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At least 685 records · Page 38Linked to original sources
PubMed1999

Enumeration of CD4(+) T-cells in the peripheral blood of HIV-infected patients: an interlaboratory study of the FACSCount system.

The aim of the present study was to assess the interlaboratory reproducibility of the FACSCount system for the enumeration of peripheral blood (PB) CD4(+) T-cells. In each of the seven participating centers, both previously stained and unstained PB samples (n = 49) were received and either analyzed or stained and then analyzed. Interlaboratory reproducibility was checked in two different groups of centers (n = 3 and n = 4) where the study was performed in parallel. In addition, both the intralaboratory precision and accuracy of this system were analyzed in comparison with results obtained with conventional flow cytometry. Accordingly, upon comparing both methods, a high degree of correlation was observed in the total number of CD3(+) T-cells (coefficient of correlation of 0.9750 +/- 0.0184, slope of the best linear fit: 0. 9214 +/- 0.0311, y-intercept of 12 +/- 47) as well as in the number of CD3(+)/CD4(+) (coefficient of correlation of 0.9794 +/- 0.1457, slope of the best linear fit: 0.9463 +/- 0.0753, y-intercept of -11 +/- 36) and CD3(+)/CD8(+) (coefficient of correlation of 0.9728 +/- 0.0192, slope of the best linear fit: 0.9682 +/- 0.0735, y-intercept of 7 +/- 95) major subsets. In addition, low coefficients of variation (CV) were obtained for replicates, indicating the method's high degree of accuracy. The present study shows that with respect to the interlaboratory reproducibility reported for most techniques used for the enumeration of PB CD4(+) T-cells, the FACSCount system results in data with much lower coefficients of variance (CVs) (mean CV of less than 10%). Upon measuring the impact on results of different variables associated with either sample preparation or data acquisition and analysis, our study clearly shows that data acquisition and analysis does not influence the results by increasing variability since the coefficients of variation obtained for samples prepared in the same laboratory under the same conditions and read in different laboratories with different instruments were identical to those obtained for the replicates of the same samples read in each individual center. In contrast, interlaboratory variability, although low, significantly increased when sample preparation was carried out in different laboratories, suggesting that pipetting still represents the major source of variability in the FACSCount system.

CD4 Lymphocyte Count↗
PubMed1996

A model based assessment of redistribution dependent elimination and bioavailability of rifabutin.

The autoinduction characteristic of rifabutin (RIF) following multiple oral dosing was investigated via pharmacokinetic modeling. A two-compartment model with first-order absorption was fit to plasma RIF data obtained from a study conducted in healthy normal volunteers following both a single and multiple oral doses. Parameter estimates showed an elimination rate constant (k10) of about 0.12-0.14 h-1 which was independent of the single or multiple-dosing condition. The lower-than-expected drug accumulation following multiple dosing seems to suggest that prolonged dosing perturbs the linear kinetic system. However, this analysis has shown no significant changes (p > 0.05) in the rate constants describing RIF absorption, tissue distribution/redistribution, and elimination. The mean rate of drug redistribution from the tissue compartment (k21; 0.04-0.06 h-1) was twofold to threefold lower than k10, and, with a large steady-state distribution volume (Vss/F after a single dose, 1630 L), RIF elimination appears to be dependent on drug redistribution. This hypothesis was further supported by a significant correlation (p < 0.01) between RIF tissue redistribution (k21) and terminal disposition phase rate (lambda z) constants. The redistribution dependent elimination of RIF also helps explain the stability of the terminal half-life under both single and multiple-dosing paradigms. Urinary excretion of RIF and its 25-O-deacetyl metabolite totalled less than 7% of the oral dose following single dosing, and decreased to about 4% after multiple dosing. For individual patients, the decrease in urinary recovery of the 25-O-deacetyl metabolite was directly proportional to the decrease in urinary RIF recovery. In addition, both estimates of the model intercepts (A and B) were lower following multiple dosing. Further analyses revealed a linear relationship between A and B intercepts, and also between the urinary RIF recovery and the B intercept. These relationships, in conjunction with the lack of significant increase in the rate of elimination, indicate that induction of presystemic extrahepatic metabolism and/or decrease in the extent of oral absorption may be the primary causes for the lower-than-expected systemic RIF plasma levels after multiple oral dosing.

