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Biomedical subjects

S Andreassen

Publications and source records attributed to S Andreassen.

At least 19 recordsLinked to original sources

DIAS--the diabetes advisory system: an outline of the system and the evaluation results obtained so far.

The present paper gives a description of the Diabetes Advisory System (DIAS), and the evaluation results obtained so far. DIAS is a decision support system for the management of insulin dependent diabetes. The core of the system is a compartment model of the human carbohydrate metabolism implemented as a causal probabilistic network (CPN or Bayesian network), which gives it the ability to handle the uncertainty, for example, in blood glucose measurements or physiological variations in glucose metabolism. The evaluation results suggest that, at least in our hands, DIAS can generate advice that is safe and of a quality that is at least comparable to what is available from experienced clinicians.

Bayes Theorem

Causal probabilistic network and power spectral estimation used in sleep stage classification.

A new method for sleep-stage classification using a causal probabilistic network as automatic classifier has been implemented and validated. The system uses features from the primary sleep signals from the brain (EEG) and the eyes (AOG) as input. From the EEG, features are derived containing spectral information which is used to classify power in the classical spectral bands, sleep spindles and K-complexes. From AOG, information on rapid eye movements is derived. Features are extracted every 2 seconds. The CPN-based sleep classifier was implemented using the HUGIN system, an application tool to handle causal probabilistic networks. The results obtained using different training approaches show agreements ranging from 68.7 to 70.7% between the system and the two experts when a pooled agreement is computed over the six subjects. As a comparison, the interrater agreement between the two experts was found to be 71.4%, measured also over the six subjects.

Adult

Analysing the hypoglycaemic counter-regulation: a clinically relevant phenomenon?

This paper describes an analysis of the temporal relation between episodes of low blood glucose (hypoglycaemia) and counter-regulations, i.e., episodes of elevated blood glucose (hyperglycaemia), in patients with insulin dependent diabetes. The relation was assessed by statistical methods based on a metabolic computer model of the human glucose metabolism. The study material was standard collected clinical data on meals, insulin injections, and measured blood glucose from hospitalised patients. We have found that a typical hypoglycaemic counter-regulation begins 6-8 h after the hypoglycaemia, that it lasts 16-18 h, giving a total duration of 24 h, and that it elevates the blood glucose by 4-10 mmol/l. The phenomenon was demonstrated in the data from more than half of the patients with hypoglycaemic episodes.

Blood Glucose

Use of the DIAS model to predict unrecognised hypoglycaemia in patients with insulin-dependent diabetes.

The Diabetes Advisory System (DIAS) is a model of human glucose metabolism implemented in a causal probabilistic network. It handles data on insulin dose, carbohydrate intake and blood glucose concentration to predict hourly blood glucose concentrations and thus provide an indication of blood glucose values between home blood tests. DIAS was used to predict blood glucose profiles in eight patients with well-controlled insulin-dependent diabetes, who are at increased risk of hypoglycaemia (abnormally low blood glucose levels). DIAS predicted nocturnal hypoglycaemia in six patients and daytime hypoglycaemia in one patient. The occurrence of nocturnal hypoglycaemia was not recognised by the patient or suspected by their doctor but was subsequently confirmed by blood testing in five patients. It is known that unrecognised nocturnal hypoglycaemia is common in patients with well-controlled diabetes. The ability of DIAS to identify such periods of hypoglycaemia with reasonable accuracy illustrates how the advanced technology it employs may provide reliable decision support to clinicians.

Adolescent

Estimation of pulmonary diffusion resistance and shunt in an oxygen status model.

A compartment model of the transport of oxygen from the alveoli to the tissues is described. In patients with both pulmonary shunt and alveolar resistance to diffusion of oxygen, the model is used to simulate their response to variations in the inspired oxygen fraction. These simulation results are compared to the responses from a patient with respiratory malfunction, indicating that the method can identify patients where not only a pulmonary shunt but also a high alveolar resistance to diffusion of oxygen is clinically significant. Estimation of pulmonary shunt and oxygen diffusion resistance can be done in two different implementations of the model. In the first implementation the estimates are generated by numerical solution of the equations of the compartment model. In the second implementation the equations have been used to construct a causal probabilistic net where biological uncertainties and uncertainties in the measurements can be represented.

Airway Resistance

Acid-base chemistry of the blood--a general model.

