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Biomedical subjects

T Lahaye

Publications and source records attributed to T Lahaye.

At least 19 recordsLinked to original sources
PubMed2006

Workplace characterisation in case of rail transport of radioactive materials.

IRSN has been asked by SNCF (French Railways) to carry out measurements in order to establish the values of ambient dose equivalents H*(10) in the vicinity of shipments of radioactive materials to assess the external exposure to ionising radiation to which employees may be subjected during the carriage of radioactive goods. Detailed dosimetric characterisations of the wagons have been made and the external exposure at different stages of the work that is done by the employees have been measured in terms of H*(10). For the study presented in this paper, and corresponding to a used fuel shipment composed of UO2 and UO2-PuO2, it has been observed that the photon and neutron doses are very similar. In addition, the order of magnitude of the total dose integrated by an employee who would carry out 100 times the series of essential operational tasks, has been found to be approximately 250 microSv. This value is compared with those observed for other previously investigated shipments involving the exposure to photon fields only.

Body Burden↗
PubMed2006

Evaluation of dose equivalent by the electronic personal dosemeter for neutron 'Saphydose-N' at different workplaces of nuclear facilities.

This paper presents the results of measurements made with the electronic personal neutron Saphydose-N during the four campaigns of the European contract EVIDOS (EValuation of Individual DOSimetry in mixed neutron and photon radiation fields). These measurements were performed at Institute for Radiological Protection and Nuclear Safety (IRSN) in France (C0), at the Krümmel Nuclear Power Plant in Germany (C1), at the VENUS Research Reactor and the Belgonucléaire fuel processing plant in Belgium (C2) and at the Ringhals Nuclear Power Plant in Sweden (C3). The results for Saphydose-N are compared with reference values for dose equivalent.

Electronics↗
PubMed2006

Performance of the electronic personal dosemeter for neutron 'Saphydose-N' at different workplaces of nuclear facilities.

This paper mainly aims at presenting the measurements and the results obtained with the electronic personal neutron dosemeter Saphydose-N at different facilities. Three campaigns were led in the frame of the European contract EVIDOS ('Evaluation of Individual Dosimetry in Mixed Neutron and Photon Radiation Fields'). The first one consisted in the measurements at the IRSN French research laboratory in reference neutron fields generated by a thermal facility (SIGMA), radionuclide ISO sources ((241)AmBe; (252)Cf; (252)Cf(D(2)O)\Cd) and a realistic spectrum (CANEL/T400). The second one was performed at the Krümmel Nuclear Power Plant (Germany) close to the boiling water reactor and to a spent fuel transport cask. The third one was realised at Mol (Belgium), at the VENUS Research Reactor and at Belgonucléaire, a fuel processing factory.

Dose-Response Relationship, Radiation↗
PubMed2006

Evaluation of individual monitoring in mixed neutron/photon fields: mid-term results from the EVIDOS project.

EVIDOS is an EC sponsored project that aims at an evaluation and improvement of radiation protection dosimetry in mixed neutron/photon fields. This is performed through spectrometric and dosimetric investigations during different measurement campaigns in representative workplaces of the nuclear industry. The performance of routine and, in particular, novel personal dosemeters and survey instruments is tested in selected workplace fields. Reference values for the dose equivalent quantities, H(*)(10) and H(p)(10) and the effective dose E, are determined using different spectrometers that provide the energy distribution of the neutron fluence and using newly developed devices that determine the energy and directional distribution of the neutron fluence. The EVIDOS project has passed the mid-term, and three measurement campaigns have been performed. This paper will give an overview and some new results from the third campaign that was held in Mol (Belgium), around the research reactor VENUS and in the MOX producing plant of Belgonucléaire.

Equipment Design↗
PubMed2006

Electronic neutron personal dosemeters: their performance in mixed radiation fields in nuclear power plants.

This work describes spectral distributions of neutrons obtained as function of energy and direction at four workplace fields at the Krümmel reactor in Germany. Values of personal dose equivalent H(p)(10) and effective dose E are determined for different directions of a person's orientation in these fields and readings of personal neutron dosemeters--especially electronic dosemeters--are discussed with respect to H(p)(10) and E.

