Adequacy of NCEP recommendations for total cholesterol, triglycerides, HDLC, and LDLC measurements.
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Cholesterol↗
Biomedical subjects
S P Caudill
Publications and source records attributed to S P Caudill.
Assessment of current National Cholesterol Education Program guidelines for total cholesterol triglyceride, HDL-cholesterol, and LDL-cholesterol measurements.
We examine the effect of systematic bias and random error, quality control, and intraperson biological variation on the National Cholesterol Education Program (NCEP) clinical classifications for reported lipid measurements. We consider misclassification to occur if a true lipid homeostatic set point is within a desirable range but the reported lipid value is in a high-risk range, or if a true lipid homeostatic set point is in a high-risk range but the reported lipid value is in a desirable range. To evaluate the overall adequacy of the NCEP guidelines to ensure correct patient classification, we construct operating characteristic curves for total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We demonstrate that if laboratories are meeting the NCEP guidelines for inherent bias and analytic precision and are using standard quality-control (QC) procedures incorporating at least two QC samples per analytical run from each of two QC pools (for a total of 4 QC samples), the current NCEP guidelines are adequate to ensure (probability >0.90) correct patient classifications regardless of the size of the systematic bias of the laboratory or increased random analytic error. Thus we suggest that at least two concentrations of QC material be included in the QC scheme to ensure that the measurement system is operating within desired specifications across the entire range of desirable and high-risk lipid concentrations and to ensure with high probability that patients are correctly classified.
Chemistry, Clinical↗
Pharmacokinetics of TCDD in veterans of Operation Ranch Hand: 10-year follow-up.
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Follow-Up Studies↗
Pharmacokinetics of TCDD in veterans of Operation Ranch Hand: 10-year follow-up.
Using multiple measurements from serum collected over 10 yr (1982, 1987, and 1992), we estimated the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in 213 veterans of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam. The potential influences of age, percent body fat, and changes in percent body fat on the half-life estimate were also examined. The mean decay rate of TCDD for these veterans is 0.0797 per year with 95% confidence interval 0.0727 to 0.0868 per year; the corresponding half-life estimate is 8.7 yr with 95% confidence interval 8.0-9.5 yr. Half-life increased significantly with increasing body fat, but not with age or relative changes in percent body fat.
Adipose Tissue↗
Results of an international round robin for serum and whole-blood folate.
Because of the increasing significance of folate nutriture to public health, a "round robin" interlaboratory comparison study was conducted to assess differences among methods. Twenty research laboratories participated in a 3-day analysis of six serum and six whole-blood pools. Overall means, SDs, and CVs derived from these results were compared within and across method types. Results reported for serum and whole-blood folate demonstrated overall CVs of 27.6% and 35.7%, respectively, across pools and two- to ninefold differences in concentrations between methods, with the greatest variation occurring at critical low folate concentrations. Although results for serum pools were less variable than those for whole-blood pools, substantial intermethod variation still occurred. The overall results underscore the urgent need for developing and validating reference methods for serum and whole-blood folate and for properly characterized reference materials. For evaluating study or clinical data, method-specific reference ranges (established with clinical confirmation of values for truly folate-deficient individuals) must be used.
Adult↗
Risk assessments of low-level exposures.
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Animals↗
An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension.
In an in-depth examination to better define the renal effects of mild hypertension, we used urinary proteins to indicate damage to the glomerulus (albumin), tubular reabsorption capability (retinol-binding protein), and turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) in a group of 18 people with mild hypertension not associated with diabetes and a control group (n = 12). The participants' activity was controlled on a high normal salt diet for 3 days followed by a low salt diet for 4 days. Two distinct patterns of albumin excretion were evident in the hypertensive group: 22% had elevated, highly variable excretion patterns, and the rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or 16 mg/L, with the lowest within-person biological variability given by albumin calculated as a ratio to creatinine. Albumin and NAG excretion primarily correlated with systolic blood pressure and the best correlations were given by ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8 mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg), diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group with mild hypertension. However, albumin excretion did not decrease when dietary salt content was lowered. The group with hypertension also had higher urinary excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in the group had a higher excretion of retinol-binding protein than did whites in the control group (P < .02). Retinol-binding protein values, however, were within the normal range, indicating that the elevated albumin values were the result of changes in selectivity of the glomerulus.
Acetylglucosaminidase↗
Determination of polychlorinated biphenyl levels in the serum of residents and in the homogenates of seafood from the New Bedford, Massachusetts, area: a comparison of exposure sources through pattern recognition techniques.
