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Biomedical subjects

S F Stewart

Publications and source records attributed to S F Stewart.

At least 19 recordsLinked to original sources
PubMed2001

Mycophenolate mofetil monotherapy in liver transplantation.

Chronic renal failure is a major cause of morbidity and mortality after orthotopic liver transplantation. We did a randomised controlled trial of mycophenolate mofetil monotherapy in liver transplant patients who developed renal failure associated with calcineurin-inhibitor (ciclosporin or tacrolimus) immunosuppressive therapy. Although renal failure improved when the calcineurin-inhibitor dose was reduced and ultimately stopped, the trial was stopped when three of five patients on monotherapy developed organ rejection requiring a second transplantation.

Calcineurin Inhibitors↗
PubMed2001

Effects of transducer, velocity, Doppler angle, and instrument settings on the accuracy of color Doppler ultrasound.

The accuracy of a commercial color Doppler ultrasound (US) system was assessed in vitro using a rotating torus phantom. The phantom consisted of a thin rubber tube filled with a blood-mimicking fluid, joined at the ends to form a torus. The torus was mounted on a disk suspended in water, and rotated at constant speeds by a motor. The torus fluid was shown in a previous study to rotate as a solid body, so that the actual fluid velocity was dependent only on the motor speed and sample volume radius. The fluid velocity could, thus, be easily compared to the color Doppler-derived velocity. The effects of instrument settings, velocity and the Doppler angle was assessed in four transducers: a 2.0-MHz phased-array transducer designed for cardiac use, a 4.0-MHz curved-array transducer designed for general thoracic use, and two linear transducers designed for vascular use (one 4.0 MHz and one 6.0 MHz). The color Doppler accuracy was found to be significantly dependent on the transducer used, the pulse-repetition frequency and wall-filter frequency, the actual fluid velocity and the Doppler angle (p < 0.001 by analysis of variance). In particular, the phased array and curved array were observed to be significantly more accurate than the two linear arrays. The torus phantom was found to provide a sensitive measure of color Doppler accuracy. Clinicians need to be aware of these effects when performing color Doppler US exams.

Blood Flow Velocity↗
PubMed1999

A rotating torus phantom for assessing color Doppler accuracy.

A rotating torus phantom was designed to assess the accuracy of color Doppler ultrasound. A thin rubber tube was filled with blood analog fluid and joined at the ends to form a torus, then mounted on a disk submerged in water and rotated at constant speeds by a motor. Flow visualization experiments and finite element analyses demonstrated that the fluid accelerates quickly to the speed of the torus and spins as a solid body. The actual fluid velocity was found to be dependent only on the motor speed and location of the sample volume. The phantom was used to assess the accuracy of Doppler-derived velocities during two-dimensional (2-D) color imaging using a commercial ultrasound system. The Doppler-derived velocities averaged 0.81 +/- 0.11 of the imposed velocity, with the variations significantly dependent on velocity, pulse-repetition frequency and wall filter frequency (p < 0.001). The torus phantom was found to have certain advantages over currently available Doppler accuracy phantoms: 1. It has a high maximum velocity; 2. it has low velocity gradients, simplifying the calibration of 2-D color Doppler; and 3. it uses a real moving fluid that gives a realistic backscatter signal.

Blood Flow Velocity↗
PubMed1998

Aliasing-tolerant color Doppler quantification of regurgitant jets.

Conservation of momentum transfer in regurgitant cardiac jets can be used to calculate the flow rate from color Doppler velocities. In this study, turbulent jets were simulated by finite elements; pseudocolor Doppler images were interpolated from the computations, with aliasing introduced artificially. Jets were also imaged by color Doppler in an in vitro flow system. To suppress aliasing errors, jet velocities were fitted iteratively to a fluid mechanical model constrained to match the orifice velocity (measured without aliasing by continuous-wave Doppler). At each iteration, the model was used to detect aliased velocities, which were excluded during the next iteration. Iteration continued until the flow rate calculated by the model and number of calculated nonaliased pixels were unchanged. The good correlations between measured and calculated flow rates in the experimental (R2 = 0.933) and computational studies (R2 = 0.990) suggest that this may be a clinically useful approach even in aliased images. Published by Elsevier Science Inc.

Algorithms↗
PubMed1997

Hyperbaric dye solution distribution characteristics after pencil-point needle injection in a spinal cord model.

