Biomedical subjects

Donald G Patterson

Publications and source records attributed to Donald G Patterson.

12 recordsLinked to original sources

PubMed2003

New high-resolution mass spectrometric approach for the measurement of polychlorinated biphenyls and organochlorine pesticides in human serum.

To increase our analytical throughput for measuring polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides without sacrificing data quality, we have developed and validated a combined PCB/OC pesticide gas chromatography-high-resolution mass spectrometry (GC-HRMS) analysis. In a single GC-HRMS analysis, both selected PCBs and OC pesticides are detected and quantified. Previously, this has been difficult, if not impossible, because of the major difference in masses of the most abundant electron-impact ions. However, we have identified slightly less abundant ions to monitor that allow us to successfully combine these analytes into a single analysis without sacrificing any analytical sensitivity or instrument reliability. Consequently, we have been able to double our analytical throughput by modification of mass spectrometric parameters alone. Our new methodology has been validated against our current GC-HRMS method, which entails using two separate injections, one for PCB analysis and one for OC pesticide analysis. The two methods differ by less than 4% overall, with no systematic bias. We used this method to analyze approximately 350 serum samples over a period of several months. We found that our new method was as reliable in automated, overnight runs as our current method.

Gas Chromatography-Mass Spectrometry↗

PubMed2003

Comprehensive solid-phase extraction method for persistent organic pollutants. Validation and application to the analysis of persistent chlorinated pesticides.

The Centers for Disease Control and Prevention (CDC) is involved in many epidemiological studies regarding the measurement of chlorinated pesticides and polychlorinated biphenyls in specimens obtained from humans. In addition to these commonly determined analytes, there is a need to include additional persistent organic pollutants (POPs) in our analyses, which further stresses the analyses because sample volumes remain small. Thus, a single method of analysis for all POPs in human serum is needed. CDC has recently developed a semiautomated and comprehensive solid-phase extraction method for POPs. The method is comprehensive since it was optimized for the extraction of many different POP compound classes. We then developed a purification and fractionation scheme that allows (a) separation of different compound classes by particular functionalities and (b) purification of those fractions to remove coextracted interferences. This paper describes the first step in the semiautomated comprehensive extraction and multiple fractionation method developed by CDC for monitoring POPs. In this paper, we validate the analysis of the persistent chlorinated pesticides, a compound class difficult to examine because of their structural diversity, in human plasma. The method was validated against an existing CDC method by using a spiked quality-control serum pool. The concentrations determined for all analytes using both methods were within 2%-14% relative standard deviations. A multilevel (i.e., 3-4 point) matrix spike showed good linearity for the analytes tested (r2 = 0.978-0.999). The method was then applied to 40-year-old archived plasma samples for the quantitative analysis of selected chlorinated pesticides. Mean recoveries of the 13C-labeled internal quantification standards ranged from 64% to 123% for the 11 monitored pesticides. The overall method proved to be robust by handling old coagulated plasma samples. It allowed faster throughput of samples than our previous methods and provided cleaner samples with less frequent interferences or background as analyzed by high-resolution mass spectrometry. The method represents a preliminary step in establishing an automated, comprehensive multiresidue analysis method for POPs in human serum.

Automation↗

PubMed2003

A review on human exposure to brominated flame retardants--particularly polybrominated diphenyl ethers.

Brominated flame retardants (BFRs) have been and are still heavily used as additive or reactive chemicals in polymers and textiles. Only a few of the BFRs have been assessed in human subjects with a major data set on internal exposures to polybrominated diphenyl ethers (PBDEs). Increasing PBDE levels have been observed in mothers' milk from Sweden as well as in blood from Germany and Norway. The levels are in general lower than PCB levels. However, the PBDE concentrations found in the North Americans are considerably higher compared to European subjects. The PBDEs are dominated by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47). Decabromodiphenyl ether (BDE-209) is reported both in the general population and in occupationally exposed persons showing the bioavailability of this high molecular weight compound. While the lower and medium brominated diphenyl ethers are persistent, BDE-209 has a fairly short half-life of approximately 2 weeks. Tetrabromobisphenol A (TBBPA) is readily eliminated in humans showing a half-life of about 2 days. Still, TBBPA is accumulated in humans but a continuous exposure to this BFR is required to maintain a certain level in the human subject. TBBPA has not been detected in the general population but in people exposed at work. The current review addresses human exposure routes and levels of BFRs.

Environmental Exposure↗

PubMed2003

Maternal serum dioxin levels and birth outcomes in women of Seveso, Italy.