Dose-Response Relationship, Radiation↗
PubMed2005

Covering small defects on the weight bearing surfaces of the foot: the free temporal fasciocutaneous flap.

Although defects in the weight bearing area of the heel can be covered by local flaps, radiodermatitis is a contraindication to these flaps. Thin free flaps, as grafted fascial or muscles flaps and thin fasciocutaneous flaps, are usually the option of choice in these particular defects. These reconstructions are prone to shearing strains resulting in ulceration, hypertrophic scars and hyperkeratosis. The authors present a retrospective study of the reconstruction of six small heel defects with the fasciocutaneous temporal free flap performed between 1996 and 2001. The mean size of the defect was 20 cm(2). All arterial anastomoses were performed end to side on the posterior tibial artery. Despite the flap thinness, swelling was present during 12-25 months and one debulking had to be performed. With a mean follow-up of 32 months, all flaps regained protective sensibility after 7 months. No sliding of the flaps could be noted but there was one transient hyperkeratosis. Although the amount of hair on the transferred flaps decreased spontaneously with time, laser hair removal was performed in two patients for psychological reasons. In conclusion, it seems that in selected cases where local flaps are contraindicated, the fasciocutaneous temporal free flap can offer an excellent alternative for heel reconstruction. Due to its particular architecture, it resembles the complex tissue of the sole of the foot resulting in fewer complications and maintenance of flap durability.

Adult↗
PubMed2005

Gender aspects in chronic myeloid leukemia: long-term results from randomized studies.

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 x 10(9)/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.

Adult↗
PubMed2005

Feasibility study of an active extremity dosimetry prototype.

In nuclear medicine departments, where radioactive sources are manipulated, the personnel can receive large radiation doses to the skin of their hands. For performing detailed characterisations and dose optimisations of these workplaces, active extremity dosemeters can be used as complementary tools to passive hand monitoring. Active extremity dosimetry is still a subject of research. In this context, IRSN has started a research and development programme. As a first step, a hospital workplace study has been performed using thermoluminescence dosemeters and has shown, in agreement with previous works, that the pads of the fingers, points that are very difficult to instrument, receive the largest doses. Numerical studies have now started, with the aim of calculating the dose equivalent gradients through the hands, in order to optimise the locations of the detectors.

Arm↗
PubMed2005

Simulations of the mean chord length of a multi-element TEPC irradiated by monoenergetic neutrons.

In recent years IRSN has developed tissue-equivalent proportional counters (TEPCs) for neutron monitoring. A detector with a multi-element geometry was studied for personal dosimetry purposes. The determination of the personal dose equivalent using a multi-element TEPC requires to calculate the mean chord length of the charged particles in the counter gas. This paper presents the results of the simulations using the MCNPX code and explains the influence of the gas parameters on the mean chord length and the consequences on the dose equivalent response.

Body Burden↗
PubMed2004

Realization of a magnetically guided atomic beam in the collisional regime.

We describe the realization of a magnetically guided beam of cold rubidium atoms, with a flux of 7 x 10(9) atoms/s, a temperature of 400 microK, and a mean velocity of 1 m/s. The rate of elastic collisions within the beam is sufficient to ensure thermalization. We show that the evaporation induced by a radio-frequency wave leads to appreciable cooling and an increase in the phase space density. We discuss the perspectives to reach the quantum degenerate regime using evaporative cooling.

Journal Article↗
PubMed2004

Numerical and experimental results of the operational neutron dosemeter 'Saphydose-N'.

