Indoor exposure to airborne endotoxin: a review of the literature on sampling and analysis methods.

Assessment of exposure to airborne endotoxins has been studied for several years, especially in occupational environments, but a large number of procedures are used for sampling and analysis. This lack of standardization makes it very difficult to compare results and set internationally accepted threshold limit values (TLVs) or occupational exposure limits (OELs) for endotoxin exposure. This paper reviews the methods reported, using advanced bibliographical search techniques: 82 papers published from 2004 to the present were selected to analyze methods for the assessment of human exposure to airborne endotoxins, with particular reference to occupational settings, and to examine their performance and critical points. Only few studies have focused on the standardization of sampling and analysis methods. The European Committee for Standardization Guidelines coincide with the procedures most frequently applied, but this does not guarantee the best results in terms of recovery and reproducibility. The factor that mainly affects endotoxin measurements is the extraction method, the main concern being the presence in the samples of a fraction insoluble in aqueous media. If substantial differences in the proportions of this fraction in different environments are confirmed in the future, the contribution of insoluble endotoxins cannot be neglected.

Urinary metabolite concentrations of phthalate metabolites in Central Italy healthy volunteers determined by a validated HPLC/MS/MS analytical method.

The main objective of this study was to determine the average concentrations for the metabolites of the four more common phthalates, industrial chemicals widely used in commercial products and potential endocrine disruptors, in the urine of a control population living in Central Italy. The study population consisted of 157 healthy subjects, not occupationally exposed to phthalates (74 males and 83 females). Urinary levels of the analytes were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) with isotopic dilution. The reference values (geometric mean) for males and females were estimated for each metabolite:. Females: for MEP was 72.94µg/g creatinine (CI 95% 3.63-149.51), for MEHP was 3.37µg/g creatinine (CI 95% 1.85-4.89), for MEHHP was 12.74µg/g creatinine (CI 95% 9.45-22.19), for MnBP was 20.26µg/g creatinine (CI 95% 8.17-28.43) and for MBzP was 14.74 (CI 95% 2.94-17.68). Males: for MEP was 56.35µg/g creatinine (CI 95% 2.32-110.39), for MEHP was 2.80µg/g creatinine (CI 95% 1.08-4.52), for MEHHP was 10.77µg/g creatinine (CI 95% 6.18-16.95), for MnBP was 17.59µg/g creatinine (CI 95% 5.72-29.45) and for MBzP was 16.44 (CI 95% 7.90-29.45). To obtain reference values for these chemicals is without doubt an important topic for evaluate the exposure of population and their possible health effects. Information from different geographical areas are important to understand the real different background concentrations.

Quantitative determination of the 1,3-butadiene urinary metabolite 1,2-dihydroxybutyl mercapturic acid by high-performance liquid chromatography/tandem mass spectrometry using polynomial calibration curves.

1,3-Butadiene is used in the production of synthetic rubber and is also a widespread environmental pollutant, produced by car exhaust, heating and cigarette smoke. According to IARC it is probably carcinogenic to humans. A method was developed and validated for the quantification in human urine of 1,2-dihydroxybutyl mercapturic acid, a butadiene metabolite for which the American Conference of Governmental Hygienists suggests a biological exposure index of 2500 microg/L. Solid phase extraction was used for analyte extraction and HPLC-MS/MS for detection. The calibration range from 20 to 2500 microg/L required the use of polynomial calibration curves, and the performance of the analytical method was tested according to an international validation guideline. Accuracy was never less than 85%, precision always higher than 15% and the LOD 3.6 microg/L. The method was applied to 33 non-smokers, non-occupationally exposed to butadiene, and gave urinary concentrations between 16 and 599 microg/L.

Intraobserver, interobserver, and day-to-day reproducibility of quantitative 99mTc-HYNIC annexin-V imaging in head and neck carcinoma.