This paper describes a general model of acid-base chemistry of the blood which can be used to simulate physiological perturbation of acid-base chemistry on addition or removal of any buffer acid or base. In particular, it is shown how this model can be used to estimate the concentrations of buffer acid or base. In particular, it is shown how this model can be used to estimate the concentrations of buffer acids and bases when blood is equilibrated to a new pCO2, when hydrogen ions H+ are added to the blood, or when two pools of blood with different concentrations of buffer acids and bases are mixed. The ability of the model to represent the addition or removal of any acid or base is a significant increase in functionality above the Siggaard-Andersen nomogram which is limited to simulating the effects of equilibrating the blood to a new pCO2. When used to represent the situation where blood is equilibrated at a new pCO2 the model enables calculation of the amount CO2 removed during equilibration, a further increase in functionality above the Siggaard-Andersen nomogram. In two experimental situations, equilibrating blood to a new pCO2 and addition of H+ ions, the model predictions are shown to be consistent with existing experimental data in the form of the Siggaard-Andersen nomogram.

Acid-Base Equilibrium

Evaluation of the diagnostic performance of the expert EMG assistant MUNIN.

The diagnostic performance of the medical expert system MUNIN for diagnosis of neuromuscular disorders was evaluated on a set of 30 test cases. The cases were provided by 7 experienced electromyographers who were subsequently invited to participate in the evaluation. To reasonably cover the range of disorders, the electromyographers were asked to provide cases from patients with different types of muscular dystrophy, with neuromuscular transmission disorders, with motor neurone disease, and with different types of polyneuropathies. In addition, patients with a range of local neuropathies were provided. Out of the 30 cases, 11 cases were evaluated by an "almost peer review" method and the remaining 19 cases were evaluated by a "silver standard" method. The number of cases evaluated by "almost peer review" was limited to 11 due to time constraints on the evaluation procedure. During the "almost peer review," each electromyographer was asked to diagnose patients, using a vocabulary that closely resembled MUNIN's vocabulary. Subsequently, we attempted to provide a consensus diagnosis for the patients based on discussion among the participating electromyographers. The electromyographers were also asked to assess how well MUNIN had performed in each case. The remaining 19 cases were evaluated by a "silver standard" procedure, where MUNIN's diagnosis was compared to the diagnosis of the expert who provided the case. The results indicated that MUNIN performed well, and the electromyographers considered "that MUNIN performed at the same level as an experienced neurophysiologist." In particular, it was noted that MUNIN handled cases with conflicting findings well, and that it was able to diagnose patients with multiple diseases.

Diagnostic Services

A probabilistic approach to glucose prediction and insulin dose adjustment: description of metabolic model and pilot evaluation study.

A model of carbohydrate metabolism has been implemented as a causal probabilistic network, allowing explicit representation of the uncertainties involved in the prediction of 24-h blood glucose profiles in insulin-dependent diabetic subjects. The parameters of the model were based on experimental data from the literature describing insulin and carbohydrate absorption, renal loss of glucose, insulin-independent glucose utilisation and insulin-dependent glucose utilisation and production. The model can be adapted to the observed glucose metabolism in the individual patient and can be used to generate predicted 24-h blood glucose profiles. A penalty is assigned to each level of blood glucose, to indicate that high and low blood glucose levels are undesirable. The system can be asked to find the insulin doses that result in the most desirable 24-h blood glucose profile. In a series of 12 patients, the system predicted blood glucose with a mean error of 3.3 mmol/l. The insulin doses suggested by the system seemed reasonable and in several cases seemed more appropriate than the doses actually administered to the patients.

Absorption

Model-based biosignal interpretation.

Two relatively new approaches to model-based biosignal interpretation, qualitative simulation and modelling by causal probabilistic networks, are compared to modelling by differential equations. A major problem in applying a model to an individual patient is the estimation of the parameters. The available observations are unlikely to allow a proper estimation of the parameters, and even if they do, the task appears to have exponential computational complexity if the model is non-linear. Causal probabilistic networks have both differential equation models and qualitative simulation as special cases, and they can provide both Bayesian and maximum-likelihood parameter estimates, in most cases in much less than exponential time. In addition, they can calculate the probabilities required for a decision-theoretical approach to medical decision support. The practical applicability of causal probabilistic networks to real medical problems is illustrated by a model of glucose metabolism which is used to adjust insulin therapy in type I diabetic patients.

Bayes Theorem

Non-reflex and reflex mediated ankle joint stiffness in multiple sclerosis patients with spasticity.

