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Biomedical subjects

T Groth

Publications and source records attributed to T Groth.

At least 91 records · Page 5Linked to original sources
PubMed1990

A combined data- and knowledge base system for the interpretation of metabolic investigations of erythrocytes from hemolytic and polycythemic patients.

A knowledge based-information system has been constructed to facilitate and standardize the interpretation of data obtained from specialized analyses in laboratory medicine. For illustration the system was applied to metabolic studies of erythrocytes from patients in whom hereditary disorders are suspected to explain the presence of a hemolytic anemia or polycythemia. The study includes assay of the catalytic activity of ten different enzymes and the concentration of some key metabolites. The knowledge based system is an excellent tool for documentation, updating and transfer of knowledge about the interpretative process. This will reduce the risk that changes in this process are made without sound motivation and documentation. Furthermore, the statistical and graphic features of the system provide data for long-term quality assessment and insights into reference sample groups which are used to update decision limits. A few cases are used to illustrate the advantages of the system.

Anemia, Hemolytic↗
PubMed1989

A knowledge-based system for automatic interpretation of an analytical profile of complement factors.

A comprehensive assay to evaluate the complement system includes functional tests of both classical and alternative pathways and immunochemical measurements of C3, C4, B, C1-INA, and C3d. The purpose of this analytical profile is to screen for rare hereditary deficiencies and acquired abnormalities of complement and to define the activation pathway in cases of complement consumptive processes. Based on several years' experience, a routine was established in our laboratory to report the data to the clinician, together with a computer-generated interpretive statement. This routine was formulated into a knowledge base by specifying a series of decision rules for each of the complement disorders. After the rules were tested and updated against some 400 complement profile analyses, reasonable analytical comments were produced by the system. This knowledge-based system for reporting and interpreting complement results offers several advantages: the interpretative work is facilitated and made more reliable; a consistent interpretative comment is generated that is recognized and therefore more meaningful for the clinician; the communication of analytical procedures and policy is enhanced.

Artificial Intelligence↗
PubMed1989

A knowledge-based information system for monitoring drug levels.

The expert system shell SMR has been enhanced to include information system routines for designing data screens and providing facilities for data entry, storage, retrieval, queries and descriptive statistics. The data for inference making is abstracted from the data base record and inserted into a data array to which the knowledge base is applied to derive the appropriate advice and comments. The enhanced system has been used to develop an intelligent information system for monitoring serum drug levels which includes evaluation of temporal changes and production of specialized printed reports. The module for digoxin has been fully developed and validated. To demonstrate the extension to other drugs a module for phenytoin was constructed with only a rudimentary knowledge base. Data from the request forms together with the S-digoxin results are entered into the data base by the department secretary. The day's results are then reviewed by the clinical pharmacologist. For each case, previous results may be displayed and are taken into account by the system in the decision process. The knowledge base is applied to the data to formulate an evaluative comment on the report returned to the requestor. The report includes a semi-graphic presentation of the current and previous results and either the system's interpretation or one entered by the pharmacologist if he does not agree with it. The pharmacologist's comment is also recorded in the data base for future retrieval, analysis and possible updating of the knowledge base. The system is now undergoing testing and evaluation under routine operations in the clinical pharmacology service. It is a prototype for other applications in both laboratory and clinical medicine currently under development at Uppsala University Hospital. This system may thus provide a vehicle for a more intensive penetration of knowledge-based systems in practical medical applications.

Data Interpretation, Statistical↗
PubMed1989

Growth hormone secretory rates in children as estimated by deconvolution analysis of 24-h plasma concentration profiles.

The kinetics of growth-hormone (GH) distribution and elimination was estimated in five GH-deficient children who received 11 intravenous single injections of GH. The plasma disappearance data were analyzed in terms of a two-compartment model. The kinetic parameters obtained were then used in calculating the GH-secretory rate by a numerical deconvolution technique. A simple formula was derived for calculation of the cumulated secretion from the area under the concentration curve of 145 healthy children of various ages, heights, and stages of puberty. The estimated 24-h GH secretion increased with age, corresponding to a two- to fourfold increase during the adolescence period. The highest secretions were found in pubertal stages 3-4. In prepubertal children the heights correlated markedly with the secretion of GH (r = 0.83). Thus an indication of the range of the GH secretion in normal growing children is found, which is important to estimate substitution doses for treatment of GH-deficient children.

Activity Cycles↗
PubMed1989

Allopurinol kinetics in humans as a means to assess liver function: design of a loading test.

