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Biomedical subjects

L L Needham

Publications and source records attributed to L L Needham.

At least 73 records · Page 4Linked to original sources

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↗

A laboratory for handling chemical toxicants safely.

The Centers for Disease Control has a special Chemical Toxicant Laboratory (CTL) for handling very hazardous chemicals. It is designed to protect the workers, prevent the release of the chemical toxicant into the surrounding environment, and provide for the scientific integrity of the experiments conducted. A discussion of laboratory ventilation and special containment devices is presented. The design of the CTL, coupled with a realistic set of safety guidelines, provides for the safe conduct of research involving highly toxic chemicals.

Centers for Disease Control and Prevention, U.S.↗

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↗

The laboratory's role in environmental health emergency investigations.

An emergency environmental health investigation of a mass poisoning of unknown origin is a multidiscipline effort that requires the cooperation and close communication of epidemiologists, toxicologists, and chemists. The laboratory's role in this effort is important; special instruments, knowledge, and experience are needed. Our approach to such an investigation is discussed and past cases are used as illustrations. The role of the analytical chemist is presented, and the major resources needed for these investigations are described.

Animals↗

Assessment of a scheme for prioritizing inorganic toxicants by using signs-and-symptoms analysis.

In cases of exposure to unknown substances, analyzing environmental or biological samples for elevated levels of toxicants can be extremely complex. We assessed a method for prioritizing toxic substances according to the agreement between toxic-specific and incident-reported signs and symptoms by analyzing 25 reported case histories of exposure to inorganic toxicants. In all but one case, this analysis scheme successfully prioritized toxicants for subsequent analysis. Despite its limitations, the scheme is a substantial improvement over other available methods.

Diagnosis, Differential↗

Simultaneous quantification of erythrocyte zinc protoporphyrin and protoporphyrin IX by liquid chromatography.

A simple, rapid, specific, and sensitive isocratic "high-performance" liquid-chromatographic procedure is described for measuring protoporphyrin (PPIX) and zinc protoporphyrin (ZPP) in erythrocytes. A 30-microL whole-blood sample is treated with a solution of formic acid, deproteinized with acetone, and centrifuged. A 20-microL aliquot of the supernate is injected into a system consisting of a stationary phase of mu-Bondapak C18 and a mobile phase of acetone, methanol, water, and formic acid. ZPP and PPIX are detected fluorometrically (lambda ex = 417 nm, lambda em = 635 nm) within 6 min. The range of linearity extends beyond 10 mg/L for ZPP and 580 micrograms/L for PPIX. The detection limits for ZPP and PPIX are 11.9 micrograms/L (6.93 pg) and 2.55 micrograms/L (1.485 pg), respectively. The precision for ZPP and PPIX determinations averaged 2.86 and 5.59%, respectively, for within-day CVs and 4.98 and 8.14, respectively, for among-day CVs. Analytical recoveries averaged 97.2% for ZPP and 101.5% for PPIX. Interferences in the form of fluorescent quenching of ZPP and PPIX by hemin are avoided by chromatographic separation. We also used this method to determine the purity of commercially prepared ZPP, and compared the results obtained with this method with those from an extraction method.

Chromatography, High Pressure Liquid↗

Assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure using a modified D-glucaric acid assay.

An enzyme-inhibition assay was evaluated and modified to quantify D-glucaric acid in a population exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The modified assay combined improvements described separately in previous reports, including pH adjustment by standard addition of buffers rather than by titration, an optimum pH of 2.3 for converting D-glucaric acid to 1,4-glucarolactone, and the use of the relation reciprocal of absorbance versus concentration for calculating unknowns. Reference limits for adult males were 0.06-5.90 mmol D-glucaric acid/mol creatinine and for adult females 0.87-6.23 mmol D-glucaric acid/mol creatinine. Children under the age of 15 yr had a reference range of 0-8.34 mmol D-glucaric acid/mol creatinine. Persons on anticonvulsant therapy excreted from 3 to 10 times the upper reference limits of D-glucaric acid. Urinary concentrations of D-glucaric acid in persons identified as being at high risk for exposure to 2,3,7,8-TCDD in Times Beach, Mo., were not significantly different from concentrations in those identified as being at low risk for such exposure.

Adolescent↗

2,3-butanediol: an unusual metabolite in the serum of severely alcoholic men during acute intoxication.

