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PubMed1986

Statistical analysis of the stability of the standard curve for some Syva EMIT assays.

Derivation of standard curves for the EMIT therapeutic drug monitoring system involves several mathematical algorithms, all of which can be rewritten in the form of a linear equation y = mx + b. We examined the stability of the standard curve in terms of slope and y-intercept for three drug assays (procainamide, gentamicin, and carbamazepine) by generating calibration curves intermittently for periods as long as 90 days. Controls at three concentrations were assayed after each calibration to validate the standard curves. On the basis of 98% confidence intervals, the slopes of standard curves for procainamide, gentamicin, and carbamazepine were stable for 89, 80, and 57 days, respectively. Control values generated from standard-curve manipulations (adjustments to the y-intercept) indicated consistent accuracy and precision throughout the entire study, as compared with control values determined after each calibration. The increased utility of the standard curve and reagents suggests that full recalibration on a regular basis is not always necessary.

Carbamazepine↗

PubMed1986

Fluorescence polarization immunoassay for ethosuximide evaluated and compared with two other immunoassay techniques.

We evaluated a new fluorescence polarization immunoassay (FPIA) for ethosuximide in the Abbott TDx and compared results with those by two other ethosuximide immunoassays, EMIT (Syva Co.) and aca (DuPont). The FPIA assay produced within- and between-day CVs of less than 5% at the low, medium, and high ranges of the standard curve. For the ethosuximide FPIA assay the standard curve was stable during the 47 days of the study. By all three methods, we analyzed 100 serum and plasma samples from patients who were receiving ethosuximide. The coefficient of determination (r2) for TDx versus EMIT was 0.973 (slope, 0.96; intercept, -0.80); for TDx vs aca it was 0.985 (slope, 1.00; intercept, -2.44); both relationships were statistically significant (p less than 0.05). Values for patient's specimens were significantly lower by the TDx than by the aca or EMIT methods (p less than 0.05).

Ethosuximide↗

PubMed1978

A sensitive manual enzyme immunoassay for thyroxine.

We describe an immunoassay for thyroxine in serum. In the assay specific antibody covalently bonded to latex particles is used, along with horseradish peroxidase as the label, and o-phenylenediamine as the chromogen. The flexible protocol is designed for manual execution. Performance is similar to that of the highest-sensitivity thyroxine radioimmunoassays. Results correlate well with radioimmunoassay (r = 0.99, slope = 0.93, y-intercept = 2.4 microgram/liter for 201 samples) and an automated enzyme immunoassay (r = 0.97, slope = 0.99, y-intercept = 4.7 coefficients of variation are less than 7.2% over the entire useful range of the assay (20--240 microgram/liter). The limit of detection is less than 94 pg/tube at 20 microgram/liter. Only D-thyroxine is known to interfere with serum assays. This assay has no discernible protein effect from 40 to 80 g of protein per liter, unlike many thyroxine radioimmunoassays. Serum preservatives known to be peroxidase inhibitors do not adversely affect assay performance because of the 56-fold dilution in the final assay mixture. Hemolyzed serum and EDTA-treated plasmas are unsuitable for this assay.

Cross Reactions↗

PubMed1987

Generation 04 sodium slides and generation 04 reference fluid evaluated for use with the Ektachem 400 Analyzer.

Evaluation of a new generation of sodium slides and reference fluid for use with the Kodak Ektachem 400 Analyzer demonstrated improved performance in generation 04 over the previous generation 03 slide for sodium determinations. A decrease in between-replicate imprecision and a correction of the "serum" assigned values of the calibrators used to calibrate the slide used with the reference fluid account for the improvement. When generation 04/Ektachem results (y) were compared with results obtained with a Beckman ion-selective electrode (x), linear regression statistics were: slope = 0.88, y-intercept = 15.4 mmol/L, and Syx = 2.1 mmol/L. The average fixed bias in comparison with the Beckman electrode decreased from +1.9 mmol/L with generation 03 to -0.6 mmol/L with generation 04 materials. Random error is indicated by a decrease in Syx from 2.8 mmol/L for generation 03 to 2.1 mmol/L for generation 04. Application of Deming's regression, a more accurate portrayal of the generation 04 sodium data set, produces a slope of 1.0 and a y-intercept of -0.6 mmol/L.

