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Biomedical subjects

K Linnet

Publications and source records attributed to K Linnet.

At least 73 records · Page 4Linked to original sources

Two-stage transformation systems for normalization of reference distributions evaluated.

In two-stage transformation systems for normalization of reference distributions, the asymmetry is first corrected, and any deviation of kurtosis is then adjusted. The simulation studies reported here show that these systems have previously been assessed too optimistically because the sample variation of the transformation parameters was neglected. Applying a goodness-of-fit test to transformed values shows that one should accept gaussianity only for p-values greater than 0.15 instead of those greater than 0.05. Further, the calculated 90% confidence intervals of reference limits should be expanded by 25%. When the correct level of significance is used, only real reference distributions that deviate moderately from the gaussian form are normalized. Calculation of confidence intervals demonstrated that 50 to 450 subjects are needed for a precise parametric estimation of the 95% reference interval. For the nonparametric approach, 125 to 700 reference subjects are necessary. The larger sample sizes are needed when distributions show pronounced skewness.

Biometry↗

Assessing diagnostic tests once an optimal cutoff point has been selected.

The specificity and sensitivity of a quantitative diagnostic test depends on the chosen cutoff point. The common practice of selecting a cutoff point that maximizes the specificity plus the sensitivity, as judged from the observed test results, is studied here by simulation. Test performance is on average assessed too optimistically by this procedure--a phenomenon of importance when sample sizes are small. For example, the average positive bias is up to 15% of the test performance for sample sizes of 25. Furthermore, binomial calculated standard errors of specificity and sensitivity estimates are incorrect. A Monte Carlo statistical method--the "bootstrap procedure"--is applied to correct for bias and to estimate standard errors, including the standard error of the optimal cutoff point. Independent and paired comparisons of two diagnostic tests are also considered when optimal cutoff points have been selected. For this purpose, binomial statistical tests behave satisfactorily. Examples of power functions are presented.

Bile Acids and Salts↗

Analysis of insulin receptors on heterogeneous eukaryotic cell populations with fluorochrome-conjugated insulin and fluorescence-activated cell sorter. Advantages and limitations to the 125I-labelled insulin methodology.

The diversity in insulin receptor expression within eukaryotic cell populations can be studied with fluorochrome conjugated reagents with high affinity to the insulin receptor in combination with flow cytometry. We studied the optimal conditions for application of fluorescein isothiocyanate (FITC) conjugated insulin in combination with the fluorescence activated cell sorter (FACS) to analyse insulin receptor expression, and also studied the feasibility of this method for identifying and isolating viable subsets with differences in insulin receptor expression within a cell population. Semisynthetic human insulin was conjugated to FITC, which resulted in at least four types of FITC-insulin molecules with different affinities to the insulin receptor. Each type of FITC-insulin was isolated by semipreparative reverse phase high pressure liquid chromatography. The preparation with a fluorescein/protein ratio of approximately 1.0 was found to have the highest affinity to the receptor, the highest biological activity (approximately 50% of native insulin), and similar antigenicity as native insulin. The optimal staining conditions with respect to pH, time of incubation, and cell number were determined, and were different in some aspects from labelling with 125I-insulin. The binding of FITC-insulin to cells was saturable and could be displaced with unlabelled insulin. The fluorescence signal could be converted to absolute numbers of fluorescein molecules by a calibration curve, and the absolute number of specifically bound FITC-insulin molecules calculated from a F/P ratio approximately 1.0. The FITC-insulin/FACS method permits estimation of the total number of insulin receptors (high plus low affinity), and the data obtained correlate well with the results from Scatchard plot of 125I-insulin binding data.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Precision of sensitivity estimations in diagnostic test evaluations. Power functions for comparisons of sensitivities of two tests.

The precision of estimates of the sensitivity of diagnostic tests is evaluated. "Sensitivity" is defined as the fraction of diseased subjects with test values exceeding the 0.975-fractile of the distribution of control values. An estimate of the sensitivity is subject to sample variation because of variation of both control observations and patient observations. If gaussian distributions are assumed, the 0.95-confidence interval for a sensitivity estimate is up to +/- 0.15 for a sample of 100 controls and 100 patients. For the same sample size, minimum differences of 0.08 to 0.32 of sensitivities of two tests are established as significant with a power of 0.90. For some published diagnostic test evaluations the median sample sizes for controls and patients were 63 and 33, respectively. I show that, to obtain a reasonable precision of sensitivity estimates and a reasonable power when two tests are being compared, the number of samples should in general be considerably larger.

Clinical Laboratory Techniques↗

Concentrations of glycine- and taurine-conjugated bile acids in portal and systemic venous serum in man.

Concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid in portal and systemic venous serum and in bile were measured in eight subjects undergoing elective cholecystectomy. Mean concentrations in systemic serum ranged from 0.07 to 0.17 mumol/l, in portal serum from 0.49 to 2.09 mumol/l, and in bile from 2.72 to 17.2 mmol/l. The percentage content of trihydroxy-bile acid conjugates in bile (49%) and in portal serum (51%) was higher than in systemic serum (35%) (P less than 0.001). The estimated hepatic fractional uptake of glycocholic acid (mean, 83%) and of taurocholic acid (83%) was higher than the uptakes of the dihydroxy-bile acid conjugates (60-68%). The percentage contents of glycine-conjugated bile acids in systemic serum (mean, 66%), portal serum (62%), and bile (65%) were not significantly different.