Administration, Oral↗
PubMed1995

Toward an optimal algorithm for ovarian cancer screening with longitudinal tumor markers.

Stored samples from women in the Stockholm screening study were reassayed for CA125II (Centocor, Malvern, PA) and OVX1. The postmenopausal women older than age 50 without ovarian cancer were randomly split into a training set to develop a screening test based on longitudinal marker levels and a second set to validate the test. The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CA125II) on time since first sample. The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot. A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women; it delineated a screening test. The specificity of this test was examined on the validation set with a specificity of 99.8%. Bayes' theorem was used to calculate the risk of ovarian cancer (ROC) based on the intercept, slope, and assay variability. It is important to account for assay variability because it can produce large slopes over short periods of time. The maximum risk, which identified 83% (5 of 6) of the ovarian cancers detected within a year of last assay, was applied as a test to the training set and confirmed a high specificity of 99.7%. With this specificity and sensitivity, the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16%, substantially greater than the positive predictive value based on a single assay. Further study is planned to confirm the sensitivity of this approach.

Aged↗
PubMed1993

Ratios as a size adjustment in morphometrics.

Simple ratios in which a measurement variable is divided by a size variable are commonly used but known to be inadequate for eliminating size correlations from morphometric data. Deficiencies in the simple ratio can be alleviated by incorporating regression coefficients describing the bivariate relationship between the measurement and size variables. Recommendations have included: 1) subtracting the regression intercept to force the bivariate relationship through the origin (intercept-adjusted ratios); 2) exponentiating either the measurement or the size variable using an allometry coefficient to achieve linearity (allometrically adjusted ratios); or 3) both subtracting the intercept and exponentiating (fully adjusted ratios). These three strategies for deriving size-adjusted ratios imply different data models for describing the bivariate relationship between the measurement and size variables (i.e., the linear, simple allometric, and full allometric models, respectively). Algebraic rearrangement of the equation associated with each data model leads to a correctly formulated adjusted ratio whose expected value is constant (i.e., size correlation is eliminated). Alternatively, simple algebra can be used to derive an expected value function for assessing whether any proposed ratio formula is effective in eliminating size correlations. Some published ratio adjustments were incorrectly formulated as indicated by expected values that remain a function of size after ratio transformation. Regression coefficients incorporated into adjusted ratios must be estimated using least-squares regression of the measurement variable on the size variable. Use of parameters estimated by any other regression technique (e.g., major axis or reduced major axis) results in residual correlations between size and the adjusted measurement variable. Correctly formulated adjusted ratios, whose parameters are estimated by least-squares methods, do control for size correlations. The size-adjusted results are similar to those based on analysis of least-squares residuals from the regression of the measurement on the size variable. However, adjusted ratios introduce size-related changes in distributional characteristics (variances) that differentially alter relationships among animals in different size classes.

Animals↗
PubMed1994

A computer-assisted stereological quantification program: OpenStereo.

At present, the stereological assessment of histological sections is made possible by the use of manual counting techniques which estimate measurement parameters. These methods are tedious, time-consuming, and subject to operator error. This paper describes a UNIX-based computer program, OpenStereo, which was developed to facilitate the quantitative investigation of innervation and vascularity from histological sections. We designed OpenStereo to reduce operator error and increase the efficiency of stereological point counting for volume estimation and intercept counting for surface area analysis. The program was written in the C language for the Sun Workstation and uses the XView graphics user interface. Digital images, obtained by a variety of modalities, may be processed using stereological point counting, interceptions, planimetry, or thresholding techniques. The program displays selected images in a random fashion for analysis or processing and records the number of manually selected points or interceptions. Delineation of the reference space provides the computer with the data necessary to calculate volume or surface densities. The efficiency of OpenStereo was demonstrated by performing a pilot study on the quantification of innervation in the normal human colon and ileum. This stereological package benefits from the features of the X-windowing environment and has proved to be suitable for what has hitherto been a tedious and time-consuming task.

