Biomedical subjects

J R Jourdain

Publications and source records attributed to J R Jourdain.

9 recordsLinked to original sources

PubMed2006

Effect of acetaminophen administration to rats chronically exposed to depleted uranium.

The extensive use of depleted uranium (DU) in both civilian and military applications results in the increase of the number of human beings exposed to this compound. We previously found that DU chronic exposure induces the expression of CYP enzymes involved in the metabolism of xenobiotics (drugs). In order to evaluate the consequences of these changes on the metabolism of a drug, rats chronically exposed to DU (40mg/l) were treated by acetaminophen (APAP, 400mg/kg) at the end of the 9-month contamination. Acetaminophen is considered as a safe drug within the therapeutic range but in the case of overdose or in sensitive animals, hepatotoxicity and nephrotoxicity could occur. In the present work, plasma concentration of APAP was higher in the DU group compared to the non-contaminated group. In addition, administration of APAP to the DU-exposed rats increased plasma ALT (p<0.01) and AST (p<0.05) more rapidly than in the control group. Nevertheless, no histological alteration of the liver was observed but renal injury characterized by incomplete proximal tubular cell necrosis was higher for the DU-exposed rats. Moreover, in the kidney, CYP2E1 gene expression, an important CYP responsible for APAP bioactivation and toxicity, is increased (p<0.01) in the DU-exposed group compared to the control group. In the liver, CYP's activities were decreased between control and DU-exposed rats. These results could explain the worse elimination of APAP in the plasma and confirm our hypothesis of a modification of the drug metabolism following a DU chronic contamination.

Acetaminophen↗

PubMed2006

Validation of a personalized dosimetric evaluation tool (Oedipe) for targeted radiotherapy based on the Monte Carlo MCNPX code.

Dosimetric studies are necessary for all patients treated with targeted radiotherapy. In order to attain the precision required, we have developed Oedipe, a dosimetric tool based on the MCNPX Monte Carlo code. The anatomy of each patient is considered in the form of a voxel-based geometry created using computed tomography (CT) images or magnetic resonance imaging (MRI). Oedipe enables dosimetry studies to be carried out at the voxel scale. Validation of the results obtained by comparison with existing methods is complex because there are multiple sources of variation: calculation methods (different Monte Carlo codes, point kernel), patient representations (model or specific) and geometry definitions (mathematical or voxel-based). In this paper, we validate Oedipe by taking each of these parameters into account independently. Monte Carlo methodology requires long calculation times, particularly in the case of voxel-based geometries, and this is one of the limits of personalized dosimetric methods. However, our results show that the use of voxel-based geometry as opposed to a mathematically defined geometry decreases the calculation time two-fold, due to an optimization of the MCNPX2.5e code. It is therefore possible to envisage the use of Oedipe for personalized dosimetry in the clinical context of targeted radiotherapy.

Computer Simulation↗

PubMed2005

Long term retention and excretion of 201Tl in a patient after myocardial perfusion imaging.

201Tl is widely used in nuclear medicine to carry out myocardial perfusion imaging (MPI). However, very limited data is available on long-term distribution in the body, excretion and corresponding dose. In this study we performed a 2 month follow-up of a patient who underwent MPI, by urine analysis and in vivo measurements. The biological half-life of thallium was consequently estimated to be 11.6-27 d, which is in partial agreement with previous studies. We also estimated excretion and retention of 200Tl, 201Tl and 202Tl isotopes using the biokinetic parameters from ICRP publication 53 and compared the forecast result with actual measurements. The latter demonstrated a higher urinary excretion and a higher body retention than what was expected. Our results therefore suggest that the long-term retention and consequently the effective dose coefficient for 201Tl considered in ICRP publications 53 and 80 may be slightly underestimated.

Aged↗

PubMed2003

Application of new imaging and calculation techniques to activity and dose assessment in the case of a 106Ru contaminated wound.