In this study, we have measured the passive, the intrinsic, and the reflex-mediated mechanical response to stretch of the ankle extensors and flexors in 13 spastic multiple sclerosis patients and 10 healthy control subjects. In the ankle flexors, the patients had no reflex-mediated stiffness. The passive stiffness was increased by 138% (95% confidence interval: 26-91%) and the intrinsic stiffness by 79% (41-158%) when compared with the healthy subjects. In the ankle extensors, the reflex-mediated stiffness and the intrinsic stiffness of the patients were equal to the reflex-mediated and the intrinsic stiffness in healthy subjects. The passive stiffness was increased by 152% (41-352%). We conclude that spastic muscles in multiple sclerosis patients have an increased non-reflex stiffness (passive plus intrinsic stiffness), and that the reflex-mediated stiffness in the extensors during a sustained voluntary contraction does not differ significantly from healthy subjects.

Adult

Stretch responses to ankle rotation in multiple sclerosis patients with spasticity.

In 13 spastic patients with multiple sclerosis and 10 control subjects, electromyographic (EMG) and mechanical responses to stretch of the ankle extensors and ankle flexors during maintained contraction were measured. The reflex EMG responses in the extensors were divided into a phasic response (40-140 msec after onset of stretch) and a tonic response (200-400 msec after onset of stretch). In the control subjects, both the onset and peak latency of the phasic EMG response decreased with the contraction level (0.01 < P < 0.02 and P < 0.002 respectively) in the extensors. In the patients the latency of the phasic EMG response in the extensors was independent of the voluntary contraction level. This could be attributed to a disruption of the normal recruitment of the motor units according to the size principle. The phasic EMG response was larger in the patients than in the control subjects (P < 0.01). The tonic EMG response was of equal size in the two groups. The larger phasic EMG response in the patients was not followed by an increase in the reflex mediated mechanical stretch response. This shows that proposed changes in the muscle function in spastic patients based on changes in EMG stretch responses must be made with caution. In the ankle flexors all patients had reduced or absent EMG responses to stretch, consistent with earlier findings of an absent mechanical reflex mediated response.

Adult

Specification of models in large expert systems based on causal probabilistic networks.

Problems involved in the specification of large expert systems are discussed. In the specification of causal probabilistic networks conditional probability tables for all nodes have to be provided. These conditional probability tables can often be described by models that specify the nature of interaction between nodes. Various types of models are described and a program that handles such models is presented. Large causal probabilistic networks often contain several copies of identical tables or structures. A header facility that provides common definitions of such repeated elements is proposed. This facility makes specifications much shorter and easier to construct and maintain.

Expert Systems

Diagnostic function of the microhuman prototype of the expert system--MUNIN.

This paper describes the diagnostic function of a prototype expert system for electromyography (EMG). The prototype was restricted to a limited "Microhuman" anatomy with only 6 muscles and 8 nerves, and a corresponding limitation on the number of local nerve lesions. It attempted to give a detailed description of the most important groups of generalized nerve and muscle disorders, and the commonly used parameters from needle EMG and nerve conduction studies were included. The system can be used both for "diagnostic" and for "causal" reasoning. In diagnostic reasoning, the system's probabilistic inference engine is used to reason from test results through 14 different aspects of neuromuscular pathophysiology to disorders. In causal reasoning, the system reasons in the opposite direction from disorders through pathophysiology to expected test results. The diagnostic function of the system was illustrated by 3 cases: a normal subject, a patient with a bilateral carpal tunnel syndrome and a patient with both a diabetic polyneuropathy and a bilateral carpal tunnel syndrome.

Carpal Tunnel Syndrome

Mechanical and electromyographic responses to stretch of the human ankle extensors.

1. During maintained ankle extension with background torques ranging from 0 to 70 N.m, the ankle extensors were stretched by a 5 degree rotation of the ankle joint. Maximal stretch velocity was 170 degrees/s. Regression analysis of simultaneous measurements of total torque and needle and surface electromyograms (EMG) from the soleus and gastrocnemius muscles showed that the soleus muscle generates about two-thirds of the maximal torque (approximately 120 Nm) with the subjects in sitting position. In addition, it was found that there is considerable cross talk between the soleus and gastrocnemius muscles when EMGs are recorded by surface electrodes. 2. The soleus EMG response to stretch began with a "phasic" response (latency 41 +/- 4 ms, mean +/- SD), consisting of two peaks, labeled M1 and M2. The phasic response ended 120-140 ms after stretch onset and was followed by a period of reduced EMG activity, ending at 170-210 ms. After this "silent period," a smaller "tonic" response was seen. The phasic responses of the soleus muscle were much larger than the corresponding responses in the anterior tibial muscle. In contrast, the tonic responses were comparable in the soleus and anterior tibial muscles. 3. The amplitudes of the phasic M1 and M2 responses were independent of the level of the background contraction. This disagrees with the "automatic gain principle," according to which the amplitudes of M1 and M2 should increase proportionally with the background EMG. In contrast to the phasic responses, the amplitude of the tonic EMG response, measured 200-400 ms after stretch onset, followed the automatic gain principle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Mechanical and electromyographic responses to stretch of the human anterior tibial muscle at different levels of contraction.

