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Biomedical subjects

T Groth

Publications and source records attributed to T Groth.

14 recordsLinked to original sources

A hyaluronan-loading test applied to patients with liver and joint diseases.

The serum hyaluronan disappearance data, after an intravenous bolus injection of hyaluronan, were evaluated in terms of model-based parameters. The loading test was performed in 10 healthy persons (basal serum hyaluronan concentration, C0, 24.9 +/- 8.9 micrograms/l [mean +/- S.D.]), 6 patients with joint disease (62.3 +/- 41.1 micrograms/l) and 19 patients with liver disease (206 +/- 214 micrograms/l). The highest maximum Michaelis-Menten elimination rate (Vmax = 287 +/- 86 micrograms/min) was found in patients with joint disease, significantly higher than in healthy persons (Vmax = 179 +/- 16, P = 0.0015) and in patients with liver disease (Vmax = 149 +/- 59, P = 0.0002). C0 and Vmax were evaluated as discriminants for assessment of residual liver function. In patients with liver disease C0 correlated with liver function score (r = 0.875, P < 0.0001) and serum albumin concentration (r = -0.813, P < 0.0001). The Vmax parameter did not correlate with conventional liver function tests or with the liver score but a significantly negative correlation of Vmax with C0 was found in patients with liver disease. A combination of the C0 level and the Vmax parameter was found to discriminate between healthy persons, patients with joint disease and patients with liver disease and should be of benefit in separating patients, with or without elevated serum hyaluronan levels, into groups having increased influx or reduced elimination, respectively, of circulating hyaluronan.

Adult

Equivalence of quantitative models for tumour response to ionizing radiation in treatment field optimisation procedures.

Three cell kinetic models of tumour response to ionising radiation were compared with regard to their prediction of variation in curability when the dose to the tumour varied between 54 and 66 Gy given in 30 fractions. It was found that a simple model emulated the results of the more complex ones when the parameters of the simple model were properly adjusted. A comparison of the simple model and the CRE formula gave a similar result.

Cell Survival

Influence of a between-run component of variation, choice of control limits, and shape of error distribution on the performance characteristics of rules for internal quality control.

A computer-stimulation study has been performed to determine how the performance characteristics of quality-control rules are affected by the presence of a between-run component of variation, the choice of control limits (calculated from within-run vs. total standard deviations), and the shape of the error distribution. When a between-run standard deviation (Sb) exists and control limits are calculated from the total standard deviation (St, which includes Sb as well as the within-run standard deviation, Sw), there is generally a loss in ability to detect analytical disturbances or errors. With control limits calculated from Sw, there is generally an increase in the level of false rejections. The presence of non-gaussian error distribution appears to have considerably less effect. It can be recommended that random error be controlled by use of a chi-square or range-control rule, with control limits calculated from Sw. Optimal control of systematic errors is difficult when Sb exists. An effort should be made to reduce Sb, and this will lead to increased ability to detect analytical errors. When Sb is tolerated or accepted as part of the baseline state of operation for the analytical method, then further increases in the number of control observations will be necessary to achieve a given probability for error detection.

Chemistry, Clinical

Power functions for statistical control rules.

We have studied power functions for several control rules by use of a computer simulation program. These power functions show the relationship between the probability for rejection and the size of the analytical errors that are to be detected. They allow some assessment of the quality available from present statistical control systems and provide some guidance in the selection of control rules and numbers of control observations when new control systems are designed.

Chemistry, Clinical

The usefulness of 125I-sodium lothalamate as a GFR-indicator in single intravenous injection tests.

Clearance of sodium iothalamate was estimated from plasma elimination curves obtained from 90 patients having varying renal function, after a single intravenous injection of 125I-sodium iothalamate. The usefulness of sodium iothalamate as a GFR-indicator with this technique was tested by a strict statistical comparison with conventional inulin clearance as a reference. The regression line, covering the clearance range 2-163 ml min-1, Clinulin = 1.08.Clsodiumiothalamate-3.7, (n = 84, r = 0.85, SEE = 2.3 ml.min-1) was not significantly different from the identity line, which means (i) that extrarenal elimination could not be detected, and (ii) that I125-sodium iothalamate should be regarded as a useful glomerular marker for single intravenous injection studies. An open two-compartment model of mamillary type was found to give an adequate representation of the plasma disappearance curve. The results are not critically dependent on the choice of approximating function. The method by Sapirstein et al., the method by Nosslin and a power-law method were used for comparison and were found to give the same results. However, the present type of curve fitting analyses requires frequent blood sampling or external counting over a long period in order to give reliable estimates of GFR. This circumstance makes these methods less attractive for clinical use.

Adult

The molecular function of hemoglobin as reflected in ligand binding data: analysis of data on erythrocytes.

Hemoglobin oxygen binding data on erythrocytes at diffrent pH, PCO2 and bisphosphoglycerate concentrations have been analyzed in terms of an extended version of the Herzfeld-Stanley model of 1972. The binding of oxygen to subunits when the tetramer is in the quaternary oxy conformation was found to be insensitive to moderate changes in pH and pCO2 (0.71 +/- 0.05 mm Hg-1). Utilizing this circumstance it has been possible to obtain, for the first time, unique estimates of energy parameters related to hemoglobin cooperativity and effector action. At 37 degrees C, pH 7.2 and pCO2 22 mm Hg the following parameter values were obtained: The allosteric constant: (1.5 + 0.4)-10(4); the oxygen binding constant of the deoxy state: (5.4 +/- 0.3).10(-3) mm Hg-1; the 2,3-bisphosphoglycerate binding constants: (3.3 +/- 1.3).10(3)1. mol-1(deoxy), (1.3 +/- 0.5).10(2)1. mol-1 (oxy). Quarternary transition most likely takes place after binding of the second O2 molecule. Following the concepts of Perutz the results suggest that (1) protons and carbon dioxide act as constraint effectors and/or as quaternary effectors; (2) the difference in total conformational energy between the two quaternary ligand-free states is almost exclusively confined to molecular constraints and very little to the difference in quaternary conformational energy. The consistency of the results indicate that the model may be regarded as a useful tool for the description of the functional interrelations in the hemoglobin oxygenation process as reflected in oxygen binding data.

