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Biomedical subjects

James E Moore

Publications and source records attributed to James E Moore.

17 recordsLinked to original sources

Image correlation algorithm for measuring lymphocyte velocity and diameter changes in contracting microlymphatics.

Efforts have recently been made to estimate wall shear stress throughout the contractile cycle of mesenteric rat lymphatics with a high speed video microscopy system. This was prompted by reports in the literature that lymphatic pumping is related to wall shear stress. While one can estimate wall shear stress by tracking lymphocyte velocity, it is prohibitively tedious to manually track particles over a reasonable time frame for a good number of experiments. To overcome this, an image correlation method similar to digital particle imaging velocimetry was developed and tested on contracting lymphatics to measure both vessel diameter and fluid velocity. The program tracked temporal fluctuations in spatially averaged velocity with a standard error of prediction of 0.4 mm/s. From these studies we have measured velocities ranging from -2 to 4 mm/s. Diameter changes were also measured with a standard error of 7 microm. These algorithms and techniques could be beneficial for investigating various changes in contractile behavior as a function of changes in velocity and wall shear stress.

Algorithms↗

Cost-effectiveness of two self-care interventions to reduce disability associated with back pain.

STUDY DESIGN: Two randomized, controlled trials. OBJECTIVE: To evaluate the incremental cost-effectiveness of psychologist-led and lay-led interventions in reducing disability in 2 cohorts of primary care patients with back pain. SUMMARY OF BACKGROUND DATA: Although activating self-care interventions have been advanced as effective tools to reduce back pain-related activity limitations, few studies have evaluated the added costs of these programs relative to their added benefits. METHODS: We estimated the incremental benefits and incremental costs associated with 2 self-care interventions for primary care patients with back pain. Effectiveness was measured as the number of low-impact back pain days (i.e., days when patients were satisfied with their level of back pain) over a 1-year follow-up. Costs of back-pain related services were estimated from health plan cost data. Incremental cost-effectiveness ratios were calculated for each intervention to determine the costs associated with an additional low-impact back pain day. RESULTS: Patients assigned to the lay and psychologist interventions had a mean of 14.3 (95% confidence interval [CI] -2.7 to 30.9) and 26.2 (95% CI 9.1-44.4) additional low-impact back pain days, respectively, compared with patients receiving usual care. The incremental per-person costs of the lay-led and psychologist-led interventions were dollar 139 (95% CI - dollar 62.13 to dollar 321.76) and dollar 161 (95% CI dollar 51.18 to dollar 275.93), respectively. The mean cost of an additional low-impact back pain day was dollar 9.70 for the lay-led intervention and dollar 6.13 for the psychologist-led intervention. CONCLUSIONS: Both the lay and psychologist interventions were associated with modest improvements in outcomes but with somewhat higher costs compared to usual care.

Adult↗

Effects of stent design parameters on normal artery wall mechanics.

A stent is a device designed to restore flow through constricted arteries. These tubular scaffold devices are delivered to the afflicted region and deployed using minimally invasive techniques. Stents must have sufficient radial strength to prop the diseased artery open. The presence of a stent can subject the artery to abnormally high stresses that can trigger adverse biologic responses culminating in restenosis. The primary aim of this investigation was to investigate the effects of varying stent "design parameters" on the stress field induced in the normal artery wall and the radial displacement achieved by the stent. The generic stent models were designed to represent a sample of the attributes incorporated in present commercially available stents. Each stent was deployed in a homogeneous, nonlinear hyperelastic artery model and evaluated using commercially available finite element analysis software. Of the designs investigated herein, those employing large axial strut spacing, blunted corners, and higher amplitudes in the ring segments induced high circumferential stresses over smaller areas of the artery's inner surface than all other configurations. Axial strut spacing was the dominant parameter in this study, i.e., all designs employing a small stent strut spacing induced higher stresses over larger areas than designs employing the large strut spacing. Increasing either radius of curvature or strut amplitude generally resulted in smaller areas exposed to high stresses. At larger strut spacing, sensitivity to radius of curvature was increased in comparison to the small strut spacing. With the larger strut spacing designs, the effects of varying amplitude could be offset by varying the radius of curvature and vice versa. The range of minimum radial displacements from the unstented diastolic radius observed among all designs was less than 90 microm. Evidence presented herein suggests that stent designs incorporating large axial strut spacing, blunted corners at bends, and higher amplitudes exposed smaller regions of the artery to high stresses, while maintaining a radial displacement that should be sufficient to restore adequate flow.