Adult↗
PubMed1998

Relationships between bone morphology and bone elastic properties can be accurately quantified using high-resolution computer reconstructions.

It would be advantageous if the mechanical properties of trabecular bone could be directly inferred from stereomorphometric parameters. For that purpose, apparent density and mean intercept length, as measures of bone mass and directionality (fabric), are commonly correlated with the elastic characteristics of bone samples, as determined in compression tests. However, complete and accurate relationships have not yet been established in this way. This may be due not only to the occurrence of artifacts in both the stereomorphometric and the mechanical assessments but also to an inherent inadequacy of mean intercept length in characterizing the full mechanical significance of bone architecture or nonhomogeneities in trabecular tissue properties not accounted for in stereomorphometry. In this study, we introduce a computer modeling approach allowing these biases to be eliminated. With use of high-resolution three-dimensional computer reconstructions of trabecular bone specimens for stereomorphometry and for microstructural finite element models to simulate mechanical tests, unbiased comparisons become feasible. The purpose was to investigate if accurate and complete relationships can be established in this way. Four different fabric measures were considered: mean intercept length and three volume-based ones. Compliance matrices were calculated from fabric tensors, with use of the mathematical relationship proposed by Cowin for 29 vertebral whale-bone specimens. These were correlated with the compliance constants determined directly from the microstructural finite element model simulation. The nine orthotropic elastic constants of all 29 specimens were well predicted from their stereomorphometric fabric and volume fraction values, with correlation coefficients ranging from R2adj = 0.9934 to 0.9963. When individual compliance components were considered (1/Ei, 1/Gij, or -v[ij]/Ei), correlation coefficients ranged from R2adj = 0.924 to 0.982. All four fabric measures performed equally well. It is concluded that volume fraction and fabric measures correlate highly with the apparent elastic properties of bone samples, provided that anisotropy and nonhomogeneity in the elastic properties of the trabecular tissue itself have negligible effects on the apparent properties. Whether this is true for bone in general remains to be seen, as only a subset was analyzed here. These methods, however, can be valuable in similar assessments of other subsets.

Animals↗
PubMed1998

Effects of thapsigargin and KCl on the O2 use of the excised blood-perfused rat heart.

We have already reported a curvilinear end-systolic pressure-volume relation and a linear oxygen consumption per beat (Vo2)-systolic pressure-volume area (PVA) relation of the left ventricle in the rat blood-perfused whole heart preparation. Recently, we have proposed that a PVA at an appropriate left-ventricular end-diastolic volume (0.15 ml/g), such as PVA0.15 and the Vo2 intercept (minimally loaded Vo2) of the Vo2-PVA relation, can be good indexes for assessing rat left-ventricular mechanoenergetics. The minimally-loaded Vo2 would mainly consist of Vo2 for Ca 2+ handling in the excitation-contraction (E-C) coupling and basal metabolism. However, the fraction of the Vo2 by the sarcoplasmic reticulum (SR) Ca2+-ATPase in the total Ca2+ handling Vo2 has not yet been examined. To study this for the first time, we investigated the effects of thapsigargin and KCl on left-ventricular mechanoenergetics. Blockade of the SR Ca2+ pump by thapsigargin (2.5 micromol/l) decreased PVA 0. 15 by 65% and decreased the Vo2 intercept by 40% without a change in the slope of the Vo2-PVA relation. We measured the basal metabolic Vo2 by intracoronary KCl and found a 75% decrease in the Vo2 intercept. We conclude that the minimally-loaded Vo2 mainly consists of Vo2 for Ca2+ handling in the E-C coupling (at least 40% is consumed by the SR Ca2+ ATPase) and basal metabolism (25%).

