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PubMed1992

Modelling bivariate relationships when repeated measurements are recorded on more than one subject.

This paper examines the problems of modelling bivariate relationships when repeated observations are recorded for each subject. The statistical methods required to test for a common group model were introduced using an example from exercise physiology, where the oxygen cost of running at four different speeds was recorded for a group of 30 recreationally active males. When data for each subject were studied individually, both the plots and correlations suggested the relationship to be linear. Hence, the homogeneity of the subjects' regression lines was compared using the appropriate ANOVA test. The analysis revealed a significant difference in the slopes and intercepts of the lines, thus precluding the use of a single linear model to represent the group. If the subjects were divided into two groups according to the median maximum oxygen consumption (VO2max), a multivariate analysis of variance of the slope and intercept parameters helped to explain some of this heterogeneity (P less than 0.05). However, for physiological rather than statistical reasons, it was necessary to re-analyse the data without the fourth running speed. The revised analysis suggested that the subjects' lines would be better modelled with a common slope but separate intercepts. As before, by dividing the subjects into two groups according to the median VO2max score, a simple t-test indicated that differences in the subjects' intercept parameters were not significant (P = 0.08). Notwithstanding the relatively homogeneous nature of the 30 subjects in terms of VO2max, the statistical methods showed that differences in running economy are, to some extent, dependent on VO2max.

Adolescent↗

PubMed1988

Dose effects of methaqualone on stimulus encoding in a memory scanning task.

Three task variables, stimulus quality, memory set size and response type, were used in a Sternberg binary classification task to define stimulus encoding, short-term memory scanning, and response selection stages within a serial stage reaction process. Mean reaction times, and the slopes and intercepts of the function relating reaction time to memory set size, were used to test the hypothesis that performance deficits seen at two doses of methaqualone (2.9 mg/kg and 5.9 mg/kg), in the range formerly in common clinical use, were specific to the stimulus encoding stage of the reaction process. Mean reaction times were increased significantly by the methaqualone at both doses, but the effects of the two doses did not differ from one another. The intercept of reaction time as a function of set size showed significant main effects of methaqualone, stimulus quality, and response type, and a significant hyper-additive interaction of methaqualone with stimulus quality. At 2.9 mg/kg, the intercept was increased by methaqualone but only with degraded stimuli. At 5.9 mg/kg, the intercept was increased by methaqualone for both high and low quality stimuli. These results suggested a dose-dependent selective effect of methaqualone on the stimulus encoding stage of the reaction process.

Adult↗

PubMed1995

Assessment of coronary vasodilator reserve by N-13 ammonia PET using the microsphere method and Patlak plot analysis.

UNLABELLED: Noninvasive quantification of regional myocardial blood flow (MBF) has been successfully achieved with N-13 ammonia. The microsphere method as a simple method for quantifying regional myocardial blood flow was reevaluated in comparison with Patlak graphical analysis. In addition coronary vasodilator reserve (CVR) was estimated by both methods. METHODS: Dynamic N-13 ammonia PET studies were performed in 10 healthy volunteers and 10 patients with coronary artery disease at baseline and after dipyridamole infusion (0.56 mg/kg). MBF was estimated by the microsphere method at various times and by Patlak graphical analysis. In order to reduce the noise level in the microsphere method, MBF estimates were also performed after data in 10-40 seconds were averaged. RESULTS: In the studies on normal subjects MBF (ml/min/g) determined by the microsphere method significantly differs from time to time. However, MBF determined by the modified microsphere method [with average (Extraction fraction) x MBF values obtained between 100 and 120 sec] linearly correlated well with MBF by Patlak graphical analysis (r = 0.97, slope = 0.98, intercept = 0.20). In the studies on patients with coronary artery disease a good agreement of the MBF estimates was also observed (r = 0.97, slope = 0.98, intercept = 0.22). In the studies on the normal subjects and patients with coronary artery disease, CVR obtained by the modified microsphere method after correcting the overestimated MBF values also correlated well with that by Patlak graphical analysis (r = 0.90, slope = 1.14, intercept = -0.15, and r = 0.92, slope = 0.82, intercept = 0.25, respectively). CONCLUSION: The modified microsphere method is a very simple and reliable approach for quantifying MBF with N-13 ammonia PET which is comparable to Patlak graphical analysis. It also makes possible CVR assessment as accurate as Patlak graphical analysis.

