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Biomedical subjects

L A Wallace

Publications and source records attributed to L A Wallace.

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

Use of PCR in resolving diagnostic difficulties potentially caused by genetic variation of hepatitis B virus.

AIMS: To assess the relevance of genetic variants of hepatitis B virus (HBV) and to demonstrate the usefulness of the polymerase chain reaction (PCR) in cases of HBV diagnostic difficulty. METHODS: Five serum samples from patients that presented diagnostic difficulty in routine laboratories were sent to a research laboratory for PCR, and if appropriate, S gene sequencing, in vitro expression, and antigenic analysis. RESULTS: The demonstration of HBV in serum by PCR allowed a definitive diagnosis of current infection. One serum sample with poor reactivity in a diagnostic assay had a minor hepatitis B surface antigen (HBsAg) variant and another with very poor reactivity had multiple variants of HBsAg. Transient HBsAg reactivity was observed in a recently vaccinated patient. A hepatitis Be antigen (HBeAg) false positive reaction was noted in a patient from a well defined risk group for HBV. One patient who was strongly HBsAg/HBeAg positive, but anti-hepatitis B core antibody negative, was viraemic. CONCLUSIONS: PCR may become the gold standard for the diagnosis of current HBV infection. HBV variants are responsible for a proportion of diagnostically difficult cases. Modification of commercial assays is necessary to increase the sensitivity of detection of such variants.

Adult↗
PubMed1998

Effect of water temperature on dermal exposure to chloroform.

We have developed and applied a new measurement methodology to investigate dermal absorption of chloroform while bathing. Ten subjects bathed in chlorinated water while breathing pure air through a face mask. Their exhaled breath was delivered to a glow discharge source/ion trap mass spectrometer for continuous real-time measurement of chloroform in the breath. This new method provides abundant data compared to previous discrete time-integrated breath sampling methods. The method is particularly well suited to studying dermal exposure because the full face mask eliminates exposure to contaminated air. Seven of the 10 subjects bathed in water at two or three different temperatures between 30 degrees C and 40 degrees C. Subjects at the highest temperatures exhaled about 30 times more chloroform than the same subjects at the lowest temperatures. This probably results from a decline in blood flow to the skin at the lower temperatures as the body seeks to conserve heat forcing the chloroform to diffuse over a much greater path length before encountering the blood. These results suggest that pharmacokinetic models need to employ temperature-dependent parameters. Two existing models predict quite different times of about 12 min and 29 min for chloroform flux through the stratum corneum to reach equilibrium. At 40 degrees C, the time for the flux to reach a near steady-state value is 6-9 min. Although uptake and decay processes involve several body compartments, the complicating effect of the stratum corneum lag time made it difficult to fit multiexponential curves to the data; however, a single-compartment model gave a satisfactory fit.

Adult↗
PubMed1997

Body burden measurements and models to assess inhalation exposure to methyl tertiary butyl ether (MTBE).

