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PubMed2002

Application of gas chromatography-tandem mass spectrometry to the analysis of pesticides in fruits and vegetables.

A new analytical method was devised using gas chromatography with tandem mass spectrometry (GC-MS-MS) for the routine analysis of 31 multi-class pesticide residues and approximately 8000 fresh fruit and vegetable samples (green bean, cucumber, pepper, tomato, eggplant, watermelon, melon, and marrow). Extraction of the pesticides with dichloromethane was carried out. The optimal ionization mode, either electron impact or chemical ionization, was selected for each pesticide in the same run. Carbofrit was used in the liner and combined with the selectivity of the detector this avoided additional clean-up. Thus, not only was money and time saved, the uncertainty of the method was decreased in its application to routine analysis. The average recoveries in cucumber obtained for each pesticide ranged between 71 and 119% at two different fortification levels (n=10 each) that ranged between 7 and 300 ng g(-1) (depending on the pesticide). The relative standard deviation was lower than 19% for all compounds tested. The calculated limits of detection and quantification were typically <1 ng g(-1) which were much lower than the maximum residue levels established by European legislations.

Fruit↗
PubMed1998

A validation of a flow quantification by MR phase mapping software.

AIM: We evaluated a Siemens software of flow quantification (FQ) by MR phase mapping, in the framework of a common practical use. METHODS: Experiments with a laminar flow phantom and in vivo pulsatile flow were performed. In particular, FQ in ascending aorta was investigated in healthy volunteers. RESULTS AND CONCLUSION: Flow phantom experiments reveal that the FQ slightly underestimates (8% on the average) actual velocities (mean velocities over a vessel area), and also that velocity uncertainties are related to the encoding velocity value, whatever the measured velocity. Furthermore, using well characterized working criteria, we found low intraobserver variability and negligible interobserver variability in ascending aorta FQs. The role played by the choice of reference area in FQ accuracy is emphasized. When recording several cardiac cycles during the same acquisition, it is shown that the FQ software may provide erroneous results. Several comments for FQ software use in the ascending aorta are added.

Adult↗
PubMed1996

Estimation of the C-cell numbers in rat thyroid glands using the optical fractionator.

We estimated the total number of calcitonin-immunoreactive C-cells in rat thyroid gland using the optical fractionator, the unbiased stereological method for estimation of numbers. It was necessary first to use a fixative composed of formalin, acetic acid, and ethanol to distinctly visualize the C-cells. The 40-microm-thick sections had to adhere to chromalum-gelatin-coated Superfrost Plus glass slides, and the immunostaining technique had to stain the C-cells evenly throughout the whole sections. Because the C-cells were irregularly distributed in the thyroid tissues, their counting required screening of about 500 fields per lobe, but the number of C-cells counted need not be high, about 90 per lobe. We estimated that rats have 185,000 +/- 42,000 C-cells (mean +/- SD; n - 7). The C-cell population did not differ significantly between the two lobes of a given rat, but it varied markedly among rats. The biological differences among the animals contributed 83% to the observed variability, whereas the methodological uncertainty contributed 17%. The serum levels of calcitonin and calcium were not closely correlated to the C-cell numbers. Our results indicate that variability in C-cell experiments can be reduced most effectively by increasing the number of animals used. However, the similar C-cell frequency found in the two thyroid lobes of each rat allows the use of one uniformly sampled lobe for quantification and the other lobe for further analysis.

Animals↗
PubMed1992

Prospects for improving the efficacy of BCG.

Since 1976, when Morales, Eidinger and Bruce first published on the treatment of human urothelial bladder cancer, bacillus Calmette-Guérin has gained worldwide acceptance as a therapy against bladder carcinoma recurrences. However, there are many uncertainties with regard to patient selection, treatment protocol, reduction of side effects, mechanisms of action, and thus room enough for laboratory researchers and clinicians to contribute to the improvement of BCG therapy. Initiation of mycobacterial binding to urothelial cells may be promoted by methods which increase fibronectin exposure on target cells, reduce inhibitory factors in the instillate, or by identification of more avidly binding substrains of BCG. Quantification of the ensuing immune response focuses on the local rather than the systemic immune reaction of the host and may give the opportunity to predict a favourable response, or even the endpoint of therapy. For this purpose, assessment of local cytokine production seems to be a valuable tool. Ultimately, revealing the mode of action(s) of live BCG may render the use of potentially dangerous live bacilli unnecessary and lead to the application of derivatives with better results.