The aim of this paper is to describe the dosimetric evaluation of a point contamination that occurred in a laboratory during the examination of an irradiated sample. The incident led to point contamination of the operator's finger due to the presence of mainly 106Ru, with its progeny, 106Rh. The paper reports on the activity and dose assessment, performed using several methods. The measured activity was obtained using a conventional device based on a germanium detector and confirmed using software developed at IRSN, based on reconstruction of voxel phantom associated with the Monte Carlo N-Particle code (MCNP) for in vivo measurement. Two dose assessment calculations were performed using both analytical and Monte Carlo methods, applying the same approach as for activity assessment based on the personal computational phantom of the finger. The results are compared, followed by a discussion on the suitability of the tools described in this study.

Computer Simulation↗

PubMed2003

Lessons learned from interlaboratory comparisons of bioassay data interpretation.

When a set of bioassay data is given to two different dosimetrists, it is likely that these data will be interpreted differently, that different methods and dosimetric models will be applied and therefore different numerical values will be obtained. Thus, it is important for laboratories dealing with internal dosimetry to undergo performance testing procedures such as interlaboratory comparisons of bioassay data interpretation. Several intercomparison exercises have already been organised at national and international levels. The largest one so far was the 3rd European Intercomparison Exercise on Internal Dose Assessment, which has been organised in the framework of the EULEP/EURADOS Action Group, 'Derivation of parameter values for application to the new model of the human respiratory tract for occupational exposure'. The most important lesson learned from these intercomparison exercises was the need to develop agreed guidelines for internal dose evaluation procedures to promote harmonisation of assessments between organisations and countries.

Benchmarking↗

PubMed2003

Design and implementation of monitoring programmes for internal exposure (project OMINEX).

The costs of monitoring for internal exposure in the workplace are usually significantly greater than the equivalent costs for external exposure. Therefore, there is a need to ensure that resources are employed with maximum effectiveness. The EC-funded OMINEX (optimisation of monitoring for internal exposure) project is developing methods for optimising the design and implementation of internal exposure monitoring programmes. Current monitoring programmes are being critically reviewed, the major sources of uncertainty in assessed internal dose investigated, and guidance formulated on factors such as programme design, choice of method/techniques, monitoring intervals, and monitoring frequency. OMINEX will promote a common, harmonised approach to the design and implementation of internal dose monitoring programmes throughout the EU.

Body Burden↗

PubMed2003

Guidance on internal dose assessments from monitoring data (project IDEAS).

Several international inter-comparison exercises on intake and internal dose assessments from monitoring data led to the conclusion that the results calculated by different participants varied significantly, mainly due to the broad variety of methods and assumptions applied in the assessment procedure. Based on these experiences, the need of harmonisation of the procedures has been formulated as an EU research project under the 5th Framework Programme, with the aim of developing general guidelines for standardising assessments of intakes and internal doses. In the IDEAS project, eight institutions from seven European countries are participating, also using inputs from internal dosimetry professionals from across Europe to ensure broad consensus in the outcome of the project. To ensure that the guidelines are applicable to a wide range of practical situations, the first step will be to compile a database on well documented cases of internal contamination. In parallel, an improved version of existing software will be developed and distributed to the partners for further use. Many cases from the database will be evaluated independently by more partners using the same software and the results will be discussed and the draft guidelines prepared. The guidelines will then be revised and refined on the basis of the experiences and discussions of two workshops, and an intercomparison exercise organised in the frame of the project which will be open to all internal dosimetry professionals.

Body Burden↗

PubMed2001

Advanced radionuclide detection techniques for in vitro and in vivo animal imaging.

This review of the different methodologies used for animal imaging with radioactive compounds presents the most recent approaches developed for both in vitro and in vivo studies. The choice of a detector for analysis of the spatial distribution of radionuclides deposited in biological tissues results in a trade-off between the size and nature of the region to study (in vitro or in vivo), the required spatial resolution and the penetrating characteristics of the ionizing radiation. Real time detectors are now available for quantitative imaging of 2D or 3D radioactive samples and offer either an increased dynamic range or a lowered sensitivity in comparison with film radioautography. For high resolution imaging, two specific techniques are proposed for applications to rodents. The usefulness of self-triggering intensified charge coupled device (STIC) is illustrated for in vitro localization in radiotoxicological studies of alpha-emitters. For in vivo techniques, the performance of positron emission tomography (PET) is discussed, as a promising method of molecular imaging of biological processes.

Alpha Particles↗

PubMed1999

Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters.

OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Autoantibodies↗