External radiation dose and cancer mortality among French nuclear workers: considering potential confounding by internal radiation exposure.

OBJECTIVES: French nuclear workers have detailed records of their occupational exposure to external radiation that have been used to examine associations with subsequent cancer mortality. However, some workers were also exposed to internal contamination by radionuclides. This study aims to assess the potential for bias due to confounding by internal contamination of estimates of associations between external radiation exposure and cancer mortality. METHODS: A cohort of 59,004 workers employed for at least 1 year between 1950 and 1994 by CEA (Commissariat à l'Energie Atomique), AREVA NC, or EDF (Electricité de France) and badge-monitored for external radiation exposure were followed through 2004 to assess vital status and cause of death. A flag based on a workstation-exposure matrix defined four levels of potential for internal contamination. Standardized mortality ratios were assessed for each level of the internal contamination indicator. Poisson regression was used to quantify associations between external radiation exposure and cancer mortality, adjusting for potential internal contamination. RESULTS: For solid cancer, the mortality deficit tended to decrease as the levels of potential for internal contamination increased. For solid cancer and leukemia excluding chronic lymphocytic leukemia, adjusting the dose-response analysis on the internal contamination indicator did not markedly change the excess relative risk per Sievert of external radiation dose. CONCLUSIONS: This study suggests that in this cohort, neglecting information on internal dosimetry while studying the association between external dose and cancer mortality does not generate a substantial bias. To investigate more specifically the health effects of internal contamination, an effort is underway to estimate organ doses due to internal contamination.

Forecasting the In Vivo Behavior of Radiocontaminants of Unknown Physicochemical Properties Using a Simple In Vitro Test.

An understanding of the "bioavailability" of disseminated radiocontaminants is a necessary adjunct in order to tailor treatment and to calculate dose. A simple test has been designed to predict the bioavailability of different actinide forms likely to be found after dissemination of radioactive elements by dispersal devices or nuclear reactor incidents. Plutonium (Pu) or Americium (Am) nitrate or MOX (U,PuO2) are immobilized in culture wells using a static gel phase simulating biological compartments (lung, wound, etc.). Gels are incubated in a fluid phase representing physiological media (plasma, sweat, etc.). Transfer of radionuclide from static to fluid phase reflects contaminant bioavailability. After 48 h of incubation in physiological saline, Am transfer from static to fluid phase was greater than for Pu (70% vs. 15% of initial activity). Transfer of Pu or Am was markedly less from the oxide form of the two elements (1% Am and 0.05% Pu transferred). Medium representing intracellular lysosomal fluid (pH 4) increased transfer of Pu and Am, whereas culture medium including serum reduced actinide transfer. Actinide transfer was also reduced by elements of the extracellular matrix present in the static gel phase. Increasing DTPA concentrations (5 to 500 µM) to the fluid phase significantly enhanced transfer of Pu and Am. Although this agarose gel cannot fully represent in vivo complexity, this simple test can be used to investigate and predict the behavior in vivo of radiocontaminants to support medical treatments and medical forensic investigations.

Mortality analyses in the updated French cohort of uranium miners (1946-2007).

PURPOSE: The objectives are to analyze mortality risks in the extended follow-up of the French uranium miners' cohort and to examine their potential relation to occupational exposure to ionizing radiation (IR). METHODS: The total cohort includes 5,086 uranium miners employed in the CEA-COGEMA group and followed up from 1946 to 2007. Vital status, causes of death, and cumulative radon exposures were recorded. The post-55 subcohort includes 3,377 miners first employed after 1955, for whom long-lived radionuclides (LLR) and external gamma-ray exposure were also recorded. External mortality analyses were performed by computing standardized mortality ratios (SMR). Excess relative risks (ERRs) due to IR exposures were estimated from Poisson regression models. RESULTS: The miners included in the total cohort were followed up for 35.4 years and exposed to 36.6 working level months (WLM) on average. There was no evidence of a difference in overall mortality between miners and the general French male population. Miners had a statistically significant excess mortality rate from lung cancer (SMR = 1.34 [95% CI 1.16-1.53]) and from kidney cancer (SMR = 1.60 [1.03-2.39]). Cumulative radon exposure was significantly associated with lung cancer risk (ERR/100 WLM = 0.71 [0.31-1.30]) and cerebrovascular risk (ERR/100 WLM = 0.41 [0.04-1.03]). In the post-55 subcohort, this excess mortality from lung cancer remained associated with exposure to radon, and also with exposure to LLR and external gamma rays. CONCLUSIONS: The analyses in the extended follow-up strengthen the results previously observed among French uranium miners about their excess risk of mortality and its association with their occupational IR exposure.