RATIONALE: For clinical application, a sufficient reproducibility of 99mTc-HYNIC annexin-V quantitative uptake measurements must be demonstrated to allow a study of cell-death changes induced by chemotherapy over time and intersubject. Thus, the aim of this study was to estimate the intra-, inter-, and day-to-day reproducibility of quantitative 99mTc-HYNIC annexin-V tumor uptake values in patients suffering from head and neck carcinomas. METHODS: Thirteen (13) patients suffering from clinically suspected, histologically confirmed squamous head and neck carcinomas were prospectively included in the study. All patients were scheduled to undergo a spiral computed tomography scan and two 99mTc-HYNIC annexin-V scintigraphies within 3-5 days from each other, referred to as day 1 and day 2 of scintigraphy. The percentage of uptake of the injected dose of 99mTc-HYNIC annexin-V in tumor lesions on scintigrams divided by the tumor volume, as derived from CT, was determined twice within an interval of 2 weeks by observer 1 and once by observer 2 on day 1 of scintigraphy and once on day 2 of scintigraphy by observer 1. RESULTS: The mean of the difference for the intra-, inter-, and day-to-day measurements were -3.4%, 2.4%, and -6%, respectively. No systematic bias was observed for the mean of the differences for the intra-, inter-, and day-to-day measurements. The respective confidence intervals for the mean of the differences of intra-, inter-, and day-to-day variability were -8.2%-1.4%, -2.9%-7.8%, and -14.7%-2.7%. CONCLUSION: The reproducibility of quantitative 99mTc-HYNIC annexin-V tumor uptake measurements using a manual method appears to be acceptable for clinical use.

Estimate of uncertainty of measurement from a single-laboratory validation study: application to the determination of lead in blood.

BACKGROUND: Lead is an environmental pollutant, and human exposure is assessed by monitoring lead concentrations in blood. Because the main source of environmental exposure has been the use of leaded gasoline, its phase-out has led to decreased lead concentrations in the general population. Therefore, validated analytical methods for the determination of lower lead concentrations in blood (<150 microg/L) are needed. In addition, new ISO standards require that laboratories determine and specify the uncertainty of their results. METHODS: We validated a method to determine lead in blood at concentrations up to 150 microg/L by electrothermal atomic absorption spectrometry with Zeeman background correction according to EURACHEM guidelines. Blood samples were diluted (1:1 by volume) with 2 mL/L Triton X-100. NH4H2PO4 (5 g/L) and Mg(NO3)2 (0.5 g/L) were used as modifiers. Matrix-matched standards were used for calibration. RESULTS: We determined the limits of detection (3.1 microg/L) and quantification (9.4 microg/L). Repeatability and intermediate imprecision within the range 35-150 microg/L were <5.5% and <6.0%, respectively. We assessed trueness by use of certified reference materials, by recovery tests, and by comparison with target values of other reference materials (candidate external quality assessment samples). The expanded uncertainty ranged from 20% to 16% (with a confidence level of 95%) depending on concentration. CONCLUSIONS: This study provides a working example of the estimate of uncertainty from method performance data according to the EURACHEM/CITAC guidelines. The estimated uncertainty is compatible with quality specifications for the analysis of lead in blood adopted in the US and the European Union.

Biological imaging for the diagnosis of inflammatory conditions.

Radiopharmaceuticals used for in vivo imaging of inflammatory conditions can be conveniently classified into six categories according to the different phases in which the inflammatory process develops. The trigger of an inflammatory process is a pathogenic insult (phase I) that causes activation of endothelial cells (phase II); there is then an increase of vascular permeability followed by tissue oedema (phase III). Phase IV is characterised by infiltration of polymorphonuclear cells, and a self-limiting regulatory process called apoptosis is observed (phase V). If the inflammatory process persists, late chronic inflammation takes place (phase VI). In some pathological conditions, such as organ-specific autoimmune diseases, chronic inflammation is present early in the disease. The aim of nuclear medicine in the field of inflammation/infection is to develop noninvasive tools for the in vivo detection of specific cells and tissues. This would allow early diagnosis of initial pathophysiological changes that are undetectable by clinical examination or by other diagnostic tools, and could also be used to evaluate the state of activity of the disease during therapy. These potential applications are of great interest in clinical practice. In this review, we describe the various approaches that have been developed in the last 25 years of experience. Recent advances in the diagnosis of inflammatory processes have led to the development of specific radiopharmaceuticals that are intended to allow specific stage-related diagnosis.