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Biomedical subjects

L L Needham

Publications and source records attributed to L L Needham.

At least 55 records · Page 3Linked to original sources
PubMed1995

The priority toxicant reference range study: interim report.

The relationship between human exposure to environmental toxicants and health effects is of utmost interest to public health scientists. To define this relationship, these scientists need accurate and precise methods for assessing human exposure and effects. One of the most accurate and precise means of assessing exposure is to measure the level of the toxicant or its primary metabolite in a biologic specimen; this has been defined as measuring the internal dose. This measurement must be quantitative to best study the dose-response relationship. Pertinent questions asked during an exposure assessment include "How do the levels of a given toxicant in a particular population compare with the levels of that toxicant in other populations?" and "What is the prevalence of exposure to that toxicant in other populations?" To answer these questions for two chemical classes of environmental toxicants, we developed state-of-the-art analytic methods and then applied them to measure the levels of 44 environmental toxicants in biologic specimens from 1000 United States residents who participated in the Third National Health and Nutrition Examination Survey (NHANES III). These 1000 people are a cross-sectional subset of the NHANES III population and were selected from urban and rural communities in four regions of the United States; all were between 20 and 59 years of age. This subset is not a probability-based sample.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Levels of non-ortho-substituted (coplanar), mono- and di-ortho-substituted polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans in human serum and adipose tissue.

We have measured non-ortho-substituted (coplanar) polychlorinated biphenyl (PCB) levels as well as polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in human adipose tissue and serum collected in Atlanta, Georgia. The results show that the concentrations of the coplanar PCBs can be more than an order of magnitude higher than the concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Our measurements in pooled serum collected in 1982, 1988, and 1989 show a decrease in coplanar PCB levels from 1982 to 1989. We found that the pattern of relative amounts of coplanar PCBs in adipose tissue varied greatly from person to person unlike the PCDD and PCDF patterns, which were more nearly the same. Age was significantly correlated with the concentrations of 2,3,7,8-TCDD,3,3'4,4'-PCB, 3,3',4,4',5-PCB, and 3,3'4,4',5,5'-PCB in adipose tissue. We also measured levels of the mono- and di-ortho chlorine-substituted PCBs in human serum. The levels for some of these PCB congeners were three orders of magnitude higher than the coplanar PCBs, PCDDs, and PCDFs. We used the international toxicity equivalency factors (TEFs) for PCDDs and PCDFs and the TEFs proposed by Safe for PCBs to calculate the 2,3,7,8-TCDD equivalents. Four PCBs (3,3',4,4',5-; 2,3',4,4',5-;2,3,3',4,4'-;2,3,3',4,4',5-) make a larger contribution than 2,3,7,8-TCDD, while four other PCBs (3,3',4,4'5,5'-; 2,2',3,4,4',5'-;2,2',4,4',5,5'-;2,2',3,4,4',5,5'-) make nearly the same contribution as 2,3,7,8-TCDD. The mono-ortho-chlorine-substituted 2,3',4,4',5-PCB, however, is the major contributor to the total 2,3,7,8-TCDD equivalents in general population samples from the United States, Sweden, and Japan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Technical and scientific developments in exposure marker methodology.

Recent advances in techniques to measure markers of exposure to environmental toxicants in humans are changing the ways in which environmental scientists, epidemiologists, and policymakers characterize and interpret such exposure. In this article we review some major technical and scientific developments in exposure marker methodology for estimating internal dose, with special reference to studies conducted at the US Centers for Disease Control and Prevention. We consider important characteristics of laboratory methods, advances in laboratory technology, analytical standards, and quality assurance of laboratory measurements; comparisons with indirect methods for estimating exposures, such as exposure indices and questionnaires; human pharmacokinetic data; sampling problems; surveillance of human exposures to toxicants; and interpretation of measurements. With a view to increasing the reliability of exposure assessment, we make recommendations for obtaining more data on human exposure to toxicants.

Biomarkers↗
PubMed1993

Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome.

In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L-tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan. We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗
PubMed1992

Current serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin in phenoxy acid herbicide applicators and characterization of historical levels.