Adult↗

PubMed2000

Early orthodontic treatment of Class-III malocclusion in Germany.

In order to evaluate current attitudes to early interceptive treatment, 2001 orthodontic offices in Germany were asked to fill in a questionnaire comprising the following topics: indication, appliances for the early correction of Class-III malocclusions, diagnostic records, duration, and benefits to overall therapy. Based on the 677 evaluable questionnaires, the following statistically significant conclusions could be drawn: 92.6% of the orthodontists see Class-III malocclusion as an indication for early treatment. Early treatment of severe crowding, diastemata, Class-II malocclusion, deep bite, increased overjet and impacted incisors was declined by most orthodontists. The interceptive treatment of further malocclusions was controversially discussed. Functional appliances (67.5%), in particular the Fränkel III (47.3%), were dominant in correction of Class-III malocclusions. Typical orthodontic records relating to early interceptive treatment include panoramic radiographs, lateral headfilms, photos and dental casts. 2.5% of the orthodontists routinely take a hand-wrist radiograph. Although recently published studies support the use of facial masks in theory, they are rarely used in practice. To what extent early interceptive treatment of Class-III malocclusion influences the overall treatment is the subject of further studies.

Attitude of Health Personnel↗

PubMed2004

Consequences of increased neuromotor noise for reaching movements in persons with stroke.

Understanding stroke-induced changes to the motor control of the more affected arm of people with stroke may lead to more effective rehabilitation interventions that improve function. Reaching movements of the more affected arm in persons with stroke are slow, segmented, and indirect. Such changes may be related to a reduced capacity to transmit motor commands in the presence of neuromotor noise. In tasks requiring both speed and accuracy, transmission capacity can be characterized by the linear relationship between movement time and task difficulty (Fitts' law). This study quantified Fitts' slope and intercept coefficients in stroke during reaching tasks and their relationship to kinematic measures of path accuracy (directness), trajectory corrections (segmentation), and planning strategy (skewness). We compared Fitts' slope and intercept and kinematics among the more and the less affected arm of 20 persons with stroke and the nondominant arm of ten healthy persons. Slope and intercept were significantly increased in the more affected arm of the group with stroke and related to clinical measurements of motor impairment and tone. For both the more and the less affected arm of the group with stroke, increased slopes and intercepts were correlated to more indirect, segmented, and positively skewed movement. Our findings suggest that stroke results in greater neuromotor noise, which has consequences for both motor execution and planning. Individuals with stroke demonstrate substantially more deviation from straight-line paths than do controls, despite using more conservative strategies (i.e., leftward shift of velocity profile) and extensive feedback control (i.e., segmentation).

Aged↗

PubMed2006

Controlling reaching movements with predictable and unpredictable target motion in 10-year-old children and adults.

We investigated interception behavior in adults and 10-year-old children. Participants had to intercept virtual targets moving on either a predictable (linear) or unpredictable (non-linear) path (with random direction changes). Targets moved at two different velocities, which varied randomly from trial to trial. Participants reached for the targets via a force-feedback device. Reaching movements for linearly moving targets in a block of linearly moving targets were compared with reaching movements for linearly moving targets in the context of non-linearly moving targets. Movement direction and maximum speed of the first sub-movement were analyzed as well as frequency of target hits and number of sub-movements. Unpredictable target motion caused faster movement speeds than predictable target motion for both children and adults. Additionally, unpredictable target motion caused children and adults to gear their initial movement direction further towards the current position of the target, while with predictable target motion, they geared their initial movement direction further ahead of the target towards an anticipated interception position. Together, these results suggest differential processing of predictable and unpredictable object behavior in an interception task, and that this differential processing is already in place in 10-year-olds.

