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Biomedical subjects

S R Bailey

Publications and source records attributed to S R Bailey.

At least 37 records · Page 2Linked to original sources

Adherence of eosinophils from allergic and normal ponies to cultured equine endothelial cells.

OBJECTIVES: To compare adherence of stimulated and unstimulated eosinophils from allergic and normal ponies to cultured equine vascular endothelial cells (equine digital vein endothelial cells; EDVEC) and examine the effect of eosinophil-derived factor(s) on cell adherence. METHODS: Eosinophil adherence to unstimulated EDVEC or EDVEC pretreated with IL-1beta or supernatants from stimulated eosinophils was measured. Supernatants were also assayed for TNFalpha and IL-1beta-like bioactivity. RESULTS: Adherence of unstimulated and rhIL-5 (10 ng/ml)-stimulated eosinophils from allergic ponies to rhIL-1beta-treated EDVEC was significantly greater than that of cells from normal ponies. Pretreatment of EDVEC with supernatants from stimulated eosinophils from both groups of ponies significantly increased adherence of autologous cells and IL-1beta- and TNFalpha-like bioactivities were detected in the supernatants. CONCLUSIONS: Mediator-induced activation of equine eosinophils may lead to further eosinophil recruitment by releasing cytokines that up-regulate endothelial cell adhesion molecule expression. Increased adherence of blood eosinophils from allergic ponies to stimulated endothelium could be explained by in vivo priming.

Animals↗

Development of a neurobehavioral battery for children exposed to neurotoxic chemicals.

In recent years there has been heightened concern over the potential impact of environmental exposures on neurological function in children. Children are thought to be especially vulnerable to neurotoxic effects due to a number offactors including play behavior, differences in metabolism, and the development state of the brain. Performance tests from the computerized Behavioral Assessment and Research System (BARS) and other non-computerized tests have been combined to develop a brief battery that assesses multiple neurobehavioral functions in preschool children aged 4-6. Tests were selected to assess a variety of cognitive functions including attention, memory, motor speed and coordination and other executive functions. The battery has also been translated into Spanish and developed for use with Latino populations. Four to six-year-old children are particularly challenging because of the shorter attention span and lower motivation to complete an extended test session. When testing this group it is important to maintain the motivation of the child throughout the entire session in order to obtain accurate performance measures. A series of sequential pilot studies were used to select and develop appropriate methods and parameters for the tests in the battery. Although English-speaking children were able to complete the initial battery with minimal difficulties, several difficulties were encountered when the tests were administered to a Latino population. Cultural differences made some material inappropriate for testing due to unfamiliarity with the material, and in some cases items in a test had more than one correct translation which made administration difficult.

Child↗

Long-term vessel response to a self-expanding coronary stent: a serial volumetric intravascular ultrasound analysis from the ASSURE Trial.A Stent vs. Stent Ultrasound Remodeling Evaluation.

OBJECTIVES: We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND: Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS: Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS: At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS: Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

Adult↗

Inflammatory mediators induce endothelium-dependent adherence of equine eosinophils to cultured endothelial cells.

Accumulation of equine eosinophils at sites of parasite infestation or allergic inflammation depends upon their adherence to vascular endothelial cells and subsequent migration through the endothelium and extracellular matrix. This study has examined whether cytokines, which cause endothelial cell-dependent eosinophil adherence in other species, and histamine and substance P, which increase adherence of equine eosinophils to protein coated plastic, induce equine eosinophil adherence to cultured equine digital vein endothelial cell (EDVEC) monolayers. The EDVEC monolayers were stimulated with recombinant human (rh) interleukin (IL)-1beta, rhTNFalpha, substance P or histamine for different times and with a range of concentrations of mediators and the adherence of blood eosinophils from normal horses examined. All four mediators caused time- and concentration-dependent increases in adherence. However, neither the response to substance P, nor that to histamine, reached a maximum at the highest concentration tested (10-3 M: 10.6 +/- 2.6% and 4.5 +/- 0.6% adherent cells vs. background adherence of 1.9 +/- 0.4% and 1.1 +/- 0.2%; values for substance P and histamine, respectively, expressed as a percentage of total cells added initially; n=4). These data suggest that, as in other species, cytokines induce endothelial cell-dependent eosinophil adherence and mediators released during allergic inflammation may play a role in eosinophil recruitment by this mechanism.

Animals↗

Past and present attempts to prevent radiocontrast nephropathy.

Radiocontrast nephropathy is an under-recognized event after coronary and radiographic angiography, with major morbidity and mortality. Patients at greatest risk for RCN can be defined prior to the procedure based on age, presence of diabetes, and presence of preexisting renal dysfunction. Despite attempts to alter preprocedural hydration, amount of dye administered, and postprocedural therapies, this clinical event continues to affect over 25% of patients at high risk. This discussion will review the literature in order to understand the attempts that have been made to prevent radiocontrast nephropathy.

