dampier; Investigators of the Sickle Cell Disease Clinical Research Network (SCDCRN)

2012

Subjects
  • Health Sciences, Medicine and Surgery
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The Sickle Cell Disease Clinical Research Network (SCDCRN) designed the PROACTIVE Feasibility Study (ClinicalTrials.gov NCT00951808) to determine whether elevated serum levels of secretory phospholipase A2 (sPLA2) during hospitalization for pain would permit preemptive therapy of sickle cell acute chest syndrome (ACS) by blood transfusion. While PROACTIVE was not designed to assess pain management and was terminated early due to inadequate patient accrual, collection of clinical data allowed a "snapshot" of current care by expert providers. Nearly half the patients admitted for pain were taking hydroxyurea; hydroxyurea did not affect length of stay. Providers commonly administered parenteral opioid analgesia, usually morphine or hydromorphone, to adults and children, generally by patient-controlled analgesia (PCA). Adult providers were more likely to prescribe hydromorphone and did so at substantially higher morphine equivalent doses than were given to adults receiving morphine; the latter received doses similar to children who received either medication. All subjects treated with PCA received higher daily doses of opioids than those treated by time-contingent dosing. Physicians often restricted intravenous fluids to less than a maintenance rate and underutilized incentive spirometry, which reduces ACS in patients hospitalized for pain.

Article

Hydrodynamic modulation of pluripotent stem cells

by Krista M Fridley; Melissa A Kinney; Todd McDevitt

2012

Subjects
  • Engineering, Biomedical
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Controlled expansion and differentiation of pluripotent stem cells (PSCs) using reproducible, high-throughput methods could accelerate stem cell research for clinical therapies. Hydrodynamic culture systems for PSCs are increasingly being used for high-throughput studies and scale-up purposes; however, hydrodynamic cultures expose PSCs to complex physical and chemical environments that include spatially and temporally modulated fluid shear stresses and heterogeneous mass transport. Furthermore, the effects of fluid flow on PSCs cannot easily be attributed to any single environmental parameter since the cellular processes regulating self-renewal and differentiation are interconnected and the complex physical and chemical parameters associated with fluid flow are thus difficult to independently isolate. Regardless of the challenges posed by characterizing fluid dynamic properties, hydrodynamic culture systems offer several advantages over traditional static culture, including increased mass transfer and reduced cell handling. This article discusses the challenges and opportunities of hydrodynamic culture environments for the expansion and differentiation of PSCs in microfluidic systems and larger-volume suspension bioreactors. Ultimately, an improved understanding of the effects of hydrodynamics on the self-renewal and differentiation of PSCs could yield improved bioprocessing technologies to attain scalable PSC culture strategies that will probably be requisite for the development of therapeutic and diagnostic applications.

Article

Aiming for a negative fluid balance in patients with acute lung injury and increased intra-abdominal pressure: a pilot study looking at the effects of PAL-treatment

by Colin Cordemans; Inneke De laet; Niels Van Regenmortel; Karen Schoonheydt; Hilde Dits; Greg Martin; Wolfgang Huber; Manu LNG Malbrain

2012

Subjects
  • Health Sciences, General
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Abstract:Close

Introduction Achievement of a negative fluid balance in patients with capillary leak is associated with improved outcome. We investigated the effects of a multi-modal restrictive fluid strategy aiming for negative fluid balance in patients with acute lung injury (ALI). Methods In this retrospective matched case-control study, we included 114 mechanically ventilated (MV) patients with ALI. We compared outcomes between a group of 57 patients receiving PAL-treatment (PAL group) and a matched control group, abstracted from a historical cohort. PAL-treatment combines high levels of positive end-expiratory pressure, small volume resuscitation with hyperoncotic albumin, and fluid removal with furosemide (Lasix®) or ultrafiltration. Effects on extravascular lung water index (EVLWI), intra-abdominal pressure (IAP), organ function, and vasopressor therapy were recorded during 1 week. The primary outcome parameter was 28-day mortality. Results At baseline, no significant intergroup differences were found, except for lower PaO2/FIO2 and increased IAP in the PAL group (174.5 ± 84.5 vs 256.5 ± 152.7, p = 0.001; 10.0 ± 4.2 vs 8.0 ± 3.7 mmHg, p = 0.013, respectively). After 1 week, PAL-treated patients had a greater reduction of EVLWI, IAP, and cumulative fluid balance (-4.2 ± 5.6 vs -1.1 ± 3.7 mL/kg, p = 0.006; -0.4 ± 3.6 vs 1.8 ± 3.8 mmHg, p = 0.007; -1,451 ± 7,761 vs 8,027 ± 5,254 mL, p < 0.001). Repercussions on cardiovascular and renal function were limited. PAL-treated patients required fewer days of intensive care unit admission and days on MV (23.6 ± 15 vs 37.1 ± 19.9 days, p = 0.006; 14.6 ± 10.7 vs 25.5 ± 20.2 days, respectively) and had a lower 28-day mortality (28.1% vs 49.1%, p = 0.034). Conclusion PAL-treatment in patients with ALI is associated with a negative fluid balance, a reduction of EVLWI and IAP, and improved clinical outcomes without compromising organ function.