Adult↗

PubMed1975

An analysis of the D-glucose influx kinetics of in vitro hamster jejunum, based on considerations of the mass-transfer coefficient.

1. A study designed specifically to investigate the effects of unstirred layers on the apparent glucose-influx kinetics of hamster jejunum was conducted. 2. The apparent V was 12.81, 10.71, 9.75, 10.17 and 9.33 mumol/cm-2 - h while the apparent Km was 7.42, 3.95, 1.87, 0.93 and 0.5 mM, respectively, when the rate of shaking the incubation flasks was 40, 80, 120, 160 and 200 cycles/min. 3. Extrapolation of the slope and reciprocal intercept of Lineweaver-Burke plots of the data to infinite shaking rate is mathematically justified to yield the slope and intercept of a Lineweaver-Burk plot which is uncomplicated by unstirred layers. These extrapolations were found to have a regression coefficient = 1 when plotted as (intercept)-1 or slope = b0 + b1b-(shake)-2 where b = 2.764 for the slope plot and 6.626 for the (intercept)-1 plot. From the values of b0 one obtains a Km of 0.41 and a V 0f 0.35 which should represent the true kinetic parameters for glucose influx into this tissue under the experimental conditions employed. 4. Values of the theoretical flux expected on a basis of unstirred-layer thickness which was calculated from the relation Cb (for J = V/2) = Km + 0.5 V/Kd agreed with the experimental values of J in some instances but the 95% confidence interval of the theoretical and experimental values did not overlap in many instances at low shaking rates and low concentrations of glucose. 5. A factor theta representing the error between the theoretical and experimental values was found to fit the relationship 1n(theoretical J) = - 3.8 + 5.77 (1/theta) with a regression coefficient of 0.98 and was proposed to be due to one or more of the following parameters: (1) a villus tip to base gradient of transport (influx) activity; (2) a dependence of brush-border influx area on substrate concentration in the bulk incubation media; and (3) an end-product inhibition of the overall transport rate. 6. It is apparent from the data that the flux of glucose across the unstirred layer is ordinarily the rate-limiting step in the trans-brush-border transport of this sugar by hamster jejunum when less than saturating concentrations of glucose are used. At high shaking rates the contribution of the unstirred layer is reduced.

Animals↗

PubMed1993

Effect of perfusion and blood content on ultrasonic backscattering of liver tissue.

The purpose of this study was to determine the effect of blood flow perfusion and red cell content on ultrasonic scattering by liver tissue. Data acquisition for ultrasonic tissue characterization (UTC) employing analysis of the backscattered echoes from the power spectrum was obtained from the same region of pig liver tissue under four conditions: 1) normal perfusion in situ, 2) ischemia in situ in the living pig, 3) ischemia in situ immediately postmortem, and 4) immediately after excision of the liver. Discriminant function analysis was used to evaluate differences in the two basic parameters from the normalized power spectrum: slope and intercept. Normal perfused liver had significantly higher intercept values and lower slope values than liver under the other three conditions. Excised liver showed the lowest intercept and highest slope values (p < 0.01). These experiments indicate that differences in perfusion produce significant differences in ultrasonic scattering by liver tissue (ischemia caused a 3 dB drop in intercept amplitude). Normal or ischemic in vivo and in vitro liver tissue is associated with different patterns of ultrasonic scattering, and scattering data under these various circumstances are not equivalent.

Animals↗

PubMedDate not supplied

Do intersections of mortality-rate and survival functions have significance?

