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Biomedical subjects

A M Muijtjens

Publications and source records attributed to A M Muijtjens.

At least 19 recordsLinked to original sources

Remodeling by ventricular pacing in hypertrophying dog hearts.

OBJECTIVE: Asynchronous electrical activation of the left ventricle (LV), induced by ventricular pacing (VP), reduces mechanical load in early- and enhances it in late-activated regions. Consequently, chronic VP leads to asymmetric hypertrophy. We investigated whether such locally induced myocardial hypertrophy also occurs in the presence of pressure overload hypertrophy (POH). METHODS: POH was induced by aortic banding in puppies. At age 9 months, seven dogs were paced at the right ventricular (RV) apex at physiological heart rate for 6 months (POH-pace group), while four POH dogs served as POH-control group. Changes in volume of the LV cavity and the total LV wall and of five LV wall sectors were measured by means of 2D-echocardiography and X-ray marker detection. RESULTS: During the last 6 months of the protocol the volume of the five LV wall sectors increased in the POH-control group, ranging from 27+/-9 to 30+/-5% (mean+/-S.D.). In POH-pace animals sector wall volume in the four sectors at intermediate to long distance from the pacing site increased to a similar extent (ranging from 31+/-16 to 35+/-17%), but wall volume in the early-activated apical septum increased significantly less (17+/-21%). In these hearts myocyte diameter was significantly smaller in the apical septum than in the lateral LV wall. The regional difference in wall volume changes (19+/-21%) was significantly smaller in the POH-pace group than in chronically paced, non-hypertrophic, canine hearts in a previous study from our laboratory (43+/-14%). CONCLUSIONS: In hypertrophying hearts chronic pacing at the RV apex suppresses the development of hypertrophy in the early-activated apical septum but does not cause additional hypertrophy in late-activated regions, as is the case in non-hypertrophic hearts. The latter suggests that the local growth response is reduced in hypertrophying hearts.

Analysis of Variance↗

Assessment of coronary reperfusion in patients with myocardial infarction using fatty acid binding protein concentrations in plasma.

OBJECTIVE: To examine whether successful coronary reperfusion after thrombolytic treatment in patients with confirmed acute myocardial infarction can be diagnosed from the plasma marker fatty acid binding protein (FABP), for either acute clinical decision making or retrospective purposes. DESIGN: Retrospective substudy of the GUSTO trial. SETTING: 10 hospitals in four European countries. PATIENTS: 115 patients were treated with thrombolytic agents within six hours after the onset of acute myocardial infarction. Patency of the infarct related artery was determined by angiography within 120 minutes of the start of thrombolysis. MAIN OUTCOME MEASURES: First hour rate of increase in plasma FABP concentration after thrombolytic treatment, compared with increase in plasma myoglobin concentration and creatine kinase isoenzyme MB (CK-MB) activity. Infarct size was estimated from the cumulative release of the enzyme alpha hydroxybutyrate dehydrogenase in plasma during 72 hours, or from the sum of ST segment elevations on admission. Logistic regression analyses were performed to construct predictive models for patency. RESULTS: Complete reperfusion (TIMI 3) occurred in 50 patients, partial reperfusion (TIMI 2) in 36, and no reperfusion (TIMI 0+1) in 29. Receiver operating characteristic (ROC) curve analyses showed that the best performance of FABP was obtained when TIMI scores 2 and 3 were grouped and compared with TIMI score 0+1. The performance of FABP as a reperfusion marker was improved by combining it with alpha hydroxybutyrate dehydrogenase infarct size, but not with an early surrogate of infarct size (ST segment elevation on admission). In combination with infarct size FABP performed as well as myoglobin (areas under the ROC curve 0.868 and 0.857, respectively) and better than CK-MB (area = 0.796). At optimum cut off levels, positive predictive values were 97% for FABP, 95% for myoglobin, and 89% for CK-MB (without infarct size, 87%, 88%, and 87%, respectively), and negative predictive values were 55%, 52%, and 50%, respectively (without infarct size, 44%, 42%, and 34%). CONCLUSIONS: FABP and myoglobin perform equally well as reperfusion markers, and successful reperfusion can be assessed, with positive predictive values of 87% and 88%, or even 97% and 95% when infarct size is also taken into account. However, identification of non-reperfused patients remains a problem, as negative predictive values will generally remain below 70%.