We measured the residues of polychlorinated biphenyls (PCBs) in the serum of 23 residents of the New Bedford, Massachusetts, area and from two homogenates each of bluefish and lobsters from the same area. We used congener-specific and total Aroclor quantitative approaches, both of which involved gas chromatography with electron capture detection. Using gas chromatography mass spectrometry (electron ionization mode), we confirmed the presence of PCBs in the combined serum samples and in the aliquots of bluefish and lobsters. In measuring the PCB levels in serum, we found good agreement between the two electron capture detector approaches (r > or = 0.97) when the serum of specific congeners was compared to total Aroclor. We used univariate and multivariate quality control approaches to monitor these analyses. Analytical results for bluefish showed a better agreement between the two techniques than did those for lobsters; however, the small number of samples precluded any statistical comparison. We also measured levels of chlorinated pesticides in the serum samples of two groups of New Bedford residents, those with low PCB levels (< 15 ng/ml) and those with high PCB levels (> or = 15 ng/ml). We found that residents with high PCB levels also tended to have higher levels of hexachlorobenzene (HCB) and 1,1-dichloro-2,2-di-(p-chlorophenyl) ethylene (p,p'-DDE). The higher concentration of all three analytes appears to be influenced by employment in the capacitor industry, by seafood consumption, or both. Using Jaccard measures of similarity and principal component analysis we compared the gas chromatographic patterns of PCBs found in the serum of New Bedford area residents with high serum PCBs with the patterns found in homogenates of lobsters (inclusive of all edible portions except the roe), in homogenates of bluefish fillets taken from local waters, and in serum from goats fed selected technical Aroclors (e.g. Aroclors 1016, 1242, 1254, or 1260). The patterns found in human serum samples were similar to the patterns found in lobster homogenates. Both of these patterns closely resembled patterns found in the serum samples of the goat fed aroclor 1254, as demonstrated by both pattern recognition techniques. In addition, the chromatographic patterns of human serum and of lobsters and bluefish homogenates all indicated the presence of PCBs more characteristic of Aroclors 1016 or 1242.
Analysis of Variance↗
Determinants of TCDD half-life in veterans of operation ranch hand.
The half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) changed significantly with body fat and age in 337 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam. Using paired TCDD measurements derived from serum collected in 1982 and in 1987, we investigated how TCDD half-life varied with percent body fat (PBF), relative changes in PBF, and age. We found that half-life increased significantly with increasing PBF and decreased significantly with increasing relative change in PBF and with age. The median observed half-life of TCDD for these 337 veterans is 11.3 yr with a nonparametric 95% confidence interval of 10.0-14.1 yr.
Adipose Tissue↗
Retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection.
We describe the use of HPLC with multiwavelength detection to measure retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, beta-carotene, and the linoleate, oleate, palmitate, and stearate esters of retinol in a single 200-microL serum sample. The method is sensitive enough to detect individual retinyl esters in fasting serum from a nonhyperlipidemic population and requires only 12 min for each sample. Serum concentration ranges and means are reported for retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and the sum of the retinyl esters from serum analyses of 3480 participants from several different studies.
Carotenoids↗
Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico.
Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound.
Drug Contamination↗
Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome.
In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L-tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan. We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)
Bacillus↗
Exploratory data analysis in two-dimensional electrophoresis.
The use of computerized matching of proteins in the analysis of multiple two-dimensional electrophoresis (2DE) gels creates volumes of data that are readily accessible for exploratory analysis. When these data are used in health-effects studies or in studies to identify factors associated with particular diseases, hundreds or even thousands of hypotheses can be tested. Interpreting so many hypothesis tests requires some preliminary statistical evaluations of the data. In addition, prior to the preliminary statistical evaluations and subsequent hypothesis tests, accurate protein quantification and correct protein matching must be verified. In this report we present an approach used at the Centers for Disease Control to address these issues. This approach consists of a randomized experimental design incorporating replicate gels for each specimen, gel image analysis, protein matching, editing, Boolean unions of all gels to obtain correspondences and contradictions of match identification numbers, resolution of correspondences and contradictions, statistical tests to identify outliers, and finally an assessment of statistical and practical significance to focus attention on the proteins most likely to be associated with the effects under study. We illustrate our approach with data from an exploratory exposure-response study.
Blood Protein Electrophoresis↗
Quantitative two-dimensional electrophoretic detection of possible urinary protein biomarkers of occupational exposure to cadmium.