The EMG response and the mechanical response to 2 degree stretch of the human anterior tibial muscle was studied during contractions ranging from 0% to 80% of maximal voluntary contraction (MVC). The EMG response showed three distinct peaks M1, M2, and M3 with peak latencies of 59 ms, 86 ms, and 120 ms respectively. At low background torques M1 dominated while M2 and M3 were small or absent. M2 and M3 dominated above 40% of MVC and M2 in particular showed "automatic gain compensation", i.e. it constituted a - more or less - constant proportion of the background EMG for all contraction levels. The ratio between M1 amplitude and background EMG steadily decreased with contraction level. Even though the summed contributions of M1, M2, and M3 to some degree showed automatic gain compensation, this was not the case for the mechanical response to stretch. Between 0% and 30% of MVC the reflex mediated mechanical response increased approximately in proportion to the contraction level, but the reflex mediated mechanical response peaked at 40% of MVC and declined to zero at 80% of MVC. This discrepancy between EMG and mechanical response was explained by a simple model. The regression line between rectified and filtered tibialis anterior EMG and torque was used to predict the mechanical response from the EMG response. At increasing contraction levels the twitch elicited by supramaximal electrical stimulation decreases, and we reduced the predicted mechanical response by the same factor as the twitch.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Simulation of concentric needle EMG motor unit action potentials.

Computer simulations of motor unit action potentials (MUAPs) as measured by a concentric needle (CN) electromyography (EMG) electrode in normal motor units (MUs) indicated that the MUAP amplitude is determined mainly by the proximity of the electrode to the closest muscle fiber. The area and duration of the simulated MUAPs were affected by all muscle fibers in front of the active recording surface but mainly by those that were less than 2 and 2.5 mm, respectively, from the active recording surface. The MUAP area was also affected by the proximity of the electrode to the closest muscle fiber. The number of phases of the simulated MUAPs increased when the dispersion of the arrival times of individual muscle fiber APs at the electrode was increased. Increased temporal dispersion of APs decreased the MUAP amplitude and area slightly but did not affect the MUAP duration. It is inferred that different features of the CN MUAP are determined by the distribution of muscle fibers within different portions of the MU territory and thus provide complementary information about the MU architecture.

Action Potentials

Muscle stiffness in human ankle dorsiflexors: intrinsic and reflex components.

1. The purpose of this study was to evaluate the mechanical response to stretch in normal human ankle dorsiflexors at different levels of voluntary contraction. In an active muscle, the total mechanical response is the sum of the intrinsic response from the contractile apparatus, the response from passive tissues, and the reflex mediated response. Each of these components was investigated. 2. The total incremental stiffness was defined as the ratio between the torque increment and the amplitude of the stretch. In 14 subjects the total stiffness increased from approximately 0.6 N.m/deg to approximately 2.5 N.m/deg at 50% of MVC and remained constant (+/- 10%) from 30 to 80% of MVC. 3. The contribution to incremental stiffness from intrinsic muscle properties was measured during electrical stimulation of the deep peroneal nerve at 7-50 Hz. Intrinsic stiffness increased linearly with torque from approximately 0.5 N.m/deg to approximately 2.5 N.m/deg at 80% of MVC. 4. The reflex component (total minus intrinsic stiffness) had a maximum of 0.5-1.5 N.m/deg at 30-50% of MVC and was approximately zero at no and maximal contraction. For intermediate levels of contraction the reflex increased the stiffness with 40-100% of the intrinsic stiffness in this flexor muscle. 5. The reflex contribution to total stiffness began approximately 50 ms after onset of stretch and peaked 150-300 ms after onset of stretch. 6. Total, intrinsic, and reflex mediated stiffness were all nearly independent of the amplitude of stretch in the range from 2 to 7 degrees. The higher stiffness observed for 1 degree stretches could be due to "short range stiffness" of the cross bridges. 7. Stretching of a contracting muscle generates large force increments even for moderate amplitudes of stretch. Approximately half of this force increment is due to the stretch reflex, which makes the muscle stiffer than predicted from the intrinsic stiffness. These findings in human flexor muscles are surprisingly similar to previous findings in extensor muscles of the decerebrate cat.

Adult