Biomarkers↗

A comparison of standard-setting procedures for an OSCE in undergraduate medical education.

PURPOSE: To compare four standard-setting procedures for an objective structure clinical examination (OSCE). METHODS: A 12-station OSCE was administered to 84 students in each of the final (fourth-) year medical classes of 1996 and 1997 at Dalhousie University Faculty of Medicine. Four standard-setting procedures (Angoff, borderline, relative, and holistic) were applied to the data to establish a cutoff score for a pass/fail decision. RESULTS: The procedures yielded highly inconsistent results. The Angoff and borderline procedures gave similar results; however, the relative and holistic methods gave widely divergent results. The Angoff procedure yielded results reliable enough to use in decision making for a high-stakes examination, but would have required more judges or more stations. CONCLUSIONS: The Angoff and borderline procedures provide reasonable and defensible approaches to standard setting and are practical to apply by non-psychometricians in medical schools. Further investigation of the other procedures is needed.

Education, Medical, Undergraduate↗

Sequential testing in the assessment of clinical skills.

PURPOSE: Educators who use standardized-patient-based (SP-based) tests may save resources by using sequential testing. In this approach, students take a short screening test; only those who fail take a second test. This study investigated whether sequential testing increases efficiency with only a minor decrease of validity. METHOD: In 1994-95, first- through fourth-year (Group 1) and sixth-year (Group 2) medical students at the University of Maastricht took SP-based tests. Each test took two days. In a simulation experiment based on the data from those tests, the authors considered the first day as the screening test and the second day as the second test. They investigated efficiency and validity as a function of the cutoff score of the screening test. They developed and evaluated a new method to determine the optimum cutoff score of the screening test, a method based on minimization of the loss represented by the (weighted) numbers of false positives and negatives in the screening test. RESULTS: The negative predictive value (probability that a student would fail the complete test if he or she had failed the screening test) was low (<60%), while the positive predictive value was high (>96%). Accordingly, stringent pass/fail cutoff scores in the screening test (75% for Group 1 and 80% for Group 2) produced optimum results. Using those cutoff values, only 26% and 11% of 'the students would have had to take the complete test to get a "true" score, while only 0.2% and 0.0% of the students who passed the screening test went on to fail the complete test (false positives). CONCLUSIONS: In a sequential SP-based test, the pass/fail cutoff score of the screening test should be stringent. This can considerably reduce testing time (30% to 40%), while keeping the percentage of false positives at an acceptably low level of less than 0.2%. As an alternative to receiver operator characteristic analysis, minimization of the loss function was found to be an appropriate method to determine the optimum cutoff value of the screening test.

Clinical Competence↗

Improving contrast and tracking of tags in cardiac magnetic resonance images.

Cardiac tagging permits non-invasive study of myocardial motion with high accuracy. Unfortunately, tagging contrast is impaired at later heart phases due to longitudinal relaxation. Histogram modification is presented as a method for improving contrast in later, faded images of a tagging series by altering these images such that their intensity histograms approximate the shape of the first, unfaded image of the series. This technique greatly improves the contrast and facilitates automatic detection of tags. Furthermore, a method is described for automatically tracking tag positions in short-axis images of the left ventricle modulated with a tagging grid. The method differs from previously reported methods in that, in one single filtering process in the Fourier domain, both the grid crossings as well as the grid centers are detected, and thus increased sampling resolution is obtained. The method was validated by applying a mathematical model of left ventricular motion to tagged images of the thigh muscle. The average discrepancy between theoretically predicted and automatically detected tag positions was 0.04 +/- 0.17 mm (mean +/- SD).