To search for new urinary protein biomarkers of cadmium toxicity, we used quantitative two-dimensional electrophoresis (2DE) and analysed urine samples from 18 male cadmium recovery plant employees whose mean age was 47 +/- 15.6 years (+/- 1 SD) and whose urine cadmium levels ranged from 0.14 microgram l-1 to 20.4 micrograms l-1 (0.06-37.1 micrograms g-1 creatinine). Image analysis of the silver-stained gels yielded intensity (concentration) values for a mean number, per person, of 825 +/- 184 urinary proteins (spots) and found 596 +/- 218 matched proteins (the same proteins in two or more gels) per person. Total urinary protein and the sum of all spot intensities were positively correlated (P = 0.0447 and P = 0.0616, respectively) with urinary cadmium (UCD), as measured by atomic absorption spectroscopy. The combined sum of the intensities of all acidic proteins with a relative molecular weight (M(r)) below 40 kDa was correlated with UCD (P = 0.0461), revealing a low M(r), acidic proteinuria as UCD increased. Multiple hypothesis testing by regression analysis of the intensities of matched proteins with UCD revealed 14 unidentified proteins that were considered candidates for biomarkers of cadmium exposure. The best two candidate proteins--those having M(r)s of less than 13.9 kDa and relative glyceraldehyde-3-phosphate dehydrogenase (G3PDHr) coordinates of -19.7 and -27.2--were excellently resolved in the 2DE gels, and their intensities increased by 323% and 857%, respectively, over the UCD range that was tested. Two other proteins with M(r)s of 23.9 kDa and 29.2 kDa and with acidic net charges were not as well resolved. Six very acidic proteins, with M(r)s ranging from 88.8 to 90.7 kDa and with intensities highly correlated with UCD, appeared to be related and were resolved as a 'charge train' (a group of related proteins, or isoforms, differing only by small changes in net charge). Four proteins appeared to increase only when the UCD concentration was above a threshold of 16 micrograms l-1.
Adult↗
Performance characteristics of a composite multivariate quality control system.
We present the results of an evaluation of the performance characteristics of a composite multivariate quality control (CMQC) system that incorporates quality control rules for univariate, multivariate, and correlation conditions. The CMQC system evaluated is designed to help analysts detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure of any pair of variables. It is also designed to be tolerant of missing data, to allow analysts to reject as few as one or as many as all variables in a run, and to provide analysts with control statistics and graphics that logically relate to sources of analytical error. We show that the various components of the CMQC system have adequate statistical power to detect systematic errors, random errors, and correlation changes under the conditions likely to be encountered with multivariate analytical measurement systems: (1) a single variable with increased systematic or random error; (2) all variables or a subgroup of variables affected by a common problem that increases systematic or random error; and (3) missing data for one or more variables in a run. We also show that the power of the multivariate component of the CMQC system to detect systematic and random errors is higher than the power of an alternative multivariate test criterion.
Chemistry Techniques, Analytical↗
Assessing the direction of causality in cross-sectional studies.
Interpretation of observational studies is difficult, particularly in cross-sectional studies, because the direction of cause and effect may be difficult to assess: Did the "outcome" affect the measured exposure level, or did the exposure affect the outcome? In this paper, the authors describe a pattern, the "checkmark pattern," which can arise in cross-sectional studies. This pattern is characterized by higher levels of the outcome in an unexposed comparison group than in some subgroups of the exposed. The pattern, if seen in certain types of observational studies, suggests that the "outcome" variable may have affected the measured exposure level. Recognition of the pattern may help the epidemiologist to decipher the causal sequence. Two examples illustrate the issues involved.
Adipose Tissue↗
Investigation of TCDD half-life heterogeneity in veterans of Operation Ranch Hand.
The half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the contaminant of Agent Orange, has been recently estimated in 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam, as 7.1 yr with a 95% [corrected] confidence interval of 5.8-9.6 yr. We investigated the variability of TCDD half-life with percent body fat in these 36 Ranch Hand veterans who have two TCDD assay results from serum drawn in 1982 and 1987. Using a repeated measures linear model, we found a marginally significant change in half-life with percentage of body fat (p = .09) and no statistically significant change in half-life with relative changes in percentage of body fat from 1982 to 1987 (p = .60).
Body Composition↗
Composite multivariate quality control using a system of univariate, bivariate, and multivariate quality control rules.
We propose a composite multivariate quality control (CMQC) system to control simultaneously measured variables. This system is designed to detect unacceptable trends and systematic error in one or more variables, unacceptable random error in one or more variables, and unacceptable changes in the correlation structure in any pair of variables. It is also designed to be tolerant of missing data, to be capable of rejecting as few as one or as many as all variables in a run, and to provide the analyst with control statistics and graphics that logically relate to sources of analytical error. Quality control rules for univariate, multivariate, and correlation conditions are incorporated in the system, as are plots displaying CMQC statistic values and control limits for univariate, multivariate, and correlation parameters. We also discuss advantages of the CMQC over the T2 and principal component multivariate quality control methods. We demonstrate the CMQC procedure using data from a laboratory process in which 40 variables were measured during 40 characterization runs and 23 runs analyzing unknowns.
Chemistry Techniques, Analytical↗