Humans↗

PubMed1987

Dose-response curves for pancuronium and tubocurarine: comparison of single and cumulative dose techniques.

Dose-response curves for pancuronium and tubocurarine were constructed using single-dose and cumulative-dose methods of administration. The dose-response curves for pancuronium were similar using the two methods, and resulted in an ED95 (dose required to produce 95% block of the twitch height) of 60 and 59 micrograms kg-1 using single-dose and cumulative-dose methods respectively. Although the dose-response curves for tubocurarine differed in their slopes and intercepts (significantly (P less than 0.01) for intercepts), the magnitudes of the ED95, 449 and 529 micrograms kg-1 respectively, were not significantly different. A cumulative-dose method for determination of the potency (ED95) of relatively long-acting drugs, such as pancuronium and tubocurarine, gives results which are similar to those obtained using a single bolus method, but has the advantage of requiring fewer subjects.

Adult↗

PubMed1986

Close proximity gunshot residues.

Intuitively, a hand held in close proximity to a firearm at the instant of discharge will intercept a significant amount of gunshot residue, even though the hand did not actually come into contact with the weapon. There is, however, little information specifically described in the forensic science literature concerning the residue levels which might be encountered in such an instance. The present work confirms that antimony levels consistent with an individual having fired or handled a firearm may be intercepted by a hand held in close proximity.

Antimony↗

PubMed1986

Quality assessment of determinations of serum fructosamine in 33 clinical chemistry laboratories.

We investigated the analytical performance of fructosamine measurement in 33 routine clinical chemistry laboratories. We prepared 12 human control sera spanning a range of nondiabetic and diabetic fructosamine concentrations and assigned target values by using commercial reagents and a Cobas Bio centrifugal analyzer. Each control serum was analyzed by participating laboratories on two separate occasions. Averaged results were compared with target values, and systematic error was determined from slope and intercept regression coefficients. Overall, we found no significant (p greater than 0.05) slope or intercept bias, although slight nonlinearity was found with bichromatic instruments. Random error was determined from the standard error of estimate and from duplicate measurements. We found a median interlaboratory CV of 5.36% and similar analytical performance with all automated instruments used. The median random error with manual techniques was 18.1%. We conclude that fructosamine measurement as currently performed in routine laboratories is sufficiently accurate and reliable to function as an index of blood glucose control in diabetic patients.

Blood Glucose↗

PubMed1986

Evaluation of antileukoprotease in surgical lung specimens.

To evaluate the presence of antileukoprotease in the lung and its possible contribution to parenchymal protection, surgically removed lungs or lobes of 41 patients were studied. Tissue slices were stained immunohistochemically for antileukoprotease. Site and number of antileukoprotease-containing cells were recorded. To measure emphysema, the mean linear intercept of each slice was determined. Antileukoprotease was observed in bronchial epithelium and glands and in at least two types of nonciliated cells and in a few basal cells of bronchiolar epithelium. No relationship existed between the frequency of antileukoprotease positive cells in membranous bronchioles and the mean linear intercept, the smoking history or lung function except for total lung capacity. These results do not support a protective activity of antileukoprotease against emphysema, but neither do they provide evidence against it.

Female↗

PubMed1985

An anion-exchange chromatographic method for measuring bilirubin covalently bound to albumin.

After alkalinizing the diazo products of serum bilirubins, we apply them to a column of anion-exchange resin. The azodipyrroles derived from unconjugated and sugar-conjugated bilirubins, as well as from one half of the tetrapyrrole covalently linked to albumin ("Bil-Alb"), are anionic and protein-free and adsorb to the resin. The other half of the azo product of Bil-Alb, with absorptivity similar to that of the protein-free azodipyrroles, remains attached to albumin (Clin Chem 28:629-637, 1982) and passes through the resin unadsorbed. The color of the eluate correlates directly with the original amount of Bil-Alb present. Estimates of authentic Bil-Alb by the method agree with those by a Jendrassik-Gróf total-bilirubin method (in mg/L: intercept = -0.8, slope = 1.005, r = 0.999) and by liquid chromatography (Clin Chem 29:800-805, 1983) (n = 52, intercept = 5.2, slope = 0.724, r = 0.965). The CV of the method for serum with Bil-Alb of 99.4 mg/L was 3.8% (n = 8).

