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Biomedical subjects

P Winkel

Publications and source records attributed to P Winkel.

At least 19 recordsLinked to original sources

Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers.

The authors determined mean day-to-day (daily over five days), mean week-to-week (weekly over five weeks) and mean hour-to-hour (800 h, 1100 h, 1400 h) physiologic intra-individual variation of concentration values of leukocyte cell types, platelet count, and erythrocyte values (hematocrit, hemoglobin) for a group of 20 healthy adult volunteers. Total leukocyte counts and concentration values of leukocyte cell types were determined in duplicate on the Hemalong-DTM Automated Leukocyte Differential Cell Counter to minimize analytic variation. The data sets were analyzed according to an analysis of variance model. The mean physiologic hour-to-hour and week-to-week intra-individual variations in terms of % coefficient of variation included: hemoglobin, 2.5, 2.2; hematocrit, 2.6, 2.7; platelets, 1.6, 6.6; total leukocyte count, 9.4, 15.7; neutrophils, 12.9, 26.0; lymphocytes, 10.3, 13.2; monocytes, 18.6, 19.3; eosinophils, 19.9, 26.9; basophils, 7.4, 15.0; large unstained cells, 13.7, 16.0; "high-peroxidase" cells, 32.7, 25.7. Hour-to-hour variation was partitioned into random diurnal variation, group-consistent diurnal variation, and subject-specific unique individual variation. Subject-specific diurnal variation contributed greatly and statistically significantly to total diurnal variation for many of the leukocyte cell types--especially in the case of eosinophils, where it represented more than half of total diurnal variation.

Adult

Relationship of day-to-day variation of serum iron concentrations to iron-binding capacity in healthy young women.

Biologic intra-individual variations in concentrations of serum iron and serum iron-binding capacity were determined for nine healthy young women in a double experiment. In each of two series approximately one month in duration, venipunctures were performed three times per week. All serum specimens were assayed for iron concentration and iron-binding capacity. The average intra-subject day-to-day biologic variations for the group in terms of coefficient of variation (CV) were 29.3% for serum iron and 8.8% for iron-binding capacity. No significant difference in variances was found for any subject in serum iron concentrations from series I to series II. Only one subject had a significant positive correlation between iron concentrations and iron-binding capacity values. Percentage iron saturation was computed for each iron and iron-binding capacity combination, and the average intra-subject CV was of the same order of magnitude as the CV for serum iron. The clinical significance of an isolated serum iron result in view of the dramatic intra-subject day-to-day variability is discussed.

Adolescent

Daily variation of lipids and hormones in sera of healthy subjects.

The physiological day-to-day variation of selected hormone and lipid concentration values in sera of healthy subjects was studied. We drew blood specimens from 14 healthy volunteers, aged 22 to 40 years, (8 male and 6 female) at 0800 h on six separate days over a ten day interval. On one occasion all the twelve specimens from each subject (6 days X 2 replicates) were assayed for the hormones: thyroxine and cortisol; and the lipips: cholesterol and triglyceride which were analyzed by enzymatic methods. The assays were performed on one occasion in order to eliminate the batch-to-batch analytical variation which would tend to blur the physiological day-to-day variation. Using an analysis of variance technique, the total variation was separated into the physiological intraindividual day-to-day variation, the biological inter-individual variation, and the within-batch analytical variation. The mean physiological day-to-day variations in terms of percent coefficient of variation were 7.5% for thyroxine, 26.6% for cortisol, 4.8% for cholesterol, , and 25.0% for triglycerides.

Adult

Variation of serum iron concentration in young healthy men: Within-day and day-to-day changes.

1. Serum iron concentration values were determined on a group of 11 healthy young men on blood specimens which were drawn at various hours of the day: 800 h, 1100 h, and 1400 h; on each of four separate days. 2. using a three-way ANOVA (analysis of variance) model, we determined the diurnal variation both for the group as a whole (main hour effect) and for the individual subjects (subject-hour and subject-day-hour interactions). 3. the total combined within-day variation as expressed in coefficients of variation was 12.9% with the peak value seen at 1400 h. 4. on a separate study, blood specimens were obtained at 1100 h on five separate days during a two week period on the same volunteers. 5. using a two-way ANOVA model (subject and day) the day-to-day coefficient of variation was found to be 26.6% for the group. In both cases (within-day and day-to-day) the biological variation was considerably greater than the analytic variation.

Adult

Biologic and analytic components of variation of concentration values of selected serum proteins.