Animals↗
PubMed1993

Constants underlying frequency changes in biological rhythmic movements.

When an animal increases or decreases the frequency of its limb motions, how should the transformation in timing be characterized? It has been hypothesized that the transformation is adiabatic, even though the biological conditions are nonconservative and non-rate-limited (Kugler and Turvey 1987). An adiabatic transformation requires that the rhythmic system's action (energy/frequency) and entropy production remain time-invariant throughout the transformation. The non-conservative adiabatic hypothesis was evaluated through an experiment on human rhythmic hand movements. On each trial, a subject began at a prescribed frequency and then, over a 30 s interval, increased (or decreased) the frequency continuously at will. For each subject, on each increasing and decreasing trial, cycle kinetic energy was a linear function of cycle frequency with a negative energy intercept. By the adiabatic hypothesis, the slope of the function defines the constant action and the intercept defines the constant dissipation - changes in cycle frequency incur no changes in energy dissipated per cycle. Slopes and intercepts were correlated suggesting a common basis for the two constants, and the variety of cycle amplitude-cycle duration relations were in agreement with the nonmonotonic, nonlinear space-time function predicted by the hypothesis. The possibilities of addressing aspects of the data through (a) muscle modeled as a continuum of Kelvin bodies with a continuous relaxation spectrum, and (b) various classes of autonomous differential equations, were discussed. Most importantly, the discussion focused on the puzzling independence of energy cost and speed exhibited by locomoting animals differing in morphology, physiology, size, and taxa. It was suggested that the independence may reflect a very general principle - adiabatic transformability of biological movement systems.

Adult↗
PubMed1992

Control strategies in directing the hand to moving targets.

We have evaluated the use of visual information about the movement of a target in two tasks--tracking and interceptions--involving multi-joint reaching movements with the arm. Target velocity was either varied in a pseudorandom order (random condition) or was kept constant (predictable condition) across trials. Response latency decreased as target velocity increased in each condition. A simple model that assumes that latency is the sum of two components--the time taken for target motion to be detected, and a fixed processing time--provides a good fit to the data. Results from a step-ramp experiment, in which the target stepped a small distance immediately preceding the onset of the ramp motion, were consistent with this model. The characteristics of the first 100 ms of the response depended on the amount of information about target motion available to the subject. In the tracking task with randomly varied target velocities, the initial changes in hand velocity were largely independent of target velocity. In contrast, when the velocity was predictable the initial hand velocity depended on target velocity. Analogously, the initial changes in the direction of hand motion in the interception task were independent of target velocity in the random condition, but depended on target velocity in the predictable condition. The time course for development of response dependence was estimated by controlling the amount of visual information about target velocity available to the subject before the onset of limb movement. The results suggest that when target velocity was random, hand movement started before visual motion processing was complete. The response was subsequently adjusted after target velocity was computed. Subjects displayed idiosyncratic strategies during the catch-up phase in the tracking task. The peak hand velocity depended on target velocity and was similar for all subjects. The time at which the peak occurred, in contrast, varied substantially among subjects. In the interception task the hand paths were straighter in the predictable than in the random condition. This appeared to be the result of making adjustments in movement direction in the former condition to correct for initially inappropriate responses.

Acoustic Stimulation↗
PubMed1995

In-vivo validation of videodensitometric coronary cross-sectional area measurement using dual-energy digital subtraction angiography.