BACKGROUND: The flow-rate limiting and directional characteristics of caudally directed microcatheters, which lead to intrathecal maldistribution of hyperbaric 5% lidocaine, are believed to have contributed to at least 11 cases of cauda equina syndrome. The authors investigated the distribution characteristics of hyperbaric dye solutions via caudally directed side port needles at various rates of injection in a spinal cord model to determine the potential for maldistribution. METHODS: Using a digital video image processing technique, we injected a hyperbaric solution of phthalocyanine blue dye through caudally directed side-port needles into a supinely oriented transparent spinal canal model filled with simulated cerebrospinal fluid. Injections via commonly used spinal needles (24-gauge and 25-gauge Sprotte, and 25-gauge and 27-gauge Whitacre) were recorded using five injection rates (2, 4, 6, 8, and 16 ml/min). RESULTS: For all needles tested, injection rate had a significant effect on the peak dye concentration (P < 0.0001). Injection rates > or = 6 ml/min (2 ml/20 s) resulted in peak dye concentrations of less than 168 mg/1 (extrapolated concentration of 1% lidocaine). Injection via the 24-gauge Sprotte needle, which has a larger orifice area and internal diameter, resulted in significantly lower peak dye concentrations than via the smaller Whitacre needles tested (P < 0.05). CONCLUSIONS: Sacral maldistribution could be minimized by using injection rates > or = 6 ml/min (2 ml/20 s), for all of the side-port spinal needles used in this model study. When very slow injection rates (2 ml/min) are used, peak dye concentrations varied inversely and significantly with needle internal diameter and orifice area.

Anesthetics, Local↗
PubMed1995

Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?

Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Selective regulation of human neutrophil functions by the cell activation inhibitor CI-959.

The cell activation inhibitor CI-959 [5-methoxy-3-(1-methylethoxy)-N-1H-tetrazol-5-ylbenzo[ b]thiophene-2- carboxamide, monosodium salt] was evaluated for its effects on human neutrophil functions. CI-959 inhibited spontaneous migration and chemotaxis toward N-formyl-methionyl-L-leucyl-L-phenylalanine (fMLP) with 50% inhibition (IC50) values of 3.6 and 3.1 microM, respectively. CI-959 also inhibited superoxide anion generation in response to C5a, fMLP, serum-opsonized zymosan (SOZ), concanavalin A (Con A), and calcium ionophore A23187 with IC50 values of 2.5, 4.7, 14.5, 5.4, and 14.8 microM, respectively. In comparison, CI-959 inhibited myeloperoxidase microM, respectively. In comparison, CI-959 inhibited myeloperoxidase release in response to C5a, fMLP, SOZ, and Con A with IC50 values of 11.6, 16.1, 7.5, and < 1.0 microM, respectively, while inhibiting the response to A23187 by only 5.5% at 100 microM. At concentrations up to 100 microM, CI-959 had no effect on the respiratory burst or degranulation in response to L-alpha-1,2-dioctanoylglycerol (DiC8) or phorbol 12-myristate 13-acetate (PMA). In addition, the compound inhibited leukotriene B4 release stimulated by fMLP and SOZ (IC50 values 4.0 and 2.5 microM, respectively), while having less activity against the A23187-stimulated response (IC50 > 100 microM). These results demonstrate that CI-959 inhibits cellular responses to stimuli that mobilize intracellular calcium. For cellular responses to inophore-mediated calcium influx, only oxygen radical production was inhibited by CI-959. CI-959 was further evaluated for its effects on neutrophil stimulus-response coupling. At 100 microM, CI-959 had no effect on human neutrophil phospholipase C or protein kinase C. CI-959 inhibited fMLP-stimulated intracellular calcium mobilization and calcium influx with IC50 values of 16.7 and 3.1 microM, respectively, and exhibited less potent calmodulin antagonist activity (IC50 = 90.5 microM). These results indicate that CI-959 may exert its stimulus- and response-specific inhibitory effects on neutrophil functions, in part, through inhibition of calcium-regulated signalling mechanisms.

Arachidonic Acid↗
PubMed1994

In vitro modeling of spinal anesthesia. A digital video image processing technique and its application to catheter characterization.