MRI assessment of local acute radiation syndrome.

OBJECTIVES: To describe local acute radiation syndrome and its radiological imaging characteristics. METHODS: We performed a retrospective study of patients who had suffered skin and deeper radiation damage who were investigated by magnetic resonance imaging (MRI). We compared the clinical findings, C-reactive protein (CRP) levels and MRI results. RESULTS: A total of 22 MRI examinations were performed between 2005 and 2010 in 7 patients; 6 patients had increased CRP levels and MRI abnormalities. They were treated by surgery and local cellular therapy. One patient had no CRP or MRI abnormalities, and had a spontaneous good outcome. Eighteen abnormal MR examinations demonstrated high STIR signal and/or abnormal enhancement in the dermis and muscle tissues. Three MRI examinations demonstrated skeletal abnormalities, consistent with radionecrosis. The four normal MRI examinations were associated only with minor clinical manifestations such as pain and pigmentation disorders. CONCLUSION: MRI seems to be a useful and promising imaging investigation in radiation burns management i.e. initial lesion evaluation, treatment evaluation and complication diagnosis. MRI findings correlated perfectly with clinical stage and no false negative examinations were obtained. In particular, the association between normal MRI and low CRP level seems to be related to good outcome without specific treatment. KEY POINTS: Local acute radiation syndrome (radioepidermitis) mainly affects the skin and superficial tissues. MRI findings correspond with clinical stage (with a strong negative predictive value). MRI outperformed X-ray examination for the diagnosis of bone radionecrosis. Diffusion-weighted imaging shows low ADC in bone and soft tissue necrosis. Perfusion sequence allows assessment of tissue microcirculation impairment.

[Use of antihypertensive drugs in France and relationship with cardiovascular disease. FLAHS 2009-2010 surveys]. / Utilisation des traitements antihypertenseurs en France et relations avec les pathologies cardiovasculaires. Enquêtes FLAHS 2009-2010.

OBJECTIVE: Describe how antihypertensive drugs are prescribed in France in 2009 and 2010 and assess the effect of the presence of cardiovascular disease on the characteristics of the treatment. METHODS: The French League Against Hypertension Surveys (FLAHS) are conducted among a representative sample of individuals aged 35 years and older living in France. For the 2009 and 2010 surveys, a sample of 2292 subjects who declared to take one or more antihypertensive drug has been studied. In addition to the details of antihypertensive medications taken the day of the survey, the personal history for cardiovascular diseases was compiled. RESULTS: Of the 2292 prescriptions with at least one antihypertensive prescription frequencies are: ARB (43%), diuretics (43%), beta-blockers (34%), CCB (26%), ACEI (26%), spironolactone (8%), central and alpha (7%), DRI (1%). The prescription is performed as monotherapy (42%), bitherapy (37%), triple therapy (16%) and quadruple or more (5%). When triple therapy is prescribed, there is an association ACEI or ARB or DRI+Diu+BB in 46%, and an association ACEI or ARB or DRI+Diu+AC in 30%. Cardiovascular disease is present or past reported by 24% of hypertensive patients: coronary artery disease (13%), heart failure (6%), arrhythmias (5%), stroke (4%), PAD (4%). The use of BB is more common in hypertensive patients who have coronary artery disease, heart failure and arrhythmia. ACE inhibitors are more common in hypertensive patients with coronary artery disease, heart failure or stroke. CCB are more frequent in cases of coronary artery disease or PAD. The ARB are less frequent in patients with coronary artery disease. CONCLUSION: The ARB, diuretics and beta-blockers are the most prescribed antihypertensives in France in 2009 to 2010. Cardiovascular diseases declared in 24% of hypertensives led to a preferential prescription of an ACE inhibitor or BB.