Algorithms↗

Skeletal muscle transverse strain during isometric contraction at different lengths.

An important assumption in 2D numerical models of skeletal muscle contraction involves deformation in the third dimension of the included muscle section. The present paper studies the often used plane strain description. Therefore, 3D muscle surface deformation is measured from marker displacements during isometric contractions at various muscle lengths. Longitudinal strains at superficial muscle fibers ( - 14 +/- 2.6% at L0, n = 57) and aponeurosis (0.8 +/- 0.9% at L0) decrease with increasing muscle length. The same holds for transverse muscle surface strains in superficial muscle fibers and aponeurosis, which are comparable at intermediate muscle length, but differ at long and short muscle length. Because transverse strains during isometric contraction change with initial muscle length, it is concluded that the effect of muscle length on muscle deformation cannot be studied in plane strain models. These results do not counteract the use of these models to study deformation in contractions with approximately - 9 % longitudinal muscle fiber strain, as transverse strain in superficial muscle fibers and in aponeurosis tissue is minimal in that case. Aponeurosis surface area change decreases with increasing initial muscle length, but muscle fiber surface area change is - 11%, independent of muscle length. Assuming incompressible muscle material, this means that strain perpendicular to the muscle surface equals 11%. Taking the relationship between transverse and longitudinal muscle fiber strain into account, it is hypothesized that superficial muscle fibers flatten during isometric contractions.

Animals↗

The effect of a 'don't know' option on test scores: number-right and formula scoring compared.

OBJECTIVES: In multiple-choice tests using a 'don't-know' option the number of correct minus incorrect answers was used as the test score (formula scoring) in order to reduce the measurement error resulting from random guessing. In the literature diverging results are reported when comparing formula scoring and number-right scoring, the scoring method without the don't-know option. DESIGN: To investigate which method was most appropriate, both scoring methods were used in true-false tests (block tests) taken at the end of a second- and third-year educational module (block). The students were asked to answer each item initially by choosing from the response options true, false or don't know, and secondly to replace all don't-know answers by a true-false answer. SETTING: Maastricht University, The Netherlands. SUBJECTS: Medical students. RESULTS: The correct scores for the don't-know answered items were found to be 4.5% and 5.9%, respectively, higher than expected with pure random guesswork. This represents a source of bias with formula scoring, because students who were less willing to guess obtained lower scores. The average difference in the correct minus incorrect score for the two scoring methods (2.5%, P < 0.001, and 3.4%, P < 0. 001, respectively) indicates the size of the bias (compare: the standard deviation of the score equals 11%). Test reliability was higher with formula scoring (0.72 vs. 0.66 and 0.74 vs. 0.66), but the difference decreased when the test was restricted to items which were close to the core content of the block (0.81 vs. 0.77, resp. 0. 75 vs. 0.70). CONCLUSIONS: In deciding what scoring method to use, less bias (number-right scoring) has to be weighed against higher reliability (formula scoring). Apart from these psychometric reasons educational factors must be considered.

Education, Medical, Undergraduate↗

Reliability and credibility of an angoff standard setting procedure in progress testing using recent graduates as judges.

INTRODUCTION: Progress testing is an assessment method that samples the complete domain of knowledge that is considered pertinent to undergraduate medical education. Because of the comprehensive nature of this test, it is very difficult to set a passing score. We obtained a progress test standard using an Angoff procedure with recent graduates as judges. This paper reports on the reliability and credibility of this approach. METHODS: The Angoff procedure was applied to a sample of 146 progress test items. The items were judged by a panel of eight recently graduated students. Generalizability theory was used to investigate the reliability as a function of the number of items and judges. Credibility was judged by comparing the pass/fail rates resulting from the standard arrived at by the Angoff procedure with those obtained using a relative and a fixed standard. RESULTS: The results indicate that an acceptable error score can be achieved, yielding a precision within one percentage on the scoring scale, by using 10 judges on a full-length progress test (i.e. 250 items). The pass/fail rates associated with the Angoff standard came closest to those of the relative standard, which takes variations in test difficulty into account. A high correlation was found between item-Angoff estimates and the item P-values. CONCLUSION: The results of this study suggest that the Angoff procedure, using recently graduated students as judges, is an appropriate standard setting method for a progress test.