BACKGROUND: Maldistribution of intrathecal local anesthetic has recently been implicated as a contributor to neurotoxic injury. In vitro modeling can be used to understand the distribution of anesthetic agents within the subarachnoid space. We describe an in vitro modeling technique that uses digital video image processing and its application to catheter injection of local anesthetic. METHODS: A clear plastic model of the subarachnoid space, including a simulated spinal cord and cauda equina, was filled with lactated Ringer's solution. Phthalocyanine blue dye of known concentration was injected into the model through small-bore (28-G) and large-bore (18-G) catheters. Injections were performed at a variety of controlled rates and sacral catheter positions, and the propagation of dye throughout the model was recorded on videotape, digitized by computer, and converted to a two-dimensional image of dye concentration. A subset of data was compared with results obtained from spectrophotometric analysis. RESULTS: There was a strong correlation (r = 0.98) between data obtained with analysis by digital video image processing and those obtained spectrophotometrically. Catheter size, catheter angle, and injection rate significantly influenced the distribution and peak concentration of simulated anesthetic. No major differences in distribution or peak concentration were observed with the two types of 28-G catheters. CONCLUSIONS: The digital video image processing technique can be used to quantify anesthetic distribution rapidly within a model of the subarachnoid space without disturbing the distribution. The current results demonstrate a strong dependence of anesthetic distribution on catheter angle, catheter size, and injection rate. Comparisons between 28-G catheters suggest that the difference in reported incidence of cauda equina syndrome associated with different 28-G catheters cannot be explained on the basis of differences in anesthetic distribution.

Anesthesia, Spinal↗
PubMed1993

Quantification of asymmetric valvular regurgitant jets by color Doppler ultrasound in vitro.

Accurate quantification of regurgitant jets in natural and prosthetic heart valves has been a goal of health care workers and researchers for many years. One promising new method applies the law of conservation of momentum transfer to velocities measured by color Doppler ultrasound to calculate the flow rate in the jet. One complicating factor is that regurgitant jets from real heart valves may be highly asymmetric. The purpose of this investigation was to determine whether the accurate calculation of the flow rate in asymmetric jets imaged by color Doppler requires an asymmetric formulation of the conservation of momentum transfer, combined with a method for imaging the jet in three dimensions. Asymmetric jets issuing from narrow slits were imaged in an in vitro, steady flow system. The ultrasound transducer was rotated around the jet axis to image the jet in three dimensions. The three-dimensional imaging confirmed that jets from slits are indeed asymmetric, but become relatively axisymmetric far from the orifice. Images were analyzed by computer and the calculated flows compared to measured flows. The accuracy of an asymmetric formulation of the conservation of momentum transfer method was compared to a simpler, axisymmetric formulation. If axisymmetry was assumed in asymmetric jets, significant errors in the calculated flow rates occurred. In these cases, the calculated flow also varied widely with distance from the orifice. When asymmetry was taken into account, the errors were considerably reduced. The results suggest that, in asymmetric jets, the momentum transfer is convected around the jet axis.

Blood Flow Velocity↗
PubMed1992

Effects of a vascular graft/natural artery compliance mismatch on pulsatile flow.

Attempts have been made to correlate small-diameter vascular graft patency with compliance matching between the graft and the host artery. Without knowledge about the mechanisms of failure by compliance mismatch, however, such correlations remain empirical. We have developed a flow system which mimics the flow in peripheral arteries and techniques to model a compliance mismatch in a straight elastic tube, as might occur with vascular repair. Our goal was to investigate one proposed mechanism of graft failure by compliance mismatch, that of a blood flow disturbance. Flow visualization experiments showed that, under pulsatile flow, a compliance mismatch caused trapping of 40 microns microspheres at the wall near the distal or downstream anastomosis. This suggests that the presence of a microscopic flow separation or stagnant zone in vivo may contribute to the intimal hyperplasia and thrombosis seen in failed grafts.

Acceleration↗
PubMed1991

Inhibition of human neutrophil activation by the allergic mediator release inhibitor, CI-949.

