PubMed Health⌕ Search

Biomedical subjects

J L Pirkle

Publications and source records attributed to J L Pirkle.

At least 37 records · Page 2Linked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1989

Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam Veterans of Operation Ranch Hand.

The half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD; commonly known as dioxin) in serum has been measured in 36 Air Force Vietnam veterans of Operation Ranch Hand, which was the operation that aerially sprayed the herbicide Agent Orange in Vietnam. From serum specimens taken in 1982 and 1987, the median half-life of 2,3,7,8-TCDD in these Ranch Hand veterans was found to be 7.1 yr (95% confidence interval about the median of 5.8-9.6 yr). These veterans reported no civilian exposure to dioxin or herbicides. Concentrations of 2,3,7,8-TCDD in the 1982 serum specimens from these veterans ranged from 16.9 to 423 parts per trillion on a lipid weight basis. The half-life estimates were not associated with the concentration of 2,3,7,8-TCDD in the 1982 serum specimens. This half-life of 7.1 yr is much longer than the half-life of 2,3,7,8-TCDD reported in animals but is consistent with recent evidence from other human exposures to 2,3,7,8-TCDD.

Adult↗
PubMed1986

2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in adipose tissue of exposed and control persons in Missouri. An interim report.

The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin, was measured in the adipose tissue of 39 persons with a history of residential, recreational, or occupational exposure in Missouri and in 57 persons in a control group. All participants had detectable levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in their adipose tissue, but the exposed group had significantly higher levels. Levels of six of the exposed persons were more than five times greater than the level of the highest control. Measuring 2,3,7,8-tetrachlorodibenzo-p-dioxin in adipose tissue provides a much improved index of exposure, an important advance for research studies evaluating the possible health effects of this compound.

Adipose Tissue↗
PubMed1985

The relationship between blood lead levels and blood pressure and its cardiovascular risk implications.

The relationship between blood pressure and blood lead levels in the second National Health and Nutrition Examination Survey (1976-1980) has been examined for white males aged 40-59 years. After adjustment for age, body mass index, nutritional factors, and blood biochemistries in a multiple linear regression model, the relationship of systolic and diastolic blood pressures to blood lead levels was statistically significant (p less than 0.01). There was no evidence of a threshold blood lead level for this relationship. Although these data alone do not prove a casual relationship between low blood lead levels and blood pressure, the findings are consistent with current epidemiologic and animal studies, indicating that a causal relationship is probable. To examine the potential health risks, the multiple logistic risk factor coefficients from the Pooling Project and Framingham studies were used to predict the impact of the 37% decrease in mean blood lead levels which occurred in adult white males from 1976 to 1980. As a result of this blood lead decrease, the calculations predicted a 4.7% decrease in the incidence of fatal and nonfatal myocardial infarction over 10 years, a 6.7% decrease in the incidence of fatal and nonfatal strokes over 10 years, and a 5.5% decrease in the incidence of death from all causes over 11.5 years. In addition, as a result of this blood lead decrease, the predicted number of white males in this age group with hypertension (diastolic blood pressure greater than or equal to 90 mmHg) decreased by 17.5%.

Adult↗
PubMed1983

Chronological trend in blood lead levels between 1976 and 1980.

Analysis of a chronological trend in data from the second National Health and Nutrition Examination Survey indicated that average blood lead levels in the United States dropped approximately 37 per cent (5.4 micrograms per deciliter) from February 1976 through February 1980. There was no evidence that this trend was due to errors in laboratory measurement or to the design of the survey. The trend was present even after accounting for differences in race, sex, age, region of the country, season, income, and degree of urbanization. Changes in exposure to lead in paint or in the diet are unlikely explanations of the trend. However, the correlation of blood lead levels with the lead level in gasoline was highly significant (P less than 0.001) overall and in population subgroups defined by race, sex, and age. Although strong correlation does not prove cause and effect, the most likely explanation for the fall in blood lead levels is a reduction in the lead content of gasoline during this period.

