Search PubMed⌕ Search

Biomedical subjects

K Linnet

Publications and source records attributed to K Linnet.

At least 55 records · Page 3Linked to original sources
PubMed1995

Comparison of the kinetic interactions of the neuroleptics perphenazine and zuclopenthixol with tricyclic antidepressives.

Using data from a therapeutic drug monitoring database, kinetic interactions between the neuroleptics zuclopenthixol and perphenazine and tricyclic antidepressives were studied. Out of 290 patients monitored for amitriptyline and 611 patients monitored for nortriptyline, 77 patients were comedicated with perphenazine and 50 patients with zuclopenthixol. Comedication with perphenazine increased the median steady-state serum concentration to daily dose ratio (C/D) of nortriptyline by 30-45%, whereas the median C/D of amitriptyline was unaffected. On the contrary, median C/D values of nortriptyline and amitriptyline were not significantly influenced by comedication with zuclopenthixol. Thus, in accordance with previous studies, perphenazine increases the concentration of tricyclic antidepressives to a moderate extent. Zuclopenthixol, on the other hand, does not exert any impact under routine therapeutic drug monitoring, even though the drug is known to partly depend on metabolism by the isozyme cytochrome P450 2D6.

Adolescent↗
PubMed1994

An HPLC-GC/MS reference method for serum total cholesterol with control for ester hydrolysis.

Currently used isotope-dilution mass spectrometry methods for serum total cholesterol are performed without control in each sample for completeness of hydrolysis of cholesterol esters. In order to monitor this step in the analysis, we developed a method based on both high-pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). 13C3-cholesterol and cholesteryl [1-14C] oleate were added to serum that was saponified and extracted into hexane. The extract was subjected to HPLC with collection of the fractions corresponding to cholesterol and cholesteryl oleate. The radio-activity of the latter was counted in order to estimate the nonhydrolysed fraction that on average amounted to less than 0.1% for commonly used ester hydrolysis procedures. The cholesterol fraction was subjected to GC/MS for quantitation using the traditional isotope-dilution principle. Evaluation of accuracy by assaying sera from the National Institute of Standards and Technology showed a deviation from the target value of < 1% with a coefficient of variation of < or = 1.0%. In conclusion, the present reference method for serum total cholesterol assures results based on complete hydrolysis of the cholesterol ester fraction.

Calibration↗
PubMed1993

[Paraclinical examination programs in Danish hospitals prior to minor surgical procedures].

Using a questionnaire, paraclinical test programs prior to minor surgery were recorded for Danish hospitals. Sixty-one out of 66 departments of surgery completed the questionnaire. Most of the departments used a basic test program for younger subjects and an extended one for elderly subjects. The most commonly used investigations were in descending order: analysis of urine for glucose, albumin and hemoglobin, B-Hemoglobin, blood typing, P-Creatinine, and P-Potassium and Sodium. In elderly persons, ECG and a chest radiograph were used rather frequently in addition. The number of tests ranged from zero to nine (median three) for younger patients and from two to ten (median six) for elderly subjects. The estimated costs of the programs ranged from zero to 1092 Danish crowns (109 pounds) (median 185) for younger patients and from 71 to 1676 Danish crowns (167 pounds) (median 714) for elderly patients. In conclusion, the variation in the extent and estimated costs of preoperative test programs used in Danish hospitals is considerable.

Adult↗
PubMed1993

Effect of the biological matrix on the urinary testosterone/epitestosterone ratio measured by gas chromatography/mass spectrometry in doping analysis.

Testosterone doping in sport is detected by measurement of an increased testosterone/epitestosterone (T/E) ratio in urine. The critical limit is 6. The present study concerns calibration curves for the T/E ratio measured by gas chromatography/mass spectrometry (electron impact) according to the guidelines of the International Olympic Committee. Testosterone (T) and epitestosterone (E) are measured as trimethylsilyl (TMS)-enol-TMS ethers in selected ion monitoring mode using m/z 432 with methyltestosterone (MT) (m/z 446) as internal standard. Calibration curves corresponding to T/E = 1, 6 and 12 prepared directly, i.e. without extraction of T and E, were non-linear. The non-linearity was caused by an increase of the relative molar response of T with respect to the internal standard MT with increasing concentration level. A mean increase of 82% was observed from T/E = 1 to T/E = 12 (E fixed). Adding T/E corresponding to 1/1, 6/1 and 12/1 to urine without endogeneous hormone content resulted in an almost linear calibration curve along the diagonal, with only a slight increase of the relative molar response of testosterone (16% from T/E = 1 to 12). Apparently, the biological matrix stabilizes the relative molar response over a wide concentration range. At a molar ratio of about 1/1 for T/MT, the relative molar response for direct measurement of T is identical to that observed in the presence of urine matrix, which is explained on the basis of a simple mathematical model. The practical conclusion of this study is that, contrary to the present-day practice, calibration curves for the T/E ratio should be based on T/E added to blank urine taken through the extraction procedure. Otherwise, the T/E ratio of urine sample is systematically easily underestimated by 30% or more.