2,3,7,8-Tetrachlorodibenzo-(italic)para(/italic)-dioxin (TCDD), a ubiquitous environmental contaminant, is associated with increased fetal loss and reduced birth weight in animal studies. In 1976, an explosion at a trichlorophenol plant near Seveso, Italy, resulted in the highest TCDD exposure known in human residential populations. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of women who resided in the most contaminated areas, zones A and B. We examined the relation of pregnancy outcome in 510 women (888 total pregnancies) to maternal TCDD levels measured in serum collected shortly after the explosion. Ninety-seven pregnancies (10.9%) ended as spontaneous abortions (SABs). There was no association of log(subscript)10(/subscript) TCDD with SAB [adjusted odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.6-1.2], with birth weight (adjusted beta = -4 g; 95% CI, -68 to 60), or with births that were small for gestational age (SGA) (adjusted OR = 1.2; 95% CI, 0.8-1.8). However, associations with birth weight (adjusted beta = -92 g; 95% CI, -204 to 19) and with SGA (adjusted OR = 1.4; 95% CI, 0.6-2.9) were stronger for pregnancies within the first 8 years after exposure. TCDD was associated with a 1.0-1.3 day nonsignificant adjusted decrease in gestational age and a 20-50% nonsignificant increase in the odds of preterm delivery. It remains possible that the effects of TCDD on birth outcomes are yet to be observed, because the most heavily exposed women in Seveso were the youngest and the least likely to have yet had a pregnancy.

Abortion, Spontaneous↗

PubMed2002

Determination of selected monohydroxy metabolites of 2-, 3- and 4-ring polycyclic aromatic hydrocarbons in urine by solid-phase microextraction and isotope dilution gas chromatography-mass spectrometry.

Eighteen monohydroxy polycyclic aromatic hydrocarbon metabolites (OH-PAHs) representing polycyclic aromatic hydrocarbons (PAHs) containing up to four rings in human urine have been measured. The method includes the addition of carbon-13 labeled internal standards, enzymatic hydrolysis, and solid-phase microextraction followed by gas chromatography with high-resolution mass spectrometry. By using response factors calculated with the carbon-13 labeled standards, results are presented for calibration, relative standard deviations and analyte levels from an unspiked human urine pool. The method detection limits ranged from 0.78 ng/l for hydroxyphenanthrenes to 15.8 ng/l for 1-hydroxynaphthalene, and the recoveries ranged between 6% for hydroxychrysene and 47% for 1-hydroxypyrene. The relative standard deviation was lowest for 3-hydroxyphenanthrene at 2.4% and went up to 18.7% for 6-hydroxychrysene. The method was calibrated from 10 to 1200 ng/l. Eleven of the 18 metabolites were found in background pooled urine samples. This validated method is a convenient and reliable tool for determining urinary OH-PAHs as biomarkers of exposure to eight PAHs.

Calibration↗

PubMed2002

Serum dioxin concentrations and menstrual cycle characteristics.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread industrial environmental contaminant. Animal studies suggest that TCDD exposure alters the estrus cycle. Twenty years after a 1976 industrial explosion in Seveso, Italy, the authors interviewed female residents to determine whether there was an association between TCDD exposure and current menstrual cycle characteristics. The authors analyzed serum samples collected soon after the explosion to quantify individual TCDD levels. Among women who were premenarcheal at the time of the explosion, a 10-fold increase in serum TCDD level was associated with a lengthening of the menstrual cycle by 0.93 days (95% confidence interval (CI): -0.01, 1.86) and a reduction in the odds of scanty menstrual flow (adjusted odds ratio = 0.33, 95% CI: 0.10, 1.06). However, among women who were postmenarcheal at the time of the explosion, TCDD was not associated with menstrual cycle length (adjusted beta = -0.03 days, 95% CI: -0.61, 0.54) or scantiness of flow (adjusted odds ratio = 1.36, 95% CI: 0.70, 2.64). In both menarche groups, TCDD levels were associated with decreased odds of having irregular cycles (adjusted odds ratio = 0.46, 95% CI: 0.23, 0.95) but were not related to days of flow (adjusted beta = 0.16 days, 95% CI: -0.08, 0.41). These results are consistent with effects of TCDD on ovarian function noted in some animal species and with greater sensitivity to TCDD during development.

Adult↗

PubMed2002

Quantification of monohydroxy-PAH metabolites in urine by solid-phase extraction with isotope dilution-GC-MS.

For measurement of biomarkers from polycyclic aromatic hydrocarbon (PAH) exposure, an analytical method is described quantifying hydroxylated PAH (OH-PAH) in urine samples. This method determined monohydroxy metabolites of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, chrysene, benzo[c]phenanthrene, and benz[a]anthracene. The sample preparation consisted of enzymatic hydrolysis, solid-phase extraction and derivatization with a silylating reagent. Five carbon-13 labeled standards were used for isotope dilution. Analytes were separated by gas chromatography (GC) and quantified with high-resolution mass spectrometry (HRMS). This method produced good recoveries (41-70%), linearity, and specificity. Data were corrected for blank levels from the naphthalene, fluorene, and phenanthrene metabolites. Method detection limits ranged from 2 ng L(-1) for 1-hydroxypyrene to 43.5 ng L(-1) for 1-hydroxynaphthalene. Using quality control charts from two urine pools, the method can be readily applied to biomonitoring PAH exposure.