Adolescent↗
PubMed1979

Pulse nuclear magnetic resonance measurements of water exchange across the erythrocyte membrane employing a low Mn concentration.

A simple, precise, and rapid pulse nuclear magnetic resonance technique for measuring the rate of water exchange across the erythrocyte membrane is presented. The technique is based upon the nonlinear fit of Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation time data of blood doped with 1.7 mM MnCl2 to the general two-compartment exchange condition. Previous approaches using CPMG data required high MnCl2 concentrations (25-53 nM), shown in this work to induce systematic errors ranging from 35 to 45%. At 23 degrees C the average residence time of a water molecule inside the erythrocyte (tau a) is 21.0 +/- 0.6 ms (SE). The Arrhenius plot for water exchange is linear over the range of 3 degrees - 37 degrees C and th Arrhenius activation energy is 4.79 +/- 0.03 kcal (SE). This value does not differ significantly from the energy required for bulk water flow. Results are compared with previous determinations, and sources of systematic error in tau a and the activation energy are evaluated.

Body Water↗
PubMed1976

The disposition and pharmacokinetics in humans of 5-azacytidine administered intravenously as a bolus or by continuous infusion.

The disposition of 5-[4-14C]azacytidine, administered i.v. as a bolus or continuous infusion, was studied in cancer patients. After bolus, plasma 14C levels exhibited as multiphasic disappearance pattern; half-life (t1/2, beta phase) = 3.4 to 6.2 hr. Of 14C in plasma, less than 2% was associated with 5-[4-14C]azacytidine 30 min after dose. The ratios of 14C levels were: red cells/plasma, approximately 0.8; leukocytes/plasma, 1.1 to 2.3; nucleic acids/leukocytes, 0.2 to 0.43; sputum/plasma, 0.05 to 0.17. Urinary excretion (3 days) accounted for 73 to 98% of 14C, LEss than 1% in feces. The relative concentration of 5-azacytidine in plasma with continuous infusion stayed higher than with bolus; urinary excretion was similar. Fewer side effects were observed with continuous infusion than with bolus. The stability of 5-azacytidine was determined in various media at several temperatures by thin layer chromatography and nuclear magnetic resonance. At 20 degrees in Ringer's lactate (pH 6.2), the t1/2 was 94 to 100 hr. Stability increased with lowering of temperature and pH. From our data we conclude that 5-azacytidine should be given by continuous infusion rather than as a bolus.

Azacitidine↗
PubMedDate not supplied

Chlorinated hydrocarbon levels in human serum: effects of fasting and feeding.

Twenty healthy adult humans had serum samples drawn on four occasions within a 24-hr period: after a 12 hr overnight fast, 4-5 hr after a high fat breakfast, at midafternoon, and the next morning after another 12 hr fast. Nonfasting samples had 22% to 29% higher mean concentrations (p less than 0.05) than did fasting samples for polychlorinated biphenyls (PCBs, 4.81 vs 3.74 ng/g serum wt), hexachlorobenzene (HCB, 0.163 vs 0.134 ng/g serum wt), and p,p'-dichlorodiphenyl-dichloroethylene (p,p'-DDE, 6.74 vs 5.37 ng/g serum wt) measured by electron capture gas liquid chromatography. Total serum lipids were estimated from measurements of total cholesterol, free cholesterol, triglycerides, and phospholipids and were 20% higher in nonfasting samples than in fasting samples (7.05 g/L vs 5.86 g/L). When PCBs, HCB, and p,p'-DDE concentrations were corrected by total serum lipids, results from fasting and non-fasting samples were not statistically different. Because of the differences in these chlorinated hydrocarbon concentrations observed with different sample collection regimens, meaningful comparison of analytical results requires standardizing collection procedures or correcting by total serum lipid levels.

Adult↗
PubMedDate not supplied

Reference range concentrations of N-acetyl-S-(2-hydroxyethyl)-L-cysteine, a common metabolite of several volatile organic compounds, in the urine of adults in the United States.