Animals↗

PubMed1985

The effect of furoyl saccharin, a novel non-peptidic acylating protease inhibitor, on experimental emphysema in the hamster.

Furoyl saccharin was evaluated for its ability to prevent the development of emphysematous lesions produced in hamsters by the exposure to aerosolized papain (3% for 3 h). Pretreatment with intratracheal furoyl saccharin (at the doses of 0.3, 1, 3 mg) reduced the appearance of papain-induced emphysema as evaluated by both physiologic (static compliance) and histologic (mean linear intercept and internal surface area of the lungs) methods. Inhibition was dose-related with maximal reduction of changes in static compliance (74%), mean linear intercept (84%) and internal surface area (65%) observed after a dose of 3 mg. This is the first time that a non-peptide acylating inhibitor of serine proteases is reported to be affective in preventing the development of experimental emphysema.

Animals↗

PubMed1985

Factors influencing the response time in extrapolation of motion studies.

The linear dependence between the response time and the concealment time in prediction of motion studies is confirmed. The parameters of the linear relationship could be considered as individual characteristics of the subjects. Our and other experimental results show that the parameters of the linear relationship could be manipulated selectively. Factors, which influence velocity perception and the subject's knowledge of the results, change mainly the slope value. Factors, changing the concealment time uncertainty, e. g. the moment of target presentation, affect the intercept value. It is supposed that the slope value reflects the subjective velocity scale and that the intercept value is related to the individual peculiarities of the subjects in organization and execution of a response in a definite moment.

Humans↗

PubMed1985

Ceruloplasmin as an indicator of copper status in cattle and sheep.

The relationship between ceruloplasmin, a metalloenzyme with oxidase activity, and copper was investigated in cattle and sheep. The oxidase activity of ceruloplasmin correlated closely with the serum or plasma copper concentrations in cattle. The respective correlation coefficients were 0.83 and 0.60. In sheep serum, a correlation coefficient of 0.92 was obtained. In each instance, the relationship remained linear from the deficient to the high normal ranges of copper. Comparison of the linear regression relationships indicated the ceruloplasmin activity in bovine serum was statistically lower than the activity in bovine plasma (P less than 0.0001), through the intercepts from the regression lines of the two relationships were similar (P = 0.412). Comparisons of ovine and bovine serum-ceruloplasmin relationships indicated that a significant species difference was present. Ovine ceruloplasmin activity increased more rapidly as compared to the corresponding bovine activity over the range of copper concentrations investigated (P less than 0.0001). The intercept from the ovine regression relationship was also lower (P less than 0.0001). A correlation coefficient of 0.35 was observed between the serum ceruloplasmin activity and hepatic copper concentrations in cattle indicating that the mathematical relationship was not as well defined. Ceruloplasmin activity appears to correlate more closely with serum or plasma copper concentrations as compared to corresponding liver copper concentrations.

Animals↗

PubMed1979

The relationship of the lithium erythrocyte: plasma ratio to plasma lithium level.

The relationship of the lithium erythrocyte:plasma ratio to plasma lithium concentration was reviewed in inpatients and outpatients with affective disorders. For some patients, there was a linear correlation between the erythrocyte lithium:plasma lithium ratio and the plasma lithium concentration. For these patients a graph of the slopes and intercepts of the lithium erythrocyte:plasma ratio vs. plasma lithium data formed a line that was not significantly different from the data of Lee et al. (1975). Significant correlations were found between the slopes and intercepts of the lithium erythrocyte:plasma ratio vs. plasma lithium data and the magnitude of active lithium efflux (Ko) from the erythrocyte. Our data confirm the finding of Lee et al. (1975) that the lithium erythrocyte:plasma ratio is dependent on the plasma lithium concentration. We relate this finding to lithium efflux from the erythrocyte.