Education, Medical, Undergraduate↗

Maximum likelihood estimation in calibrating a stereo camera setup.

Motion and deformation of the cardiac wall may be measured by following the positions of implanted radiopaque markers in three dimensions, using two x-ray cameras simultaneously. Regularly, calibration of the position measurement system is obtained by registration of the images of a calibration object, containing 10-20 radiopaque markers at known positions. Unfortunately, an accidental change of the position of a camera after calibration requires complete recalibration. Alternatively, redundant information in the measured image positions of stereo pairs can be used for calibration. Thus, a separate calibration procedure can be avoided. In the current study a model is developed that describes the geometry of the camera setup by five dimensionless parameters. Maximum Likelihood (ML) estimates of these parameters were obtained in an error analysis. It is shown that the ML estimates can be found by application of a nonlinear least squares procedure. Compared to the standard unweighted least squares procedure, the ML method resulted in more accurate estimates without noticeable bias. The accuracy of the ML method was investigated in relation to the object aperture. The reconstruction problem appeared well conditioned as long as the object aperture is larger than 0.1 rad. The angle between the two viewing directions appeared to be the parameter that was most likely to cause major inaccuracies in the reconstruction of the 3-D positions of the markers. Hence, attempts to improve the robustness of the method should primarily focus on reduction of the error in this parameter.

Biomechanical Phenomena↗

Steady-state and dynamic behavior of ventricular repolarization and refractoriness in the dog: the effect of multiple cycle length changes and d-sotalol administration.

In anesthetized dogs with chronic, complete AV block we studied the characteristics of ventricular repolarization and refractoriness. Therefore, we determined: (1) steady-state values of ventricular effective refractory period (VERP), action potential duration (APD), and stimulus T interval (STI) before and after d-sotalol treatment at various pacing cycle lengths (PCLs); and (2) the dynamics of VERP, APD, and STI before and after d-sotalol treatment after the abrupt PCL decreases. VERP, APD, and STI showed a normal frequency dependency. All three parameters increased significantly after d-sotalol administration. During steady-state and dynamic measurements, STI was always longer than APD and APD was always longer than VERP in an individual animal, irrespective of PCL and conditions. Standard deviations of steady-state and dynamic values indicated a considerable interindividual variation. However, the dynamics of VERP, APD, and STI after an abrupt decrease in PCL were highly correlated (linear regression analysis: r2 > or = 0.93). The best mathematical model to describe these dynamics was a bi-exponential model (r2 > or = 0.98) with a very short first and a much longer second time constant. We found that there was a very consistent relation between VERP, APD, and STI, not only during steady-state but also in the dynamic situation after various abrupt PCL decreases. This relation does not change after the administration of d-sotalol. Therefore, STI could be used to predict steady-state and dynamic values of VERP and APD. Since STI can be made available online in implantable pacing systems this could lead to the development of new features in these devices.

Animals↗

Tracking markers with missing data by lower rank approximation.

Motion and deformation of an object may be quantified by following attached markers in video or cine frame sequences. When recording cardiac motion by video (256 x 256 pixels, 50 Hz), generally no more than approximately 20 markers can be followed due to difficulties in proper identification of marker images. In the present study we developed the lower rank (LR) tracking method which can automatically follow considerably more than 20 markers. The performance of the method was evaluated in computer simulations of naturally moving myocardial markers observed in a sequence of 60 video frames. White noise was added to the marker coordinates. Realistic loss of data due to detection failure was simulated by deleting a generated marker image when the distance to another marker image was below a given minimum value. In a test, realistic values were substituted for the noise level sigma (0.5 pixel) and the minimum marker distance dm (4 pixels). For numbers of markers ranging from 50 to 100, 95-90% of the detected marker images was correctly tracked. Less than 0.7% was part of a false track, i.e. a track containing images of different markers. Under less favourable conditions (sigma = 1 pixel; dm = 8 pixels) the method was robust: for 75 markers with 40% of the marker images missing, still 70% of the detected images was correctly tracked, while the fraction in false tracks did not increase. The LR tracking method appears reliable for automatic tracking of large amounts of moving markers in a sequence of video or cine frames.