Common points of intersections have frequently been reported among members of families of linearized mortality-rate and survival functions. A general condition for the existence of such intersections is derived. It is shown that a common point of intersection between straight-line functions exists if and only if the intercepts of the functions are linearly related to their slopes. This slope-intercept condition is applied to a didactic model to illustrate its generality and to three models, the Gompertz-Makeham, the Weibull, and the logistic, which are often used in the analysis of mortality data. The slope-intercept condition for the Gompertz-Makeham mortality-rate model proves to be the well-known Strehler-Mildvan correlation. Families of mortality-rate functions or of the corresponding survival functions but not both may display common points of intersection. Differences between the ages at which survival functions intersect and those at which the associated mortality-rate functions intersect are calculated to be of the order of magnitude of 10 to 20 years. Survival function intersections lie close to the limit of human life span but often arise in consequence of unsupported extrapolations of data obtained at younger ages. These and other results lead to the conclusion that, in themselves, the intersections of survival and mortality-rate functions are not of great importance. To the extent that significance can be attributed to the intersections, it lies in the existence of linear relationships between their slopes and intercepts.

Data Interpretation, Statistical↗

PubMed1994

Comparative efficacy of three indexes of left ventricular performance derived from pressure-volume loops in heart failure induced by tachypacing.

OBJECTIVES: The purpose of this study was to serially evaluate the response and variability of the end-systolic pressure-volume relation, the left ventricular end-diastolic volume-peak positive first derivative of left ventricular pressure (dP/dt) relation and the left ventricular end-diastolic volume-stroke work relation in the development of progressive left ventricular dysfunction. BACKGROUND: Evaluation of systolic performance of the failing left ventricle may be enhanced by using relatively load-insensitive measures of left ventricular performance. The end-systolic pressure-volume, left ventricular end-diastolic volume-peak positive dP/dt and left ventricular end-diastolic volume-stroke work relations adequately define left ventricular performance under multiple loading conditions, but efficacy has not been fully assessed in the failing heart, particularly in the intact circulation. METHODS: Fourteen dogs underwent instrumentation and rapid pacing to heart failure. Variably loaded pressure-volume beats were produced by inferior vena cava occlusion. The dogs were evaluated at baseline and at three progressively more severe levels of left ventricular dysfunction. RESULTS: There was a progressive increase in left ventricular volumes at end-diastole ([mean value +/- SE] 60 +/- 28 to 73 +/- 29 ml, p < 0.001) and end-systole (39 +/- 19 to 61 +/- 27 ml, p < 0.001) during the 3 weeks of rapid pacing and a progressive decline in peak positive dP/dt (1,631 +/- 410 to 993 +/- 222 mm Hg/s, p < 0.001) and ejection fraction (37 +/- 8% to 16 +/- 11%, p < 0.001). There was a corresponding decline in the slope of each of the three relations: for end-systolic pressure-volume, 6.3 +/- 2.2 to 2.8 +/- 0.7 (p < 0.05); for left ventricular end-diastolic volume-stroke work, 61.9 +/- 9.1 to 26.5 +/- 2.4 (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 47.1 +/- 13.6 to 20.31 +/- 6.8 (p < 0.05). There was also a corresponding increase in position volumes: for end-systolic pressure-volume, 33.6 +/- 3.9 to 61.2 +/- 6.6 ml (p < 0.05); for left ventricular end-diastolic volume-stroke work, 46.2 +/- 3.6 to 89.3 +/- 7.6 ml (p < 0.05); and for left ventricular end-diastolic volume-peak positive dP/dt, 29.1 +/- 19.1 to 68.6 +/- 25.9 ml (p < 0.05). The relative degree of change in each of the three relations was similar as more severe heart failure developed. The coefficients of variation for position were significantly less than the variation for slopes. The response of volume intercepts was heterogeneous. For left ventricular end-diastolic volume-stroke work, the intercept increased as ventricular performance decreased. The intercept of the end-systolic pressure-volume relation was significantly more variable than the left ventricular end-diastolic volume-stroke work relation and did not change with progressive heart failure. The intercept for left ventricular end-diastolic volume-peak positive dP/dt was highly variable and showed no consistent changes as left ventricular function declined. CONCLUSIONS: All three relations consistently describe changes in left ventricular performance brought about by tachypacing. Evolution of left ventricular dysfunction causes a decline in slope and a rightward shift of these relations. The position of the relation is the most sensitive and least variable indicator of left ventricular systolic performance.