[Assessment of antihypertensive monotherapies effectiveness by home blood pressure self-measurement in hypertensive patients]. / Évaluation par l'automesure au domicile de l'efficacité de monothérapies antihypertensives chez des hypertendus traités en France.

OBJECTIVE: To evaluate the blood pressure (BP) control and the efficacy of antihypertensive monotherapy using home BP self-measurement in a French population of treated hypertensive subjects in 2007 2009 and 2010. METHODS: The French League Against Hypertension Surveys (FLAHS) are conducted among a representative sample of individuals aged 35 years and older living in France. For the 2007, 2009 and 2010 surveys, a sample of 1467 subjects who owned a BP self-measurement device and performed three consecutive morning BP measurements were included. Among the 60% of subjects who reported taking at least one antihypertensive drug, we analyzed subjects treated with one of the following antihypertensive monotherapy, i.e., beta-blocker (BB), ACE inhibitors, calcium channel blocker (CCB) and angiotensin receptor blockers (ARB). RESULTS: Among treated hypertensive subjects (n=886), 66% (n=586) had home BP below the 140/90mmHg threshold and 50% (n=449) below 135/85mmHg. Three hundred two subjects were treated with a single antihypertensive drug, 33% had ARB, 25% BB, 19% CCB and 13% ACE inhibitors. Age (years) for each treatment group is different (P<0.01) CCB (72.1±9.3), BB (65.6±9.8), ARB (68.6±8.9) and ACEI (67.3±10.2). The mean systolic/diastolic BP (mmHg) is not comparable between monotherapy 130.7/76.1 (ARB), 130.7/78.7 (BB), 134.0/75.2 (CCB) and 139.1/80.3 (ACEI) for ARB, BB, CCB and ACE inhibitors respectively. Compared to ACE inhibitors, BP was significantly lower with ARB (P<0.01). The proportion of subjects with a BP below 140/90mmHg was 73% for ARB, 52% for BB, 68% for CCB and 47% for ACE with a statistical significance (P=0.03) for ARB vs. ACEI and CCB vs. ACEI. CONCLUSION: Among subjects treated for hypertension who owned a BP self-measurement device, 50 to 66% had a controlled BP (depending on the threshold used). It is observed differences between antihypertensive efficacy of monotherapy with a larger number of patients controlled with ARB or CCB.

[Alpha emitters inhalation: detection by a process with flags]. / Intérêt de l'évaluation de l'inhalation des émetteurs alpha par la technique des drapeaux.

This work relates to the contaminated people survey (alpha emitters inhalation) with nasal mucus sample analysis. Alpha emitters detection by liquid wander on flags (blotting paper) was employed. Compared to the current technique with paper handkerchiefs, this process improves considerably the time, reduced to 10 min between the sampling's reception and the results of the analysis. The detection's sensitivity of the process is also higher. This process with flags concerns the occupational survey on people leaving an alpha contaminated area (nuclear power plant). It is also available to the monitoring of intervention teams leaving the contaminated area during the immediate response phase and the follow-on response phase (management of the crisis and site restoration).

[Urinary uranium analysis results on Gulf war or Balkans conflict veterans]. / Bilan du dosage urinaire de l'uranium appauvri chez des vétérans des conflits du Golfe ou des Balkans.

During the 1991 Gulf War, the 1995 Bosnia conflict and the 1999 Kosovo conflict, munitions containing depleted uranium (DU) have been employed by the coalition forces. Altough the radioactivity of this metal is about 40-50% lower than that of natural uranium, and that health concerns are based primarily on the metal's kidney toxicity, DU has been quoted among the causes of the different pathologies developped by some soldiers a few time after they went back home. In order to evaluate the potential relation between a DU exposition and some of the pathologies described, more than 200 urine uranium analysises have been done between 1999 and 2003 by the laboratory of the french Army radioprotection service. The method used is the standard method for determining uranium in excretion of nuclear workers: a chemical uranium isotopes separation (including 234, 235+236 and 238) followed by an alpha ray spectrometry. All results were negative and quite all of the detection limits were lower than the ones recommanded by the International Commission on Radiological Protection (10mBq/L per isotope). The summary is that none of the available analysises for uranium excreted in urine suggests that any subjects examined had incorpored DU that could explain pathologies appeared after the conflicts.