N-acetyl-S-(2-hydroxyethyl)-L-cysteine (2-hydroxyethyl mercapturic acid, HEMA) is a urinary metabolite of several hazardous chemicals, including vinyl chloride (VC), ethylene oxide (EO), and ethylene dibromide (EDB). Information about the levels of HEMA in the general population is useful for assessing human exposures to HEMA parent compounds, including VC, EO, and EDB. To establish reference range concentrations for HEMA, we analyzed urine samples from 412 adult participants in the Third National Health and Nutrition Examination Survey (NHANES II) by using isotope-dilution high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). HEMA was detected in 71% of the samples examined. Creatinine-corrected concentrations ranged from less than 0.68 microg/g creatinine to 58.7 microg/g creatinine; the 95th percentile concentration was 11.2 microg/g creatinine; and the geometric mean and median creatinine-corrected concentrations were both 1.6 microg/g creatinine. We observed a statistically significant difference (P=0.0001) in the creatinine-corrected geometric mean concentration values of HEMA between smokers (2.8 microg/g creatinine) and nonsmokers (1.1 microg/g creatinine). The high levels of HEMA seen among smokers likely originated from HEMA-producing chemicals known to be present in tobacco smoke.

Acetylcysteine↗
PubMedDate not supplied

p-Dichlorobenzene exposure among 1,000 adults in the United States.

p-Dichlorobenzene is used widely in the United States as a room deodorizer, a moth repellent, and a precursor for a polymer. In a previous study of selected children in Arkansas, we found that 96% of the children had detectable urinary concentrations of 2,5-dichlorophenol, the metabolite of p-dichlorobenzene. In the current study, we found that, in a sample of 1,000 adults who lived throughout the United States, 98% had detectable levels of 2,5-dichlorophenol in their urine, and 96% had detectable levels of p-dichlorobenzene in their blood. Urinary 2,5-dichlorophenol concentrations ranged up to 8,700 micrograms/l (median and mean concentrations of 30 micrograms/l and 200 micrograms/l, respectively). p-Dichlorobenzene blood concentrations ranged up to 49 micrograms/l, with median and mean concentrations of 0.33 micrograms/l and 2.1 micrograms/l, respectively. The Pearson correlation coefficient for 2,5-dichlorophenol in urine and p-dichlorobenzene in blood was .82 (p < .0001), thus demonstrating a strong association between these exposure measurements. Neither age nor gender was related to urinary 2,5-dichlorophenol or blood p-dichlorobenzene concentrations (p > .40). When these results are viewed with data from other studies, the collective data show that p-dichlorobenzene is a common, worldwide contaminant. The high prevalence of exposure to p-dichlorobenzene, coupled with its potential for adverse health effects, indicate the need for more detailed studies, including studies of long-term health effects on exposed populations.

Adult↗
PubMedDate not supplied

Comparison of serum and salivary cotinine measurements by a sensitive high-performance liquid chromatography-tandem mass spectrometry method as an indicator of exposure to tobacco smoke among smokers and nonsmokers.

Exposure to tobacco smoke, both from active smoking and from passive exposure to environmental tobacco smoke, can be monitored by measuring cotinine, a metabolite of nicotine, in a variety of biological sources including blood, urine, and saliva. Previously, a sensitive atmospheric-pressure ionization, tandem mass spectrometric (LC-API-MS-MS) method for cotinine measurements in serum was developed in support of a large, recurrent national epidemiologic investigation. The current study examined the application of this LC-API-MS-MS method to both serum and saliva cotinine measurements in a group of 200 healthy adults, including both smokers and nonsmokers. The primary objective of this study was to evaluate the relationship between serum and saliva cotinine concentrations to facilitate the linking of results from epidemiologic studies using salivary cotinine measurements to existing national data based on serum cotinine analyses. The results indicate that a simple, linear relationship can be developed to describe serum and saliva cotinine concentrations in an individual, and the expression describing this relationship can be used to estimate with reasonable accuracy (approximately +/- 10%) the serum cotinine concentration in an individual given his or her salivary cotinine result. It was further confirmed that saliva cotinine samples are generally quite stable during storage after collection, even at ambient temperatures, and this sample matrix appears to be well-suited to the requirements of many epidemiologic investigations.