Acute Kidney Injury↗

Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE) study.

BACKGROUND: Intravascular ultrasound (IVUS) can assess stent geometry more accurately than angiography. Several studies have demonstrated that the degree of stent expansion as measured by IVUS directly correlated to clinical outcome. However, it is unclear if routine ultrasound guidance of stent implantation improves clinical outcome as compared with angiographic guidance alone. METHODS AND RESULTS: The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study, a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was designed to assess the impact of IVUS on stent deployment in the high-pressure era. Nine centers were prospectively assigned to stent deployment with the use of ultrasound guidance and 7 centers to angiographic guidance alone with documentary (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were enrolled with completed quantitative coronary angiography, quantitative coronary ultrasound, and clinical events adjudicated at 9 months for 499 patients. The IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0. 5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary ultrasound. Target vessel revascularization, defined as clinically driven repeat interventional or surgical therapy of the index vessel at 9 month-follow-up, occurred significantly less frequently in the IVUS-guided group (8.5% versus 15.3%, P<0.05; relative reduction of 44%). CONCLUSIONS: These data suggest that ultrasound guidance of stent implantation may result in more effective stent expansion compared with angiographic guidance alone.

Aspirin↗

Rotational atherectomy or balloon angioplasty in the treatment of intra-stent restenosis: BARASTER multicenter registry.

The BARASTER registry was formed to evaluate the initial success and long-term results of rotational atherectomy in the management of in-stent restenosis. Rotational atherectomy was used in 197 cases of in-stent restenosis: 46 with stand-alone rotational atherectomy or at most 1 atmosphere of balloon inflation (Rota strategy), and 151 with rotational atherectomy and adjunctive balloon angioplasty <1 atmosphere (Combination strategy). These were compared with 107 episodes of in-stent restenosis treated with balloon angioplasty alone. In this observational study, the use of Combination therapy was associated with a slightly higher initial success rate (95% vs. 87% with the Rota strategy and 89% with Balloons, P = 0.08). There was a reduction in one year clinical outcomes (death, myocardial infarction or target lesion revascularization) in the combination group (38% vs. 60% with Rota and 52% with balloons, P = 0.02). These data support a benefit of the strategy of debulking with rotational atherectomy followed by adjunctive balloon angioplasty, in the management of in-stent restenosis.

Aged↗

Differential activation of platelets from normal and allergic ponies by PAF and ADP.

OBJECTIVE AND DESIGN: Altered platelet responsiveness has been demonstrated in human atopic dermatitis. This study has compared the in vitro function of platelets from normal ponies and those with the allergic skin disease, sweet itch. SUBJECTS: Ponies with a clinical history of sweet itch and normal ponies were used as blood donors. METHODS: PAF and ADP-induced platelet aggregation was measured and TxB2 production quantitated at the time of maximal aggregation; 12-HETE was additionally measured in some samples. Agonist-induced release of 3[H]5-HT was also studied. RESULTS: Although both PAF and ADP caused equine platelet aggregation, only PAF stimulated eicosanoid and 5-HT release. There were no differences between the responses of platelets from allergic and normal ponies to PAF or ADP (analysis of variance). CONCLUSIONS: There is no evidence of altered platelet responsiveness in ponies with sweet itch. The profile of responses to PAF and ADP suggest differential activation of intracellular signalling pathways in equine platelets.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Actions and interactions of ADP, 5- HT, histamine and PAF on equine platelets.

Platelets are thought to play a role in equine diseases such as acute laminitis and verminous arteritis and may be involved in allergic disease. Mediators implicated in the pathophysiology of these conditions activate platelets and responses may be enhanced by interactions between mediators. The present study compared platelet aggregation, thromboxane production and release of radiolabelled [(3)H]5- HT in response to 5- HT, histamine, ADP and PAF alone and in combination in vitro.PAF caused concentration-related aggregation, [(3)H]5- HT release and thromboxane production. In contrast, ADP caused aggregation and 5- HT induced the release of [(3)H]5- HT with little effect on other platelet functions. Histamine had little or no effect on equine platelets. Addition of 5- HT (10 microM) prior to ADP significantly displaced the aggregation response curve to the left. The profile of responses to PAF, ADP and 5- HT suggests differential activation of intracellular signalling pathways regulating these events. The enhanced response to ADP in the presence of 5- HT may have implications in thromboembolic disease in the horse.

Adenosine Diphosphate↗

Heparin infusion prior to stenting (HIPS) trial: final results of a prospective, randomized, controlled trial evaluating the effects of local vascular delivery on intimal hyperplasia.