The magnitude and statistical significance of the various biologic and analytic sources of variation of the serum concentration values of seven proteins: albumin, alpha1-antitrypsin, transferrin, orosomucoid, IgG, IgM, and IgA, were evaluated in 12 healthy subjects. Blood specimens were obtained at 0800 h, 1100 h, and 1400 h on one particular day. The analytic error was partitioned into pre-instrumental and instrumental components; the biologic variation was separated into inter-subject variation of mean levels and intra-individual within-day variation. The mean levels of the subjects differed significantly for all seven proteins studied. For the group as a whole there were no consistent diurnal variations of significance. However, for all the proteins, except for IgM, significant individual within-day biologic fluctuations were noted. The within-day biologic variation was smaller than the total analytic variation for transferrin, IgG, orosomucoid, and IgM. When the total analytic variation was separated into pre-instrumental and instrumental components, it was found that the pre-instrumental sources of variation were of a relatively greater magnitude for albumin, IgG, IgA, alpha1-antitrypsin, and IgM.

Adult

Variations of cholesterol and total lipid concentrations in sera of healthy young men. Differentiating analytic error from biologic variability.

Three major sources of variation affecting serum cholesterol and serum total lipid concentration values were studied in a group of healthy men. The first source of variation, analytic error, was separated into pre-instrumental and instrumental components. The pre-instrumental component, which consisted of all uncertainties occurring from the instant of venipuncture to the entrance of the sample into the instrument, was statistically significant for total lipids. The second major source of variation-preparation of the subject-was evaluated for four major stresses: diet, exercise, posture prior to venipuncture, and duration of tourniquet application. Diet affected total lipids, while the specifics of posture and tourniquet application were statistically significant for both serum cholesterol and total lipids. The third source of variation considered was the within-day and the day-to-day changes. Within-day changes were divided into within-hour and hour-to-hour effects. Day-to-day changes occurred over a two-week period. The magnitude and statistical significance of the changes were evaluated using an ANOVA model. The C.V.'s of day-to-day changes for cholesterol and total lipids (biologic) were 5.3% and 10.2%, respectively while the hour-to-hour within-day C.V.'s were 3.8% for cholesterol and 10.4% for serum total lipids. In all cases the biologic variation was in far excess of the analytic variation. The significance of these factors affecting intraindividual variation in healthy subject is discussed.

Adult

Factors contributing to intra-individual variation of serum constituents: Physiological day-to-day variation in concentrations of 10 specific proteins in sera of healthy subjects.

Using an automated immunoprecipitin method, we assayed human sera for 10 proteins: haptoglobin, orosomucoid, transferrin, alpha1 antitrypsin, alpha2-macroglobulin, IgG, IGa, IgM, complement C3, and complement C4. Blood from 14 healthy subjects (25-40y) was sampled on six separate days. From each venipuncture serum was divided into four eliquots; two were assayed on the day of venipuncture and two were frozen and kept until the end of the study, when all of the frozen samples were analyzed in one batch. With this experimental design, batch-to-batch analytical variation could be estimated, and we avoided confounding it with the biological variation. Data analysis was based on the analysis of variance technique. The average physiological intra-individual coefficient of variation ranged from 2.5% for transferrin to 11.1% for orosomucoid. THe interindividual variation ranged from 9.5% for transferrin to 70.5% for haptoglobin and the ratio between intra-individual variation and interindividual variation ranged from 0.66 for IgM to 0.26 for orosomucoid and transferrin.

Adult

The clinical significance of classifications of cirrhosis. A comparison between conventional criteria and numerical taxonomy.

Classification of patients with cirrhosis serves the clinical purpose of selecting patients for adequate therapy. A material of 441 patients from a randomized clinical trial of prednisone treatment were classified according to different criteria, and the effect of this therapy was assessed by comparing the survival curves of controls and treated patients in the groups. Six classifications based on single criteria were studied, viz. females vs. males, alcoholics vs. non-alcoholics, compensated vs. decompensated cases, active vs. inactive cases, manifest vs. latent cases, and non-primary biliary vs. primary biliary cirrhosis. The latter group was too small for further analysis. Furthermore, the material was classified by numerical taxonomy, based on 56 clinical symptoms and signs and histological and serological changes. The taxonomical classification showed interdependence with all the clinical classifications, except that of primary biliary cirrhosis. Three clinical classifications, viz. those based on sex, alcoholism, and compensation, and one taxonomic class showed a significant therapeutic relevance. Combination of these criteria revealed that female patients with compensated non-alcoholic cirrhosis, previously demonstrated to benefit from prednisone treatment, showed a markedly greater prednisone effect if they belonged to the taxonomic group than if they did not. According to clinical, histologic, and laboratory data, the latter group was characterized as less severe cases than the former one. Whereas this discrepancy between clinical severity and therapeutic effect cannot be fully explained, the data do suggest that clinical criteria may not be ideal for selection of patients with cirrhosis for steroid therapy, and that numerical taxonomy may provide clues for more clinically significant classifications.