BCG Vaccine↗
PubMed2003

Characterization and propagation of uncertainty in diffusion-weighted MR imaging.

A fully probabilistic framework is presented for estimating local probability density functions on parameters of interest in a model of diffusion. This technique is applied to the estimation of parameters in the diffusion tensor model, and also to a simple partial volume model of diffusion. In both cases the parameters of interest include parameters defining local fiber direction. A technique is then presented for using these density functions to estimate global connectivity (i.e., the probability of the existence of a connection through the data field, between any two distant points), allowing for the quantification of belief in tractography results. This technique is then applied to the estimation of the cortical connectivity of the human thalamus. The resulting connectivity distributions correspond well with predictions from invasive tracer methods in nonhuman primate.

Algorithms↗
PubMed1998

In vivo nuclear transport kinetics in Saccharomyces cerevisiae.

We have described a direct fluorescence assay to measure the relative rates of NLS-directed import and passive export of an NLS-GFP fusion protein in yeast. The design and construction of the reporter GFP fusion, its spectral qualities, size, use of inducible promoters, and the choice of NLS, are variables that could extend the method's utility. Future applications will almost certainly demand the quantification of transport rates in single cells using image analysis techniques. As is the case whenever cellular processes are studied in vivo, the in vivo nuclear trafficking properties of NLS-GFP are complicated and poorly understood. Some will be attracted to NLS-GFP kinetic assays simply because so little is known about the function and regulation of the transport apparatus in living cells. At the same time, the uncertainties that accompany in vivo work necessarily prevent the rigorous interpretation of data, which biochemists expect from experiments performed in vitro using highly purified enzymes.

Amino Acid Sequence↗
PubMed2005

Quantification of benzodiazepines in whole blood and serum.

A high-performance liquid chromatography method for the determination of benzodiazepines and their metabolites in whole blood and serum using mass spectrometry (MS) and photodiode array (PDA) detection is presented. The combination of both detection types can complement each other and provides extensive case relevant data. The limits of quantification (LOQ) with the MS detection lie between 2 and 3 microg/l for the following benzodiazepines or metabolites: 7-amino-flunitrazepam, alprazolam, desalkyl-flurazepam, desmethyl-flunitrazepam, diazepam, flunitrazepam, flurazepam, alpha-hydroxy-midazolam, lorazepam, midazolam, nitrazepam, nordazepam and oxazepam, respectively 5 microg/l for lormetazepam and 6 microg/l for bromazepam. The LOQ of clobazam determined with the PDA detector is 10 microg/l. A convenient approach for determining the measurement uncertainty of the presented method--applicable also for other methods in an accreditation process--is presented. At low concentrations (<10 microg/l), measurement uncertainty was estimated to be about 50%, and at concentrations >180 microg/l, it was estimated to be about 15%. One hundred and twenty-eight case data acquired over 1 year are summarised.

Anti-Anxiety Agents↗
PubMed2003

Survey of dioxin sources in the Baltic Region (extended summary).

The present paper summarises the results of the project: 'Survey of Anthropogenic Sources of Dioxins and Furans in the Baltic Region'. As a part of the project, inventories have been carried out in Estonia, Latvia, Lithuania and Poland by applying the toolkit for quantification of dioxin and furan releases developed by UNEP Chemicals. The main route of direct releases to the environment is emission to air. Total emission to air from Poland was estimated at 490 (88-1,300) g I-TEQ/year, whereas the emissions from Estonia, Latvia and Lithuania were estimated as being 14 (2.4-54), 23 (2.6-63) and 17 (2.6-38) g I-TEQ, respectively. In general, the uncertainty on the estimates is very high, and recommendations regarding further development of the inventories have been made, and measures for reducing the releases have been provided.

Air Pollutants↗
PubMed2006

Quantification of total native compounds on phenanthrene-specific adsorption sites in the very slow desorption domain of 16 sediments and soils.

We determined the maximum amount of added phenanthrene that could be adsorbed in the very slow desorption domain of 16 sediments and soils with and without native compounds present. The differences in the amount of phenanthrene taken up in this domain with and without native compounds present indicates to what extent native compounds occupy those adsorption sites in the very slow desorption domain which may accommodate phenanthrene. For the two aquifer materials, presence of native compounds was less than the uncertainty associated with the methodology. For the sediments, 41-84% of the adsorption sites appeared to be occupied by native compounds.