Biomarkers of methyl tertiary butyl either (MTBE) exposure and the partitioning of inhaled MTBE into the body were investigated in a human chamber study. Two subjects were exposed to an environmentally relevant nominal 5,011 micrograms/m3 (1.39 ppm) MTBE for 1 hour, followed by clean-air exposure for 7 hours. Breath and blood were simultaneously sampled, while total urine was collected at prescribed times before, during, and after the exposure. Mass-balance and toxicokinetic analyses were conducted based upon the time series measurement of multiple body-burden endpoints, including MTBE in alveolar breath, and MTBE and tertiary butyl alcohol (TBA) in venous blood and urine. The decay of MTBE in the blood was assessed by fitting the post-exposure data to a 2- or 3-exponential model that yielded residence times(tau) of 2-3 min, 15-50 min, and 3-13 h as measured by alveolar breath, and 5 min, 60 min, and 32 h as evaluated from venous blood measurements. Based on observations of lower than expected blood and breath MTBE during uptake and a decreasing blood-to-breath ratio during the post-exposure decay period, we hypothesize that the respiratory mucous membranes were serving as a reservoir for the retention of MTBE. The decay data suggest that 6-9% of the MTBE intake may be retained by this non-blood reservoir. The compartmental modeling was further used to estimate important parameters that define the uptake of inhaled MTBE. The first of these parameters is f, the fraction of C(air) exhaled at equilibrium, estimated as 0.60 and 0.46 for the female and male subject, respectively. The second parameter is the blood-to-breath partition coefficient (P) estimated as approximately 18. The product of these parameters provides an estimate of the blood concentration at equilibrium as 8-11 times the air concentration. Blood TBA lagged MTBE levels and decayed more slowly (tau = 1.5-3 h), providing a more stable indication of longer term integrated exposure. The concentration ranges of MTBE and TBA in urine were similar to that of the blood, ranging from 0.37 to 15 micrograms/L and 2 to 15 micrograms/L, respectively. In urine, MTBE and TBA by themselves bore little relationship to the exposure. However, the MTBE:TBA ratio followed the pattern of exposure, with peak values occurring at the end of the exposure (20- and 60-fold greater than pre-exposure values) before decaying back to pre-exposure levels by the end of the 7-h decay period. Urinary elimination accounted for a very small fraction of total MTBE elimination (< 1%).

Administration, Inhalation↗
PubMed1995

Recent advances in measuring exhaled breath and estimating exposure and body burden for volatile organic compounds (VOCs).

An improved portable breath measurement method has been developed that allows 1-min sampling times. The equipment has been successfully tested in field and chamber studies. Results of these studies suggest that breath levels following known exposures are predictable and reproducible across a small number of volunteers. The residence times in the body and the distribution in body compartments of several common air toxics have been determined. A simple four-compartment linear model is capable of fitting the observed data. The main parameters of the model include the fraction f of the parent compound exhaled under steady-state conditions and the residence times tau i, in the tau ith compartment. The values of these parameters for several VOCs and for the four body compartments (blood, vessel-rich tissues, vessel-poor tissues, and fat) are provided.

Body Burden↗
PubMed1994

Clinical implications of hepatitis B virus envelope protein variation.

The envelope proteins of hepatitis B virus are highly conserved. They are involved in viral attachment to hepatocytes, virion assembly and secretion and induction of humoral and T-cell immune responses. The major neutralisation epitope is located within the S protein and is conformation dependent, probably due to the formation of disulphide bridges. Variation in the envelope proteins of hepatitis B virus has been described in vaccinees and in patients receiving monoclonal and polyclonal antibody therapy. These arise through point mutations in the surface gene and appear to be selected by the immune response. The emergence of such variants has clinical relevance, in particular with regard to vaccine failure and diagnostic difficulties.

Amino Acid Sequence↗
PubMed1994

Molecular characterization of envelope antigenic variants of hepatitis B virus from Spain.

In a survey of hepatitis B virus (HBV) subtypes using one set of monoclonal typing antibodies, 96.6% of the samples were ad or ay and 3.3% (31) were untypeable. Using two additional antibody panels, 23 samples were ay and ad. Six samples required a third panel to be typed as ay. One sample was not typeable. These last 7 samples were nonreactive or had low reactivity with some antibodies to the common a determinant. Sequencing the HBsAg gene of these 7 samples revealed that amino acid (aa) 122 was arginine, as expected for the y determinant. However, mutations giving rise to serine at aa 120, leucine at aa 143, and glutamic acid at aa 144 were found singly or in combination and correlated with the monoclonal antibody binding patterns. These results have implications for further subtyping surveys, vaccines, immunotherapy, and the design of diagnostic assays, and they give clues to the structure of the major neutralizing epitope of HBV.

Amino Acid Sequence↗
PubMed1994

Can long-term exposure distributions be predicted from short-term measurements?