Animals↗
PubMed1993

Analytical goals for accuracy and precision of plasma creatinine determinations evaluated by reference method measurements.

Using approaches based on "medical needs" and biological variation, goals for analytical accuracy were assessed to 0.072-0.15 expressed as relative deviations, and goals for analytical precision were estimated to 0.022-0.14 expressed as relative standard deviations. A representative clinical method was evaluated using a reference method. On this basis, it is concluded that accuracy goals are fulfilled at high but not at low levels, and that precision goals are met according to medical needs but not with respect to biological variation.

Chemistry, Clinical↗
PubMed1993

Analytical goals for P-bilirubins.

Analytical goals for P-Bilirubins (total) were assessed on the basis of biological variation and "medical needs". Goals for analytical accuracy were from 0.01 to 0.18 expressed as relative deviations. Goals for analytical precision were 0.11-0.12 expressed as relative standard deviations. Using a reference method, we found that the average values of clinical laboratories deviated from 0.03 to 0.10 from reference method values. The average intra-laboratory precision was 0.088, i.e. within the goal limits.

Bilirubin↗
PubMed1991

Mean and variance rules are more powerful or selective than quality control rules based on individual values.

Quality control rules based on individual values are compared with mean and variance rules using theoretical computations and simulations. Simple (1(3)s) and combined individual value rules, e. g. a 1(3)s/2(2)s/4(1)s/6 means rule, are all less powerful for detection of shifts of location than a mean rule, given identical type I errors. The mean rule is also more robust towards non-normality of data distributions. In most cases, the variance rule has more power towards increased scatter than individual value rules, and it always has the highest selectivity. Thus, the simple computations that are required for derivation of the mean and variance result in increased power or selectivity. In particular, in the computerization of quality control, the traditional mean and variance rules are preferable to more or less complicated "multi-rules" proposed for computerized quality control.

Analysis of Variance↗
PubMed1991

HPLC with enzymatic detection as a candidate reference method for serum creatinine.

We present a candidate Reference Method for determining the concentration of serum creatinine. The method is based on HPLC combined with enzymatic determination. Creatinine plus 14[C]creatinine is extracted by cation-exchange chromatography, subjected to reversed-phase HPLC, and finally quantified enzymatically. Enzymatic measurement ensures no interference from co-eluting compounds, which has been a problem for some reported HPLC assays relying on ultraviolet detection. The average corrected recovery was 100.1% (SEM = 1.1%; n = 15). The accuracy was verified by assaying five sera with target values determined by isotope dilution mass spectrometry. The total interassay CV was less than or equal to 2.5%. We applied the method to study the specificity of HPLC-ultraviolet detection, using 72 plasma samples from hospitalized patients; no interference was noted. Thus, HPLC-ultraviolet detection appears to be specific, provided that sample cleanup is based on cation-exchange chromatography. Our diode-array detector studies of peak homogeneity supported this conclusion. Still, combined HPLC-enzymatic determination ensures even greater accuracy, ranking close to that by isotope dilution mass spectrometry.

Chromatography, High Pressure Liquid↗
PubMed1990

Estimation of the linear relationship between the measurements of two methods with proportional errors.

The linear relationship between the measurements of two methods is estimated on the basis of a weighted errors-in-variables regression model that takes into account a proportional relationship between standard deviations of error distributions and true variable levels. Weights are estimated by an interative procedure. As shown by simulations, the regression procedure yields practically unbiased slope estimates in realistic situations. Standard errors of slope and location difference estimations are derived by the jackknife principle. For illustration, the linear relationship is estimated between the measurements of two albumin methods with proportional errors.