Animals↗

Cardiotrophin-1 protects cortical neuronal cells against free radical-induced injuries in vitro.

Cardiotrophin-1 (CT-1) was initially defined as a mediator of cardiomyocyte hypertrophy. Additional studies have showed that CT-1 enhanced survival of differentiated cardiac muscle cells and inhibited cardiac myocyte apoptosis after serum deprivation or cytokine stimulation. Moreover, CT-1 has recently been shown to act as a neuroregulatory cytokine in the peripheral nervous system. However, its effects in the central nervous system have not been determined. In the present study, we evaluated whether CT-1 protects cultured cortical neurons against oxidative injuries caused by the hydroxyl radical-producing agent FeSO4 and by the peroxynitrite-producing agent 3-morpholinosydnonimine (SIN-1). CT-1 reduced neuronal cell death caused by FeSO4 and also attenuated the neurotoxic effect of SIN-1 in a dose-dependent manner. These results indicate that CT-1 is neuroprotective in an in vitro model of cerebral ischemia. This study indicates that further evaluation of CT-1 in acute brain injury should be investigated in vivo.

Animals↗

Spatial distribution of platelet deposition in stented arterial models under physiologic flow.

This paper presents dynamic flow experiments with fluorescently labeled platelets to allow for spatial observation of wall attachment in inter-strut spacings, to investigate their relationship to flow patterns. Human blood with fluorescently labeled platelets was circulated through an in vitro system that produced physiologic pulsatile flow in a parallel plate flow chamber that contained three different stent designs that feature completely recirculating flow, partially recirculating flow (intermediate strut spacing), and completely reattached flow. Highly resolved spatial distribution of platelets was obtained by imaging fluorescently labeled platelets between the struts. Platelet deposition was higher in areas where flow is directed towards the wall, and lower in areas where flow is directed away from the wall. Flow detachment and reattachment points exhibited very low platelet deposition. Platelet deposition within intermediate strut spacing continued to increase throughout the experimental period, indicating that the deposition rate had not plateaued unlike other strut spacings. The spatial uniformity and temporal increase in platelet deposition for the intermediate strut spacing confirms and helps explain our previous finding that platelet deposition was highest with this strut spacing. Further experimental investigations will include more complex three-dimensional geometries.

Arteries↗

Bio-fluids educational issues: an emerging field aims to define its next generation.

There are numerous processes in the body under healthy and pathologic conditions in which bio-fluid mechanics play a central role. The delivery of various substances to and from tissues is accomplished through a combination of complex active and passive mass transfer processes. Bio-fluid mechanics also play a central role in locomotion, from water-bound amoeba and fish to the soaring of birds. Educating undergraduate and graduate students in such wide-ranging fluid mechanical phenomena has proved challenging within the typical context of a biomedical engineering program. The diversity of biomedical engineering topics entails increased biological sciences curricular content, possibly limiting the opportunities to provide a fundamental knowledge base in fluid mechanics which may be expected in the more traditional engineering disciplines. The lack of textbooks in the area, while problematic in the past, is being alleviated with some recent texts and several new ones are due to appear soon. Today's bio-fluids educators are presented with the challenge of providing sufficient fundamental knowledge in bio-fluid mechanics within one- or two-semester courses. The richness of this topic has led to a variety of approaches to course development. This article outlines some of the current approaches and presents some strategies that we hope would help in constructing effective bio-fluids courses.

Biomechanical Phenomena↗

A trial of an activating intervention for chronic back pain in primary care and physical therapy settings.

