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Biomedical subjects

E R Carson

Publications and source records attributed to E R Carson.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1996

Effects of intravenous infusion of lipid-free apo A-I in humans.

Apolipoprotein (apo) A-I is the principal protein component of the plasma high density lipoproteins (HDLs). Tissue culture studies have suggested that lipid-free apo A-I may, by recruiting phospholipids (PLs) and unesterified cholesterol from cell membranes, initiate reverse cholesterol transport and provide a nidus for the formation, via lipid-poor, pre-beta-migrating HDLs, of spheroidal alpha-migrating HDLs. Apo A-I has also been shown to inhibit hepatic lipase (HL) and lipoprotein lipase (LPL) in vitro. To further study its functions and fate in vivo, we gave lipid-free apo A-I intravenously on a total of 32 occasions to six men with low HDL cholesterol (30 to 38 mg/dL) by bolus injection (25 mg/kg) and/or by infusion over 5 hours (1.25, 2.5, 5.0, and 10.0 mg.kg-1.h-1). The procedure was well tolerated: there were no clinical, biochemical, or hematologic changes, and there was no evidence of allergic, immunologic, or acute-phase responses. The 5-hour infusions increased plasma total apo A-I concentration in a dose-related manner by 10 to 50 mg/dL after which it decreased, with a half-life of 15 to 54 hours. Coinfusion of Intralipid reduced the clearance rate. The apparent volume of distribution exceeded the known extracellular space in humans, suggesting extensive first-pass clearance by one or more organs. No apo A-I appeared in the urine. Increases in apo A-I mass were confined to the pre-beta region on crossed immunoelectrophoresis of plasma and to HDL-size particles on size exclusion chromatography. Increases were recorded in HDL PL, but not in HDL unesterified or esterified cholesterol. Increases also occurred in LDL PL and in very low density lipoprotein cholesterol, triglycerides, and PL but not in plasma total apo B concentration. These results can all be explained by combined inhibition of HL and LPL activities. Owing to the effects that this would have had on HDL metabolism, no conclusions can be drawn from these data about the role of lipid-free apo A-I in the removal of PL and cholesterol from peripheral tissues in humans. The kinetic data suggest that the fractional catabolic rate of lipid-free apo A-I exceeds that of spheroidal HDLs and is reduced in the presence of surplus PL.

Aged↗
PubMed1994

Modelling the dynamic ventilatory response to hypoxia in normal subjects.

We have developed a mathematical model to describe the dynamic ventilatory response to hypoxia. The ventilatory response to both transient (two to three breaths nitrogen) and 3 min step change hypoxic stimuli were measured in ten normal subjects during moderate exercise (oxygen consumption 0.96 +/- 0.08 1 min-1). The simplest model relating ventilation to ear oxygen saturation which adequately described the responses in all subjects consisted of two linear differential equations in parallel; both using the fall in oxygen saturation as input, and with the outputs summed to give the rise in ventilation. One equation had a fast time constant (< 3 sec), and the other a slow time constant. Non-linear terms included were (i) a "saturating" effect, similar to that described by the Michaelis-Menten equation, reducing the gain of the equation with the slow time constant as oxygen saturation falls, and (ii) "inhibition" or "potentiation" of the gain of the equation with a slow time constant as the output of the fast time constant equation increased. Repeated measurements in four subjects showed intra- and inter-subject variability for all parameters, with significant between-subject variability for the gain of the fast time constant equation. The final model structure is similar to that describing the peripheral chemoreceptor-mediated hypoxic ventilatory response in anaesthetized cats.

Adult↗
PubMed1994

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↗
PubMed1994

Time series analysis and control of blood glucose levels in diabetic patients.

This paper describes features of a computer-based decision support system which is being developed to assist in the management of insulin-dependent diabetic patients. The clinical context is the provision of advice on the adjustment of the basic insulin regimen such as occurs at regular visits to the clinician. The integrated system combines data processing and interpretation, generation of qualitative advice and testing the implications of that advice using a glucose/insulin dynamic simulator. The two major features described in this paper are time series analysis of blood glucose data, and their interpretation in relation to the provision of advice for controlling the patient's blood glucose level. It is demonstrated that two approaches may be adopted in such time series analysis: an intuitive approach, manipulating symbolic representations of the data, and formal time series methods which decompose the series into clinically related components.

Blood Glucose↗
PubMed1994

AIDA: an interactive diabetes advisor.