Adult↗

PubMed1979

Disopyramide determination by gas chromatography, liquid chromatography, and gas chromatography--mass spectrometry.

Disopyramide is determined in serum by gas chromatography with a nitrogen-selective detector, by liquid chromatography, and by gas chromatography--mass spectrometry. Comparable results are obtained with the three techniques, with a within-run and between-run precision of 5 to 10% (coefficient of variation). Least-squares analysis of data on patients' sera, analyzed first by gas chromatography (y) and then liquid chromatography (x), gave a slope of 1.12; y-intercept, -0.31; standard error of estimate, 0.46; and correlation coefficient, 0.94. Comparison of patients' sera by gas chromatography (y) and then by gas chromatography--mass spectrometry (x) gave a slope of 0.94; y-intercept, 0.42; standard error of estimate, 0.38; and correlation coefficient, 0.97. Interferences observed when using one technique--for example, gas chromatography--can be eliminated by analyzing the sample extract with one of the other techniques.

Chromatography, Gas↗

PubMed1982

The use of drug-receptor affinity measures in the differentiation of receptors.

The drug-receptor dissociation constant (K), determined by pharmacological procedures, is measured from a dose-effect relation and the modification of that relation by the presence of a second compound (antagonist) that competes for the same receptor. These procedures differ from those that use radiolabeled compounds and do not measure an effect but instead determine the K of the compound by quantitating its displacement of the labeled substance. In several examples the dissociation constants determined from pharmacological procedures are shown to be unique for a particular drug-receptor interaction and can therefore discriminate among receptors. A further demonstration is that K does not equal D50, the potency index. For competitive antagonists the Schild plot is commonly used to measure K. This plot, theoretically linear with a slope of -1, often leads to slopes different from -1 (using conventional linear regression), in which case its x intercept, pA2, and y intercept, -log KB, differ by an amount that depends on the slope. Even when this differences is small, the 95% confidence limits of pA2 and -log KB may be very different and are invariably larger for -log KB, the value that is presumably sought from this analysis. A Schild plot constrained to slope -1 (and, accordingly, different regression equations) should therefore be used in cases of known competitive antagonism such as that between naloxone and morphine. The special problems associated with measuring K for agonists are discussed and illustrated with recent work done in our laboratories in which we employed the new narcotic analgesic buprenorphine to determine by pharmacological methods the dissociation constant for morphine, a value previously undetermined.

Adrenergic alpha-Agonists↗

PubMed1977

Search in short-term memory during inhalation of a general anesthetic in man.

Effects of controlled subanesthetic concentrations of enflurane on short-term memory functions were studied in male volunteers. Short-term memory processes were assessed through a search task: A series of digits, words, or familiar pictures, was visually presented, followed by a test digit which in half the trials was part of the series, and in half of the trials it was not. The subject responded by a press on one of two switches signalling 'yes' or 'no' accordingly. Memory set size varied between 1 to 11 for digits and 1 to 8 for words and pictures. Enflurane in air was delivered through a non-rebreathing system. Low concentrations of enflurane did not change the slope of the search function, but increased the intercept by few hundred milliseconds. This was interpreted to indicate anesthetic effect on the cognitive processes reflected in the intercept, that is, stimulus reception and evaluation and response variables. No effect was observed on retrieval time from the short-term store.

Adult↗

PubMed1977

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↗

PubMed1978

Marrow stem cell release in the autorepopulation assay.

The early migration of stem cells from a shielded marrow to an irradiated spleen has been re-evaluated, and the findings have been compared with the results of earlier studies. The composite data reveal a constant rate during the first 24 h after irradiation, with a slope of 1.6 cells per h and an intercept of 2.4. The positive intercept is interpreted to signify an immediate brief perturbation of CFU's release. The low concentration of CFUs in the bloodstream, despite their continuous migration from the shielded marrow, is indicative of a rapid, and probably greatly increased, blood turnover. Despite the constancy of stem cell seeding, it is not yet possible to determine whether the rate of stem cell release is different in shielded marrow than in normal marrow. The resolution of this question requires more precise information about spleen seeding efficiency in the autorepopulation assay and about the normal turnover rate of stem cells in the bloodstream.

Animals↗