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Biomedical subjects

S P Caudill

Publications and source records attributed to S P Caudill.

At least 19 recordsLinked to original sources

Prevalence of C282Y and H63D mutations in the hemochromatosis (HFE) gene in the United States.

CONTEXT: Population-based estimates of the prevalence of disease-associated mutations, such as hemochromatosis (HFE) gene mutations, are needed to determine the usefulness of genetic screening. OBJECTIVE: To estimate the prevalence of the HFE mutations C282Y and H63D in the US population. DESIGN: Cross-sectional population-based study of samples in the DNA bank from phase 2 of the Third National Health and Nutrition Examination Survey conducted from 1992 to 1994. SETTING AND PARTICIPANTS: Genotyped samples of cells from a total of 5171 participants, cross-classified by sex, age, and race/ethnicity in the analysis. MAIN OUTCOME MEASURES: Estimates of the prevalence of C282Y and H63D mutations. RESULTS: The prevalence of C282Y homozygosity is estimated to be 0.26% (95% confidence interval [CI], 0.12%-0.49%); 1.89% (95% CI, 1.48%-2.43%) for H63D homozygosity; and 1.97% (95% CI, 1.54%-2.49%) for compound heterozygosity. The prevalence estimates for C282Y heterozygosity (C282Y/wild type) are 9.54% among non-Hispanic whites, 2.33% among non-Hispanic blacks, and 2.75% among Mexican-Americans. The prevalence estimates of the C282Y mutation in the US population are 5.4% (95% CI, 4.7%-6.2%) and 13.5% (95% CI, 12.5%-14.8%) for the H63D mutation. CONCLUSIONS: Estimates of prevalence of HFE mutations are within the expected range for non-Hispanic whites and blacks but the estimated prevalence of the C282Y mutation among Mexican-Americans is less than expected. Mutation data now need to be linked to clinically relevant indices, such as transferrin saturation level.

Genotype↗

Exposure of the U.S. population aged 6 years and older to cadmium: 1988-1994.

Cadmium was measured in urine specimens from 22,162 participants in the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994). Urine cadmium, expressed either as uncorrected (microg/L) or creatinine corrected (microg/g creatinine) increased with age and with smoking. The arithmetic mean value for urine cadmium in the U.S. population was 0.57 microg/L or 0.48 microg/g creatinine. Based on our estimates, about 2.3% of the U.S. population have urine cadmium concentrations greater than 2 microg/g creatinine, and 0.2% have concentrations greater than 5 microg/g creatinine, the current World Health Organization health-based exposure limit.

Adolescent↗

Analysis of factors influencing the comparison of homocysteine values between the Third National Health and Nutrition Examination Survey (NHANES) and NHANES 1999+.

Two important changes occurred in the time between the Third National Health and Nutrition Examination Survey (NHANES III) (1991-1994) and the later survey (NHANES 1999+) regarding total homocysteine (tHcy), i.e., a change in matrix from serum to plasma and a change in analytical methods. The goals of this study were to determine the magnitude of potential differences between plasma and serum with regard to tHcy concentrations, and between the two analytical methods used in these surveys. Optimally prepared plasma, serum allowed to clot for 30 and 60 min at room temperature and serum allowed to clot for 30 and 60 min and subjected to four freeze-thaw cycles, prepared from blood samples collected from 30 healthy people, were analyzed by both methods. Serum samples had significantly higher tHcy concentrations than plasma samples, and the difference increased with longer clotting time. Freeze-thaw cycles had little or no effect on the variability or bias in the serum sample results. The tHcy results produced by the two analytical methods were significantly different, but consistent across sample types. On average, the results of the method used in NHANES III were lower by 0.64 micromol/L; however, the relative bias varied with tHcy concentration. The tHcy results determined in surplus serum from NHANES III overestimated tHcy concentrations by approximately 10% compared with optimally prepared plasma. The average method bias was 6% between the two analytical methods. On the basis of changes in matrix and methodology, direct comparison of tHcy results between the two surveys is inappropriate.

Adult↗

Levels of methyleugenol in a subset of adults in the general U.S. population as determined by high resolution mass spectrometry.

We developed a sensitive and accurate analytical method for quantifying methyleugenol (ME) in human serum. Our method uses a simple solid-phase extraction followed by a highly specific analysis using isotope dilution gas chromatography-high resolution mass spectrometry. Our method is very accurate; its limit of detection is 3.1 pg/g and its average coefficient of variation is 14% over a 200-pg/g range. We applied this method to measure serum ME concentrations in adults in the general U.S. population. ME was detected in 98% of our samples, with a mean ME concentration of 24 pg/g (range < 3.1-390 pg/g). Lipid adjustment of the data did not alter the distribution. Bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race/ethnicity and sex/fasting status with serum ME concentrations. Although no demographic variable was a good predictor of ME exposure or dose, our data indicate prevalent exposure of U.S. adults to ME. Detailed pharmacokinetic studies are required to determine the relationship between ME intake and human serum ME concentrations.

Adolescent↗

Levels of seven urinary phthalate metabolites in a human reference population.

Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a reference population of 289 adult humans. This analytical approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compounds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3,750 ppb, 2,610 microg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 microg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 microg/g creatinine), reflecting exposure to diethyl phthalate, dibutyl phthalate, and benzyl butyl phthalate. Women of reproductive age (20-40 years) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. Our findings strongly suggest that health-risk assessments for phthalate exposure in humans should include diethyl, dibutyl, and benzyl butyl phthalates.

Adult↗

Uranium and thorium in urine of United States residents: reference range concentrations.

We measured uranium and thorium in urine of 500 U. S. residents to establish reference range concentrations using a magnetic-sector inductively coupled argon plasma mass spectrometer (ICP-MS). We found uranium at detectable concentrations in 96.6% of the urine specimens and thorium in 39.6% of the specimens. The 95th percentile concenetration for uranium was 34.5 ng/L (parts per trillion); concentrations ranged up to 4080 ng/L. Thorium had a 95th percentile concentration of 3.09 ng/L; concentrations ranged up to 7.7 ng/L.

Body Burden↗

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.

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↗

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↗