AIDA is a prototype computer system that incorporates a model of glucose-insulin interaction in type I diabetes mellitus alongside a knowledge-based system to make glycaemic predictions and to generate insulin dosage adjustment advice. The model attempts to reflect the underlying (patho)physiology of insulin action and carbohydrate absorption in quantitative terms. The prototype is intended to be used as a decision support system by clinical personnel in the context of day-to-day management of insulin-dependent diabetic patients. It is designed for use during consultations, as a simulator of patient response following changed insulin and dietary regimen and as a system for providing education on planning insulin therapy. Joe Daniels is a 41-year-old, 70-kg, male insulin-dependent diabetic patient who was diagnosed as being diabetic in 1972, at the age of 22. Joe recently found that he was having hypoglycaemic symptoms. Using self-monitoring blood glucose equipment, glycaemic levels below 3.0 mmol/l were recorded at least once a week, while hyperglycaemic readings (> 16 mmol/l) were observed two to three times per week. Joe came into hospital to have his glycaemic control improved, as doctors were concerned about the risks of him suffering a serious hypoglycaemic attack. Using some of the data collected by Joe while in hospital, we will demonstrate how AIDA might be applied either in a clinical setting to provide therapeutic advice or in an educational setting to interactively teach diabetic patients about their diabetes and educate them to adjust their own insulin injections and diet.

Adult↗
PubMed1994

Combining rule-based reasoning and mathematical modelling in diabetes care.

A prototype computer system utilising a model of carbohydrate metabolism linked to an expert system is described. The prototype which integrates quantitative and qualitative computational methodologies can be used to predict blood glucose profiles and adjust insulin doses in insulin-dependent (type I) diabetic subjects. A feedback loop insulin-dosage optimisation procedure which allows quantitative advice to be generated is also described. Possible clinical applications for the system, which is intended for educational use and clinically as a research tool to try and attain normoglycaemia, are discussed.

Algorithms↗
PubMed1994

Methodological issues in validating decision-support systems for insulin dosage adjustment.

Safety and reliability of advice from new computer systems should be confirmed before embarking on prospective hospital trials. This process of preliminary testing is termed 'validation'. Though it forms a fundamental stage in system development, few standards exist for choosing and implementing tests. In the present paper, a validation methodology is developed in the domain of diabetes and intended for general use in chronic health management. It is based on a peer review protocol and incorporates empirical measures indicating: applicability of results to the real environment; variation among doctors; comparisons between doctors' and computer advice; and relative merits of different computer algorithms.

Algorithms↗
PubMed1993

Five-compartment model of insulin kinetics and its use to investigate action of chloroquine in NIDDM.

We have constructed a five-compartment model of insulin kinetics. The model structure was chosen to reflect insulin distribution in systemic plasma, hepatic plasma, and interstitial fluid and insulin binding to the liver and peripheral receptors, and it included receptor-mediated and non-receptor-mediated insulin degradation. Model parameters were estimated from plasma insulin concentrations measured during hyperinsulinemic euglycemic clamp studies. In the fasting condition, the model-derived mean residence time of endogenously secreted insulin was 71 min, of which 62 min were spent bound to the liver receptor, 6 min bound to the peripheral receptor, 2 min circulating in hepatic or systemic plasma, and 1 min in the interstitial fluid. More than 80% of total insulin was bound to the liver receptor, indicating that the liver is by far the largest insulin reservoir. The model was employed to assess the effect of chloroquine on insulin kinetics in patients with non-insulin-dependent diabetes mellitus (NIDDM). Chloroquine significantly altered parameter vector. However, the mean residence times of insulin in the system and in the periphery were not affected, indicating that the beneficial effect of chloroquine in patients with NIDDM under conditions of euglycemia could not be attributed to changes in insulin kinetics.

Chloroquine↗
PubMed1990

Diurnal variation in glucose and leucine metabolism in non-insulin-dependent diabetes.

Glucose and leucine metabolism were investigated in 5 poorly controlled non-insulin-dependent diabetics (NIDDM) following an i.v. injection of 3-[3H]glucose and 1-[14C]leucine in the morning and evening. In the morning glucose concentration (11.2 +/- 0.8 mmol/l) (mean +/- SEM) and production rate (14.2 +/- 1.3 mumol/min/kg) were significantly greater (P less than 0.001, P less than 0.05) and glucose metabolic clearance rate (MCR) (1.3 +/- 0.2 ml/min/kg) significantly lower (P less than 0.05) than in a group of control subjects. Glucose concentration was lower in the evening (P less than 0.05) as a result of a decrease in glucose production rate (P less than 0.05). Leucine concentration and production rate were not significantly different from normal but leucine oxidation rate was increased (P less than 0.05). There was no diurnal variation in leucine metabolism. Since leucine production is a measure of protein breakdown, the higher morning glucose production rate was not due to an increased supply of gluconeogenic precursors from protein catabolism.

Adult↗
PubMed1990

The decision-making process in child language assessment.

