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Biomedical subjects

L E Widman

Publications and source records attributed to L E Widman.

10 recordsLinked to original sources

An evaluation of pulsus alternans in closed-chest dogs.

Pulsus alternans is a condition in which the arterial pressure generated by the heart oscillates between two levels on a beat-to-beat basis. We evaluated the onset of pulsus alternans in chronically instrumented dogs subjected to tachycardia and inferior vena caval occlusion. During pulsus alternans, the left ventricular (LV) end-diastolic volume (EDV) was larger before the strong beats (28.7 +/- 5.3 vs. 25.9 +/- 4.5 ml, P less than 0.001 by paired t test), suggesting that the Frank-Starling mechanism participates in the alternating difference in end-systolic pressure. In addition, however, the ratio of pressure to volume at end systole was greater in the strong beats (2.01 +/- 0.36 vs. 1.46 +/- 0.45, P less than 0.005 by paired t test), a difference that cannot be explained by the Frank-Starling mechanism alone. This indicates that there is also a difference in end-systolic inotropic states between strong and weak beats. These changes occurred without significant alterations in beat-to-beat levels of coronary flow. The time constant of isovolumic pressure fall (T) was faster for the strong beats (37.5 +/- 4.2 vs 61.1 +/- 12.7 ms, P less than 0.002 by paired t test). The onset of oscillation in T preceded the onset of changes in LVEDV and LV systolic pressure in every case by an average of seven beats (range 3-11), suggesting that abnormalities of intracellular calcium handling led to the occurrence of pulsus alternans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Model-based interpretation of the ECG: a methodology for temporal and spatial reasoning.

A new software architecture for automatic interpretation of the electrocardiogram is presented. Using the hypothesize-and-test paradigm, a semi-quantitative physiological model and production rule-based knowledge are combined to reason about time- and space-varying characteristics of complex heart rhythms. A prototype system implementing the methodology accepts a semi-quantitative description of the onset and morphology of the P waves and QRS complexes that are observed in the body-surface electrocardiogram. A beat-by-beat explanation of the origin and consequences of each wave is produced. The output is in the standard cardiology ladder diagram format. The current prototype can perform the full differential diagnosis of 2:1 atrioventricular (AV) block, and can handle correctly complex rhythms such as AV nodal reentrant tachycardia with either hidden or visible P waves, and varying degrees of AV block.

Computer Simulation

Digitization of electrocardiograms by desktop optical scanner.

The fidelity of a semiautomated technique for converting paper electrocardiogram (ECG) tracings to digital form by optical scanning was examined. Sample tracings from one nonmechanical and three mechanical ECG writers (recorders) were used. The optically scanned signals were compared with the digitized version (402 Hz, 12-bit precision) of the original analog signals using time- and frequency-domain correlation coefficients and root mean square error. A total of 261 QRS complexes and 207 RR intervals were examined in 21 leads acquired from 8 patients. When data were low-pass filtered at 25 Hz, the correlation coefficients for the 261 QRS complexes were 0.997 +/- 0.005 (mean +/- SD) for the time domain data, 0.992 +/- 0.010 for the complex frequency domain (amplitude and phase) data, and 0.998 +/- 0.002 for the power spectrum. The corresponding correlations for the 207 RR intervals were 0.993 +/- 0.008, 0.992 +/- 0.008, and 0.993 +/- 0.009. The RMS errors, normalized for signal amplitude, were 2.62 +/- 1.28 (percent +/- SD) for QRS complexes and 1.82 +/- 0.87 for RR intervals. The correlations for the mechanical ECG recorder tracings were the same or better than those of the nonmechanical recorder, and the RMS errors were generally smaller. When data were low-pass filtered at 105 Hz, the correlation coefficients ranged from 0.984 to 0.996 for the QRS complexes and 0.982 to 0.988 for RR intervals. Root mean square errors were 4.54 +/- 2.03 and 2.38 +/- 1.14, respectively. For purposes of arrhythmia analysis by QRS classification, digitization of ECG signals by optical scanning appears equivalent to acquisition via standard analog-to-digital conversion.

Analog-Digital Conversion

The EINTHOVEN system: toward an improved cardiac arrhythmia monitor.

Contemporary cardiac arrhythmia monitors, used commonly in intensive care settings, are highly sensitive to artifact, resulting in high false alarm rates, inability to detect P waves reliably, and crude rhythm interpretation. We report on two new approaches that address these problems: a noise preprocessor that characterizes the type and degree of artifact in an ECG, and a model-based rhythm interpretation algorithm.

Algorithms

Infection of an implantable cardioverter defibrillator: management without removal of the device in selected cases.

A case is presented in which an implantable cardioverter defibrillator (ICD) became infected in the abdominal wall pocket 5 weeks following implantation. There was no evidence clinically or by computed tomographic scan suggesting mediastinal extension of the infection. The infection was treated successfully by debriding the abdominal wall pocket followed by a combination of pocket irrigation with antibiotic solution, parenteral antibiotics, and long-term oral antibiotics. This conservative therapy was successful and avoided removal of the device.

Abdominal Muscles

A-to-D conversion from paper records with a desktop scanner and a microcomputer.

A novel method for digitizing signals contained in paper records is presented. This method is based on the use of an inexpensive optical scanner to translate the image on paper into a binary, bit map data structure. Several algorithms which recognize the signal line in the bit map and translate it into a series of numbers which are equivalent to the output of electronic analog-to-digital converters are described. The method was validated by comparison both with idealized test patterns of varying frequency content and with electronically digitized pressure and pressure time derivative tracings from chronically instrumented dogs. The root mean square error for the physiological signals was 3.5-3.9% of peak-to-peak full scale, corresponding to roughly 50% more than the thickness of the signal line on the paper.