BACKGROUND: Workers who sprayed phenoxy acid herbicides, especially those who sprayed before 1975, may have been exposed to significant amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent animal carcinogen present in herbicide preparations as a contaminant. PURPOSE: The aims of this study were (a) to determine serum levels of TCDD in a representative sample of workers occupationally exposed to the agent during the spraying of phenoxy acid herbicides; (b) to compare serum levels in workers exposed before 1965, when concentrations in herbicide products were unregulated and high, with levels in workers exposed after 1974, when concentrations were lower as a result of government regulations worldwide; and (c) to examine the correlation, if any, between serum levels and duration of employment in spraying. METHODS: Thirty-seven subjects were randomly selected from a group of 654 men who had sprayed the herbicides 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) in Australia for at least 12 months. The workers were classified as follows: eight who sprayed only before 1965, nine who sprayed only during the period after 1964 and before 1975, and 20 who sprayed during the period after 1974 and before 1991. Serum from the workers was analyzed for TCDD by high-resolution gas chromatography and high-resolution mass spectrometry at a detection limit of 0.6 parts per trillion (ppt) on a lipid-weight basis. In addition, rates of exposure to TCDD were estimated, as were TCDD serum concentrations at termination of employment and intensity of herbicide use. RESULTS: Only one worker, with a serum TCDD level of 34 ppt, had a serum level higher than the maximum level of 26 ppt reported for the general population. Assuming a half-life of 7.1 years, we estimated the mean exposure rates to be 2.7, 2.3, and 0.06 ppt/mo for the three epochs, respectively. We found the highest serum level of TCDD at the time of cessation of employment to be 329 ppt. Calendar period and intensity of use of 2,4,5-T and 2,4-D were statistically significant determinants of rate of exposure to TCDD, but 2,4-D was associated with exposure rate only for the pre-1975 periods. Estimated rates prior to 1965 were more than an order of magnitude higher than those after 1974. CONCLUSION: The highest estimated exposure rate was 20.7 ppt/mo, which suggests that some sprayers may have been exposed to levels comparable with those that produce cancer in laboratory animals.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1992

Determining volatile organic compounds in human blood from a large sample population by using purge and trap gas chromatography/mass spectrometry.

Volatile organic compounds (VOCs) are a major public health concern, because of their ubiquitous nature and the possible health effects associated with exposure to them. An analytical method has been developed that enabled the determination of parts per trillion levels of 32 VOCs in 10 mL of blood. Special efforts toward reducing blank levels and improving measurement sensitivity have resulted in an analytical method that shows excellent reproducibility and recovery even at these ultratrace levels. Results on normal human blood indicate that quantifiable levels of eleven VOCs can be found in virtually all whole blood samples. In a fraction of the samples, six other VOCs can also be determined at levels above detection limits. This method shows promise as a technique for estimating the normal baseline level of VOCs in human blood and may have future applications in cases of exposure.

Blood Chemical Analysis↗
PubMed1992

Serum 2,3,7,8-tetrachlorodibenzo-p-dioxin levels of New Zealand pesticide applicators and their implication for cancer hypotheses.

BACKGROUND: The phenoxyherbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) has been widely used by professional pesticide applicators in New Zealand since before 1950. Epidemiologic studies of the risk of cancer and birth defects have been conducted in this group of workers, but little is known about the extent of their exposure to the 2,4,5-T contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent carcinogen in animals. PURPOSE: The objective of this study was to determine whether the blood serum levels of TCDD in a group of professional 2,4,5-T applicators in New Zealand were greater than those of a matched control group not involved in 2,4,5-T spraying. METHODS: Of 548 men employed as professional pesticide applicators in New Zealand from 1979 through 1982, nine were selected who had sprayed pesticides, although not necessarily 2,4,5-T, for at least 180 months. These applicators had sprayed 2,4,5-T for a range of 83-372 months. We measured the blood serum levels of polychlorinated dibenzo-p-dioxins and dibenzofurans, which were substituted with chlorine at the 2,3,7,8 position, in the nine pesticide applicators and in a matched group of nine control subjects. RESULTS: The average serum level of TCDD for applicators was almost 10 times that for the matched control subjects, while the average levels of all other congeners and isomers measured in the two groups did not differ substantially. TCDD levels in eight of the nine applicators were higher than those in the control subjects (mean difference, 47.7 parts per trilion). The variation in TCDD levels among the applicators was related to their duration of work exposure to 2,4,5-T. CONCLUSIONS: On the basis of our findings in these subjects in New Zealand, we conclude that increased risks of cancer from brief exposure to phenoxyherbicides reported in other countries are probably not attributable to the TCDD that contaminates 2,4,5-T. We cannot determine from these results, however, whether TCDD exposure from prolonged use of 2,4,5-T poses significant health risks.

Humans↗
PubMed1991

Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy.

2,3,7,8-Tetrachlorodibenzo-p-dioxin levels (TCDD) were measured in serum specimens from Seveso, Italy, residents, who were potentially highly exposed to the 1976 explosion, and in controls. The residents were chosen so as to represent those who did and did not develop chloracne. Levels of TCDD as high as 56,000 parts per trillion (ppt) were found in these serum specimens that were collected in 1976. These TCDD levels are the highest ever reported, and yet almost all clinical laboratory tests on these individuals were normal; any abnormal test result was only transitory in nature. These findings are unique in linking clinical histories to TCDD levels following an acute exposure.

Accidents↗
PubMed1991

Environmental pathology. Mast cell and eosinophil infiltration in intestinal mucosa of Lewis rats treated with L-tryptophan implicated in human eosinophilia myalgia syndrome.