In a controlled experiment 15 (79%) of 19 severely alcoholic men but only 1 of 22 controls had a serum concentration of greater than or equal to 5 mumol/l 2,3-butanediol after ingestion of distilled spirits. Another diol, 1,2-propanediol, was found in a concentration of greater than or equal to 5 mumol/l in all patients' specimens after drinking; but it was also present in lower concentrations in the reference specimens of most of the patients. These data are consistent with the experimental evidence that ethanol can be metabolised in rats to produce 2,3-butanediol and with the epidemiological hypothesis that severely alcoholic men metabolise ethanol by a different pathway than do control subjects.

Acute Disease↗

Gas-liquid chromatographic determination of polychlorinated biphenyls and a selected number of chlorinated hydrocarbons in serum.

A method is proposed for concurrently determining the levels of multiple intact exogenous compounds in serum, particularly polychlorinated biphenyls (PCBs) as Aroclor (AR) 1254 and chlorinated hydrocarbons (CHs). Bovine serum pools containing in vivo-bound PCBs (as AR 1254) and in vitro-spiked CHs are used to evaluate the method, which encompasses serum denaturation with methanol, mixed solvent extraction, multiple solvent fractionation from activated silica gel, and determination by electron capture gas-liquid chromatography. Mean recoveries of the in vitro-spiked 9 CHs at levels of 2.0-29.1 ppb ranged from 52.8 to 98.4% from trial environmental pools; mean recoveries of the in vivo-bound PCBs (as AR 1254) were 114.1 and 92.6% at levels of 10 and 50 ppb, respectively.

Animals↗

Assessment of methods to determine PCB levels in blood serum: interlaboratory study.

Twenty-five laboratories participated in a study to determine the levels of polychlorinated biphenyls (PCBs) in 3 bovine serum pools, referred to as trial environmental pools (TEPs). TEPs 2 and 3 contained, respectively, low (9.97 ppb) and high (49.64 ppb) levels of PCBs (as in vivo-bound Aroclor 1254) and the same level of 9 commonly occurring chlorinated hydrocarbons. TEP 1 contained only naturally occurring levels of these analytes. Laboratories analyzed each sample in duplicate by the method used in their laboratory for measuring PCBs in blood serum. The coefficients of variation (CV) for the 12 laboratories reporting quantitative data and the required number of analyses for TEP 2 and TEP 3 were 37.0 and 30.7%, respectively. The mean recoveries for these 12 laboratories were 239.3 and 165.4% for TEP 2 and TEP 3, respectively. Three laboratories reported data with mean values for TEP 2 and TEP 3 within +/- 3 standard deviations of the CDC characterized mean. Their coefficients of variation were 12.4 and 18.8% for TEP 2 and TEP 3, respectively. The mean recoveries for these 3 laboratories were 150.7 and 98.4% for TEP 2 and TEP 3, respectively. Our most significant observations were the laboratories' failure to separate PCBs from DDTs and the excessive background of the reagent blanks. The widely discrepant results indicate a definite need to standardize methodology for this analysis.

Animals↗

Evaluation of potential analytical approach for determination of polychlorinated biphenyls in serum: interlaboratory study.

Forty-four laboratories participated in evaluation of a method for determining polychlorinated biphenyls (PCBs) as AR 1254 in serum at the parts per billion level. The method involves deproteinating serum with methanol, extracting with hexane-ethyl ether, and eluting PCBs from deactivated silica gel for gas-liquid chromatographic determination with electron capture detection. Compounds are quantitated by using the Webb-McCall factors. Five serum pools, 4 containing in vivo-fortified PCBs (as AR 1254) or 8 in vitro-fortified chlorinated hydrocarbons (CHs), or both, were used. For PCB fortification levels of 9.89 (EP 2), 24.74 (EP 3), and 74.20 ppb (EP 4), interlaboratory coefficients of variation (CVs) for collaborators that adhered to protocol were 92.7, 67.6, and 25.8%, respectively. CVs on the same pools analyzed by the Centers for Disease Control (CDC) were 7.4, 7.8, and 4.6%, respectively. Average interlaboratory recoveries for pools EP 2, EP 3, and EP 4 were 138.1, 111.2, and 91.1%, respectively, and 99.8, 89.6, and 90.4%, respectively, for CDC on the same pools. There was a general decrease in the mean error for those laboratories that had participated in an earlier study in which they were allowed to use their own methods.

Animals↗