Diagnosis of internal radionuclide contamination by mobile laboratories.

To support patient management of possible radiation casualties in case of a radiological or a nuclear event, the Defence Radiation Protection Service (SPRA) is able, 24 h a day, to supply intervention means in France and overseas if requested by military authorities or civilian institutions. SPRA has developed mobile laboratories for the diagnosis of internal radionuclide contamination. The mission of this mobile unit is to study health and environment risks linked to radiological hazards for exposed people: workers, soldiers and also civilians. The mobile laboratories are able to be deployed in all types of nuclear or radiological events, and give the results of analysis to physicians and authorities in a short time. The vehicles are fully equipped to detect and to survey exposure to alpha, beta and gamma emitters for the supervision of people exposed to ionising radiation, by whole body counting or analysis of biological samples. Environmental survey by analysis of wipes, soil, water, vegetation or air filters can also be achieved.

Multiplexed immunoassay for detection of rheumatoid factors by FIDISTM technology.

Our objective was to (i) compare FIDIS Rheuma, a new multiplexed immunoassay designed for simultaneous detection of IgM class rheumatoid factors (RF) directed against Fc determinants of IgG from humans and animals, with agglutination and ELISA (conventional methods) and (ii) evaluate the clinical sensitivity and specificity of biological markers for rheumatoid arthritis (RA). To do this, FIDIS technology was employed using the Luminex system. It consists of distinct color-coded microsphere sets, a flow cytometer, and digital signal processing hardware and software. Agglutination and ELISA tests were performed with commercial kits. The study included 134 samples from RA patients and 105 from healthy blood donors. For human specificity, we compared FIDIS with latex agglutination and ELISA. Relative sensitivities were 98.9% and 88.5% and specificities were 90.2% and 94.6%, respectively. For animal specificity, we compared FIDIS with Waaler-Rose and ELISA. The results were 84.9% and 71.9% for the sensitivities and 97.5% and 98.4% for the specificities, respectively. Detection of IgG anti-CCP by ELISA and IgG antikeratin by immunofluorescence was also determined in order to compare their clinical sensitivity and specificity with IgM-RF, according to the method used. The results were: IgG anti-CCP 72.3%, 97.2%; IgG antikeratin 36.6%, 100%; latex agglutination 66.4%, 97.2%; Waaler-Rose 55.9%, 96.3%; FIDIS human 73.9%, 92.1%; FIDIS animal 49.2%, 97.2%; ELISA human 93.2%, 95.5%; and ELISA animal 74.6%, 91.3%. The results showed the efficiency of FIDIS with analytical performance equivalent to the conventional methods, but having the advantage of giving quantitative results (IU/mL).

Characterisation and dissolution of depleted uranium aerosols produced during impacts of kinetic energy penetrators against a tank.

Aerosols produced during impacts of depleted uranium (DU) penetrators against the glacis (sloping armour) and the turret of a tank were sampled. The concentration and size distribution were determined. Activity median aerodynamic diameters were 1 microm (geometric standard deviation, sigma(g) = 3.7) and 2 microm (sigma(g) = 2.5), respectively, for glacis and turret. The mean air concentration was 120 Bq m(-3), i.e. 8.5 mg m(-3) of DU. Filters analysed by scanning electron microscopy (SEM) and X ray diffraction showed two types of particles (fine particles and large molten particles) composed mainly of a mixture of uranium and aluminium. The uranium oxides were mostly U3O8, UO2.25 and probably UO3.01 and a mixed compound of U and Al. The kinetics of dissolution in three media (HCO3-, HCl and Gamble's solution) were determined using in-vitro tests. The slow dissolution rates were respectively slow, and intermediate between slow and moderate, and the rapid dissolution fractions were mostly intermediate between moderate and fast. According to the in-vitro results for Gamble's solution, and based on a hypothetical single acute inhalation of 90 Bq, effective doses integrated up to 1 y after incorporation were 0.54 and 0.56 mSv, respectively, for aerosols from glacis and turret. In comparison, the ICRP limits are 20 mSv y(-1) for workers and 1 mSv y(-1) for members of the public. A kidney concentration of approximately 0.1 microg U g(-1) was predicted and should not, in this case, lead to kidney damage.