A six-compartment model of allopurinol and oxipurinol kinetics, after intravenous allopurinol injection in the human, is studied further to improve the blood and urine specimen collection schedule for clinical use. The effects of various error sources are also investigated by simple techniques like real data set truncation and adding normally distributed random errors to data obtained from simulation of allopurinol and oxipurinol plasma curves with preset parameters. All parameters estimation is performed with the NONLIN parameter estimation program. Main interest was focused on estimation of the fractional rate constant of transport from the central "extracellular" compartment to the metabolically active compartment. This parameter is regarded as a lumped measure of liver perfusion and liver cell membrane transport. The blood sampling schedule can be reduced to six specimens collected over 60 min, without affecting the accuracy and precision of estimated clinical parameters. The maximum allowable coefficient of variation for preanalytical errors and the analytical within-run and between-run errors are around 5, 4, and 5%, respectively. Analytical between-run bias up to 20% does not affect the estimate of the principal parameter, when both allopurinol and oxipurinol are biased in the same direction. Collection and analysis of urine samples was shown to be unnecessary.

Allopurinol↗
PubMed1988

The influenza virus-induced fusion of erythrocyte ghosts does not depend on osmotic forces.

The role of osmotic forces and cell swelling in the influenza virus-induced fusion of unsealed or resealed ghosts of human erythrocytes was investigated under isotonic and hypotonic conditions using a recently developed fluorescence assay (Hoekstra, D., De Boer, T., Klappe, K., Wilschut, J. (1984) Biochemistry 23, 5675-5681). The method is based on the relief of fluorescence selfquenching of the fluorescent amphiphile octadecyl rhodamine B chloride (R18) incorporated into the ghost membrane as occurs when labeled membranes fuse with unlabeled membranes. No effect neither of the external osmotic pressure nor of cell swelling on virally mediated ghost fusion was established. Influenza virus fused unsealed ghosts as effectively as resealed ghosts. It is concluded that neither osmotic forces nor osmotic swelling of cells is necessary for virus-induced cell fusion. This is supported by microscopic observations of virus-induced fusion of intact erythrocytes in hypotonic and hypertonic media. A disruption of the spectrin-actin network did not cause an enhanced cell fusion at acidic pH of about 5 or any fusion at pH 7.4.

Erythrocyte Membrane↗
PubMed1988

An extended physiological pharmacokinetic model of methadone disposition in the rat: validation and sensitivity analysis.

An extended physiological model of methadone disposition in the rat was constructed and evaluated in various tests of model validity. A separate circulation model of the fetus was included due to the large tissue concentration differences obtained after a constant rate infusion but also to propose the use of this type of model for optimization of toxicological tests. Simulations were performed with the animal model and scaled-up models of humans to elucidate the determinants of methadone disposition. The rationale of the use of an extended model for methadone was also discussed.

Animals↗
PubMed1988

Allopurinol kinetics in humans as a means to assess liver function: evaluation of an allopurinol loading test.

A newly developed liver function test was performed on 18 apparently healthy individuals and 29 patients with liver disease. After intravenous injection of a low dose allopurinol (17.1 mumol/kg body mass), blood specimens were collected during 1 h. Plasma analyses of allopurinol and its metabolite oxipurinol were performed and the data were processed by means of a computer-based biodynamic model. This modelling approach makes it possible to estimate parameters, containing information about liver perfusion, hepatocyte membrane transport and hepatocyte cell mass. One parameter (kA31) showed complete discrimination between the reference sample group of healthy individuals and patients with severe liver dysfunction. In a reference sample group of patients with slightly to moderately reduced liver function, only a few patients (5/20) had a kA31 value over the decision limit. In this respect, the allopurinol loading test is superior to the conventional intravenous galactose tolerance test.

Adolescent↗
PubMed1987

The influence of the antiviral drugs amantadine and rimantadine on erythrocyte and platelet membranes and its comparison with that of tetracaine.

The influence of the antivirus drugs amantadine and rimantadine and of the anionic analogue 1-adamantane-carboxylic acid on a range of properties of human erythrocyte membrane and of thrombocytes has been compared with the effect of the local anaesthetic tetracaine. At low antiviral drug concentrations the abilities of the drugs to induce erythrocyte shape change and suppress osmotic haemolysis were quantitatively proportional to their clinical potency (rimantadine more effective than amantadine at the same concentration). Rimantadine was also more effective than amantadine in suppressing influenza virus-erythrocyte fusion and viral induced haemolysis. The antiviral drug effects were qualitatively similar to those induced by tetracaine. At the quantitative level, tetracaine was more efficient than the antiviral drugs in inhibiting osmotic haemolysis, virus membrane fusion and platelet aggregation. In the absence of any specificity of the antiviral drug effects we argue for a lysosomotropic mode of drug action, i.e. that the drugs modify virus-membrane interactions by changing the endosomal or lysosomal pH.