Adult↗

Cholecystokinin-stimulated and postprandial serum concentrations of bile acids in alcoholic liver cirrhosis.

This investigation was undertaken to examine the alterations in serum bile acid concentration after intravenous administration of cholecystokinin and a standard meal in 13 patients with alcoholic cirrhosis. Total 3 alpha-hydroxy bile acids in serum (SBA) were monitored for 2 h after injection of cholecystokinin and for 3 h after the standard meal. The median fasting value of SBA was 39.9 mumol/l (range, 3.2-148 mumol/l). The increase in SBA after cholecystokinin started earlier and lasted shorter than after standard meal stimulation (median, 30 min and 120 min, respectively). The appropriate relative peak levels of SBA were 173% and 212% of the fasting value. The increments were significant (P less than 0.01) within groups but insignificant between groups. Day-to-day variation of postprandial SBA was more pronounced than after cholecystokinin stimulation. The difference, however, was insignificant. An inverse correlation was detected between both fasting and stimulated peak levels of SBA and P-coagulation factors 2, 7, and 10.

Adult↗

Differential diagnostic value in hepatobiliary disease of serum conjugated bile acid concentrations and some routine liver tests assessed by discriminant analysis.

Serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a HPLC-enzymatic assay in 104 patients with hepatobiliary diseases. The capability of discriminating between four major diagnostic categories by the serum bile acid concentrations, alone and in conjunction with five commonly used biochemical liver tests, was evaluated by stepwise linear discriminant analysis. The serum bile acid pattern alone was inferior to the routine liver tests in separating the diagnostic groups. When the two sets of analytes were combined, the generalized group distance (Rao's V) was significantly increased, showing that the serum bile acid pattern contained discriminatory information in addition to the routine liver tests. The gain in correct reclassification of patients obtained by adding the serum bile acids, however, was only marginal.

Adolescent↗

Liver function under long-term treatment with neuroleptic drugs assessed by serum concentrations of bile acids, alkaline phosphatase, and aspartate aminotransferase.

Serum concentrations of total 3 alpha-hydroxy-bile acids, alkaline phosphatase, and aspartate aminotransferase were measured in 35 psychotic patients who had been under treatment with neuroleptic drugs for more than 1 year. Serum concentrations of total bile acids were from 1.0 to 9.4 mumol/l (mean 2.9 mumol/l) in the patients and from 0.6 to 4.8 mumol/l (mean 2.2 mumol/l) in 20 healthy controls; the mean values were not significantly different. Serum concentrations of alkaline phosphatase and aspartate aminotransferase in patients and controls were not significantly different either. In conclusion, none of the patients had signs of manifest hepatobiliary dysfunction.

Adolescent↗

Postprandial plasma concentrations of glycine and taurine conjugated bile acids in healthy subjects.

Fasting and postprandial plasma concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured by a high pressure liquid chromatography-enzymatic assay in nine healthy subjects. The mean value of each bile acid concentration increased significantly (2.4-4.7 times) in the postprandial period. The total glycine taurine ratio of 2.5 in the fasting state increased significantly to a maximum value of 3.3 at one to 1 1/2 hours postprandially and then declined. This shift in glycine taurine ratio shows, that the relative increase in concentrations of glycine conjugates exceeds the relative increase in concentrations of taurine conjugates in the early postprandial period, and supports the view that there is significant absorption of glycine conjugated bile acids from the proximal small intestine.

Adolescent↗

Diagnostic values of fasting and postprandial concentrations in serum of 3 alpha-hydroxy-bile acids and gamma-glutamyl transferase in hepatobiliary disease.

Fasting and postprandial concentrations in serum of 3 alpha-hydroxy-bile acids and gamma-glutamyl transferase were measured in 138 consecutive patients, 62 with (D) and 76 without (D) hepatobiliary disease. The maximum efficiencies of the three tests--that is, the fractions of patients allocated correctly to the D or D group at the optimum discrimination values--were 0.85, 0.84, and 0.83, respectively. Furthermore, the predictive values and nosographic sensitivities and specificities were rather similar. When the three tests were combined, the nosographic sensitivity increased significantly to a value of 0.84, and the corresponding specificity was 0.91. The diagnostic value of the absolute postprandial increase in serum bile acid concentration was slightly inferior to the diagnostic values of the fasting and postprandial serum bile acid concentrations and, finally, the relative postprandial serum bile acid increase was of no diagnostic value at all.

Adolescent↗

Fasting and postprandial serum concentrations of glycine- and taurine-conjugated bile acids in Crohn's disease.

Fasting and postprandial serum concentrations of glycine and taurine conjugates of cholic, chenodeoxycholic, and deoxycholic acid were measured with a high-pressure liquid chromatographic-enzymatic assay in 17 patients with ileal Crohn's disease and in 17 controls. The postprandial concentrations of the taurine-conjugated bile acids in the patients were significantly lower than in the controls, whereas the concentrations of the glycine conjugates were not significantly different. The total glycine to taurine ratios of serum bile acids were significantly higher in the patients (means, 2.9 fasting and 4.8 postprandial) than in the controls (1.9 and 2.6). Of the patients, 65% had a postprandial total G/T ratio of serum bile acids which was above the control interval.

Adult↗