Gingival bleeding, epistaxis and haematoma three days after gastroenteritis: the haemorrhagic lupus anticoagulant syndrome.

UNLABELLED: A 3 year and 9 month-old girl presented with gingival bleeding, epistaxis, and multiple haematomas 3 days after an acute episode of gastroenteritis. Prothrombin time and activated partial thromboplastin time were prolonged with reduced clotting activity of factor II (< 10%), VIII (<1%), IX (3%), XII (10%) and evidence of a high titre inhibitor. Prothrombin (factor II) level was below the detection limit, both in a functional and immunological assay. It did not increase after administration of vitamin K or fresh frozen plasma. Further studies revealed presence of a strong lupus anticoagulant and a specific IgG antibody against prothrombin. Factor VIII antigen levels also were reduced (31%), but to a lesser extent than functionally determined factor VIII (<1%). Blood coagulation normalised following clinical recovery 6 weeks after admission. The pathophysiology of this acquired inhibitor phenomenon (accelerated clearance of complexes of clotting factors and phospholipids) is discussed. CONCLUSION: The haemorrhagic lupus anticoagulant syndrome (acquired hypoprothrombinaemia lupus anticoagulant syndrome) is a rare presentation of acquired bleeding diathesis in childhood. Since most cases in post-infectious children are asymptomatic, it might be underdiagnosed. In children with newly appearing bleeding symptoms or unclear prolonged prothrombin time or activated partial thromboplastin time, one has to consider this syndrome which could lead to relevant bleeding.

[Percutaneous absorption of metallic cations: uranium particulates]. / Absorption percutanée des cations métalliques: particularités de l'uranium.

Washing is usually used to reduce the risk of a skin contamination. Skin biopsies were used and contaminations were realised with 1) soluble radioactive calcium 2) insoluble particles of uranium. The result obtained with different wash liquids are presented here. Water and soap had no effect but hypertonic DTPA was the better therapy to remove uranium from skin.

[Reduction of renal uranium uptake by acetazolamide: the importance of urinary elimination of bicarbonate]. / Réduction de la fixation rénale de l'uranium par l'acétazolamide: importance de l'élimination urinaire du bicarbonate.

Acetazolamide was compared with bicarbonate for the treatment of contamination with uranium. Uranium was injected peritoneally in rats, and its distribution was investigated. Acetazolamide was three times more efficient than bicarbonate in reducing the renal content of uranium. On the other hand, it had no effect on hepatic or skeletal content. In this study, renal physiology provides the basis for understanding the mode of action of acetazolamide and bicarbonate. In this context, it is of interest to determine the alkalinity of the urine, with the aim of knowing whether bicarbonate is present to mobilize uranium.

The immunogenicity and safety of a new combined diphtheria, tetanus and poliomyelitis booster vaccine (Td-eIPV).

In view of the continuing risk of contracting tetanus, diphtheria and poliomyelitis, and the well-documented decline in immunity with time, the need for booster vaccinations is substantial. The immunogenicity and safety of a new combined booster vaccine against tetanus, diphtheria and poliomyelitis (REVAXIS) developed by Pasteur Mérieux Connaught (Lyon, France) were evaluated in four clinical studies. This vaccine (Td-eIPV) combines an adsorbed tetanus toxoid and low-dose diphtheria toxoid vaccine (Td) with an enhanced, inactivated polio vaccine against poliovirus types 1, 2 and 3 (eIPV). In 256 healthy young adults, a single dose of Td-eIPV was shown to be immunogenic, eliciting antibody levels considered protective against disease for each vaccine component in > or = 99.6% of the subjects. In 112 healthy older subjects (> 40 years of age), two doses of Td-eIPV elicited seroprotective levels of antibodies in 94% of the subjects for diphtheria, and in all subjects for tetanus and poliovirus types 1, 2 and 3. Safety data from all 368 subjects, as well as 31 phase I volunteers and 1,742 subjects included in a safety study, reveal that the vaccine is safe. Most reactions were predictable, temporary and mild. There was no evidence that the vaccine was associated with any clinically serious event or modification of clinical laboratory parameters. The data reviewed here show that Td-eIPV is immunogenic and safe when administered as a booster vaccination in healthy adults of all ages.