Adamantane↗
PubMed1987

Carbon dioxide production during mechanical ventilation.

Because of large stores of CO2 in different body tissues, metabolic change cannot be detected by measuring gas exchange until the CO2 stores have adapted to the new situation. Similarly, changes in the CO2 stores not due to metabolic alterations, may lead to error in gas exchange measurements. We studied CO2 production (VCO2) and oxygen consumption (VO2) in mechanically ventilated ICU patients, where CO2 stores were altered by: a) changing minute ventilation by 15%, b) reducing body temperature, and c) changing the level of sedation. Expired gases went through a mixing chamber and were analyzed continuously by a mass spectrometer. Signals from this instrument, together with gas-volume signals from the ventilator, were fed to a computer for calculation of VO2 and VCO2. Twenty to 120 min were required to reach a stable level, depending on the patient's size and circulatory response. Similar results were obtained by computer simulation using a five-compartment model of CO2 stores. These experiments indicate that measuring VO2 (for calculation of metabolic respiratory quotient [RQ]) in ventilated patients should occur after the patients maintain a 60-min period of stable body temperature and awareness. Ventilatory variables should not be changed substantially during the 90-min period before gas sampling. Cardiac output and muscle blood flow should not have changed 2 to 3 h before measuring RQ. If muscle blood flow is low, the stable periods for body temperature and ventilatory variables should be increased.

Carbon Dioxide↗
PubMed1987

Allopurinol kinetics in humans as a means to assess liver function: comparison of different models.

To describe the mechanisms involved in allopurinol kinetics after intravenous injection in humans, a number of alternative computer-based biodynamic models were designed. Distribution processes were described with two-compartment as well as with three-compartment kinetics for both allopurinol and its metabolite oxipurinol. These two major physiological alternatives were combined with biochemical models assuming either competitive or tight-binding-complex inhibition kinetics. The four resulting basic models were evaluated (and successively improved) using sets of plasma allopurinol and oxipurinol concentration curves, measured after intravenous injection in healthy subjects and in patients with different degrees of liver function. A three-compartment model with tight-binding-complex inhibition was selected and used to analyze the 35 loading tests performed. One of the parameters estimated in this way, the fractional rate constant for transport of allopurinol from the central compartment to the metabolically active (liver) compartment (kA31), turned out to be a powerful discriminative parameter between a group of healthy subjects, a group of patients with slightly to moderately reduced overall liver function, and a group with severely reduced overall liver function [kA31(min-1) = 0.136 +/- 0.042 (mean +/- SD, n = 13), 0.072 +/- 0.024 (n = 13), and 0.025 +/- 0.015 (n = 8), respectively].

Allopurinol↗
PubMed1987

Optimal discrimination of mild hyperparathyroidism with total serum calcium, ionized calcium and parathyroid hormone measurements.

The serum concentrations of calcium, albumin and parathyroid hormone (PTH) and the plasma levels of ionized calcium were determined in 124 healthy subjects, 89 patients with primary hyperparathyroidism (HPT), 23 of whom had the syndrome of multiple endocrine neoplasia type 1 (MEN-1) and 43 patients who had hypercalcaemia of other causes than HPT (non-HPT), in most cases due to widespread malignancies. The total serum calcium was corrected for the serum albumin concentration (CaM). Healthy females over the age of 50 had higher CaM, than younger females and the women of all ages also had, higher serum PTH levels than males. For all study groups both the intra- and inter-diurnal variations were small for all the studied variables. Discriminant function and optimal discriminatory limits were calculated with the help of computer programs. A consideration of all the individuals in the discriminant analysis, revealed that measurements of CaM alone separated most HPT patients both from the healthy subjects and from the non-HPT patients. However, when only those who had borderline values (defined as CaM between 2.45 and 2.75 mmol/l) were included it turned out that measurements of ionized calcium markedly improved the delineation of mild HPT from the healthy subjects and that, in addition, PTH measurements helped to exclude those with non-HPT hypercalcaemia. The optimal discriminatory levels of serum calcium were calculated as the levels which caused the minimum loss in terms of misclassification when attention was paid to the relative importance of false positive to false negative classifications and to the prevalence of HPT. The optimal discriminatory level for serum calcium for a weighting ratio between false positive to false negative of 1:1, and a prevalence of HPT of 1%, was calculated to be 2.68 mmol/l and for a prevalence of 50% 2.56 mmol/l. In the latter situation a weighting ratio of 10:1 for false positive to false negative gave a level of 2.63 mmol/l while a weighting ratio of 1:10 corresponded to an optimal discriminatory level of 2.47 mmol/l.