Algorithms↗

Relation between torsion and cross-sectional area change in the human left ventricle.

During the ejection phase, motion of the left ventricular (LV) wall is such that all myocardial fibers shorten to the same extent. In a mathematical model of LV mechanisms it was found that this condition could be satisfied only if torsion around the long axis followed a unique function of the ratio of cavity volume to wall volume. When fiber shortening becomes non-uniform due to cardiac pathology, this pathology may be reflected in aberration of the torsional motion pattern. In the present study we investigated whether the predicted regular motion pattern could be found in nine healthy volunteers, using Magnetic Resonance Tagging. In two parallel short-axis cross-sections, displacement, rotation, and area ejection were derived from the motion of tags, attached non-invasively to the myocardium. Information from both sections was combined to determine area ejection, quantified as the change in the logarithm of the ratio of cavity area to wall area, and torsion, represented by the shear angle on the epicardium. Linear regression was applied to torsion as a function of area ejection. The slope thus found (-0.173 +/- 0.024 rad, mean +/- S.D.) was similar to the slope as predicted by the model of LV mechanics (-0.194 +/- 0.026 rad). In conclusion, the relation between area ejection and torsion could be assessed noninvasively in humans. In healthy volunteers, the relation was close to what was predicted by a mathematical model of LV mechanics, and also close to what was found earlier in experiments on animals.

Algorithms↗

Macroscopic three-dimensional motion patterns of the left ventricle.

The pattern of displacements in the left ventricle (LV) can be described by 13 modes of motion and deformation. Three functional modes of deformation are essential for ejection: a decrease in cavity volume, torsion, and ellipticalization. Four additional modes are used to describe asymmetric deformation. Six modes of rigid body motion describe rotation and translation. In the LV 14-20 radiopaque markers were inserted in the wall of the LV. They were distributed more or less evenly from base to apex and around the circumference. Torsion and volume changes require the definition of a cardiac coordinate system. The point at which ejection focuses is used as the origin, and the torsion axis is used as the z-axis. In the present study the coordinate system was positioned objectively by a least squares fit of the kinematic model to the measured motion of markers. In five dogs in the control state the kinematic parameters were determined as a function of time for all 13 modes. The torsion axis was displaced 4 +/- 2 mm (mean +/- sd) from the center of the cross-section of the LV towards the lateral free wall. The direction of the torsion axis closely coincided with anatomical landmarks at the apex and base. During systole, a unique relation was found between the ratio of cavity volume to wall volume and torsion. This relation was universal to all LVs, the cylinder-symmetric mathematical model of cardiac mechanics inclusive. In diastole the patterns of deformation seem less universal and reproducible.

Animals↗

Extrapolation of incomplete marker tracks by lower rank approximation.

Motion and deformation of an object such as the heart may be measured by tracking optical or radiopaque markers. In the experimental situation markers may fail to be detected due to occlusion or lack of contrast. As a result a continuous marker track is observed in separated parts, which often cannot be directly identified as corresponding to one marker. This paper presents a method of extrapolating a partly known track by using information provided by the known track part and the available complete tracks of other markers. The extrapolations are obtained by iteratively fitting a lower rank matrix to the set of noisy, incomplete marker tracks. The performance is evaluated with computer-simulated data and data obtained in an animal experiment. In both cases 43% of the available complete tracks were made incomplete by removal of track parts varying in length from 3% up to 44%. For the simulated data comparison of the extrapolations with true signal values results in a root mean square (RMS) error about equal to the noise level. For the animal experiment, when comparing the extrapolations with the measured values, in images of 256 x 256 pixels, the RMS error was found to be +/- 0.5 pixel, which is quite small relative to the total excursion of a marker (20 pixels). Estimation of the missing data by applying BMDPAM (BMDP Statistical Software Inc.) to the same data results in RMS errors which are about twice as high.

