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Biomedical subjects

D G Patterson

Publications and source records attributed to D G Patterson.

At least 37 records · Page 2Linked to original sources

Selectivity of electron-donor- and electron-acceptor-bonded silica packing materials for hydrophobic environmental contaminants in polar and non-polar eluents.

Electron-acceptor-bonded stationary phases, 2-(nitrophenyl)ethylsilyl (NPE) and 3-(p-nitrophenoxy)propylsilyl (NPO), and electron-donor-bonded phases, 3-(N-carbazolyl)propylsilyl (CZP), 2-(1-pyrenyl)ethylsilyl (PYE), and 5-coronenylpentylsilyl (COP), were prepared from silica particles and their selectivities were examined in both polar and non-polar solvents for specific isomers of polychlorodibenzo-p-dioxins (PCDDs), hexachloronaphthalenes (HxCNs) and planar and non-planar polychlorobiphenyl (PCB) congeners. Although no single stationary phase was able to separate all the isomer pairs that are coproduced during the synthesis of the PCDDs and HxCNs, pairs can be separated by selecting a suitable stationary phase and solvent. The separation of mixtures of PCDD isomers were found to be most successful with PYE and NPO phases, which yielded the opposite elution orders for each isomer pair that is produced as a mixture. Similar results were obtained for the HxCN isomers that were separated on PYE and CZP phases. The COP phase provided easier separation of non-ortho-substituted and mono-ortho-substituted PCBs from the other PCBs based on the planarity than PYE phase.

Chromatography, High Pressure Liquid↗

Coplanar PCBs and the relative contribution of coplanar PCBs, PCDDs, and PCDFs to the total 2,3,7,8-TCDD toxicity equivalents in human serum.

Coplanar PCBs in human serum were measured by high-resolution gas chromatography/isotope-dilution high-resolution mess spectrometry in 46 pulp and paper mill workers and 16 community residents with no specific known source of PCB exposure. The relative contribution of coplanar PCBs, PCDDs, and PCDFs to the total 2,3,7,8-TCDD toxicity equivalents (TEQs) were compared using the toxic equivalency factors proposed by Safe [1] and the factors recently proposed by WHO [2]. The mean concentrations of PCB-126 and PCB-169 were higher in paper mill workers than in community residents. However, these differences were not statistically significant. Serum PCB-126, but not PCB-169, was correlated with body mass index (Spearman's r = 0.40, p = 0.002). Serum PCB-169, but not PCB-126, was correlated with age (Spearman's r = 0.54, p = 0.0001). Multiple linear regression analysis for log-transformed combined PCBs showed that age (p = 0.008), body mass index (p = 0.031), and eating locally caught fish (p = 0.019) were statistically significant predictors. The majority of the total TEQ in serum is due to PCDDs (63%), whereas PCDFs account for 21% and coplanar PCBs account for 15% when calculated using the TEFs proposed by Safe. The percent contributions from PCDDs, PCDFs, and coplanar PCBs were 66%, 24%, and 10% respectively when calculated based on the TEFs proposed by WHO. Age, body mass index, and consumption of locally caught fish are significant predictors for coplanar PCB levels in human serum. Serum PCDDs were the major contributors to the total 2,3,7,8-TCDD equivalent toxicity in this study.

Benzofurans↗

Correlation of environmental carbaryl measurements with serum and urinary 1-naphthol measurements in a farmer applicator and his family.

In exposure or risk assessments, both environmental and biological measurements are often used. Environmental measurements are an excellent means for evaluating regulatory compliance, but the models used to estimate body burden from these measurements are complex. Unless all possible routes of exposure (i.e., inhalation, dermal absorption, ingestion) are evaluated, exposure to a toxicant can be underestimated. To circumvent this problem, measurements of the internal dose of a toxicant in blood, serum, urine, or tissues can be used singularly or in combination with environmental data for exposure assessment. In three separate laboratories, carbaryl or its primary metabolite, 1-naphthol, was measured in personal air, dermal samples, blood serum, and urine from farmer applicators and their families. The usefulness of both environmental and biological data has been demonstrated. For the farmer applicator, the environmental levels of carbaryl would have been sufficient to determine that an exposure had occurred. However, biological measurements were necessary to determine the absorbed dose of each member of the applicator's family. In addition, a correlation between serum and urinary 1-naphthol measurements has been shown; therefore, either matrix can be used to accurately evaluate occupational carbaryl exposure.

Agriculture↗

Community psychiatric nurse aftercare for alcoholics: a five-year follow-up study.