Adolescent↗
PubMedDate not supplied

Evaluation of four maternal smoking questions.

OBJECTIVE: The authors evaluated four questions about maternal smoking during pregnancy for use on birth certificates. METHODS: Question 1 (yes/no format) and Question 2 (trimester-specific design) were tested among 1171 women who delivered at two Kaiser Permanente medical centers in northern California. Responses to Questions 1 and 2 were compared with smoking information provided by participants in telephone interviews conducted during pregnancy. Question 3 (multiple choice format) and Question 4 (month- and grouped month-specific design) were tested among 900 women who enrolled in a statewide prenatal screening program and who delivered in 20 hospitals in four Central Valley counties. Responses to Questions 3 and 4 were compared with mid-pregnancy serum cotinine levels. The authors evaluated the four questions in terms of conciseness, response rate, data accuracy, and type of data requested. RESULTS: Questions 1 and 2 were the most concise. Response rates could not be calculated for Questions 1 and 2. Response rates were 86.0% for Question 3 and 74.2% for Question 4. Sensitivity was 47.3% for Question 1, 62.1% for Question 2, 83.8% for Question 3, and 86.7% for Question 4. The types of data requested by Questions 2 and 4 seem to best satisfy the needs of the broad audience of birth certificate users. CONCLUSIONS: No single question was clearly superior. The authors propose a combination of Questions 2 and 4, which asks about average number of cigarettes smoked per day in the three months before pregnancy and in each trimester of pregnancy.

Birth Certificates↗
PubMedDate not supplied

Effects of measurement error on estimating biological half-life.

Direct computation of the observed biological half-life of a toxic compound in a person can lead to an undefined estimate when subsequent concentration measurements are greater than or equal to previous measurements. The likelihood of such an occurrence depends upon the length of time between measurements and the variance (intra-subject biological and inter-sample analytical) associated with the measurements. If the compound is lipophilic the subject's percentage of body fat at the times of measurement can also affect this likelihood. We present formulas for computing a model-predicted half-life estimate and its variance; and we derive expressions for the effect of sample size, measurement error, time between measurements, and any relevant covariates on the variability in model-predicted half-life estimates. We also use statistical modeling to estimate the probability of obtaining an undefined half-life estimate and to compute the expected number of undefined half-life estimates for a sample from a study population. Finally, we illustrate our methods using data from a study of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure among 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam.

Environmental Exposure↗
PubMedDate not supplied

Indices of TCDD exposure and TCDD body burden in veterans of Operation Ranch Hand.

Using responses from a questionnaire detailing herbicide exposure during service in Vietnam and information on job classifications, we investigated the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) body burden and self-reported exposure in enlisted members of Operation Ranch Hand, the United States Air Force herbicide spraying mission in Vietnam. We constructed three TCDD exposure indices from the questionnaire data: the number of days of skin exposure (DAYS), the percentage of skin area exposed (PCNT), and a combined index (SRI) which was the product of these and the concentration of TCDD in the herbicide. A fourth index (AFI) based on gallons of herbicide sprayed and the number of men on the job was also studied. The regression model most predictive of TCDD levels (R2 = 0.61) included job classification (divided into four categories), the number of days of skin exposure, percent body fat during the tour of duty, and relative change in body fat. A model with job classification alone had an R2 of 0.60. The four exposure indices were constructed to further explain TCDD exposure in the job classifications with the highest potential for exposure: Ranch Hand flight engineers and ground crew. In these two groups, days of skin exposure was the index most significantly associated with TCDD levels. Overall, the best index of exposure was the number of days of skin exposure to herbicide.

Adipose Tissue↗