Since 1993, the Institute for Radiological Protection and Nuclear Safety (IRSN) has lead, in association with Electricité de France (EDF), a R&D study of a neutron personal electronic dosemeter. This dosemeter, called 'Saphydose-N', is manufactured by the SAPHYMO company. This paper presents first the optimisation of some detector components using Monte Carlo calculations, and second the test of the manufactured Saphydose-N under radiation following the IEC 1323 standard's recommendations for active personal neutron dosemeters. The measurements with the manufactured dosemeter were performed on the one hand at PTB (Physikalisch-Technische Bundesanstalt) in mono-energetic neutron fields and, on the other hand at IRSN in neutron fields generated by a thermal facility (SIGMA), radionuclide ISO sources and a realistic spectrum (CANEL/T400). The manufactured dosemeter Saphydose-N was also tested during measurement campaigns of the European programme EVIDOS ('Evaluation of Individual Dosimetry in Mixed Neutron and Photon Radiation Fields') at different nuclear workplaces. The study showed that Saphydose-N complies with the recommendations of standard IEC 1323 and can be used at any workplace with no previous knowledge of the neutron field characteristics.

Algorithms↗
PubMed2004

Performance of a cylindrical tissue-equivalent proportional counter for use in neutron monitoring.

Tissue-equivalent proportional counters (TEPC) allow the measurements of the absorbed dose and the ambient dose equivalent for neutron fields. A device based on this approach, called NAUSICAA((1,2)), has already been developed by IRSN to be used in high energy neutron fields for space applications. The response of this detector underestimates significantly the dose equivalent at low energies (several hundred keV) which represent the major component of neutron fields at workplaces in the nuclear industry. A counter with a similar geometry (cylindrical detector) and a lower gas pressure was studied in order to simulate a 1 microm biological site. In 2003, the performance of the device was further improved by adding a small amount of 3He to the tissue-equivalent gas (propane based) in order to increase the response for the lower energies of neutrons. Three amplification circuits were used to cover lineal energy range from 10(-1) to 10(4) keV microm(-1). Tests were performed in monoenergetic neutron and source fields. This paper presents the experimental results obtained with this change.

Body Burden↗
PubMed2003

Molecular monitoring of response to imatinib (Glivec) in CML patients pretreated with interferon alpha. Low levels of residual disease are associated with continuous remission.

A significant proportion of chronic myeloid leukemia (CML) patients achieve a major cytogenetic remission (MCR) to imatinib therapy after failing interferon (IFN) alpha-based protocols. We sought to determine levels of residual disease in patients with MCR using various molecular methods and to establish a relation between residual BCR-ABL transcript levels and rate of relapse in complete cytogenetic remission (CCR). Response was measured by conventional cytogenetic analysis, hypermetaphase and interphase fluorescence in situ hybridization (HM-FISH, IP-FISH) of bone marrow (BM) cells, qualitative nested and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for BCR-ABL transcripts. We investigated 323 peripheral blood (PB) and BM samples from 48 CML patients who achieved a complete (Ph+ 0%; n=41) or partial (Ph+ 1-34%; n=7) cytogenetic remission after 3-20 months of imatinib therapy. Prior to imatinib, 35 patients were in chronic phase (CP), eight in accelerated phase (AP), four in myeloid and one in lymphoid blast crisis. HM-FISH results correlated with ratios BCR-ABL/ABL in PB and BM. In patients with CCR, residual disease was detectable by HM-FISH (31%), IP-FISH (18%), and RT-PCR (100%). During follow-up, BCR-ABL became undetectable in two patients (one CP, one AP) by both nested and quantitative RT-PCR. CCR is ongoing in 30 evaluable patients, 11 patients have relapsed. At the time of best response, median ratios BCR-ABL/ABL were 2.1% (range 0.82-7.8) in patients with subsequent relapse and 0.075% (range 0-3.9) in patients with ongoing remission (P=0.0011). All 16 CP patients, who achieved ratios BCR-ABL/ABL <0.1% as best molecular response are in continuous remission, while 6/13 patients (46%) with ratios >/=0.1% have relapsed (P=0.0036). We conclude that: (i) in patients with CCR to imatinib, HM-FISH and RT-PCR usually reveal residual BCR-ABL+ cells; (ii) RT-PCR results derived from PB and BM are comparable in CP CML; and (iii) low levels of residual disease with ratios BCR-ABL/ABL &<0.1% are associated with continuous remission.