The aim of this study was to determine if community psychiatric nurse (CPN) aftercare for 1 year improved the 5-year outcome in patients following inpatient treatment for alcohol dependence. A 5-year follow-up study, observer blind, with non-random allocation of subjects to aftercare by CPN for 1 year or standard outpatient care, was used. Subjects had all received inpatient treatment for 6 weeks in a rural alcohol treatment unit. Subjects were traced and assessed in the community 5 years after the index admission. The participants consisted of 127 white male alcoholics. All were first admissions, who had been selected for inpatient treatment and who completed a 6-week inpatient stay. Seventy-three subjects received intensive aftercare by CPN for 1 year, 54 subjects received standard outpatient appointments not due to random allocation but because no CPN was available. Data were collected by semi-structured interview at entry to the trial, namely background epidemiological information, details of drinking history, previous hospital admission, educational, employment and criminal information. At 5-year follow-up, data on drinking status, use of other drugs, hospital admissions, criminal behaviour and gambling, attendance at self-help groups, relationships and employment were collected. Thirty-six per cent of the CPN aftercare group was completely abstinent during the 5 years after treatment compared to 6% of the standard aftercare group (p < 0.001). Subjects receiving CPN aftercare were less likely to report blackouts (p < 0.05) or gambling (p < 0.05). They were more likely to attend hospital meetings (p < 0.0001). CPN aftercare is an effective way of maximizing the effects of inpatient treatment. The effects endured for 5 years after treatment.

Adolescent↗

Development and validation of sensitive method for determination of serum cotinine in smokers and nonsmokers by liquid chromatography/atmospheric pressure ionization tandem mass spectrometry.

We describe a sensitive and specific method for measuring cotinine in serum by HPLC coupled to an atmospheric pressure chemical ionization tandem mass spectrometer. This method can analyze 100 samples/day on a routine basis, and its limit of detection of 50 ng/L makes it applicable to the analysis of samples from nonsmokers potentially exposed to environmental tobacco smoke. Analytical accuracy has been demonstrated from the analysis of NIST cotinine standards and from comparative analyses by both the current method and gas chromatography/high-resolution mass spectrometry. Precision has been examined through the repetitive analysis of a series of bench and blind QC materials. This method has been applied to the analysis of cotinine in serum samples collected as part of the Third National Health and Nutrition Examination Survey (NHANES III).

Chromatography, High Pressure Liquid↗

Quantification of polycyclic aromatic hydrocarbons and polychlorinated dibenzo-p-dioxins in human serum by combined micelle-mediated extraction (cloud-point extraction) and HPLC.

Quantification of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated dibenzo-p-dioxins (PCDDs) usually requires preconcentration and cleanup prior to analysis. These procedures often involve using large amounts of toxic organic solvents. The sample preparation from serum is even more complex because of the coextraction of lipids and other nonpolar serum components. We describe the unprecedented use of cloud-point extraction to preconcentrate, extract, and clean up PAHs and PCDDs from human serum using the nonionic surfactant Triton X-100. The samples were analyzed by high-performance liquid chromatography with ultraviolet detection. The phase separation was induced by the addition of salt to the micellar serum solutions. The surfactant-rich phase was treated with acetonitrile and water to precipitate and remove some of the unwanted substances in the serum sample extract without significantly affecting the recoveries of the analytes. The favorable characteristics of cloud-point extraction discussed here strengthen its potential use as an alternative to other techniques of separation.

Chromatography, High Pressure Liquid↗

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↗

Isotope dilution--mass spectrometric quantification of specific proteins: model application with apolipoprotein A-I.

An enzymatic hydrolysis isotope dilution-mass spectrometric method was developed for reference quantification of specific proteins. The analytical procedure involved measuring a reproducibly hydrolyzed peptide (serving as the primary standard) unique to a specific protein. This new mass spectrometric method was evaluated by assessing the concentration of apolipoprotein (apo) A-I in the European Community Bureau of Reference (BCR) lyophilized Certified Reference Material (CRM 393). We used the method to make 96 measurements (4 replicate analyses of 4 enzymatic digests of 6 vials of BCR-CRM 393), which gave an average total protein mass of 1.048 mg (+/- 1.0% at 99% confidence limits). The total overall analytical CV was 3.95%. The results of this evaluation of our model approach to determine the concentration of a specific protein in a purified preparation demonstrated that our new mass spectrometric method can be used to measure apolipoproteins and other specific proteins without the use of epitopic immunoassay methods.

Amino Acid Sequence↗

Relation of a seafood diet to mercury, selenium, arsenic, and polychlorinated biphenyl and other organochlorine concentrations in human milk.