The allergic mediator release inhibitor Cl-949 [5-methoxy-3-(1-methylethoxy)-1-phenyl-N-1H-tetrazol-5-yl-1H -indole-2-carboxamide, L-arginine salt] was evaluated for its effects on human neutrophil functions. Cl-949 (100 microM) inhibited spontaneous migration and chemotaxis toward f-met-leu-phe (FMLP) by 49.1% and 45.8%, respectively. At the same concentration, Cl-949 inhibited the phagocytosis of serum-opsonized zymosan (SOZ) by 39.0%. Cl-949 inhibited leukotriene B4 and thromboxane B2 release in response to SOZ with IC50s of 2.0 microM and 3.3 microM, while inhibiting the response to FMLP with IC50s of 1.7 and 2.0 microM. Cl-949 also inhibited myeloperoxidase release from primary lysosomal granules in response to the following stimuli with the respective IC50s (microM): C5a (40.3); FMLP (34.4): SOZ (21.4); concanavalin A (Con A) 3.9); and calcium ionophore A23187 (91.2). In contrast, Cl-949 inhibited lysozyme release from secondary granules in response to SOZ and Con A with IC50s of 99.3 and 56.1 microM, while inhibiting the response to C5a, FMLP, and A23187 by 41.2%, 52.4%, and 10.0%, respectively, at 100 microM. Cl-949 (100 microM) had no inhibitory effect against lysozyme release in response to L-alpha-1,2 dioctanoylglycerol (DiC8), or phorbol 12-myristate 13-acetate (PMA). Cl-949 inhibited superoxide anion generation stimulated by FMLP and Con A with IC50s of 33.9 and 25.8 microM, while inhibiting the response to C5a, SOZ, and A23187 by 36.6%, 24.8%, and 14.1% and having no effect on the response to DiC8 or PMA at 100 microM. These results demonstrate preferential inhibition of arachidonic acid metabolism and degranulation of primary lysosomal granules by Cl-949 with selectivity for stimuli which promote intracellular calcium mobilization or calcium influx.

Arachidonic Acid↗
PubMed1991

Errors in pressure gradient measurement by continuous wave Doppler ultrasound: type, size and age effects in bioprosthetic aortic valves.

The accuracy of continuous wave Doppler ultrasound in deriving pressure gradients across bioprosthetic heart valves was evaluated in an in vitro pulse duplicator. Simultaneous pressure transducer and Doppler measurements were made in new and explanted aortic bioprosthetic valves of several sizes and four types: Carpentier-Edwards, Ionescu-Shiley, Hancock standard and Hancock modified. The mean and peak gradients calculated by the modified Bernoulli equation from Doppler velocity measurements were always greater than those measured manometrically, despite corrections for location dependence of the manometric gradient (or pressure recovery). The relation between manometric and ultrasonically determined gradient was found to be statistically dependent on the valve type (mean gradient p less than 0.0001; peak gradient p = 0.0003) and size (mean gradient p = 0.0089; peak gradient p = 0.0107). Effects of implantation were observed, but were not shown to be significant. It is concluded that the continuous wave Doppler velocity data overestimated prosthetic valve pressure gradient in all cases, even when pressure recovery was taken into account. Clinicians should be wary of Doppler data when making major diagnostic or therapeutic decisions.

Aortic Valve↗
PubMed1990

Predicting the compliance of small diameter vascular grafts from uniaxial tensile tests.

The compliance hypothesis states that the compliance of vascular grafts should match that of the host artery for optimal patency. Although this has not been proven, the literature shows that much effort has gone into measuring compliance. Uniaxial circumferential tensile tests are simpler than compliance tests, but do not give the compliance (a multiaxial property) directly. Therefore, we have used mechanical models to correlate the two. Simple models suffer from inappropriate simplifying assumptions. In a clinically useful range, a Laplace law model and an incremental elasticity model do not predict the compliance from the rigidity as well as does a model derived from finite elasticity. This latter model has helped locate sources of errors. Variations in graft thickness, diameter, and anisotropy may be responsible for scatter in the experimental correlations between compliance and uniaxial rigidity.

Animals↗
PubMed1989

Solid state line scan cameras for measuring strain in soft tissues and implants.

The line scan camera, or LSC, is an inexpensive and easily applied technique for optical strain measurement of soft biomaterials. The LSC is based on a linear array of photodiodes; in gauging applications, where measurements between dark/light interfaces are important, the digital nature of the array can be exploited. Advantages of the LSC include low cost, high frequency response, applicability to front- or back-lighted samples, insensitivity to stray and nonuniform lighting as well as to accidental overexposure, ease and linearity of calibration, and lack of temperature sensitivity. With the 1024 element arrays used herein, the relative resolution is theoretically limited to 1 part in 1024, or 0.1%; in practice, the relative resolution is somewhat poorer. LSCs have been successfully used in mechanical tests to measure the diameter of arteries and compliant vascular grafts, the longitudinal strain of vascular grafts, and the dynamic diameter of elastic tube models of graft/artery systems in pulsatile flow visualization experiments.