Chromatography, High Pressure Liquid↗

PubMed2002

Characterization of dioxin exposure in residents of Chapaevsk, Russia.

Since 1967, a chemical plant in the town of Chapaevsk (Samara province, Russia) has produced large amounts of chlorinated compounds and is suspected to be a major source of local environmental dioxin contamination. Dioxins have been detected in the local air, soil, drinking water, vegetables, and cow's milk. Human exposure to dioxins is suspected as a factor in the deteriorating local public health. In an effort to characterize nonoccupational dioxin exposure among local residents, during the summer of 1998, 24 volunteers were recruited to donate blood and to provide information about their residence, employment, demographics, medical history, and dietary habits. Selected polychlorinated dibenzodioxins, dibenzofurans, and coplanar biphenyls were measured in blood serum samples. The mean concentration of total dioxin World Health Organization toxic equivalents (WHO-TEQ(98)) based on polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (PCBs) was 61.2 (range 16.4-168.1) pg/g lipid. Subjects living in close proximity to the plant (less than 5 km) had significantly higher dioxin levels (mean WHO-TEQ(98), 75.7 pg/g lipid), as compared to subjects living more than 5 km from the plant (mean WHO-TEQ(98), 44.1 pg/g lipid) (P<0.04). Comparisons of the study results with available published data indicate that average blood dioxin levels were substantially higher in Chapaevsk residents than in nonoccupationally exposed populations of other parts of Russia, Europe, and North America. Chronic exposures of such magnitude may have appreciable adverse effects on public health.

Adult↗

PubMed2002

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation.

Accidents↗

PubMed2002

Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis.

Adult↗

PubMed2002

Measurement of p-nitrophenol in the urine of residents whose homes were contaminated with methyl parathion.

During the last several years, illegal commercial application of methyl parathion (MP) in domestic settings in several U.S. Southeastern and Midwestern States has affected largely inner-city residents. As part of a multiagency response involving the U.S. Environmental Protection Agency (U.S. EPA), the Agency for Toxic Substances and Disease Registry (ATSDR), and state and local health departments, our laboratory developed a rapid, high-throughput, selective method for quantifying p-nitrophenol (PNP), a biomarker of MP exposure, using isotope dilution high-performance liquid chromatography-tandem mass spectrometry. We measured PNP in approximately 16,000 samples collected from residents of seven different states. Using this method, we were able to receive sample batches from each state; prepare, analyze, and quantify the samples for PNP; verify the results; and report the data to the health departments and ATSDR in about 48 hr. These data indicate that many residents had urinary PNP concentrations well in excess of those of the general U.S. population. In fact, their urinary PNP concentrations were more consistent with those seen in occupational settings or in poisoning cases. Although these data, when coupled with other MP metabolite data, suggest that many residents with the highest concentrations of urinary PNP had significant exposure to MP, they do not unequivocally rule out exposure to PNP resulting from environmental degradation of MP. Even with their limitations, these data were used with the assumption that all PNP was derived from MP exposure, which enabled the U.S. EPA and ATSDR to develop a comprehensive, biologically driven response that was protective of human health, especially susceptible populations, and included clinical evaluations, outreach activities, community education, integrated pest management, and decontamination of homes.

Biomarkers↗

PubMedDate not supplied

Pharmacokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Seveso adults and veterans of operation Ranch Hand.

A combined analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elimination in Seveso adults and Ranch Hand veterans found a period of fast elimination within the first 0.27 years after exposure in Seveso, followed by a period of slower elimination between 3 and 16.35 years from exposure. The mean TCDD elimination rate within the first 0.27 years after exposure among six adult males in the Seveso cohort was 2.0646 year(-1) (half-life=0.34 years). The mean rate from 3 to 16.35 years was 0.1011 year(-1) (half-life=6.9 years). The mean Ranch Hand elimination rate, 00924 year(-1) (half-life=6.9 years), measured between 9 and 33 years after exposure, was significantly less than the Seveso mean in the first 0.27 years after exposure, but not significantly different from the Seveso mean between 3 and 16.35 years after exposure. The fast elimination within the first 0.27 years followed by a slower rate after 3 years is consistent with the expected pattern in a two-compartment open model, with a distribution phase of rapid elimination followed by a slower elimination phase.

Accidents, Occupational↗