Human transition milk was sampled from 88 mothers at the Faroe Islands, where the seafood diet includes pilot whale meat and blubber. Milk mercury concentrations (median, 2.45 micrograms/liter) were significantly associated with mercury concentrations in cord blood and with the frequency of pilot whale dinners during pregnancy. Milk selenium concentrations (mean, 19.1 micrograms/liter) correlated significantly with concentrations in cord blood but not with seafood consumption. Arsenic concentrations were very low. Twenty-four of the milk samples were separated into four pools based on fish intake and milk mercury concentrations. The polychlorinated biphenyl (PCB) concentrations (1.8-3.5 micrograms/g lipid) were high and mainly due to congener numbers 153, 180, and 138. One pool contained a congener 77 concentration of 1380 ppt, which is the highest ever reported in a human specimen for a coplanar PCB. The highest PCB concentrations were seen in the pools from women who had eaten frequent whale dinners and whose milk contained high mercury concentrations. The concentrations of chlorinated dibenzo-p-dioxins and furans were not similarly elevated. Given the advantages associated with breast-feeding, advice to nursing mothers in this population should take into regard the possible risks associated with long-term exposure to milk contaminants.

Adult↗

Photodecomposition of 1,2,3,4- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in water-alcohol media on a solid support.

We used a hydrophobic solid support, octadecylsilylated silica gel (C18), packed in a quartz column as a reaction medium for the photolysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and 1,2,3,4-tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD). When we exposed the column to a 450 W UV lamp, the adsorbed 1,2,3,4-TCDD or 2,3,7,8-TCDD in 10% 2-propanol/water decomposed completely in 20 minutes and 5 minutes, respectively. The large estimated partition coefficient of 1,2,3,4-TCDD in 10% 2-propanol/water (> 1000) indicates that on the C18 stationary phase, both the saturated hydrocarbon chains and the absorbed 2-propanol may act as proton donors and accelerate the photolysis. In direct sunlight, the adsorbed 1,2,3,4-TCDD in 10% 2-propanol/water decomposed much faster than in a nonaqueous solvent (50% 2-propanol/methanol). This solvent effect is advantageous for the practical use of the C18 photolysis process in aqueous waste treatment. We have demonstrated that complete C18 trapping with continuous photodecomposition of TCDD contained in an aqueous alcohol waste is possible.

Adsorption↗

PCDD/PCDF levels in the blood of workers at a pulp and paper mill.

Blood samples from 34 workers at a pulp and paper mill and from 14 control persons were analysed for 2,3,7,8-substituted PCDDs and PCDFs. There were no statistically significant differences in total lipid-adjusted PCDD/PCDF concentrations, expressed as toxic equivalents, in blood plasma between the potentially exposed bleaching plant or paper mill workers and the controls. The mean level was 61 pg/g I-TEQ in bleaching plant workers, 60 pg/g I-TEQ in paper mill workers and 49 I-TEQ pg/g in controls. Regarding the concentrations of individual isomers, however, there was an indication that the blood plasma concentrations might be affected by the living and working environment.

Adult↗

Case studies of the use of biomarkers to assess exposures.

Because many environmental toxicants are ubiquitous, humans are continuously exposed to them. At other times, certain populations may be more highly exposed to these toxicants from point sources. The evaluation of the degree of the exposure to either a population or an individual is frequently based on indirect surrogates of exposure, such as questionnaire data on time-activities and/or concentrations measured in environmental media. We prefer to assess the degree of the exposure to a given toxicant by measuring the concentration of the toxicant, its metabolite(s), or reaction product(s) in human specimens. Then by applying pharmacokinetic information for that toxicant, we can best reconstruct the exposure scenario. These data are then compared to reference range levels of these toxicants in the preferred biologic specimen. The development and uses of the reference range data are exemplified by case studies including potential exposure to dioxin and solvents.

Animals↗

Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand.

We studied whether paternal exposure to Agent Orange and its dioxin contaminant (2,3,7,8-tetrachlorodibenzo-p-dioxin) during the Vietnam War is related to adverse reproductive outcomes after service in Southeast Asia. The index cohort comprises conceptions and children of veterans of Operation Ranch Hand, the unit responsible for aerial spraying of herbicides in Vietnam from 1962 to 1971. The comparison cohort comprises conceptions and children of Air Force veterans who served in Southeast Asia during the same period but who were not involved with spraying herbicides. We found no meaningful elevation in risk for spontaneous abortion or stillbirth. In analyses of birth defects, we found elevations in risk in some organ system categories, which, after review of the clinical descriptions, were found to be not biologically meaningful. There was an increase in nervous system defects in Ranch Hand children with increased paternal dioxin, but it was based on sparse data. We found no indication of increased birth defect severity, delays in development, or hyperkinetic syndrome with paternal dioxin. These data provide little or no support for the theory that paternal exposure to Agent Orange and its dioxin contaminant is associated with adverse reproductive outcomes.

