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Biomedical subjects

L L Needham

Publications and source records attributed to L L Needham.

At least 37 records · Page 2Linked to original sources
PubMed1998

Serum concentrations of organochlorine compounds and endometrial cancer risk (United States).

OBJECTIVES: Endogenous and exogenous estrogens are important in the development of endometrial cancer. Several organochlorine compounds, such as o,p'-DDT, have estrogenic properties. The objective of this case-control analysis was to examine serum concentrations of organochlorine compounds and risk of endometrial cancer. METHODS: Analyses were based on a sample of 90 endometrial cancer cases and 90 individually matched community controls from a multicenter case-control study in five geographic regions of the United States. Information on potential confounders, including menstrual and reproductive factors, cigarette smoking, diet, and weight, was obtained by interview. RESULTS: The adjusted relative risk of endometrial cancer in the highest quartile of exposure compared with women in the lowest quartile was 0.7 (95 percent confidence interval [CI] = 0.2-2.0) for p,p'-DDE, and 0.9 for total polychlorinated biphenyls (PCBs) (CI = 0.4-2.5). CONCLUSIONS: These findings do not support the hypothesis that organochlorine compounds are linked to the development of endometrial cancer.

Adolescent↗
PubMed1998

2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident.

In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD levels in soil, and cohort including all residents was enumerated. The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population. Two decades after the accident. plasma TCDD levels were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident site (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes.

Accidents, Occupational↗
PubMed1997

A nested case-control study of non-Hodgkin lymphoma and serum organochlorine residues.

BACKGROUND: The steady worldwide increase in the incidence of non-Hodgkin lymphoma during the past few decades remains mostly unexplained. Several studies suggest that there may be an association between the agricultural use of the organochlorine 1,1,1-trichloro-2,2'bis(p-chlorophenyl)ethane (DDT) and increased risk of non-Hodgkin lymphoma. We have investigated the association between risk of non-Hodgkin lymphoma and body burden of selected organochlorines in the general population in a nested case-control study. METHODS: We measured prediagnostic serum concentrations of DDT, its metabolites, and other organochlorines, including polychlorinated biphenyls (PCBs), in 74 cases of non-Hodgkin lymphoma and 147 matched controls identified from a prospective cohort of 25,802 adults, established in 1974 in Washington County, Maryland, USA. We report results for total lipid-corrected serum concentrations of DDT and total PCBs. FINDINGS: There was a strong dose-response relation between quartiles of total lipid-corrected serum PCB concentrations and risk of non-Hodgkin lymphoma overall (odds ratios by quartile: 1.0; 1.3 [95% CI 0.5-3.3]; 2.8 [1.1-7.6]); and 4.5 [1.7-12.0]; p for trend = 0.0008) and separately in men and in women. There was also evidence suggesting that seropositivity for the Epstein-Barr virus early antigen potentiated the effects of serum PCBs. By contrast, total lipid-corrected serum concentrations of DDT were not associated with risk of non-Hodgkin lymphoma. INTERPRETATION: These results should be regarded as hypothesis-generating. Before causal inferences can be made about exposure to PCBs and increased risk of non-Hodgkin lymphoma, our findings require replication and the biological plausibility of the association needs further investigation.

Adult↗
PubMed1997

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↗
PubMed1996

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↗
PubMed1996

Analytical characterization of peptide contaminants of L-tryptophan.

Reversed-phase liquid chromatographic fractions of extracts of 2 preparations of eosinophilia-myalgia syndrome (EMS)-associated L-tryptophan were analyzed by proton nuclear magnetic resonance spectrometry, mass spectrometry, microbial-growth inhibition, and amino acid residue analyses. Fraction components demonstrated properties of an antibiotic peptide resembling bacitracin. Many peptide antibiotics like bacitracin are secondary metabolites of Bacillus species, genus of the tryptophan producer organism for the implicated manufacturer. In order to determine whether a correlation exists between individual EMS cases and the concentration of peptides or bacitracin consumed, reliable methods must be developed for quantification of the total of isoforms.

Amino Acids↗
PubMed1996

Products of aniline and triglycerides in oil samples associated with the toxic oil syndrome.