BACKGROUND: Local delivery of pharmacologic agents or genes at the site of angioplasty is a promising approach to reduce restenosis. However, there are unresolved questions concerning the safety and feasibility of local vascular delivery in clinical practice as well as the efficacy of delivered drug. To this end, the safety, feasibility, and efficacy of local delivery of heparin were evaluated in the Heparin Infusion Prior to Stenting (HIPS) trial. METHODS AND RESULTS: A total of 179 patients were enrolled in this multicenter, randomized, prospective, core laboratory-evaluated trial. Patients were randomly assigned to 5000 U heparin either administered to the coronary artery lumen or infused into the arterial wall immediately after angioplasty and before stent placement. End points included procedural events and clinical, angiographic, and intravascular ultrasound events at 6 months. Patient groups were evenly matched. There was no difference in the incidence of arterial injury, defined as an increase in arterial dissection, acute closure, or decrease in Thrombolysis In Myocardial Infarction grade blood flow in the group receiving local delivery. At follow-up there was no difference in the major adverse event rate between intraluminal (22.7%) and local groups (24.7%). There was no difference between intraluminal and local therapy in the angiographic in-stent restenosis rate (12.5%, 12.7%) or the in-stent volumetric analysis by intravascular ultrasound (IVUS) (37.19 +/- 20. 86 mm(3) vs 43.79 +/- 25.52 mm(3)). CONCLUSIONS: Local delivery of 5000 U heparin into the arterial wall before stent implantation is safe and feasible. There was not a favorable effect of locally delivered heparin on clinical, angiographic, or IVUS end points of restenosis. The use of IVUS to measure volume of intimal hyperplasia in a multicenter, core laboratory-controlled trial is feasible.

Blood Flow Velocity↗

Endovascular stents: update on stents in practice.

Endovascular stent use has expanded at an unprecedented rate; they are currently being used in more than 50% of coronary angioplasty procedures. This rapid acceptance is due to excellent in-hospital results coupled with improved long-term clinical endpoints from small randomized trials, which have investigated only a few stent designs in small patient subsets. The generalized use of stents in all lesions has yet to be substantiated. Current limitations of stents include the occurrence of subacute thrombosis, late neointima proliferation, and design issues such as stent visibility and deliverability. New designs, including stent coatings and stents for bifurcations, will increase the use of stents for endovascular procedures.

Angioplasty, Balloon, Coronary↗

Endotoxin and dietary amines may increase plasma 5-hydroxytryptamine in the horse.

Uptake of 5-hydroxytryptamine (5-HT) into platelets is an important mechanism by which low plasma concentrations are maintained, and platelet activation may therefore result in significant release of this vasoconstrictor. The present study examined the kinetics of active uptake of radiolabelled [3H]5-HT by washed equine platelets in vitro, and investigated the effects on this process of 4 other naturally occurring monoamines which may be released from the caecum in conditions of carbohydrate overload. The release of [3H]5-HT by platelets was also studied, since platelet accumulation and activation has been associated with acute laminitis. Release of [3H]5-HT was measured in response to platelet activating factor (PAF), unlabelled 5-HT and the indirect activation of platelets by endotoxin in the presence of blood leucocytes. Km value for the uptake of 5-HT by equine platelets was 2.4 +/- 0.6 micromol/l and the Vmax was 8.3 +/- 0.6 pmol [3H]5-HT/10(7) platelets/min. The rate of uptake of 5 micromol/l [3H]5-HT was significantly decreased by the uptake inhibitors fluvoxamine and clomipramine. The 4 other monoamines examined all inhibited the uptake of [3H]5-HT in a noncompetitive manner, decreasing Vmax by between 17 and 82%. Incubation of platelets with LPS (0.1 mg/ml) in the absence of leucocytes did not result in significant release of [3H]5-HT; however, in the presence of leucocytes 3.8 +/- 1.7 pmol [3H]5-HT/10(7) platelets (mean +/- s.e.) were released. This release was significantly inhibited by parthenolide and WEB2086, but not by aspirin. This suggests that PAF from activated leucocytes was responsible for the 5-HT release. These data show that 5-HT uptake by equine platelets is a saturable process operating most efficiently at substrate concentrations in the low micromolar range. The noncompetitive inhibition of 5-HT uptake by other naturally occurring monoamines may result in increased plasma concentrations of 5-HT, as would its release by endotoxin. Such a rise in plasma 5-HT concentrations may contribute to selective vasoconstriction in the equine digital circulation.

Amines↗

Establishing stable test performance in tests from the Behavioral Assessment and Research System (BARS).