Article

Hypoplastic Left Heart Syndrome Current Considerations and Expectations

by Jeffrey A. Feinstein; D. Woodrow Benson; Anne M. Dubin; Meryl S. Cohen; Dawn M. Maxey; William Mahle; Elfriede Pahl; Juan Villafane; Ami B. Bhatt; Lynn F. Peng; Beth Ann Johnson; Alison L. Marsden; Curt J. Daniels; Nanacy A. Rudd; Christopher A. Caldarone; Kathleen A. Mussatto; David L. Morales; D. Dunbar Ivy; J. William Gaynor; James S. Tweddell; Barbara J. Deal; Anke K. Furck; Geoffrey L. Rosenthal; Richard G. Ohye; Nancy S. Ghanayem; John P. Cheatham; Wayne Tworetzky; Gerard R. Martin

2012

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
  • File Download
  • View Abstract

Abstract:Close

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

Article

Visualization of flow structures in Fontan patients using 3-dimensional phase contrast magnetic resonance imaging

by Kartik S. Sundareswaran; Christopher M. Haggerty; Diane de Zelicourt; Lakshmi P. Dasi; Kerem Pekkan; David H. Frakes; Andrew J. Powell; Kirk R Kanter; Mark A. Fogel; Ajit Yoganathan

2012

Subjects
  • Health Sciences, Medicine and Surgery
  • Engineering, Biomedical
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Objective: Our objective was to analyze 3-dimensional (3D) blood flow patterns within the total cavopulmonary connection (TCPC) using in vivo phase contrast magnetic resonance imaging (PC MRI). Methods: Sixteen single-ventricle patients were prospectively recruited at 2 leading pediatric institutions for PC MRI evaluation of their Fontan pathway. Patients were divided into 2 groups. Group 1 comprised 8 patients with an extracardiac (EC) TCPC, and group 2 comprised 8 patients with a lateral tunnel (LT) TCPC. A coronal stack of 5 to 10 contiguous PC MRI slices with 3D velocity encoding (5-9 ms resolution) was acquired and a volumetric flow field was reconstructed. Results: Analysis revealed large vortices in LT TCPCs and helical flow structures in EC TCPCs. On average, there was no difference between LT and EC TCPCs in the proportion of inferior vena cava flow going to the left pulmonary artery (43% ± 7% vs 46% ± 5%; P = .34). However, for EC TCPCs, the presence of a caval offset was a primary determinant of inferior vena caval flow distribution to the pulmonary arteries with a significant bias to the offset side. Conclusions: 3D flow structures within LT and EC TCPCs were reconstructed and analyzed for the first time using PC MRI. TCPC flow patterns were shown to be different, not only on the basis of LT or EC considerations, but with significant influence from the superior vena cava connection as well. This work adds to the ongoing body of research demonstrating the impact of TCPC geometry on the overall hemodynamic profile.

Article

Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants

by Davide Bruno; Nunzio Pomara; Jay J. Nierenberg; James C Ritchie; Michael W. Lutz; Henrik Zetterberg; Kaj Blennow

2012

Subjects
  • Biology, Neuroscience
  • Health Sciences, Mental Health
  • Health Sciences, Pathology
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Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE ε4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE ε4. Our results show that the presence of APOE ε4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE ε4 have higher CSF NFL levels than non-ε4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of ε4.

Article

Renal Replacement Therapy in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation

by David J. Askenazi; David T. Selewski; Matthew Paden; David S. Cooper; Brian C. Bridges; Michael Zappitelli; Geoffrey M. Fleming

2012

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
  • File Download
  • View Abstract

Abstract:Close

Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure used in neonates, children, and adults with severe, reversible, cardiopulmonary failure.On the basis of single-center studies, the incidence of AKI occurs in 70%-85% of ECMO patients. Those with AKI and those who require renal replacement therapy (RRT) are at high risk for mortality, independent of potentially confounding variables. Fluid overload is common in ECMO patients, and is one of the main indications for RRT. RRT to maintain fluid balance and metabolic control is common in some but not all centers. RRT on ECMO can be performed via an in-line hemofilter or by incorporating a standard continuous renal replacement machine into the ECMO circuit. Both of these methods require specific technical considerations to provide safe and effective RRT. This reviewsummarizes available epidemiologic data and how they apply to our understanding of AKI pathophysiology during ECMO, identifies indications for RRT while on ECMO, reviews technical elements for RRT application in the setting of ECMO, and finally identifies specific researchfocused questions that need to be addressed to improve outcomes in this at-risk population.

Article

A Multicenter International Survey of Renal Supportive Therapy During ECMO: The Kidney Intervention During Extracorporeal Membrane Oxygenation (KIDMO) Group

by Geoffrey M. Fleming; David J. Askenazi; Brian C. Bridges; David S. Cooper; Matthew Paden; David T. Selewski; Michael Zappitelli

2012

Subjects
  • Health Sciences, Public Health
  • Health Sciences, General
  • File Download
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Acute kidney injury and fluid overload (FO) are associated with increased mortality in critically ill patients, including the subset supported with extracorporeal membrane oxygenation (ECMO). The indication for and method of application of renal support therapy (RST) during ECMO is largely unknown beyond single-center experiences. The current study uses a survey design to document practice variation regarding RST, including indication, method of interface with the ECMO circuit, and prescribing practices. Sixty-five international ECMO centers (31%) responded to an online electronic survey regarding RST during ECMO. Nearly a quarter of centers (23%) reported using no RST during ECMO. Among those using the therapy, the predominant mode of therapy applied was convection and included slow continuous ultrafiltration and continuous venovenous hemofiltration. The predominant indication for RST was the treatment (43%) or prevention (16%) of FO. Nephrology rather than critical care medicine is reported as the prescribing service in a majority of centers with a significant difference between US centers and non-US centers. The results of this study identify a wide variation in practice regarding RST during ECMO that will offer multiple important avenues for further research by this group and others regarding the interface of RST and ECMO.
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