Animals↗

PubMed2006

The rule parameters in liquid adsorption chromatography of polymer homologous series and their determination.

The separation of polymer homologous series is governed by two rule parameters: the interaction parameter c of the repeat unit and the sorbent surface S (relation of pore volume to pore diameter). The interaction parameter is independent on column dimensions and pore diameter. In a plot of elution volumes Vn versus the difference DeltaV =Vn -Vn-1 in elution volumes of consecutive oligomers, straight lines are obtained, the intercept of which yields the accessible volume. Using the accessible volume as the hold-up volume in the calculation of the retention factor k, a strictly linear dependence of ln k versus the number of the repeat units n is observed (Martin's plot). The interaction parameter c can be determined experimentally by three different approaches: from the slope in a plot of V versus DeltaV, from the slope in Martin's plot (ln k versus n), and from the intercept in a plot of ln(DeltaV) versus n. The pore surface is obtained from the intercept in Martin's plot (ln k versus n) or the intercept in a plot of ln(DeltaV) versus n. The results obtained by the different approaches agree very well. The theoretical predictions are verified by comparison with the experimental data obtained on columns with different pore diameter and pore volume and thus, different pore surface at conditions corresponding to the same interaction parameter.

Adsorption↗

PubMed2005

Three- to eight-month-old infants' catching under monocular and binocular vision.

We report a cross-sectional and a longitudinal experiment that examined developmental changes in the relative contribution of monocular and binocular variables in the guidance of interceptive arm movements. Three- to eight-month-old infants were observed while presented with differently sized balls that approached frontally with a constant velocity under both monocular and binocular viewing conditions. Movement onset indicated that with age infants increasingly came to rely on binocular variables in controlling the timing of the interceptive arm movements. That is, from 7 to 8 months of age movement onset was independent from object size under binocular but not under monocular viewing. In contrast, binocular viewing enhanced the spatial accuracy of the interceptive arm movements at all ages. We concluded that attunement to binocular information is a key process in infants' gaining adaptive control of goal-directed arm movements. However, interceptive arm movements entail the formation of multiple on-line couplings between optic and movement variables, each of which appears to develop at its own pace.

Humans↗

PubMed1997

Comparison of continuous left ventricular volumes by transthoracic two-dimensional digital echo quantification with simultaneous conductance catheter measurements in patients with cardiac diseases.

Automated border detection enables real-time tracking of left ventricular (LV) volume by 2-dimensional transthoracic echocardiography. This technique has not been previously compared with simultaneously measured continuous LV volumes at rest or during transients in humans. We performed 18 studies in 16 patients (age 50 +/- 15 years, range 22 to 70; ejection fraction 63 +/- 20%, range 15% to 85%) in which continuous LV volumes acquired by digital echo quantification (DEQ) were compared with simultaneous conductance catheter volume obtained by cardiac catheterization. Both volume signals were calibrated by thermodilution-derived cardiac output and ventriculogram-derived ejection fraction. Volume traces acquired at rest were averaged to generate a comparison cycle. The averaged volume waveforms acquired by DEQ and by conductance catheter were similar during all phases of the cardiac cycle and significantly correlated (conductance catheter = slope. DEQ + intercept, slope = 0.94 +/- 0.09, intercept = 5 +/- 8 ml, r2 = 0.86 +/- 0.12, all p <0.0001). Steady-state hemodynamic parameters calculated using either averaged volume signal were significantly correlated. Transient obstruction of the inferior vena cava yielded a 45 +/- 13% decrease in end-diastolic volume. Successful recordings of DEQ volume during preload reduction were obtained in only 50% of studies. End-diastolic volumes from the 2 methods were significantly correlated (mean slope 0.88 +/- 0.31, mean intercept 14 +/- 37 ml, average r2 = 0.89 +/- 0.11, all p <0.01), as were end-systolic volumes: mean slope 0.80 +/- 0.43, intercept = -20 +/- 26 ml, r2 = 0.67 +/- 0.18, all p <0.05). We conclude that automated border detection technique by DEQ is reliable for noninvasive, transthoracic, continuous tracking of LV volumes at steady state, but has limitations in use during preload reduction maneuvers in humans.