The toxic oil syndrome (TOS) was a devastating disease that occurred in Spain in 1981. The disease was associated with the consumption of aniline-denatured and refined rapeseed oil that had been illegally sold as olive oil. Many aniline-derived oil components have been identified in the oils; however, no etiological agent has ever been identified for this disease. We have continued the study of the TOS problem by applying new technology in the form of liquid chromatography interfaced via atmospheric pressure ionization with tandem mass spectrometry. Using liquid chromatography tandem mass spectrometry, we studied diluted TOS-associated oils by direct analysis without prior sample treatment. Using this technology, we found new classes of compounds that are associated with disease-related oils. The compounds that have been identified are esters and ester amides of 3-(N-phenylamino)-1,2-propanediol and are products of aniline and triglycerides. Because of the varied fatty acid (oleic acid, etc.) content of the oils, many variations of the above compounds are possible. We now report the identities of more than 20 compounds not previously identified. These compounds are strongly associated with oils that caused the toxic oil syndrome. We believe these compounds should be considered for future animal studies.

Anilides↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

Pesticide residues in urine of adults living in the United States: reference range concentrations.

We measured 12 analytes in urine of 1000 adults living in the United States to establish reference range concentrations for pesticide residues. We frequently found six of these analytes: 2,5-dichlorophenol (in 98% of adults); 2,4-dichlorophenol (in 64%); 1-naphthol (in 86%); 2-naphthol (in 81%); 3,5,6- trichloro-2-pyridinol (in 82%); and pentachlorophenol (in 64%). The 95th percentile concentration (95th PC) for 2,5-dichlorophenol (indicative of p-dichlorobenzene exposure) was 790 micrograms/liter; concentrations ranged up to 8700 micrograms/liter. 2,4-Dichlorophenol concentrations ranged up to 450 micrograms/ liter, and the 95thPC was 64 micrograms/liter. 1-Naphthol and 2-naphthol (indicative of naphthalene exposure) had 95thPCs of 43 and 30 micrograms/liter, respectively; concentrations of 1-naphthol ranged up to 2500 micrograms/liter. Chlorpyrifos exposure was indicated by 3,5,6-tricholoro-2-pyridinol concentrations of 13 (95thPC) and 77 micrograms/liter (maximum observed). Pentachlorophenol had a 95thPC of 8.2 micrograms/liter. Other analytes measured included 4-nitrophenol (in 41%); 2,4,5-trichlorophenol (in 20%); 2,4,6-trichlorophenol (in 9.5%); 2,4-dichlorophenoxyacetic acid (in 12%); 2-isopropoxyphenol (in 6.8%); and 7-carbofuranphenol (in 1.5%). The 95thPCs of these analytes were < 6 micrograms/liter. p-Dichlorobenzene exposure is ubiquitous; naphthalene and chlorpyrifos are also major sources of pesticide exposure. Exposure to chlorpyrifos appears to be increasing. Although pentachlorophenol exposure is frequent, exposure appears to be decreasing. These reference range concentrations provide information about pesticide exposure and serve as a basis against which to compare concentrations in subjects who may have been exposed to pesticides.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Determination of pesticide metabolites in human urine using an isotope dilution technique and tandem mass spectrometry.

A method that measures 12 analytes in urine and reflects possible exposure to pesticides was developed. The sample preparation involves enzyme hydrolysis and solvent extraction through the use of laboratory robotics, followed by phase-transfer catalysis derivatization and silica cleanup. Samples are analyzed by capillary gas chromatography and tandem mass spectrometry using an isotope dilution technique with 13C-labeled internal standards. The limit of detection is 1 microgram/L (1 part per billion) for most analytes, and most analytes have a linear response up to 100 micrograms/L. The precision of the method is reflected in the variation observed in quality control materials over 33 months; the variation averaged 17% for these analytes. On the basis of the detectable analyte levels of unspiked urine samples collected from unexposed volunteers, this method can be used to measure the low levels necessary for establishing reference range values of the selected pesticides or metabolites.

Calibration↗
PubMed1995

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↗
PubMed1995

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↗