Adsorption↗
PubMed2005

Rapid quantification of bacteria in activated sludge using fluorescence in situ hybridization and epifluorescence microscopy.

A rapid quantification method for bacteria in activated sludge has been developed, based on fluorescence in situ hybridization (FISH) and epifluorescence microscopy. Samples are hybridized on slides and analyzed by direct microscopic observation. Abundance categories were designed based on digital images of the target organisms. These rating systems were developed for the filamentous bacteria Microthrix parvicella and for different morphotypes of nocardioform actinomycetes, but can easily be adapted to other types of microorganisms. Due to the quantification by direct microscopic observation, this method is suitable for samples that are difficult to be processed by semi-automated image analysis techniques, such as samples containing fluorescent debris, cells of different fluorescence intensities and target organisms that need partial enzymatic digestion prior to FISH. In contrast to commonly used rating systems consisting of photographs, the newly developed categories allow to quantitatively compare results of different categories and different organisms. The uncertainties of the results were calculated by a non-parametric bootstrap procedure; a thorough uncertainty analysis was performed including sample variability and operator subjectivity.

Bacteria↗
PubMed2005

Assessing occupational and environmental exposure.

Exposure assessment is a poorly understood component of the science of epidemiology. The relationship between exposure to chemicals and ill-health outcomes is often calculated using crude exposure measures such as ever/never exposed or duration. When investigating subtle effects, exposures need to be characterized much more fully in terms of intensity, frequency, duration and route. While occupational exposures tend to be much greater than those experienced from the wider environment there is a need to remember that, for many chemicals, exposure can occur occupationally, environmentally and through consumer use of products containing the material of interest. Inhalation exposure has generally been the traditional focus for most epidemiological investigations but there is now growing awareness of the importance of the dermal and ingested routes of contact and internalization. Quantification of the exposure also needs to be related to a biological mechanism of action and exposure metrics need to be selected accordingly. Occupational exposures can generally be measured using simple well-validated techniques. Environmental exposures require much more sensitive instruments and are more difficult to assess. Exposure modelling, particularly for the environmental fate of chemicals has undergone many recent developments and Monte Carlo techniques can be used to characterize model uncertainty and variability. This approach to exposure assessment can now be used in the setting of the wider environment and will enable a far better understanding of the relationship between exposure and disease.

Environmental Exposure↗
PubMed2005

Highly sensitive high-performance liquid chromatography/selective reaction monitoring mass spectrometry method for the determination of cyclophosphamide and ifosfamide in urine of health care workers exposed to antineoplastic agents.

In recent years, the potential for exposure of health care workers to antineoplastic agents has led to the establishment of more restrictive government and professional standards and procedures for handling cytotoxic drugs. Therefore, the detection of low exposure levels is a new and important aim of biological monitoring. In the present paper we report an assay for the simultaneous determination of cyclophosphamide (CP) and ifosfamide (IF) in urine, using electrospray ionization liquid chromatography/tandem mass spectrometry with selective reaction monitoring (HPLC/SRM-MS). A rapid sample preparation procedure uses a solid-phase extraction stage with C18 columns. The urine assay is linear over the range 0.02 to 0.4 microg/L, with lower limits of quantification (LLOQs) of 0.02 and 0.04 microg/L for CP and IF. The accuracy and precision have been carried out through the validation study. The intra-day precision, expressed as relative standard deviation (RSD), is found to be always less than 14.7% for both analytes. The overall precision, assessed on three different days, is less than 15.0%. The recovery of ozaxaphosphorines ranges from 83.5% (CP) to 88.5% (IF) with a RSD always less than 14.6%. The uncertainty of the overall method was also evaluated, to identify possible sources of error. The combined uncertainty was less than 25% over all the days of the validation study. This method is selective and sensitive enough to determine trace levels of CP and IF in a range of urine concentrations relevant to performing low exposure assessment.

Antineoplastic Agents↗
PubMed2006

Geometric stability of intracavitary pulsed dose rate brachytherapy monitored by in vivo rectal dosimetry.