Previous studies indicate that conventional geometric edge detection techniques, used in quantitative coronary arteriography (QCA), have significant limitations in quantitating coronary cross-sectional area of small diameter (D) vessels (D < 1.00 mm) and lesions with complex cross-section. As a solution to this problem, we have previously reported on an in-vitro validation of a videodensitometric technique that quantitates the absolute cross-sectional area including small vessel diameter (D < 1.00 mm) and any complex shape of the vessel cross-section. For in-vivo validation, plastic tubing (5-8 mm long) with different shape complex cross-section with known cross-sectional area (A = 0.8-4.5 mm2) were percutaneously wedged in the coronary arteries of anesthetized pigs (40-50 kg). Contrast material injections (6-10 ml at 2-4 ml/sec) were made into the left main coronary artery during image acquisition using a motion immune dual-energy subtraction technique, where low and high X-ray energy and filtration were switched at 30 Hz. A comparison was made between the actual and measured cross-sectional area using the videodensitometry and edge detection techniques in tissue suppressed energy subtracted images. In eighteen comparisons the videodensitometry technique produced significantly improved results (slope = 0.87, intercept = 0.24 mm2, r = 0.94) when compared to the edge detection technique (slope = 0.42, intercept = 1.99 mm2, r = 0.39). Also, a cylindrical vessel phantom (D = 1.00-4.75 mm) was used to test the ability to calculate and correct for the effect of the out of plane angle of the arterial segment on the cross-sectional area estimation of the videodensitometry technique. After corrections were made for the out of plane angle using two different projections, there was a good correlation between the actual and the measured cross-sectional area using the videodensitometry technique (slope = 0.91, intercept = 0.11 mm2, r = 0.99). These data suggest that it is possible to quantitate absolute cross-sectional area without any assumption regarding the arterial shape using videodensitometry in conjunction with the motion immune dual-energy subtraction technique.

Angiography, Digital Subtraction↗
PubMed1992

Similar oxygen cost of myocardial contractility between DPI 201-106 and epinephrine despite different subcellular mechanisms of action in dog hearts.

The effects of DPI 201-106 (a novel, cyclic AMP-independent positive inotropic agent with Ca(2+)-sensitizing and Na(+)-channel agonistic mechanisms) on myocardial mechanics and energetics were assessed in the excised cross-circulated dog left ventricle. In the first protocol, the relation between left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA) was analyzed before and during administration of DPI 201-106. The reciprocal of the slope of the VO2-PVA relation has been shown to reflect the contractile efficiency, and the VO2-intercept consists of the oxygen cost of contractility-dependent excitation-contraction coupling and basal metabolism. DPI 201-106 increased Emax (contractility index) and elevated the VO2-PVA relation in a parallel manner, i.e., the VO2-intercept increased without a change in the slope. In the second protocol, the increase in the VO2-intercept of the VO2-PVA relation for a unit increase in Emax (i.e., oxygen cost of enhanced contractility) was compared between DPI 201-106 and epinephrine in a paired manner in each heart. Epinephrine significantly abbreviated the time to end systole, whereas DPI 201-106 did not, suggesting that the mechanism of inotropic action differed between the two drugs. However, the oxygen cost of enhanced contractility was the same between the two drugs in each heart. Therefore, DPI 201-106 did not alter the contractile efficiency nor spare the oxygen cost of enhanced contractility as compared to epinephrine under the present experimental conditions. This suggests that the Ca(2+)-sensitizing effect of DPI 201-106, if any, is too small to spare the oxygen cost of contractility in the blood-perfused, non-failing dog heart.

Animals↗
PubMed2004

Long overlooked historical information on Agent Orange and TCDD following massive applications of 2,4,5-T-containing herbicides, Eglin Air Force Base, Florida.