In primary care and physical therapy settings, we evaluated an intervention for chronic back pain patients which incorporated fear reducing and activating techniques. Primary care patients seen for back pain in primary care were screened to identify persons with significant activity limitations 8-10 weeks after their visit. Eligible and willing patients were randomized (N=240). A brief, individualized program to reduce fear and increase activity levels was delivered by a psychologist and physical therapists. Over a 2 year follow-up period, intervention patients reported greater reductions in pain-related fear (P<0.01), average pain (P<0.01) and activity limitations due to back pain (P<0.01) relative to control patients. The percent with greater than a one-third reduction in Roland Disability Questionnaire scores at 6 months was 42% among Intervention patients and 24% among control patients (P<0.01). Over the 2 year follow-up, fewer intervention patients reported 30 or more days unable to carry out usual activities in the prior 3 months (P<0.01). The adjusted mean difference in activity limitation days was 4.5 days at 6 months, 2.8 days at 12 months, and 6.9 days at 24 months. No differences were observed in the percent unemployed or the percent receiving worker's compensation or disability benefits, but these outcomes were relatively uncommon. We conclude that an intervention integrating fear reducing and activating interventions into care for chronic back pain patients produced sustained reductions in patient fears, common activity limitations related to back pain, and days missed from usual activities due to back pain.

Activities of Daily Living↗

Stress distribution in a circular membrane with a central fixation.

Clinical interventions can change the mechanical environment of the tissues targeted for therapy. In order to design better procedures, it is important to understand cellular responses to altered mechanical stress. Rigid fixation is one example of a constraint imposed on living tissues as a result of implanted devices. This results in disturbed stress and strain fields, with potentially strong gradients. Herein, we numerically solve the governing nonlinear ordinary differential equation for the stress distribution in a finitely deformed anisotropic circular membrane with a concentric fixation by applying a zero-displacement condition at the inner circumference. Results show that rigid fixations yield distributions of stress and strain that are markedly different from tissue defects with traction-free boundaries. Moreover the material anisotropy plays a significant role in the manner the stress redistributes regardless of the size of fixation. The present study will contribute to the design of experiments to determine cellular reactions involved in the failure of interventional treatments.

Animals↗

Blood flow in stented arteries: a parametric comparison of strut design patterns in three dimensions.

BACKGROUND: Restenosis after stent implantation varies with stent design. Alterations in secondary flow patterns and wall shear stress (WSS) can modulate intimal hyperplasia via their effects on platelet and inflammatory cell transport toward the wall, as well as direct effects on the endothelium. METHOD OF APPROACH: Detailed flow characteristics were compared by estimating the WSS in the near-strut region of realistic stent designs using three-dimensional computational fluid dynamics (CFD), under pulsatile high and low flow conditions. The stent geometry employed was characterized by three geometric parameters (axial strut pitch, strut amplitude, and radius of curvature), and by the presence or lack of the longitudinal connector. RESULTS: Stagnation regions were localized around stent struts. The regions of low WSS are larger distal to the strut. Under low flow conditions, the percentage restoration of mean axial WSS between struts was lower than that for the high flow by 10-12%. The largest mean transverse shear stresses were 30-50% of the largest mean axial shear stresses. The percentage restoration in WSS in the models without the longitudinal connector was as much as 11% larger than with the connector The mean axial WSS restoration between the struts was larger for the stent model with larger interstrut spacing. CONCLUSION: The results indicate that stent design is crucial in determining the fluid mechanical environment in an artery. The sensitivity of flow characteristics to strut configuration could be partially responsible for the dependence of restenosis on stent design. From a fluid dynamics point of view, interstrut spacing should be larger in order to restore the disturbed flow; struts should be oriented to the flow direction in order to reduce the area of flow recirculation. Longitudinal connectors should be used only as necessary, and should be parallel to the axis. These results could guide future stent designs toward reducing restenosis.

Animals↗

DPIV measurements of flow disturbances in stented artery models: adverse affects of compliance mismatch.