BACKGROUND AND PURPOSE: To evaluate geometric stability of applicator and rectum during pulsed dose rate (PDR) intracavitary brachytherapy. PATIENTS AND METHODS: A total of 14 patients with cervical cancer (stages IIB-IVA) were analysed retrospectively. A dose of 10 Gy to point A was prescribed per brachytherapy session, and PDR was given with 1 Gy/pulse, 1 pulse/h, using a ring applicator (Varian). A rectal dosimeter consisting of five diodes spaced by 1.5 cm was routinely placed in the rectum. The diodes detected the progression of each pulse of radiation, as the stepping source was advanced through the applicator. A mathematical model has been developed for spatial analysis of the pattern of the dose readings. The model transforms dose measurement into a quantification of the geometric relationship between rectum diodes and applicator. RESULTS: The model could be used for all treatment sessions, and the relative positions of diodes and applicator were calculated for each pulse of radiation. The SD of displacements during the treatment was below 2.8mm in all directions for all patients. The mean SD in lateral, longitudinal and anterior-posterior directions were 1.2 +/- 0.7, 1.2 +/- 0.7 and 0.9 +/- 0.6 mm, respectively. The mean measurement uncertainty was below 0.8 +/- 0.5 mm in all directions. CONCLUSIONS: A new mathematical method has been developed, enabling us to quantitate and monitor relative positions of applicator and rectal diodes during a PDR treatment. The spatial relation between rectal dosimeter and applicator was very stable during extended PDR treatments suggesting that the geometric stability of PDR treatment is at the same level as the stability reported for HDR brachytherapy.

Algorithms↗
PubMed2006

Quantification problems in depth profiling of pwr steels using Ar+ ion sputtering and XPS analysis.

The oxide scales of AISI 304 formed in boric acid solutions at 300 degrees C and pH = 4.5 have been studied using X-ray photoelectron spectroscopy (XPS) depth profiling. The present focus is depth profile quantification both in depth and chemical composition on a molecular level. The roughness of the samples is studied by atomic force microscopy before and after sputtering, and the erosion rate is determined by measuring the crater depth with a surface profilometer and vertical scanning interferometry. The resulting roughness (20-30 nm), being an order of magnitude lower than the crater depth (0.2-0.5 microm), allows layer-by-layer profiling, although the ion-induced effects result in an uncertainty of the depth calibration of a factor of 2. The XPS spectrum deconvolution and data evaluation applying target factor analysis allows chemical speciation on a molecular level. The elemental distribution as a function of the sputtering time is obtained, and the formation of two layers is observed-one hydroxide (mainly iron-nickel based) on top and a second one deeper, mainly consisting of iron-chromium oxides.

Journal Article↗
PubMed2002

Quantitative trace element analysis of individual fly ash particles by means of X-ray microfluorescence.

A new quantification procedure was developed for the evaluation of X-ray microfluorescence (XRF) data sets obtained from individual particles, based on iterative Monte Carlo (MC) simulation. Combined with the high sensitivity of synchrotron radiation-induced XRF spectroscopy, the method was used to obtain quantitative information down to trace-level concentrations from micrometer-sized particulate matter. The detailed XRF simulation model was validated by comparison of calculated and experimental XRF spectra obtained for glass microsphere standards, resulting in uncertainties in the range of 3-10% for the calculated elemental sensitivities. The simulation model was applied for the quantitative analysis of X-ray tube and synchrotron radiation-induced scanning micro-XRF spectra of individual coal and wood fly ash particles originating from different Hungarian power plants. By measuring the same particles by both methods the major, minor, and trace element compositions of the particles were determined. The uncertainty of the MC based quantitative analysis scheme is estimated to be in the range of 5-30%.

Air Pollutants, Occupational↗
PubMed1999

Methodologic issues in epidemiologic risk assessment.

This paper reviews methodologic issues pertinent to the application of epidemiology in risk assessment and discusses concerns in the presentation of results from such an activity. Assessment of the health risks associated with occupational and environmental exposures involves four phases: hazard identification, i.e., the detection of the potential for agents to cause adverse health effects in exposed populations; exposure assessment, i.e., the quantification of exposures and the estimation of the characteristics and sizes of the exposed populations; dose-response assessment, i.e., the modeling for risk realization; and risk characterization, i.e., the evaluation of the impact of a change in exposure levels on public health effects. The risk-assessment process involves limitations of exposure data, many assumptions, and subjective choices that need to be considered when using this approach to provide guidance for health policy or action. In view of these uncertainties, we suggest that the provision of estimates of individual risk and disease burden in a population must be accompanied by the corresponding estimates of precision; risks should be presented in a sufficiently disaggregated form so that population heterogeneities are not lost in the data aggregation; and different scenarios and risk models should be applied. The methods are illustrated by an assessment on the health impacts of exposure to silica.