BACKGROUND: From 1961-1971, The Air Development Test Center, Eglin Air Force Base (AFB), Florida, developed, tested, and calibrated the aerial spray systems used in support of Operation RANCH HAND and the US Army Chemical Corps in Vietnam. Twenty major test and evaluation projects of aerial spray equipment were conducted on four fully instrumented test grids, each uniquely arrayed to match the needs of fixed-wing, helicopter, or jet aircraft. Each of the grids was established within the boundary of Test Area 52A of the Eglin Reservation. METHODS: The tests, conducted under climatic and environmental conditions similar to those in Vietnam, included the use of the military herbicides (Agents) Orange, Purple, White, and Blue. Approximately 75,000 kg of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 76,000 kg of 2,4-dichlorophenoxyacetic acid (2,4-D) were aerially disseminated on an area of less than 3 km2 during the period 1962-1970. Data from the analysis of archived samples suggested that an estimated 3.1 kg of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), present as a contaminant, were aerially released in the test area. Because most of the vegetation had been removed before establishing the test site in 1961, there was an opportunity to follow ground-based residues independent of canopy interception, and the resulting high solar exposure of initial residues. Studies of the soils, fauna, flora, and aquatic ecosystems of the test grids and associated perimeters of Test Area C-52A (an area totally more than 8 km2) were initiated in 1969 and concluded in 1984. RESULTS AND DISCUSSION: Data from soil samples collected from 1974 through 1984 suggested that less than one percent of the TCDD that was present in soil when sampling began persisted through the ten-year period of sampling. More than 340 species of organisms were observed and identified within the test area. More than 300 biological samples were analyzed for TCDD and detectable residues were found in 16 of 45 species examined. Examination of the ecological niches of the species containing TCDD residues suggested each was in close contact with contaminated soil. Indepth field studies, including anatomical, histological and ultrastructural examinations, spanning more than 50 generations of the Beachmouse, Peromyscus polionotus, demonstrated that continual exposure to soil concentrations of 0.1 to 1.5 parts-per-billion (ng/g) of TCDD, had minimal effects upon the health and reproduction of this species. CONCLUSIONS: Since Agent Orange with its associated TCDD contaminant was aerially disseminated on the test grids, Test Area C-52A provided a 'field laboratory' for what may have happened in Vietnam, had there been no intercepting forest cover. However, in Vietnam a 'typical' mission would have disseminated 14.8 kg of 2,4,5-T/ha, most of which was intercepted by the forest canopy, versus the 876 kg 2,4,5-T/ha on the test grid at Eglin. Moreover, each hectare on the Eglin test grid received at least 1,300 times more TCDD than a hectare sprayed with Agent Orange in Vietnam. The disappearance or persistence of TCDD is dependent upon how it enters the ecosystem. Spray equipment test and evaluations missions at Eglin were generally scheduled and conducted with environmental conditions that were optimal for spray operations. This suggests that conditions favorable for dissemination of herbicide were the same conditions favorable for photodegradation of TCDD. It was likely that 99 percent of the TCDD never persisted beyond the day of application. No long-term adverse ecological effects were documented in these studies despite the massive quantities of herbicides and TCDD that were applied to the site. Reviews by the US Environmental Protection Agency and the National Academy of Sciences' Institute of Medicine did not address the fate of Agent Orange and TCDD as described in these studies from Eglin AFB, Florida.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed2006

Assessment of airway closure from deflation lung volume-pressure curve: sigmoidal equation revisited.