Chemistry, Clinical↗
PubMed1989

Assessing diagnostic tests by a strictly proper scoring rule.

Evaluation of univariate quantitative diagnostic tests by strictly proper scoring rules is considered as an alternative to the traditional error rate measures. In principle, the posterior probability of disease as a function of the test value is estimated from training observations, and subsequently the score is assessed on a set of test samples. The same subjects may serve as training and test samples when the bootstrap procedure is applied for estimation of standard errors and correction of bias. The method is demonstrated using serum bile acids and bilirubin in patients with liver disease. The power for comparison of scores from two tests is compared with that from error rate measures for some typical situations.

Bile Acids and Salts↗
PubMed1989

The between-run component of variation in internal quality control.

Design of control charts for the mean, the within-run component of variance, and the ratio of between-run to within-run components of variance is outlined. The between-run component of variation is the main source of imprecision for analytes determined by an enzymo- or radioimmunoassay principle; accordingly, explicit control of this component is especially relevant for these types of analytes. Power curves for typical situations are presented. I also show that a between-run component of variation puts an upper limit on the achievable power towards systematic errors. Therefore, when the between-run component of variation exceeds the within-run component, use of no more than about four controls per run is reasonable at a given concentration.

Analysis of Variance↗
PubMed1989

Choosing quality-control systems to detect maximum clinically allowable analytical errors.

Critical systematic and random analytical errors for 17 common clinical chemical components were estimated from published values for analytical imprecision, biological variation, and "medically important changes." Appropriate quality-control systems for these analytes are discussed on the basis of power considerations. The simple rule 1(3)s, with one control per run, is minimally sufficient for the analytes (about one quarter of those considered here) for which the magnitude of critical error is at least 3 analytical standard deviations. The more powerful rule 1(2)s, with one control per run, is the minimal requirement for analytes for which critical errors are about 2 analytical standard deviations; these are about half the remaining analytes. Greater power values are achieved by using multiple rules based on several controls per run. In general, this study does not support the view put forward by some authors that the quality-control rules in use today are too restrictive.

Chemistry, Clinical↗
PubMed1988

On the sensitivity of linear discriminant analysis to sampling variation and analytical errors.

The influence of analytical inaccuracy and imprecision on the linear discriminant function is considered. Analytical shifts occurring between the analysis of samples from each of two groups give spuriously low error rates if the function is evaluated on the training set, notably at high dimensions. Inaccuracy arising after the establishment of a discriminant function may change considerably the individual group error rates whereas the overall error rate is moderately affected. Imprecision decreases the group separation by an amount comparable to that in the univariate situation. In conclusion, evaluation of the error rates of a discriminant function on an independent test set is important to obtain realistic estimates of the performance and is preferable to using unbiased statistical methods or the split-sample principle based solely upon the training set.

Biometry↗
PubMed1988

A review on the methodology for assessing diagnostic tests.

Evaluation of diagnostic tests by the following principles are reviewed: error rates, scores based on posterior probabilities, and the excess loss considered in a decision theoretic context. Error rates or the complementary non-error rates, specificity and sensitivity, are simple measures which provide a rough indication of the discriminative value. In clinical practice, where a test serves as a decision support together with other information, conversion of test results to posterior probabilities is recommended. An aggregate score of these probabilities expresses the value of the test. Finally, in simple, well-defined cases--for example, screening situations, where the prevalence of disease and the relative consequences of false-positive and -negative classifications can be estimated--a Bayesian decision analysis is appropriate. The optimal discrimination limit is selected, and the total loss is minimized. The likelihood ratio LR(x) plays a central role in probability calculations and in the decision analysis. An example illustrates application of the procedures.

Algorithms↗
PubMed1987

Comparison of quantitative diagnostic tests: type I error, power, and sample size.

For a quantitative laboratory test the 0.975 fractile of the distribution of reference values is commonly used as a discrimination limit, and the sensitivity of the test is the proportion of diseased subjects with values exceeding this limit. A comparison of the estimates of sensitivity between two tests without taking into account the sampling variation of the discrimination limits can increase the type I error to about seven times the nominal value of 0.05. Correct statistical procedures are considered, and the power and required sample size are studied for Gaussian and log-Gaussian distributions of diagnostic test values. The results may be useful for the planning phase of studies to evaluate quantitative diagnostic tests.

Biometry↗