Decision Support Techniques↗
PubMedDate not supplied

[Multicenter evaluation of four homogenous LDL-cholesterol assays].

International guidelines emphasize the importance of LDL cholesterol (LDL-C) assay in the care and follow-up of patients with cardiovascular risk. Most studies and common practice use Friedewald's formula for LDL-C calculation. The accuracy of the result depends closely on the precision of the input parameters (total cholesterol, triglycerides (TG) and HDL cholesterol), and discrepancies between calculated LDL-C and measurement by reference methods appear when TG exceed 4.5 mmol/L, or in the presence of abnormal lipoproteins. These restrictions and uncertainties in calculations have prompted the recent development of direct and homogeneous methods that fit all analyzers. A multicenter evaluation of four direct assays of LDL-C (Daiichi, Denka Seiken, Kyowa, Wako) was carried out on 45 serum samples (TG below 3.1 mmol/L) in eight laboratories using different analyzers. For three methods (Daiichi, Kyowa, Wako), the interlaboratory reproducibility was markedly improved relative to that of calculation. A strong correlation was found for all new methods when compared with a beta-quantification assay. Average bias in Denka Seiken assays was greater than Kyowa's and Daiichi's (although less dispersed for the latter) and for Wako all bias were positive. The relationship between bias variations and the lipid parameters of the samples was studied. Three methods, Daiichi, Kyowa and Wako, revealed a significant positive correlation between bias and serum VLDL-C/TG ratio, clearly indicating that cholesterol enrichment of VLDL was a source of variability in these assays. Specificity of the four methods was tested in situation of dyslipidemia by spiking isolated lipoproteins (chylomicrons, VLDL and HDL). This experiment revealed differences in behavior, most evidently upon addition of VLDL. No method was truly specific, but up to 8 mmol/L of TG the variations were acceptable. In the presence of type III hyperlipoproteinemia, however, only the Denka Seiken method was reliable. Linearity up to 20 mmol/L (Daiichi, Denka Seiken) or 14 mmol/L (Kyowa, Wako) of LDL-C allows these tests to be used in main routine cases. New direct assays are an obvious technological advance in terms of analytical performance and conveniency. Their use for the diagnosis and follow-up of hyperlipidemic patients offers an alternative that overcomes the limitations of the Friedewald calculation.

Blood Chemical Analysis↗
PubMed2001

Quantitative reverse transcription-polymerase chain reaction detection of cytokeratin 20 in noncolorectal lymph nodes.

PURPOSE: Unexpected reverse transcription-PCR detection of cytokeratin 20 (CK20) in samples from healthy individuals and cancer types not expected to express CK20 has cast uncertainty on the role of CK20 as a specific marker of disseminated colorectal cells. We aimed to clarify the specificity of CK20 by examining its expression profile by real-time reverse transcription-PCR. EXPERIMENTAL DESIGN: A quantitative real-time PCR assay on the LightCycler instrument was developed and used to examine CK20 expression in tumors and lymph nodes from subjects with colorectal and breast carcinoma, head and neck and vulval squamous cell carcinoma, and melanoma. To select a method for reproducible quantification, four approaches were evaluated. RESULTS: The developed assay allowed rapid, convenient-to-use, specific, sensitive, and reproducible CK20 quantification amenable to large-scale analysis. For quantity calculation, an efficiency-adjusted relative ratio method was selected that controls for RNA loading and integrity as well as inefficient PCR reactions and provides a platform for standardization across laboratories. Using this assay, we detected CK20 in 41 of 89 (46%) lymph nodes from noncolorectal cancer types. There was a strong association between CK20 detection and lymph node metastasis determined by histology (P < 0.0001). Quantitatively, CK20 expression levels in colorectal cancer lymph nodes significantly exceeded the levels obtained in lymph nodes of extracolonic carcinomas (P < 0.05). Mean CK20 levels in lymph nodes and tumors from subjects with colorectal and breast cancers were similar in a tumor-type specific fashion. CONCLUSIONS: These results characterize low-level, epithelial cell-specific CK20 expression in infiltrated lymph nodes from subjects with noncolorectal cancer types and demonstrate the potential advantages of detecting circulating epithelial cells by quantitative PCR.

Biomarkers, Tumor↗