[Thorium a radioactive element in current use: physical-chemical properties and biological processing]. / Le thorium, un radioélément d'actualité: propriétés physico-chimiques et devenir biologique.

The radioactive properties and physicochemistry of thorium were studied and correlations drawn between thorium and element sof the titanium group, lanthanides and plutonium. It appears that the behavior of Th4+ and Pu4+ are similar, particularly their distribution pattern on bone surfaces. Chelating agents are reviewed and the structure of metal chelates indicated.

[Thorium: analysis and dosimetry of thorium welding electrodes]. / Le thorium: analyse et dosimétrie des électrodes de soudures thoriées.

The use of thoriated tungsten electrodes may be at the origin of a potential hazard for the personnel involved in the use of electrodes, as well as the general population. To assess this hazard, the electrode radioactivity measurements by alpha and beta counting has been conducted. The radioelements were identified by alpha and gamma spectromety. It appeared that there was a radioactive disequilibrium between thorium-232 (Th-232) and it daughters atoms. Additionally, some thorium 230 (Th-230) belonging to the uranium chain, was present. The chemical separation and the milling processing had affected the radioactive composition and the thorium in the electrodes, doesn't exactly corresponds to natural thorium. Radiation doses were also assessed: film and photoluminescence dosimetry were undertaken. Finally smears method showed a alpha removable area contamination. Even if the hazard is weak. As a matter of fact, it must not be neglected because it was complex, for the thorium was always accompanied by Th-232 progeny, alpha emitters but also beta and gamma emitters.

[Modeling of cutaneous radio-contamination: effects of washings by soap and by solutions of DTPA]. / Modélisation des radiocontaminations cutanées: effets de lavages par le savon et par les solutions de DTPA.

Some neutral chirurgical soap, a solution of diethylen penta acetic acid (DTPA) at 1% and a solution at 25% of monocalcic trisodium salt of DTPA in serum have been studied on models of cutaneous contamination. Cesium 137 (137Cs) and Plutonium 239 (239Pu) have been used for the contamination. This research gives a protocol for external cutaneous decontamination which could be used in reception units for radiocontaminated wounded. Even the radioelement is unknown, DTPA at 25% represents a good solution for the treatment of general contamination, which is not the case for DTPA at 1%. A soap in which DTPA at 1% has been added is adapted for large cutaneous contamination. The treatment of ocular contamination is also studied in this article.

Technical report: effect of cryopreservation on chromosomal aberration yield in irradiated lymphocytes.

Cryopreservation is the usual method to store cells before analysis or use, for instance for biological dosimetry purposes. Some investigations have shown that thawing following freezing may induce cell injury but few studies have been made of the effect of cryopreservation on cells containing radiation-induced unstable chromosomal aberrations. In this work, lymphocytes were irradiated with 1 to 4 Gy gamma rays and stored in liquid nitrogen. The dicentric and centric ring yields were analysed after storage periods of 1 week, 1 month and 3 months. No difference in aberration frequency from control, unfrozen samples was observed over this period. Lymphocytes stored at -196 degrees C for up to at least 3 months may therefore be used for chromosome aberration scoring when over-exposure to ionizing radiation is suspected.

Advantage of using both anionic and zwitterionic phospholipid antigens for the detection of antiphospholipid antibodies.

To investigate the benefit of assaying for antiphospholipid antibodies (aPA) with different antigenic specificities, sera from 141 patients suspected of having aPA were tested by ELISA for IgG and IgM antibodies directed against the following phospholipids (PL) coated individually or together: cardiolipin, phosphatidylinositol, phosphatidylserine and phosphatidylethanolamine. Nonspecific background optical density (OD) was systematically subtracted from the test OD value. Positive reactions were defined as having an OD greater than the 97th percentile OD distribution obtained with sera from 100 healthy individuals. Although the majority of the 79 detected aPA (89% IgG and 77% IgM) were polyspecific, 11 reacted with a single PL and, moreover, belonged to only one isotype. Seven of these 11 patients presented recurrent fetal losses or thrombotic events. These results suggest that routine use of a mixture of both anionic and zwitterionic PL antigens to coat ELISA plates would better detect aPA involved in suggestive pathologies and enhance the ability to identify patients with these mono- or polyspecific antibodies directed or not against cardiolipin, the current standard.