2,4,5-Trichlorophenoxyacetic Acid↗

Using biological monitoring to assess human exposure to priority toxicants.

Scientifically valid exposure assessment is crucial to risk assessment, risk management, and prevention of environmental disease. Scientists have used three tools to assess exposure: exposure history/questionnaire, environmental monitoring (including personal monitoring), and biological monitoring. Combinations of these tools usually provide the exposure information needed to meet objectives of human studies evaluating the exposure-health effect relationship. Biological monitoring is a capable exposure assessment tool that has provided important information used in public health decisions. We briefly describe how risk assessment and risk management decisions for lead, dioxin, and volatile organic compounds have substantially benefited from exposure information obtained from biological monitoring.

Dioxins↗

Comprehensive two-dimensional gas chromatography for the fast separation and determination of pesticides extracted from human serum.

A comprehensive two-dimensional gas chromatograph with flame ionization detection was constructed and evaluated for the fast separation and analysis of pesticides. A two-stage thermal desorption modulator served as an interface between the two capillary GC columns. By controlling the temperature of the modulator chamber, all sample substances covering a wide polarity and volatility range were modulated without sample breakthrough. Orthogonal separations were achieved with a nonpolar first column and a moderately polar second column. The system allows fast separations of complex mixtures. When we used the method to analyze pesticides extracted from human samples, we achieved complete separation of 15 pesticides in less than 4 min. The flame ionization detector gave detection limits for particular pesticides that ranged from 1.8 to 3.8 pg on-column. The relative standard deviations were from 6.2% to 8.8% over the linear dynamic range.

Chromatography, Gas↗

Field-amplified sample stacking in micellar electrokinetic chromatography for on-column sample concentration of neutral molecules.

On-column concentration of neutral molecules was achieved for the first time in micellar electrokinetic chromatography by means of field-amplified sample stacking. The stacking process was accomplished by dissolving the neutral analytes in a low-concentration micellar solution that was still above the critical micelle concentration. The lower total ionic strength in the sample buffer compared to the electrophoresis buffer allowed the negatively charged micelles to migrate rapidly into the boundary between the sample and the running buffer where they slow down. This field-amplified sample stacking was achieved by using normal or reversed electrode polarity and produced a 75-85-fold increase in sensitivity for 1,2,4,7- and 1,2,4,8-tetrachlorodibenzo-p-dioxins. The peak area counts obtained from the sample stacking process were proportional to the sample volume injected, and the stacking efficiency was dependent on the micellar concentration. The best stacking efficiency was obtained when the micelle concentration was slightly higher than the critical micelle concentration. When the injection volume was relatively small, the normal-polarity stacking procedure produced a higher stacking efficiency. However, when the injection volume was large, reversed polarity produced a higher stacking efficiency because the non-uniform distribution of the electrical field strength had been eliminated.

Chromatography↗

Chemical characterization and disposition studies with 1,2,7,8-tetrabromodibenzofuran in the rat.

Polybrominated dibenzo-p-dioxins and dibenzofurans have been identified as potential environmental contaminants. The present studies were designed to characterize the chemical disposition of a tetrabrominated dibenzofuran. The isomer-specific pattern of 1,2,7,8-tetrabromodibenzofuran (TBDF) was chemically characterized using high-pressure liquid chromatography, gas chromatography/mass spectrometry, infrared absorption, and proton nuclear magnetic resonance techniques. The absorption, distribution, and elimination of 1,2,7,8-[4,6-3H]-TBDF were examined in the rat following a single oral, dermal, or intravenous dose of 1 nmol/kg. The 1,2,7,8-TBDF was rapidly excreted in the bile (approximately 50% of the dose in 8 h). Likewise, over half of the administered dose was found in the feces and intestine contents 24 h after iv administration and in feces 72 h after oral administration. Thus, the half-life of 1,2,7,8-TBDF is approximately 1 d. Major tissue depots included the liver, adipose tissue, and skin. The decline in hepatic concentrations observed in the iv and bile studies occurred in conjunction with metabolic elimination as well as a slight accumulation in adipose tissue. Dermal absorption of 1,2,7,8-TBDF, quantified as the amount contained in tissues (excluding the skin site) and excreta at 72 h, was estimated to be 29% of the administered dose. Thus, the general disposition profile of 1,2,7,8-TBDF in the rat is similar to that of other polyhalogenated aromatic hydrocarbons. Due to its rapid elimination, which is consistent with its predicted susceptibility to metabolic elimination, acute exposure to 1,2,7,8-TBDF would not be expected to result in the degree of toxicity associated with other more persistent congeners.

Absorption↗