Adult↗

PubMed1998

Left coronary pressure-flow relations of the beating and arrested rabbit heart at different ventricular volumes.

OBJECTIVE: To study the effect of cardiac contraction on left coronary artery pressure-flow relations at different vascular volumes and to compare these relations in the beating heart with those in the heart arrested in systole and diastole. METHODS: Maximally vasodilated, Tyrode perfused, rabbit hearts (n = 6) with an intra-ventricular balloon were used. The left coronary artery was separately perfused via a cannula in the left main coronary artery. The slopes and the intercepts of left coronary pressure-flow relations were determined in the beating and arrested heart at different chamber volumes. A 3-factor design with repeated measures was used to compare the effect of three factors: phase of contraction (systole and diastole), chamber volume (V0 and V1, left ventricular end-diastolic pressure 1.4 and 20 mm Hg, respectively) and the type of contraction (beating and arrested; a measure of capacitive effects). RESULTS: The phase of contraction has a significant effect on the intercepts (> 40 mmHg, p = 0.00032) but not on the slopes of the pressure-flow relations. Chamber volume had a small effect on the intercepts (< 5 mm Hg, p = 0.037), but not on the slopes of the pressure-flow relations. The type of contraction has a significant effect on the slopes (approximately 10%, p = 0.00021) but not on the intercepts of the pressure-flow relations. CONCLUSIONS: In the isolated Tyrode perfused rabbit heart left coronary pressure-flow relations are mainly determined by contraction, while left ventricular chamber volume and capacitive effects contribute little.

Animals↗

PubMed2003

Lipase and pancreatic amylase versus total amylase as biomarkers of pancreatitis: an analytical investigation.

OBJECTIVE: To evaluate the biomarkers of pancreatitis Colorimetric Lipase, Total Amylase and Pancreatic Amylase (immunoinhibition) assays on the Roche COBAS INTEGRA 700. RESULTS: Pancreatic and Total Amylase assays and Colorimetric Lipase showed excellent imprecision of 1.6 to 2.3% and linearity (slope = 0.94-0.99, y-intercepts-1 to +3 U/L, r = 0.999) over the range of 17 to 900, 35 to 880, and 21 to 150 U/L, respectively. There was an excellent correlation between Pancreatic and Total Amylase: Pancreatic Amylase = 0.99 (+/- 0.02) x Total Amylase-36(+/- 8) (n = 106, r = 0.97, p < 1 x 10(-5), y intercept p < 1 x 10(-5)). Colorimetric Lipase showed some correlation to Total and Pancreatic Amylase results: Colorimetric Lipase = 1.54 (+/- 0.16) x Total Amylase-81(+/- 37) (n = 100, r = 0.70, p < 1 x 10(-6), y intercept p = 0.03), and Colorimetric Lipase = 1.78 (+/- 0.15) x Pancreatic Amylase-50(+/- 29) (n = 99, r = 0.78, p < 1 x 10(-6), y intercept p = 0.09). CONCLUSION: We recommend running the more specific Pancreatic Amylase as biomarker of pancreatitis on the Roche COBAS INTEGRA.

Amylases↗

PubMedDate not supplied

Ultrasound biomicroscopy dark room provocative testing: a quantitative method for estimating anterior chamber angle width.