Alcoholism

Method for monitoring plasma progesterone concentrations in pregnancy.

We present a time-series model for monitoring concentrations in plasma of hormones produced in the placenta, progesterone being chosen as an example. The model, which is based on the assumption that variations in plasma progesterone concentration in pregnant subjects mainly reflect variations in the growth rate of the placenta, was applied to eight series of progesterone values measured during pregnancy in eight subjects. In the model, which was found to fit the data, it is assumed that progesterone concentration is proportional to the size of the placenta and that the growth rate of the placenta varies at random, with a mean value alpha. The variation of alpha was of the same magnitude among and within the subjects. If the average of many subjects alpha values is used, a single subject may be used as her own reference, based on only one previous observation. When two observations are available, an individual's own alpha value may be estimated and used for the prediction. The predictive power of the new method was found to be far superior to the conventional method in which a single sample reference material is used. Furthermore, one need not know the gestational age in order to use the method.

Abortion, Spontaneous

Alcoholic hepatitis superimposed on cirrhosis. Clinical significance and effect of long-term prednisone treatment.

Of 483 patients with biopsy-verified cirrhosis who entered the controlled trial of prednisone treatment conducted by the Copenhagen Study Group for Liver Diseases, 99 had alcoholic hepatitis as defined by morphological criteria in the initial biopsy. The maximum period of observation varied from 5 to 12 years. The survival of prednisone-treated patients (median survival time 38 months) and placebo-treated patients (median survival time 34 months) with alcoholic hepatitis did not differ significantly. This was also true for each of the two subgroups comprising mild and severe cases respectively. The presence of morphologically defined alcoholic hepatitis was postively correlated with the daily consumption of alcohol but poorly correlated with the clinical syndrome usually attributed to alcoholic hepatitis.

Adult

Correlation of selected serum constitutents: 2. Consistency of intra-individual correlation values, means, and variances during four months.

We examined whether inter-individual differences in correlation coefficients previously found among subjects truly reflect consistent inter-individual differences or are time-related within an individual. The consitutents studied in this investigation were (a) the enzmes aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase; and (b) the non=protein nitrogen-containing constituents urea, uric acid, and creatinine. Ten healthy women were each subjected to 15 venipunctures over a five-week period (Series I), and, after a two-month interval, were again subjected to 15 venipunctures over a second five-week period (Series II). Before statistical analysis, the data were corrected for the batch-to-batch (day-to-day) arnalytical variation. There was a signiificant (P less than .05) change in the covariance structure (variances or correlation coefficients, or both) between the two series in four of the 10 subjects for the combination of enzymes, and in three other subjects for the combination of nonprotein nitrogen constitutents. Although we found a significant (P lees than .05) average intra-individual variation in the mean values from series to series in the cases of the three enzymes and urea, the magnitude of the inter-series variation in means was relatively small. CV's were: alkaline phosphatase, 3.4%; lactate dehydrogenase, 2.3+; aspartate aminotransferase, 3.3%; urea, 5.0%; uric acid, 1.0%; and creatinine, 1.2%.

Adult

The effects of time of venipuncture on variation of serum constituents. Consideration of within-day and day-to-day changes in a group of healthy young men.

Within-day and the day-to-day variations of serum constituents were evaluated in 11 healthy young men. Eighteen constituents, including electrolytes, metabolites, proteins, and enzymes, were assayed using the AutoChemist MultiChannel Analytic System. Venipunctures were performed at three hours of the day, 8 A.M., 11 A.M., and 2 P.M., on five separate experimental days. A three-factor analysis of variance model was employed to separate analytic variation from biological sources of variation. Statistically significant (p less than .05) group diurnal patterns (main effect of hour) during the six-hour period were found for serum lipids, iron, urea, albumin, total protein, and chloride. A unique individual diurnal pattern (subject-hour interaction) was statistically significant for serum potassium. Statistically significant main effect of month (main effect of day) for the group of subjects was seen for total lipids and potassium; however, the subject-day interaction term, which is an index of the day-to-day variation for the subjects, was significant (p less than .05) for all of the constituents except for sodium ion. The comparison of the variation expected within-day versus the variation seen day-to-day over four months was made by pooling the sources of within-day variation (main effect of hour + subject-hour interaction + subject-day-hour interaction) and by pooling the day-to-day variation terms (main effect of day + subject-month interaction). For serum cholesterol, potassium, acid phosphatase, and phosphate ion, the within-day variation was greater than the day-to-day variation occurring over four months, while the other constituents showed day-to-day variations of a greater magnitude than that experienced during the six-hour period.

Acid Phosphatase