OBJECTIVE: To assess a sigmoidal equation for describing airway closure. DESIGN: Experimental study. SETTING: University laboratory. PARTICIPANTS: Eight piglets mechanically ventilated on zero end-expiratory pressure (ZEEP). INTERVENTIONS: Control and lung saline lavage. MEASUREMENTS AND RESULTS: Lungs were inflated up to transpulmonary pressure of 30 cmH(2)O at constant flow (0.12l s(-1)) then deflated at the same flow rate up to the point at which oesophageal pressure was constant, which was assumed to represent complete airway closure. The deflation volume-transpulmonary pressure curve was fitted to: (1) a sigmoidal equation focusing on inflexion point and pressure at maximal compliance increase and (2) an exponential equation above an inflexion point determined by eyeballing. Data deviate from the exponential equation at the point of airway closure onset. The zero-volume intercept was determined. Complete airway closure was reached at -8.3+/-3.5cmH(2)O in control conditions and at -1.3+/-3.7 cmH(2)O after lavage (p < 0.05). Between control and lavage, onset of airway closure was 3.0+/-1.9 vs. 6.0+/-2.8 cmH(2)O (p <0.05), inflexion point 3.2+/-1.8 vs. 7.7+/-2.6 cmH(2)O (p <0.001), pressure at maximal compliance increase -1.9+/-0.7 vs. -0.03+/-2.1cmH(2)O (p <0.05) and zero-volume intercept -1.5+/-1.4 vs. 0.3+/-2.3cmH(2)O (p <0.05). CONCLUSIONS: During mechanical ventilation airways stay open and close around ZEEP in control but are closed above ZEEP after lavage. Inflexion point might reflect onset of airways closure in control. Pressure at maximal compliance increase was not a marker of complete airways closure. In control and lavage, pressure at maximal compliance increase and zero-volume intercept were reasonably equivalent.

Airway Obstruction↗
PubMed1999

Movement reversals in ball catching.

This study aimed to determine whether the interception of a moving object is achieved by implementing a predictive or a prospective strategy. We examined the kinematics of catching movement in a situation in which the catching hand was constrained to move along a single dimension. In line with predictions based on a prospective strategy, the results obtained indicated that, for the same interception point and the same initial hand position, modification of the spatiotemporal characteristics of the ball's trajectory (via modification of the angle of approach of the ball) gave rise to systematic changes in the kinematics of catching movement. Moreover, the production of movement reversals when the hand was already positioned at the interception point, while in line with the predictions of the prospective strategy formalized by Bootsma et al. (1997), allowed for rejection of a predictive strategy.

Adult↗
PubMed1997

Parametric imaging of patient pharmacokinetics.

This paper presents an approach to extracting patient pharmacokinetic information from a set of longitudinal scintigraphic images and representing the kinetic information in parametric image form. In this approach, three or four pairs of simultaneously acquired anterior and posterior images, for internal dosimetry with iodine-131, are obtained at 24-h intervals. Each pair of anterior and posterior images is converted to a "conjugate-view" image. The sequential conjugate-view images are then spatially registered to each other using a symmetric phase-only matched filter technique. With the registered images, the value at each pixel location, over time, is fitted to a monoexponential function. The resulting decay constant and intercept parameters are then represented as "decay-constant" and "intercept" images. Further analytical integration of the exponential function results in a "cumulated-activity" image. Phantom studies demonstrated that the proposed method is accurate and reliable in the registration and kinetic data extraction of the longitudinal images. Clinical application of the approach to patients with thyroid carcinoma showed that regions of rapid uptake or clearance that would not otherwise be highlighted were easily identified and some regions with unexpected kinetics were observed. It is concluded that decay-constant, intercept, and cumulated-activity images provide a rapid and comprehensive visual assessment of patient pharmacokinetics. The technique may have a greater impact on the care of patients with extensive and distributed disease.

Algorithms↗
PubMed2006

Evaluating a three dimensional model of diffuse photosynthetically active radiation in maize canopies.

Diffuse photosynthetically active radiation (DPAR) is important during overcast days and for plant parts shaded from the direct beam radiation. Simulation of DPAR interception by individual plant parts of a canopy, separately from direct beam photosynthetically active radiation (PAR), may give important insights into plant ecology. This paper presents a model to simulate the interception of DPAR in plant canopies. A sub-model of a virtual maize canopy was reconstructed. Plant surfaces were represented as small triangular facets positioned according to three-dimensionally (3D) digitized data collected in the field. Then a second sub-model to simulate the 3D DPAR distribution in the canopy was developed by dividing the sky hemisphere into a grid of fine cells that allowed for the anisotropic distribution of DPAR over the sky hemisphere. This model, DSHP (Dividing Sky Hemisphere with Projecting), simulates which DSH (Divided Sky Hemisphere) cells are directly visible from a facet in the virtual canopy, i.e. not obscured by other facets. The DPAR reaching the center of a facet was calculated by summing the amounts of DPAR present in every DSH cell. The distribution of DPAR in a canopy was obtained from the calculated DPARs intercepted by all facets in the canopy. This DSHP model was validated against DPAR measurements made in an actual maize (Zea mays L.) canopy over selected days during the early filling stage. The simulated and measured DPAR at different canopy depths showed a good agreement with a R (2) equaling 0.78 (n=120).