Vascular stents influence the post-procedural hemodynamic environment in ways that may encourage restenosis. Understanding how stents influence flow patterns may lead to more hemodynamically compatible stent designs that alleviate thrombus formation and promote endothelialization. This study employed time-resolved Digital Particle Image Velocimetry (DPIV) to compare the hemodynamic performance of two stents in a compliant vessel. The first stent was a rigid insert, representing an extreme compliance mismatch. The second stent was a commercially available nitinol stent with some flexural characteristics. DPIV showed that compliance mismatch promotes the formation of a ring vortex in the vicinity of the stent. Larger compliance mismatch increased both the size and residence time of the ring vortex, and introduced in-flow stagnation points. These results provide detailed quantitative evidence of the hemodynamic effect of stent mechanical properties. Better understanding of these characteristics will provide valuable information for modifying stent design in order to promote long-term patency.

Animals↗

Effects of periodic body acceleration on the in vivo vasoactive response to N-omega-nitro-L-arginine and the in vitro nitric oxide production.

Periodic acceleration (pGz), a novel method of ventilatory support, is achieved using a platform that moves cyclically in the headward-footward direction. PGz has been shown to increase vascular shear stress and regional blood flows, as well as decrease pulmonary and systemic vascular resistances. PGz also increases nitric oxide (NO) production. This study was undertaken to determine the effects of pGz on the NO inhibiting effects of N-w-nitro-L-arginine (L-NAME) in vivo, and to determine if increased NO production due to pGz could be reproduced in vitro with isolated arteries. Pigs were assigned to conventional ventilation (CV), or pGz, with no additional breathing assistance. L-NAME was infused in cumulative doses of 1, 3, 10, 30, and 100 mg/kg. Cardiac output decreased in both groups by 50%. There was also a dose-dependent increase in blood pressure, pulmonary artery pressure, and vascular resistances. However, pGz attenuated the vascular response of L-NAME. Isolated porcine aortas exposed to nonpulsatile, pulsatile, and pulsatile flow plus pGz exhibited an increase in nitrites with the addition of pulsatile flow (300%, relative to steady flow), and a further increase with pGz (1000%, relative to steady flow). It has been determined that pGz, a novel method of increasing shear stress on the vascular endothelium. attenuates the vasoactive response to L-NAME. The in vitro experiments demonstrated that increases in NO production in vivo could be reproduced in vitro, which provides the opportunity to investigate the mechanisms of cardiovascular pGz effects.

Acceleration↗

Platelet adhesion to simulated stented surfaces.

PURPOSE: To determine if the protrusion of stent struts into the flow stream, which creates stagnation along the wall dependent on the strut spacing, has an effect on platelet adhesion. METHODS: Three 2-dimensional stents with different strut spacings were placed in a flat-plate flow chamber. Human blood was collected and platelets were labeled with indium 111. The blood with radioactive platelets was pumped through the flow chamber for 30 minutes to produce a pulsatile wall shear stress of 10+/-5 dynes/cm2 (mean +/- amplitude at 1 Hz). A gamma counter measured radioactivity along the surface and on the stents. Computational flow simulations provided specific data on flow separation and wall shear stress for each stent strut spacing tested (2.5, 4.0, and 7.0 times the strut height). RESULTS: The presence of any stent provoked an elevation in platelet adhesion within the stented region (p<0.05). The stents with larger strut spacing had higher platelet adhesion on the substrate in the stented region (1.71+/-0.63 normalized platelet deposition for the 7.0 model and 2.11+/-1.02 for the 4.0 model) than stents with smaller strut spacing (1.37+/-0.68 for the 2.5 model, p<0.05). The stents themselves showed platelet adhesion levels that were 3 to 7 times higher than the substrates, with a similar dependence on stent strut spacing. CONCLUSIONS: Additional knowledge of the role of mechanical factors in stent restenosis will aid in designing stents that minimize intimal hyperplasia and restenosis. The results of this study demonstrate the importance of stent design-mediated blood flow patterns, with smaller strut spacings minimizing platelet adhesion per unit strut area.

Blood Platelets↗

Computational fluid dynamics and stent design.