A method for estimating long-term distributions of exposure based on repeated short-term measurements within the same population is developed. If the short-term measurements span seasonal variation, and if the distributions are log-normal or nearly so, then long-term distributions can be estimated from as few as two visits to the same population. The method is illustrated using examples drawn from EPA's TEAM Study of exposures to volatile organic compounds.

Air Pollutants↗
PubMed1991

Comparison of risks from outdoor and indoor exposure to toxic chemicals.

Environmental Protection Agency TEAM (Total Exposure Assessment Measurement) Studies have measured exposures of about 800 persons to 25 volatile organic compounds (VOCs) and exposures of about 300 persons to 32 pesticides. These persons were selected to represent more than 1 million residents of industrial manufacturing cities such as Bayonne and Elizabeth, New Jersey, and Los Angeles, California; cities with light industry, such as Greensboro, North Carolina, and Baltimore, Maryland; rural areas such as Devils Lake, North Dakota; and cities with high pesticide use such as Jacksonville, Florida, as well as low-to-moderate pesticide use such as Springfield, Massachusetts. The TEAM data provide an opportunity to estimate the risks from airborne exposure to a number of suspected carcinogens for a substantial number of persons residing in a wide variety of urban, suburban, and rural areas. Because all of the TEAM Studies measured outdoor concentrations near the homes of the participants, it is possible to apportion the risks between outdoor and indoor sources. Upper-bound lifetime risks of cancer are calculated for both indoor and outdoor sources of 12 VOCs and about 23 pesticides measured in the TEAM Studies. These risk calculations are supplemented by calculations based on other studies for some additional pollutants, including radon and environmental tobacco smoke. The relationship of these upper-bound risk estimates to "best-guess" values is discussed. Sharper estimates of risk based on identifying population subgroups exposed to major sources are also discussed. Important gaps in our knowledge of exposure measurements are identified, e.g., particulates (including polyaromatic hydrocarbons); 1,3-butadiene, asbestos, chromium, cadmium, arsenic, vinyl chloride, methylene chloride, and most polar organics.

Air Pollution↗
PubMed1990

Controlled comparison of the characteristics of long-term benzodiazepine users in general practice.

From three general practices, served by 11 principals, 205 long-term benzodiazepine users were identified and matched for age and sex with controls. Benzodiazepine users had significantly higher rates of previous physical illness, consultation and non-psychotropic drug consumption than controls. The characteristics of those receiving prescriptions for benzodiazepine hypnotics alone, anxiolytics alone and anxiolytics plus hypnotics were also investigated. Significant differences emerged between these three groups. Patients receiving hypnotics only were older, had a history of more physical illness and had received more non-psychotropic medication than patients receiving anxiolytics only. The anxiolytic plus hypnotic group had previously received more hypnotics and were currently receiving more medication than the group receiving anxiolytics alone. The results are discussed in relation to current concerns about benzodiazepine dependence and withdrawal.

Adult↗
PubMed1990

Controlled comparison of pharmacological and psychological treatment of generalized anxiety disorder in primary care.

A sample of 101 patients with generalized anxiety disorder were randomly allocated to one of five groups--diazepam, placebo, cognitive-behaviour therapy, diazepam plus cognitive-behaviour therapy, or placebo plus cognitive-behaviour therapy--and treated over 10 weeks in a primary care setting. All groups received a similar amount of contact with the psychologist and general practitioner. The greatest improvement in ratings of severity of symptoms and overall change in symptoms occurred with cognitive-behaviour therapy combined with diazepam; cognitive-behaviour therapy alone also performed well and cognitive-behaviour therapy plus placebo performed slightly less well. Diazepam alone showed improvement relative to placebo alone. There was a high level of agreement between ratings by the general practitioners, psychologist, and the patients of the response to treatment. At six months follow-up there was no difference between treatment groups in the proportion of patients receiving psychotropic medication after the end of the study. However, cognitive-behaviour therapy, either alone or in combination with drug or placebo, showed the lowest incidence of referral for psychological or psychiatric treatment at six months follow-up.