Adolescent↗
PubMed1987

Prediction of myocardial infarct size from early serum myoglobin observations.

Different possibilities to predict infarct size were analysed. The basic method was the fitting of a mathematical model to serial serum myoglobin concentration values from the very early phase of infarction. Correlation was performed with infarct size estimated from the complete serum curves of 53 patients. An observation period up to and including the serum peak value (on the average 6.8 h after onset) was required in order to give a well-determined value of infarct size. A correlation coefficient of r = 0.85 (n = 38) was then obtained. The serum peak concentration value of myoglobin correlated even better (r = 0.89). The initial slope of the serum curve (obtained on the average 4.3 h after onset of symptoms) also correlated well to infarct size (r = 0.80; n = 53). In conclusion, estimation of infarct size appears to be as good with the serum peak value of myoglobin as with model-based parameters. The most useful measure for early prediction of infarct size could be the initial slope of the serum curve.

Aged↗
PubMed1986

Conformational alterations within the glycocalyx of erythrocyte membranes studied by spin labelling.

The structure of the glycocalyx of the membrane of human erythrocytes and spectrin-depleted vesicles was studied under various conditions by two spin-labelling approaches: covalently labelling sialic acid residues of the glycocalyx and incorporation of a charged hydrophobic spin probe, CAT 16, being sensitive to alterations on the membrane surface into the lipid phase. Although cell electrophoretic measurements which were performed, additionally, indicated an erection of the glycocalyx upon decreasing the ionic strength of the suspension medium a more restricted mobility of spin-labelled sialic acid residues was found, in this case probably due to electrostatic interactions. The enhanced mobility of the spin probe CAT 16 at low ionic strength as well as in the case of neuraminidase-treated cells could be caused by reduced steric and electrostatic interaction with glycoproteins and glycolipids. La3+ adsorption and virus attachment on the human erythrocyte membrane were accompanied with a reduced mobility of sugar headgroups of the surface coat. No indication of cluster formation or lateral segregation of glycophorin molecules was found upon virus binding. After denaturation of the spectrin cytoskeleton of intact erythrocytes, increased mobility of spin-labelled sialic acid residues was observed.

Electron Spin Resonance Spectroscopy↗
PubMed1986

Structural alterations of the human erythrocyte membrane upon influenza virus attachment.

Molecular events on the human erythrocyte membrane subsequent to influence virus binding were investigated by electron spin resonance (ESR) measurements after spin labeling of the cell membrane at different positions. Virus binding affected the glycocalyx structure as well as the physical state of the cytoskeleton at the inner leaflet, but not the lipid phase. A lateral reorganization of spin-labeled glycophorin was not indicated after virus attachment.

Absorption↗
PubMed1986

Kinetics of carbon dioxide during cardiopulmonary resuscitation.

CO2 kinetics during CPR was investigated in 15 anesthetized piglets. BP, blood gases, and acid-base balance were monitored through catheters in the carotid artery and a central vein, as well as in cerebrospinal fluid. Cardiac arrest was induced by a transthoracic direct current shock. CPR was begun immediately by artificial ventilation and simultaneous external chest compressions. Epinephrine was administered after 8 min of CPR. One group (n = 5) of animals received no buffer treatment while another (n = 5) received an infusion of 75 mmol sodium bicarbonate and a third group (n = 5) received an equivalent amount of tris-buffer mixture. The results of these experiments, as well as previously described circulatory variables during CPR, were analyzed using a computer model describing the CO2 kinetics of the pig. Our main finding was that PaCO2 was positively correlated to cardiac output during CPR; improved cardiac output during CPR resulted in more efficient tissue CO2 elimination and was associated with increased survival rates. PaCO2 was also somewhat reduced by efficient alveolar hyperventilation. The arterial PCO2 and pH did not reflect the acid-base balance in peripheral tissues. During CPR, bicarbonate and tris-buffer mixture both quickly passed through the blood-brain barrier. When buffer treatment is indicated during CPR, a buffer which does not increase tissue PCO2 may be the drug of choice.

Acid-Base Equilibrium↗
PubMed1986

Analytical quality, test quality and quality costs.

This paper discusses briefly: analytical quality and its determinants; design of quality assurance procedures on the basis of quality; specifications and quality-cost models; test quality and medical costs; external quality assessment and harmonization of clinical chemical test results; the potential role of computers, database and knowledge-based systems in achieving quality goals in decentralized analytical activities.

Chemistry, Clinical↗