Algorithms

Expert system reasoning about dynamic systems by semi-quantitative simulation.

Current symbolic knowledge representation techniques are inadequate for describing complex dynamic systems, which are time-varying and contain feedback loops. These systems are particularly difficult to represent when quantitative knowledge about the relationships within the system is incomplete. This paper describes a symbolic extension of the system dynamics method which can answer 'what if' questions about system dynamics models semi-quantitatively. The method consists of (1) definition of generic model 'building blocks' which map directly onto difference equations; (2) development of a symbolic causal model of a system in terms of the generic functional 'building blocks', any available quantitative or semi-quantitative parameters, and a set of generic default values; (3) automatic translation of the model into a system of first-order difference equations; and (4) numerical integration of the equations by standard methods. A complex model with semi-quantitative parameters, representing the human cardiovascular system, is used to illustrate the method. This method couples the descriptive abilities of mathematics with the symbolic power of causal inference methods by providing the same knowledge base for both computational levels. It also eases truth maintenance, knowledge acquisition, and explanation. It may prove useful for expert system development in a variety of application domains whose processes are time-varying and homeostatic.

Computer Simulation

Electrocardiographic body surface potential maps of the QRS and T of normal young men. Qualitative description and selected quantifications.

A qualitative and quantitative analysis of the Body Surface Potential Maps (BSPM) of 40 young men, ages 19-41, is presented utilizing a 180 electrode system, with 135 anterior leads and 45 posterior leads. Evidence for epicardial right ventricular breakthrough was demonstrated in 36/40 at 27.9 +/- 6.8 ms, whereas our previous studies on normal children (average age 12.5 years) have demonstrated evidence for epicardial right ventricular breakthrough at 25.0 +/- 8.9 ms. The peak-to-peak magnitude at maximal potential (at 42.3 +/- 4.8 ms) was not significantly different from that of the children (4,430 +/- 1,165 microV), and the peak-to-peak magnitude of ST-T was virtually the same as that of the children (1,182 +/- 376.2 microV). The terminal activation pattern of late QRS on the body surface map appeared in the true posterior, anterior superior, posterior right superior and/or right anterior superior positions, in order of frequency. There were other regions appearing less frequently. In contrast, this pattern in children was seen only in the anterior superior, right anterior superior, posterior right superior, and true posterior in order of frequency. In 18/40, the body surface manifestation of repolarization was seen an average of 9.4 +/- 4.8 ms before the end of the QRS. A new pseudocolor display with 31 color levels representing body surface potentials allowed excellent resolution of isopotential detail.

Adult

Multihormonal induction of alpha 2u-globulin in an established rat hepatoma cell line.

A subclone of the FU5-5 rat hepatoma cell line has been isolated which is inducible more than several hundred fold for the 20,000 dalton form of the major rat urinary protein alpha 2u-globulin. The basal relative synthetic rate (RSR) in growth medium containing 10% fetal calf serum was less than 2 X 10(-6) of total protein synthesis. Both dexamethasone and insulin were necessary for induction, and yielded a maximum induced RSR of 4-8 X 10(-3). Triiodothyronine (T3), dihydrotestosterone (DHT), rat growth hormone (GH), and estrogen, all of which have been shown to influence the induction of alpha 2u-globulin in the intact rat, were without effect on the cell line. A factor present in fetal calf serum was also necessary for maximum induction, since dexamethasone plus insulin in serum-free medium raised the RSR to only 3 X 10(-5); exogenous T3, GH, and DHT could not substitute for this serum factor. The kinetics of induction by dexamethasone were slow, with a lag of approximately 48 hr followed by a period of increasing RSR for 6-20 days. Removal of dexamethasone from induced cells led to an exponential decline in the RSR (t 1/2 15 hr). The concentrations of dexamethasone and insulin that could yield half maximum induction were 5 X 10(-8)M and 3 X 10(-11)M, respectively. Higher concentrations of insulin, although still in physiological range (10(-9)M), inhibited induction. At yet higher insulin levels, beyond the physiological range, alpha 2u-globulin synthesis returned to maximum values. The lack of DHT, T3, and GH requirement for alpha 2u-globulin induction in this cell line may mean that a regulatory aberrancy has occurred in this transformed cell line, or, alternatively, that these hormones act indirectly in the intact animal. This cell line should prove useful for the study of the molecular events associated with alpha 2u-globulin induction and for genetic approaches to the problem of multihormonal regulation of gene expression.

Alpha-Globulins

Immortalization of normal liver functions in cell culture: rat hepatocyte-hepatoma cell hybrids expressing ornithine carbamoyltransferase activity.

Normal rat hepatocytes have been fused with highly differentiated rat hepatoma cells. Some of the hybrids express a physiologically significant level of activity of the urea cycle enzyme ornithine carbamoyltransferase (OCT), a liver-specific function not found in the hepatoma cells. These hybrids have 10% of the adult rat liver OCT specific activity, incorporate 3H-ornithine into protein arginine, and can be selectively grown in arginine-free medium supplemented with ornithine. Somatic cell hybridization of normal differentiated cells with highly differentiated neoplastic cells of the same tissue type may be useful as a general method for obtaining permanent cell lines with new tissue-specific phenotypes.

Animals