Animals↗
PubMed1989

CI-943, a potential antipsychotic agent. II. Neurochemical effects.

The effects of CI-943 (a novel 8-ethyl-7,8-dihydro-1,3,5-trimethyl-1H-imidazo[1,2-c]pyrazolo[3,4- e]pyrimidine compound exhibiting a favorable antipsychotic profile in animal tests) on neurochemical parameters related to biogenic amine neurons have been studied in rat brain. CI-943 (1-40 mg/kg p.o. and 20 mg/kg i.p.) accelerated the turnover of dopamine (DA) in rat brain as demonstrated by the enhancement of levels of the DA metabolites homovanillic acid, 3,4-dihydroxyphenylacetic acid or 3-methoxytyramine and by the enhancement rate of DA synthesis in either striatum or mesolimbic regions. These increases in DA turnover induced by CI-943 are not due to DA receptor blockade as CI-943, unlike known antipsychotics, did not exhibit affinity for DA receptors either in vitro or in vivo and did not affect rat serum basal prolactin levels. Amfonelic acid enhanced the action of haloperidol in increasing striatal homovanillic acid with no effect on that of CI-943 and clozapine, suggesting that CI-943, like clozapine, would be predicted to have a low risk of extrapyramidal side effects as compared to haloperidol. Chronic administration of CI-943 (40 mg/kg i.p.) to rats for 28 days did not affect the affinity or number of striatal DA receptors; in comparison haloperidol (0.5 mg/kg i.p.) caused an increase in number of DA receptors with no change in affinity. Measures of serotonergic function were increased; noradrenergic function was not affected by CI-943, nor did it exhibit affinity for a number of central nervous system receptors in vitro. The molecular mechanism by which CI-943 increases brain DA turnover is not known at this time but appears to be unique in comparison to known antipsychotic agents.

Animals↗
PubMed1988

Finite elasticity modeling of the biaxial and uniaxial properties of compliant vascular grafts.

Compliant vascular grafts were modeled by finite elasticity theory. A linear, biaxial model satisfactorily described the stress-strain behavior in inflation tests, where the sample length was fixed longitudinally and inflated. The model was then used to predict the behavior in a longitudinal test (where the longitudinal stretch was varied while keeping the pressure zero), and in a uniaxial test of a circumferential strip. The model satisfactorily predicted the longitudinal Young's modulus measured in the longitudinal test. The model was less successful in predicting the circumferential Young's modulus measured in the uniaxial test, possibly because the state of stress was not purely uniaxial.

Blood Vessel Prosthesis↗
PubMed1987

CI-922--a novel, potent antiallergic compound--I. Inhibition of mediator release in vitro.

CI-922 (3,7-dimethoxy-4-phenyl-N-1H-tetrazol-5-yl-4H-furo[3,2-b]-indole- 2-carboxamide, L-arginine salt) is a novel antiallergy compound which inhibits the release of the inflammatory mediators histamine and leukotriene (LT) from stimulated cells. CI-922 showed potent, effective inhibition of antigen-induced mediator release from human basophils and isolated guinea pig lung. The drug inhibited ragweed or housedust-induced histamine release from basophils of allergic human donors (IC50 = 8.6 microM). The antiallergy agents proxicromil (IC50 = 80 microM) and cromolyn (100 microM) were less potent than CI-922 or inactive, respectively. In fragmented lung from actively sensitized guinea pigs, CI-922 (IC50 = 1.5 microM), blocked the antigen-induced production of LT and was a more potent inhibitor of histamine release (IC50 = 13.4 microM) than proxicromil (IC50 = 72.9 microM), or cromolyn (inactive at 1 mM). CI-922 (IC50 = 0.9 microM) completely inhibited repeated contractions of guinea pig lung strips that were induced by low antigen concentration in the presence of antihistamine (H1). Nordihydroguaiaretic acid (NDGA) (IC50 = 2.8 microM), proxicromil (IC50 = 6.2 microM) and the LT antagonist FPL-55712 (IC50 = 3.3 microM) also were fully effective, but cromolyn (300 microM) was inactive. In other experiments, CI-922 (IC50 = 7.0 microM) inhibited a strong, nonrepeatable lung contraction induced with high antigen concentration (histamine responses blocked), and was six times more potent than FPL-55712. Other investigations in isolated tissue preparations showed CI-922 to be a weak inhibitor of LT or histamine-induced effects with no anticholinergic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