PURPOSE: To describe a quantitative method for measuring the iridocorneal angle recess area, and, using this, to evaluate factors associated with appositional angle-closure during dark room provocative testing using ultrasound biomicroscopy (UBM). METHODS: All patients (178 patients, 178 eyes) with clinically narrow angles referred for UBM dark room provocative testing between September 1996 and March 1998 were enrolled in this study. Images of the inferior quadrant of the angle taken under standardized dark and light conditions were analyzed. The angle recess area (ARA) was defined as the triangular area demarcated by the anterior iris surface, corneal endothelium, and a line perpendicular to the corneal endothelium drawn from a point 750 microm anterior to the scleral spur to the iris surface. ARA, and acceleration and gamma-intercept of the linear regression analysis of the ARA were calculated. In the linear regression formula, y = ax + b, the acceleration a describes the rate at which the angle widens from the scleral spur; the y-intercept b describes the distance from the scleral spur to the iris. RESULTS: Under dark conditions, the angles in 99 patients (55.6%) showed evidence of appositional angle-closure during testing. ARA (0.11 +/- 0.04 vs. 0.15 +/- 0.05 mm2, P < .0001, Student t-test), acceleration a (0.22 +/- 0.15 vs. 0.26 +/- 0.17, P = .068), and y-intercept b (66 +/- 46 vs. 92 +/- 47 microm, P = .0003) were smaller in eyes that were occluded. In the eyes that were not occluded, y-intercept b showed no significant difference between light and dark conditions (P = .1, paired t-test), while acceleration a did (P < .0001). In the eyes that were occluded, both decreased significantly under dark conditions (P < .0001). CONCLUSIONS The ARA linear regression formula provides useful quantitative information about angle recess anatomy. The more posterior the iris insertion on the ciliary face, the less likely the provocative test will be positive.

Adult↗

PubMed1999

Choosing the calibration model in assay validation.

Data transformations and weighting schemes are normally used to obtain the best-fit of standard curves in bioanalysis and the calibration model is usually selected during prevalidation. In the present study, a comparison has been made between unweighted and weighted (1/x, 1/x2, and 1/square root of x) regression models with or without an intercept in achieving the best-fit for the standard curve of CDRI compound 81/470, a new anthelmintic agent, in cow milk. Validation samples in milk at the LLOQ, medium, and high concentrations were also analysed by each of the calibration models. An unweighted regression equation with an intercept overestimated the concentrations at the LLOQ. An unweighted equation without intercept and weighted equations with or without an intercept significantly minimized the bias at the LLOQ without distorting the results at higher concentrations. Hence, an unweighted equation for a straight line passing through the origin was found to be the best model for a standard curve of 81/470 in milk. Similar results were obtained for 81/470 and UMF-078 in serum and plasma, respectively. Bioanalysts should routinely test these models to obtain the best fit model for their calibration curves as part of their assay validation not during prevalidation.

Animals↗

PubMed1985

Human brain monoamine oxidase type B: mechanism of deamination as probed by steady-state methods.

Recently, evidence has been published which suggests that [Husain, M., Edmondson, D. E., & Singer, T.P. (1982) Biochemistry 21, 595-600] monoamine oxidase [amine:oxygen oxidoreductase (MAO), EC 1.4.3.4] deaminates phenylethylamine and benzylamine via two distinct kinetic pathways which involve either binary or ternary complex formation, respectively. These conclusions were drawn largely from stopped-flow kinetic analysis performed on purified enzyme removed from its native membrane and in the presence of the inhibitory detergent Triton X-100. In this study, d-amphetamine and alternative substrates were used as steady-state probes of the kinetics of deamination by the B form of human brain MAO using native membrane-bound enzyme. Initial velocity studies showed mixed-type patterns for amphetamine inhibition of phenylethylamine, tryptamine, and tyramine when either amine or oxygen was the varied substrate. Slope and intercept vs. amphetamine concentration replots were linear in all cases except for phenylethylamine (hyperbolic); Ki values obtained from linear replots of slope or intercept values were comparable. In contrast, amphetamine was a competitive inhibitor of benzylamine deamination when amine concentration was varied and uncompetitive when oxygen concentration was varied; slope and intercept replots were linear for both. When benzylamine was the alternative substrate inhibitor and tyramine and tryptamine deamination was measured, mixed-type inhibition patterns were obtained when either amine or oxygen concentration was varied; replots of slope and intercept were linear in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