Binding Sites

A simple method for the estimation of glomerular filtration rate.

A simple method is presented for indirect estimation of the glomerular filtration rate from two venous blood samples, drawn after a single injection of a small dose of [125I]sodium iothalamate (10 muCi). The method does not require exact dosage, as the first sample, taken a few minutes (t = 5 min) after injection, is used to normalize the value of the second sample, which should be taken in between 2-4 h after injection. The glomerular filtration rate, as measured by standard inulin clearance, may then be predicted from the logarithm of the normalized value and linear regression formulas with a standard error of estimate of the order 1-2 ml/min/1.73 m2. The slope-intercept method for direct estimation of glomerular filtration rate is also evaluated and found to significantly underestimate standard inulin clearance. The normalized 'single-point' method is concluded to be superior to the slope-intercept method and more sophisticated methods using curve fitting technique, with regard to predictive force and clinical applicability.

Adult

Performance characteristics of rules for internal quality control: probabilities for false rejection and error detection.

When assessing the performance of an internal quality control system, it is useful to determine the probability for false rejections (pfr) and the probability for error detection (ped). These performance characteristics are estimated here by use of a computer stimulation procedure. The control rules studied include those commonly employed with Shewhart-type control charts, a cumulative sum rule, and rules applicable when a series of control measurements are treated as a single control observation. The error situations studied include an increase in random error, a systematic shift, a systematic drift, and mixtures of these. The probability for error detection is very dependent on the number of control observations and the choice of control rules. No one rule is best for detecting all errors, thus combinations of rules are desirable. Some appropriate combinations are suggested and their performance characteristics are presented.

Chemistry, Clinical

Combined Shewhart-cusum control chart for improved quality control in clinical chemistry.

We describe the adaptation of the decision limit cumulative sum method (cusum) to internal quality control in clinical chemistry. With the decision limit method, the cusum is interpreted against a numerical limit, rather than by use of a V-mask. The method can be readily implemented in computerized quality-control systems or manually on controls charts. We emphasize the manual application here and demonstrate how the technique can be implemented on existing Shewhart or Levey-Jennings control charts. This permits both cusum and Shewhart control rules to be used simultaneously on a single control chart and also minimizes the data calculations necessary for the cusum method. Computer simulation studies are used to determine the performance characteristics of several different cusum rules, alone and in combination with a Shewhart rule. These studies indicate that improvements in existing quality-control systems should be possible by addition of this simple cusum method and by use of a combined Shewhart-cusum control chart. This should be particularly advantageous when introducing the cusum method in laboratories with manual quality-control systems.

Chemistry, Clinical

An off-line system for in-time analysis of cardiac catheterization data and for establishment of a cardiological database for retrospective studies.

The system described may be divided in two major parts: (i) automatic analysis of cardiac catheterization data running off-line on a Siemens 305 computer; (ii) storage and retrieval of the results from these analyses and additional data from related departments (thoracic surgery, internal medicine and clinical physiology) in a cardiological database on an IBM 370/155 computer. The first part is described with special regard to (i) operation and control during the phases of data collection, pre-processing, processing and storage of results; (ii) the presentation of the results in a complete and readable form and (iii) the modular design of the software. The results of an evaluation of the computer methods versus manual methods are also presented. The second part has been described with regard to the type of data entered in the cardiological database. The structure of the database and the programs used for storage and retrieval have not been described in detail in the present publication.

Analog-Digital Conversion

Cell kinetic approach to optimising dose distribution in radiation therapy.

A simple tumour-cell radiation-response model was coupled to a dose-calculation routine and applied to a clinical situation in radiation therapy. The dose distributions resulting from various settings of two radiation fields, as well as the tumour response under various assumptions regarding sensitivity and distribution of tumour cells, were calculated automatically. The probability of zero surviving tumour cells after 30 fractions was taken as a measure of goodness of the dose distributions and was found to vary rather smoothly over the parameter intervals considered. For some parameters a distinct optimum was found, rather insensitive to different assumptions regarding cell response. A tolerance factor for healthy tissue, based on a dose-volume relationship, was also considered. It is concluded that a cell kinetic approach to automatic optimisation of field parameters in external radiation therapy might be realistic both from computional and economic points of view.

Cell Survival

Errors and uncertainties in external radiation therapy. A system analysis with a cell kinetic model.

The relative importance of accurate knowledge and control of various biologic and physical factors in external radiation therapy was estimated with a simple cell kinetic treatment response model for a simulated tumour therapy situation. A set of parameter values was chosen for a reference case so that the calculated probability of zero surviving tumour cells was about 0.5. The parameters were varied, one at a time, over a range that was considered representative with respect to uncertainty in dose calculation, dose delivery and the description of the pertinent patient data. Also parameters in the cell kinetic model were varied. The calculations demonstrated a strong influence on the number of surviving cells from even moderate changes in the parameters which affect the tumour dose. Predictions with regard to curability are heavily dependent on the reliability of the biologic parameters in the model.

Cell Survival