Stents are small, usually metallic tubes that are intended to prop open arteries blocked with atherosclerotic plaques. While stents have been used successfully in recent years, they still suffer from failure due to development of new tissue in stented segment (restenosis). Variations in the failure rates associated with different stent designs have led researchers to investigate the role of near-wall flow patterns. While there is no direct evidence yet, the patterns of flow stagnation as the blood flows past the stent struts may affect the restenosis process. Computational fluid dynamics (CFD) approaches are well suited for obtaining detailed information on stent flow patterns. Many CFD simulations make use of a two-dimensional model. The strong dependence of flow stagnation on stent strut spacing has been clearly demonstrated. These results have been employed to interpret the results of in vitro experiments designed to elucidate the mechanisms of restenosis.

Arteriosclerosis↗

A randomized trial of a cognitive-behavioral program for enhancing back pain self care in a primary care setting.

Back pain is a significant health care problem that has been managed unsatisfactorily in primary care settings. Providers typically address medical issues but do not adequately address patient concerns or functional limitations related to back pain. We evaluated a brief intervention for primary care back pain patients designed to provide accurate information about back pain, instill attitudes favorable towards self care, reduce fears and worries, assist patients in developing personalized action plans to manage their back pain, and improve functional outcomes. Patients enrolled in a large health maintenance organization were invited to participate in an educational program to improve back pain self care skills 6-8 weeks after a primary care back pain visit. Patients (n=226) were randomly assigned to a Self Care intervention or to Usual Care, and were assessed at baseline, 3-, 6-, and 12-months. The intervention involved a two-session Self Care group and an individual meeting and telephone conversation with the group leader, a psychologist experienced in chronic pain management. The intervention was supplemented by educational materials (book and videos) supporting active management of back pain. The control group received usual care supplemented by a book on back pain care. Participants assigned to the Self Care intervention showed significantly greater reductions in back-related worry and fear-avoidance beliefs than the control group. Modest, but statistically significant, effects on pain ratings and interference with activities were also observed.

Adult↗

Risk of misinterpretation of MMPI Schizophrenia scale elevations in chronic pain patients.

Seventy-three chronic pain patients with elevated MMPI Schizophrenia (Sc) scale scores (T score greater than 70) were compared with 55 psychotic and 87 non-psychotic psychiatric patients with elevated Sc scores to examine group differences in item content patterns on the Harris and Lingoes subscales. Chronic pain patients evidenced lower scores on all Harris and Lingoes Sc subscales, except for the Bizarre Sensory Experiences subscale on which they scored significantly higher than the psychiatric groups. Results demonstrate that Sc is elevated in many chronic pain patients because they endorse somatic symptoms and items suggestive of depression and inertia, whereas psychotics endorse more items reflecting bizarre and disordered thinking, social alienation and defective inhibition, and non-psychiatric patients endorse more depression, despair, thought disorganization and social alienation. These data suggest that high Sc scores of many chronic pain patients reflect symptoms and sequelae of their physical problems, and do not necessarily reflect severe psychopathology.

Adult↗

Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics.

OBJECTIVE: To measure lymphocyte velocity, lymphatic contraction, and shear stress in phasically contracting lymphatics in situ. METHODS: A high-speed video system was used to capture multiple contraction cycles in rat mesenteric lymphatic preparations. The images were analyzed to determine fluid velocity, volume flow rate, wall shear stress, and retrograde flow. RESULTS: Lymphocyte density and flux varied from 326 to 35,500 cells/microL and 206 to 2,030 cells/min, respectively. Lymphatics contracted phasically, with a mean diameter 91 +/- 9.0 microm and amplitudes of 39%. Lymph velocity varied with the phasic contractions in both direction and magnitude with an average of 0.87 +/- 0.18 and peaks of 2.2-9.0 mm/s. The velocity was approximately 180 degrees out of phase with the contraction cycle. The average lymph flow was 13.95 +/- 5.27 microL/h with transient periods of flow reversal. This resulted in an average shear of 0.64 +/- 0.14 with peaks of 4-12 dynes/cm(2). CONCLUSIONS: High-speed lymphocyte tracking provided the spatial and temporal resolution to measure lymphocyte flux throughout the phasic contraction. Poiseuille flow was a reasonable model for estimating wall shear stress through most of the phasic contraction cycle of the intervalvular lymphatic segments. Shear rate was low but had large variations in magnitude compared to that seen in blood vessels.

Animals↗