Adult↗
PubMed2003

Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C.

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.

Adult↗
PubMed2002

[Resistance to tumor specific therapy with imatinib by clonal selection of mutated cells].

HISTORY AND CLINICAL FINDINGS: A 60-year-old woman presented with night-sweats and increasing weakness. Physical examination revealed no abnormalities. For 27 years she had been treated for Philadelphia-positive chronic myeloid leukemia (CML). Because of progressive disease treatment with the tyrosine kinase inhibitor imatinib (STI571, Glivec (R)) had been started 9 months before. She had achieved complete hematological remission within 8 weeks, but not a cytogenetic response. INVESTIGATIONS: Elevated WBC count (26.7/nl) with a differential displaying typical features of acceleration in bone marrow aspirate confirmed CML in accelerated phase. Sequencing of the ATP binding site of the BCR-ABL gene, which - at protein level - is the target for imatinib, revealed the clonal selection of cells harboring a point mutation leading to the exchange of amino acid 253 from tyrosine to histidine. This was considered to be the cause of resistance to imatinib. TREATMENT AND COURSE: Dose increase of imatinib up to 600 mg daily and administration of cytarabine did not overcome resistance. Imatinib therapy was discontinued; hematologic remission was induced by oral therapy with hydroxyurea and mercaptopurine. In the course of the following 6 months a gradual decrease of the resistant clone from 100 % down to lower than the detection limit of the method was demonstrated. CONCLUSIONS: Clonal mutations are often the cause of resistance to imatinib therapy. They can be detected by sequencing of the ATP binding site of BCR-ABL in specialized laboratories. This case shows that discontinuation of imatinib therapy can significantly reduce the mutated (resistant) clone and thereby restore sensitivity to imatinib.

Amino Acid Substitution↗
PubMed2002

Early reduction of BCR-ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha.

The degree of tumor load reduction as measured by cytogenetic response is an important prognostic factor for chronic myelogenous leukemia (CML) patients on therapy. We sought to determine whether BCR-ABL transcript levels can predict chromosomal response. Residual disease was evaluated in 120 CML patients in chronic phase (CP) treated with the selective tyrosine kinase inhibitor imatinib after resistance or intolerance to interferon alpha (IFN). Median time of therapy was 401 days (range 111-704). BCR-ABL and total ABL transcripts were measured in 486 peripheral blood (PB) specimens with a real time RT-PCR approach using fluorescent-labeled hybridization probes (LightCycler technology) and results were expressed as the ratio BCR-ABL/ABL. Cytogenetic response was determined in 3-monthly intervals: From 101 evaluable patients, 42 achieved a complete (CR, 0% Philadelphia chromosome (Ph)- positive metaphases), 18 a partial (PR, 1-34% Ph+), 13 a minor (MR, 35-94% Ph+), and 26 no response (NR, >94% Ph+). All PB samples were RT-PCR positive. The proportion of Ph+ metaphases and simultaneous BCR-ABL/ABL ratios correlated with r = 0.74, P < 0.0001. In order to investigate whether early molecular analysis may predict cytogenetic response, quantitative RT-PCR data obtained after 1 and 2 months of therapy were compared with cytogenetic response at 6 months. BCR-ABL/ABL ratios after 1 month were not predictive, but results after 2 months correlated with the consecutive cytogenetic response (P = 0.0008). The probability for a major cytogenetic response was significantly higher in patients with a BCR-ABL/ABL ratio <20% after 2 months of imatinib therapy. We conclude that: (1) quantitative determination of residual disease with real time RT-PCR is a reliable and sensitive method to monitor CML patients on imatinib therapy; (2) BCR-ABL/ABL ratios correlate well with cytogenetic response; (3) in IFN-pretreated patients all complete responders to imatinib have evidence of residual disease with the limited follow-up available; and (4) cytogenetic response at 6 months of therapy in CP patients is predictable with real time RT-PCR at 2 months.

Adult↗