The task of assessing a child's language for the purpose of intervention requires the ability to interpret information from a variety of sources. Knowing how that information is to be used during therapy plays an important part in deciding what type of information needs to be collected and how it will be interpreted. There needs to be a plan that will assist the speech therapist in analysing and interpreting most of the data that would be needed when making therapy-related diagnostic statements. A systems approach offers concepts and methods for devising a plan which will outline the necessary decisions. The purpose of this paper is to present, in a flow chart, the questions that need to be asked in the process of assessing a child's language development for the purpose of intervention; to indicate the type of information that would be needed to answer the questions; to state how the information would be interpreted; to suggest the type of tools that would be needed to collect this information; and to outline how the information can be presented so that a greater quantity of data can be summarised and interpreted in a systematic manner.

Child↗
PubMed1989

ANABEL: intelligent blood-gas analysis in the intensive care unit.

ANABEL (ANalysis of Acid-Base status by Evaluating Lisp) is a prototype medical intelligent decision-support system aiming to assist clinicians in an Intensive Care Unit environment with the interpretation of blood-gas measurements. Its architecture is based on the merging of representations for declarative (domain-descriptive) and procedural (problem-solving) medical knowledge. The system performs diagnosis in two stages (tentative and differential) by first evaluating elementary computational units of procedural knowledge (procedures) and then abstracting their symbolic outputs in generating text. Thus, a 'semantic trace' is built which reflects the system's line of reasoning in reaching its conclusion. This paper describes the design aspects, development and clinical validation of ANABEL.

Acid-Base Imbalance↗
PubMed1989

The principles and prototyping of a knowledge-based diabetes management system.

This paper describes the principles and prototyping of a computer-based system being developed to assist in the management of diabetes mellitus. Unlike other approaches based upon mathematical modelling or the use of computer algorithms, this system adopts one derived from artificial intelligence, seeking to incorporate the dynamics of glucose and insulin in a manner which reflects their clinical importance. The resultant logical model (qualitative algebra) defines the relationships between changes in insulin dose and site and time of injection and glycaemic response. In this manner the computer-based system, implemented in Prolog, can be used to provide advice concerning insulin therapy by means of making qualitative predictions of patient outcome of blood glucose profile resulting from alternative insulin regimens.

Blood Glucose↗
PubMed1986

The effect of metabolic control on leucine metabolism in type 1 (insulin-dependent) diabetic patients.

Leucine production rate, metabolic clearance rate and oxidation rate were measured in 10 Type 1 (insulin-dependent) diabetic patients after 24 h insulin withdrawal, conventional insulin therapy and an overnight insulin infusion to maintain normoglycaemia, and in 10 control subjects. In the insulin-withdrawn patients, leucine concentration (259 +/- 17 mumol/l), production rate (2.65 +/- 0.29 mumol . min-1 . kg-1) and oxidation rate (0.69 +/- 0.10 mumol . min-1 . kg-1) were significantly greater (p less than 0.001; p less than 0.05; p less than 0.005 respectively) than corresponding values in control subjects (127 +/- 6; 1.81 +/- 0.12; 0.19 +/- 0.02). Following conventional insulin therapy, leucine concentration (162 +/- 12 mumol/l) and oxidation rate (0.43 +/- 0.05 mumol . min-1 . kg-1) were lower than after insulin withdrawal but were still significantly greater than in control subjects (p less than 0.05; p less than 0.005). Although leucine concentration, production rate and metabolic clearance rate were normal after an overnight insulin infusion, leucine oxidation rate was still greater than normal (0.34 +/- 0.06 mumol . min-1 . kg-1; p less than 0.05). These results suggest that increased leucine concentration in insulin deficiency is due to elevated leucine production rate caused by increased proteolysis, and that leucine concentration is restored to normal by insulin treatment.

Adolescent↗
PubMed1984

Number and affinity of insulin receptors in intact human subjects.

A simple model of the distribution and metabolism of insulin in vivo has been evaluated using data from insulin infusion into a group of normal subjects. The major rate-limiting step for access to degradation pathways is assumed to consist of binding of the ligand to a single population of insulin receptor sites, except that provision is made for the possibility of linear non-receptor-mediated degradation and for the phenomenon of negative cooperativity. The model has been shown to accommodate the non-linearity of insulin metabolism, allows, evaluation of receptor association and dissociation constants and provides for the first time an estimate of total accessible receptor number in the intact organism. For normal fasting man the model predicts 1.00 +/- 0.05 nmol accessible binding sites/kg (mean +/- SD).

Humans↗
PubMed1984

Validation of simple and complex models in physiology and medicine.

The problem of assessing the value of mathematical models in physiology and medicine is considered. The role of validation within the modeling process is clearly defined. An appropriate vocabulary and validation procedures to be adopted are outlined for simple and complex models, with these two classes defined operationally on the basis of theoretical identifiability. Some examples illustrating these validation procedures are briefly discussed. It is shown that simple and complex models each have a role both in physiology and clinical application when properly validated.

Animals↗