Research to identify adverse effects in humans chronically exposed to neurotoxic substances in the workplace or environment typically assesses people at one point in time in a cross-sectional study. The most widely used strategy employs performance measures taken from a single point in time and compares these with either performance of a control group or established normative data. However, multiple comparison points of the same people on the same test allow the dissection of acute--from chronic--exposure effects, among other important questions. When performance measures are used from multiple points in time, within-subject deviations are examined. For either research design, the goal is to minimize the effects of practice and to obtain stable performance on a test. Demographic variables such as age, education, and cultural background or ethnicity influence performance on neurobehavioral tests. These variables may also influence the development of stable performance. Different populations may have different learning curves so that stable performance on a test is achieved with different amounts of practice. This is especially important when making comparisons across groups that may not have equivalent backgrounds. The performance of three groups, English-speaking adults, Spanish-speaking adolescents, and Spanish-speaking migrant adolescents, was examined. Each group completed a battery of neurobehavioral tests from the Behavioral Assessment and Research System (BARS) during four sessions. Repeated measures ANOVAs were used to investigate performance across time. Tests measuring motor performance produced stable performance from the first session. More complex tasks that involved attention and memory showed a practice effect across sessions.

Adolescent↗

Smiling faces and other rewards: using the Behavioral Assessment and Research System (BARS) with unique populations.

Concern about the exposure of children and adolescents to occupational and environmental hazards has increased, and so has the need to develop testing methods that can adequately assess the effects of exposure in children. A computerized testing system, the Behavioral Assessment and Research System (BARS), was successfully modified to test both younger populations and populations which do not speak English, the original language of the battery. These adaptations were modifications of the existing features of the BARS system which was designed to assess the broadest possible audience: simple language instructions broken down into basic concepts (step-by-step training with competency testing at each instruction step); a token dispenser along with a "smiling face" stimulus that reinforced appropriate performance; and adjustable parameter settings (e.g., number of trials, difficulty). Data from four groups demonstrate the feasibility of using BARS with children as young as preschool age and for non-English speaking children.

Child↗

The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels.

Endotoxin has been implicated in the pathophysiology of acute laminitis. The aim of this study was to examine the direct effects of endotoxin on isolated equine digital blood vessels. Equine digital veins (EDV), incubated in Krebs-Henseleit solution containing lipopolysaccharide (LPS) (1 microg/ml) became hyporesponsive to 5-HT after 16 h. Cycloheximide and ibuprofen blocked this effect of LPS and increased the maximum response obtained to 5-HT when compared to control vessels. L-nitroarginine methyl ester (L-NAME) reversed the hyporesponsiveness caused by LPS. Vessels maintained in culture medium containing LPS also became hyporesponsive to 5-HT, an effect which was completely prevented by ibuprofen but only partially reversed by L-NAME. Measurements were made of 6-keto PGF1alpha and nitrite production by segments of equine digital artery and vein in culture medium alone or co-cultured with peripheral blood leucocytes. LPS did not stimulate nitrite production from vessel segments but increased nitrite release from leucocytes, an effect which was inhibited by cycloheximide and L-NAME. Lipopolysaccharide increased 6-keto PGF1alpha production by blood vessels, an effect which was inhibited by cycloheximide and ibuprofen but not L-NAME. No synergistic effect on release of nitrite or 6-keto PGF1alpha was noted in co-cultures of blood vessels and leucocytes. These data suggest that induction of cyclo-oxygenase by LPS was a major cause of hyporesponsiveness of digital blood vessels to 5-HT. Release of nitric oxide was not detectable in LPS-stimulated blood vessels maintained in culture even in the presence of activated leucocytes yet L-NAME did protect against LPS-induced hyporesponsiveness indicating nitric oxide synthase induction may play some role in the effect of LPS. These findings are important in furthering our understanding of the pathophysiological mechanisms underlying the vascular changes which occur in acute laminitis.

6-Ketoprostaglandin F1 alpha↗

Evidence for different 5-HT1B/1D receptors mediating vasoconstriction of equine digital arteries and veins.

5-hydroxytryptamine (5-HT) is a potent vasoconstrictor of equine digital arteries and veins which may play a role in the ischaemic disease, laminitis. The present investigation compared the properties of 5-HT1B/1D receptors in arteries with those in veins using isolated rings of equine digital blood vessels. The 5-HT1B/1D receptor-selective agonists, anpirtoline and sumatriptan were 17.9 and 10 times more potent and produced 4.1 and 5.6 times greater maximum contractions, respectively, in veins when compared to arteries. Other agonists tested were of equal potency and produced the same maximum responses in veins and arteries. Propranolol competitively inhibited 5-HT1B/1D receptor mediated responses in arteries, with a pKB of 6.7, but had no significant effects on responses in veins at 1 microM. Metergoline competitively inhibited 5-HT1B/1D receptor mediated responses in veins, with a pKB of 8.1, but had no significant effect in arteries at 0.1 microM. These data suggest that 5-HT1B/1D receptors mediating vasoconstriction in equine digital arteries are pharmacologically different to those found in digital veins.

Animals↗