A recently developed animal model for the L-tryptophan-associated eosinophilia myalgia syndrome was used to examine the small intestine and colon, because there is clinical involvement at these sites in patients. Increased perivascular inflammatory infiltrates rich in degranulating mast cells, eosinophils, and monocytes were seen in the lamina propria of experimental animals when compared with controls. L-Tryptophan-associated disease also shares many clinical features with idiopathic scleroderma/eosinophilic fasciitis, in which there is gastrointestinal involvement as well. These features are similar to those found in the recently described animal model. The apparent morphologic and clinical similarities between these entities suggest that the animal model is suitable for further studying the pathogenesis of the gastrointestinal involvement in all these diseases.

Animals↗
PubMed1990

Use of reference pools to compare the qualitative and quantitative determination of polychlorinated biphenyls by packed and capillary gas chromatography with electron capture detection. Part 1. Serum.

Serum for reference pools of in vivo polychlorinated biphenyls (PCBs) was obtained from four goats that had received one dose (100 mg kg-1) of a selected technical Aroclor (AR) (1016, 1242, 1254 or 1260) and were allowed to recover for 30 d. These pools were used to assess the differences in an analytical method that determines and quantifies PCBs using packed-column gas chromatography (PCGC) (quantified on the basis of mean mass percent. data for grouped PCB peaks) and capillary-column gas chromatography (CCGC) (quantified on the basis of percent. composition data for specific congeners). With CCGC, results were statistically significantly different (p less than or equal to 0.0002) from results with PCGC for ARs 1016, 1242 and 1254 but not for AR 1260 (p = 0.23). When comparing these gas chromatographic methods using bovine serum spiked in vitro with the same ARs at 17-25 p.p.b., it was found that the methods were not statistically significantly different for any of the ARs (p = 0.30-0.92). Levels of serum PCB determined by the two methods for 12 persons, divided into two groups according to exposure, were compared using the paired t-test. Group 1 consisted of three persons with dietary and/or environmental exposure; one with dietary and/or environmental exposure in addition to occupational exposure dating back 20 years. Group 2 consisted of eight persons with recent occupational exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

L-tryptophan implicated in human eosinophilia-myalgia syndrome causes fasciitis and perimyositis in the Lewis rat.

Tryptophan-associated eosinophilia-myalgia syndrome (L-TRP-EMS) is a newly described syndrome which occurred in epidemic fashion in the United States in the summer and fall of 1989. Epidemiologic data has linked the syndrome to intake of L-tryptophan (L-TRP) from one specific manufacturer, but the precise etiologic compound(s) must be established by replication of the syndrome in an appropriate animal model. In this study, implicated L-TRP, United States Pharmacopeia (USP) grade L-TRP, or vehicle was administered by gavage in a blinded fashion for 38 d to female Lewis rats at doses comparable with those ingested by patients who developed the eosinophilia-myalgia syndrome. Animals receiving implicated L-TRP, but not those receiving USP grade L-TRP or vehicle, developed histologic signs consistent with fasciitis and perimyositis, specific pathologic features of human L-TRP-EMS. Peripheral blood eosinophilia was not observed. Hypothalamic corticotropin releasing hormone mRNA levels were lower and plasma corticosterone levels tended to be lower in the animals that received implicated L-TRP. Plasma L-kynurenine was higher in both L-TRP-treated groups compared to the vehicle-treated animals. The female Lewis rat is known to be susceptible to a wide variety of inflammatory diseases. Identification of specific inflammatory changes in this rat following exposure to implicated L-TRP indicates that this animal model will be important in subsequent investigations into the etiology, pathogenesis, and treatment of human L-TRP-EMS.

Animals↗
PubMed1989

Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Review of employment and chemical production records at a Missouri chemical plant and of questionnaires with self-reported occupational exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin (2,3,7,8-TCDD) for 16 Missouri workers has explained the wide diversity of 2,3,7,8-TCDD levels previously reported in the workers' adipose tissue (3.5-750 ppt on whole-weight basis). We show that the highest exposures reported to date in the United States occurred in a group of nine production workers who made products contaminated with 2,3,7,8-TCDD. The nine workers had adipose tissue levels with a mean of 246 ppt and a range of 42 to 750 ppt. Seven persons who worked at the same chemical company, but not in the 2,3,7,8-TCDD-contaminated process, had a mean of 8.7 ppt and a range of 3.5 to 25.8 ppt. We also report serum levels of 2,3,7,8-TCDD in these individuals. The adipose tissue from a subset of four production workers with elevated levels of 2,3,7,8-TCDD and seven Missouri residents with normal 2,3,7,8-TCDD levels was also analyzed for other isomers of the PCDDs and PCDFs. The mean adipose tissue level of 2,3,7,8-TCDD in the subset of production workers was 45 times higher than the mean level in the unexposed Missouri residents, but similar levels of the other PCDDs and PCDFs were found in both groups.

Adipose Tissue↗