Light↗
PubMed2007

Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine spot saliva samples II. Model application.

To develop and compare methods that predict individual nicotine (NIC) clearance, which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3'-hydroxycotinine (3HC) measurements. COT and 3HC saliva concentrations in smokers were simulated utilizing a mechanistic population pharmacokinetic model of NIC metabolism that was adapted from the one described in a companion paper. Four methods to predict NIC clearance using the metabolites concentrations were compared. The precision bias, and the fraction of predictions that are made with an absolute error below 25% were the performance measures evaluated. Four prediction methods were compared: (M1) reference method, an intercept slope model of the metabolite concentration ratios ([3HC]/[COT]) (M2) an intercept slope model of the natural logarithm of the metabolite ratios (M3) a spline of the logarithm of the metabolite ratios (M4) Maximal Posteriori Bayesian estimate of NIC clearance conditioned on the model, COT and 3HC concentrations. In addition, the effect of smoking patterns on the concentrations of COT and 3HC was evaluated. The precision, accuracy, and the fraction of predictions with an absolute error below 25%, were higher for methods M2-M4 compared to method M1. However, the differences between M2 and M4 were small. Additionally, smoking pattern did not affect the metabolite concentration profiles. Predicting NIC clearance using an intercept slope model of the natural logarithm of the ratio of 3HC to COT appears to be a relatively simple method that is better than using the metabolite ratio directly. This method has a bias of approximately -10%, precision of approximately 60%. The fraction of estimates below an absolute error of 25% is 43%. These results support use of M2 to estimate CYP2A6 activity in smokers in the clinical setting.

Aryl Hydrocarbon Hydroxylases↗
PubMed1983

Radionuclide evaluation of the systolic blood pressure/end-systolic volume relationship: response to pharmacologic agents in patients with coronary artery disease.

To assess the response of the relationship between systolic blood pressure and end-systolic volume to pharmacologic agents with known cardiac effects, we studied 21 patients with known coronary heart disease by means of gated radionuclide angiograms during the infusion of phenylephrine. Each individual was studied during the infusion of phenylephrine twice, once as a control and the second time after the administration of either intravenous dobutamine, topical nitroglycerin ointment, or intravenous propranolol. Eight individuals received 10 micrograms/kg/min of dobutamine, which reduced resting cardiac volumes (p less than 0.01), raised ejection fraction (p less than 0.01), and shifted the slope (1.38 +/- 0.50 to 2.03 +/- 0.69, p less than 0.01) and pressure intercept received 2 inches of nitroglycerin ointment. Nitroglycerin increased ejection fraction (p less than 0.05) and reduced volumes (p less than 0.05) but did not alter either the slope (1.46 +/- 0.68 to 1.49 +/- 0.61, p = NS) or intercept (10.6 +/- 5.4 to 10.1 +/- 6.4 mm Hg, p = NS) of the relationship. Eight patients received 15 mg of intravenous propranolol. Propranolol reduced resting ejection fraction (p less than 0.05), increased volumes (p less than 0.05), and reduced both the slope (1.67 +/- 0.58 to 1.51 +/- 0.53, p less than 0.05) and the intercept (13.8 +/- 2.5 to 7.5 +/- 2.3 mm Hg, p less than 0.05) of the pressure-volume relationship. Thus the systolic blood pressure/end-systolic volume relationship can be assessed from radionuclide angiograms.

Blood Pressure↗