Adult↗
PubMed1989

The influence of personal activities on exposure to volatile organic compounds.

Seven persons volunteered to perform 25 common activities thought to increase personal exposure to volatile organic chemicals (VOCs) during a 3-day monitoring period. Personal, indoor, and outdoor air samples were collected on Tenax cartridges three times per day (evening, overnight, and daytime) and analyzed by GC-MS for 17 target VOCs. Samples of exhaled breath were also collected before and after each monitoring period. About 20 activities resulted in increasing exposure to one or more of the target VOCs, often by factors of 10, sometimes by factors of 100, compared to exposures during the sleep period. These concentrations were far above the highest observed outdoor concentrations during the length of the study. Breath levels were often significantly correlated with previous personal exposures. Major exposures were associated with use of deodorizers (p-dichlorobenzene); washing clothes and dishes (chloroform); visiting a dry cleaners (1,1,1-trichloroethane, tetrachloroethylene); smoking (benzene, styrene); cleaning a car engine (xylenes, ethylbenzene, tetrachloroethylene); painting and using paint remover (n-decane, n-undecane); and working in a scientific laboratory (many VOCs). Continuously elevated indoor air levels of p-dichlorobenzene, trichloroethylene, 1,1,1-trichloroethane, carbon tetrachloride, decane, and undecane were noted in several homes and attributed to unknown indoor sources. Measurements of exhaled breath suggested biological residence times in tissue of 12-18 hr and 20-30 hr for 1,1,1-trichloroethane and p-dichlorobenzene, respectively.

Activities of Daily Living↗
PubMed1989

An enzyme-linked immunosorbent assay for antibodies to the envelope glycoproteins of divergent strains of HIV-1.

We have developed an enzyme-linked immunosorbent assay (ELISA) specific for antibodies to the envelope glycoproteins gp120 and gp160 of HIV-1. An antibody to a conserved epitope on gp120 is adsorbed to a solid phase and used to capture gp120 and/or gp160 from solution. This may be purified recombinant protein or in simple, non-denaturing detergent extracts of different strains of HIV-1. Human serum antibodies bound to the captured antigen are subsequently detected with an anti-human antibody conjugated to alkaline phosphatase, and the AMPAK ELISA amplification system (Novo BioLabs, Cambridge, UK). With this procedure, antibodies can be detected that recognize gp120 from a wide range of divergent HIV-1 strains. The ELISA is sufficiently sensitive to detect env antibodies in sera from HIV-positive individuals at dilutions of 1:300,000. No repeatable false-positives were detected in a screen of 250 normal serum samples. Env antibodies were detected in all 37 strongly HIV-positive sera tested, and in four sera that were borderline or weakly positive in commercial ELISA. However, 55 sera positive in commercial ELISA but unconfirmable by Western blot ('ambiguously' positive) did not contain detectable env antibodies.

Animals↗
PubMed1989

Major sources of benzene exposure.

Data from EPA's TEAM Study allow us to identify the major sources of exposure to benzene for much of the U.S. population. These sources turn out to be quite different from what had previously been considered the important sources. The most important source of exposure for 50 million smokers is the mainstream smoke from their cigarettes, which accounts for about half of the total population burden of exposure to benzene. Another 20% of nationwide exposure is contributed by various personal activities, such as driving and using attached garages. (Emissions from consumer products, building materials, paints, and adhesives may also be important, although data are largely lacking.) The traditional sources of atmospheric emissions (auto exhaust and industrial emissions) account for only about 20% of total exposure. Environmental tobacco smoke is an important source, accounting for about 5% of total nationwide exposure. A number of sources sometimes considered important, such as petroleum refining operations, petrochemical manufacturing, oil storage tanks, urban-industrial areas, service stations, certain foods, groundwater contamination, and underground gasoline leaks, appear to be unimportant on a nationwide basis.

Air Pollutants, Occupational↗