Algorithms↗

Description of the deformation of the left ventricle by a kinematic model.

A model of left ventricular (LV) kinematics is essential to identify the fundamental physiological modes of LV deformation during a complete cardiac cycle as observed from the motion of a finite number of markers embedded in the LV wall. Kinematics can be described by a number of modes of motion and deformation in succession. An obvious mode of LV deformation is the ejection of cavity volume while the wall thickens. In the more sophisticated model of LV kinematics developed here, seven time-dependent parameters were used to describe not only volume change but also torsion and shape changes throughout the cardiac cycle. Rigid-body motion required another six parameters. The kinematic model employed a deformation field that had no singularities within the myocardium, and all parameters describing the modes of deformation were dimensionless. Note that torsion, volume and symmetric shape changes all require the definition of a cardiac coordinate system, which has generally been related to the measured cardiac geometry by reference to approximate anatomical landmarks. However, in the present study the coordinate system was positioned objectively by a least-squares fit of the kinematic model to the measured motion of markers. Theoretically, at least five markers are needed to find a unique set of parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Noise reduction in estimating cardiac deformation from marker tracks.

Deformation of the cardiac wall is measured by using optical or radiopaque markers attached to the wall. When digitized images are used, the accuracy of the measurement of a marker position is limited by pixel resolution and the size of the marker. The spatial accuracy is improved by singular value decomposition (SVD) filtering. This filtering procedure is based on the assumption that displacements of markers are mutually related because they are embedded in a common continuum. In a computer stimulation with 48 markers in 51 video frames, the accuracy of the measurement of a marker position improved from 0.14 to 0.045 (SD) pixel. In an open-chest animal experiment, with markers on the surface of the heart, the deformation patterns were extracted more clearly using SVD filtering, while mutually related high-frequency components were not suppressed. In a 50-frame sequence of 256 X 256 video images of a 45 mm X 35 mm deforming surface with 50 markers of 8 pixels in diameter, the marker position resolution improves from 0.1 to 0.03 (SD) pixel (6 microns). Strain is determined with an accuracy of 0.002 over a distance of 30 pixels (6 mm).

Animals↗

Velocity profiles of blood platelets and red blood cells flowing in arterioles of the rabbit mesentery.

Velocity profiles were determined in rabbit mesenteric arterioles (diameter 17-32 micron). A good spatial resolution was obtained by using the blood platelets as small and natural markers of flow, providing for the first time in vivo detailed, quantitative information about the shape of the velocity profiles in microvessels. In some experiments red blood cell velocity profiles were recorded as well. Easy detection of the cells of interest could be achieved by labelling them selectively with a fluorescent dye and visualizing them by intravital fluorescence video microscopy, using flashed illumination. Pairs of flashes were given with a short, preset time interval between both flashes, yielding in one TV picture two images of the same cell displaced over a certain distance for the given time interval. Velocity and mean radial position of cells, flowing within an optical section around the median plane of the vessel, were determined. The shape of the velocity profiles of platelets and red blood cells was similar. The profiles were flattened as compared to a parabola, both in systole and diastole. Vessel diameter did not change measurably during the cardiac cycle. As an index of the degree of blunting of the profiles, the ratio of the maximal and mean velocity of the profile was used, which is 2 for a parabola and 1 for complete plug flow. The index ranged from 1.39 to 1.54 (median 1.50), and increased with vessel diameter. Calculations showed that the blunting of the profiles cannot be explained by an influence of the finite depth of the optical section.

Animals↗