Development of a job exposure matrix for the epidemiological follow-up of workers in the French nuclear industry

BACKGROUND: A pilot study was carried out in the AREVA NC Pierrelatte nuclear facility in order to investigate a possible carcinogenic effect of internal radiation exposure among nuclear workers in France. The objective of this study was to develop a method for retrospective reconstruction of the occupational exposure to internal radiation from uranium and associated chemical exposures. METHODS: A plant- and period-specific job exposure matrix (JEM) was designed. Job groups and exposure agents groups including uranium compounds and other chemical agents known as being carcinogenic, mutagenic or toxic were defined by an expert committee. Exposure was evaluated by active and retired workers included in the evaluator committee. A quantitative assignment of quantity and frequency of handling (both coded from 0 to 3) was performed for each agent groups using a method derived from the Delphi technique. RESULTS: In all, 23 experts and 353 evaluators participated to the JEM elaboration. A final JEM involved 232 "job-periods" presenting throughout the plant period 1960-2006 and 22 exposure agents groups in use at the plant. Six of them involved uranium compounds classified by their blood-transferability and toxicity characteristics. A first validation of the JEM by experts in radiological protection and industrial hygiene showed an acceptable internal consistency. CONCLUSION: In the context of missing past exposure measurement data, the plant- and period-specific job exposure matrices may be considered as a valid alternative for exposure estimation. This method may be applied to other nuclear plants and offers allowance to investigate a possible carcinogenic effect of internal radiation exposure among nuclear workers.     

Microtubular inclusions in normal skin of systemic lupus erythematosus patients

Biopsy specimens of clinically normal skin of 9 consecutive patients with SLE were examined ultrastructurally to determine the presence and frequency of microtubular inclusions. Ten blood vessels were examined in each specimen; every specimen contained at least two positive blood vessels, and some contained 80 to 100% positive vessels. No correlation was found between the frequency of the inclusions and either the disease duration or antinuclear factor titer. The inclusions tended to be more frequent in patients with more acute disease. The absence of inclusions in normal skin may mitigate a diagnosis of SLE.     

Isolation of antihemorrhagic factors in opossum (Didelphis virginiana) serum using a monoclonal antibody immunoadsorbent

The antihemorrhagic factor in opossum (Didelphis virginiana) serum isolated by Sephadex G-200 gel filtration and DEAE A-50 ion exchange chromatography was used as antigen to immunize BALB/c mice. Hybrid cell lines secreting monoclonal antibodies against antihemorrhagic factor were produced by fusion of Sp2/0 myeloma cells with spleen cells of the immunized mice. The ascites fluid was produced in BALB/c mice. The monoclonal antibody in the ascites fluid was partially purified by DEAE A-50 ion exchange and coupled to CNBr-activated isolation of isolation of antihemorrhagic factor. The neutralization capacity of the conventionally isolated antihemorrhagic factor was 14.6 times and the affinity isolated antihemorrhagic factor was 16.8 times that of crude opossum serum. Both antihemorrhagic factors were homogeneous, with one fast migrating band in the area of albumin shown by polyacrylamide gel electrophoresis. However, the antihemorrhagic factor showed one heavy band and one faint band in SDS-polyacrylamide electrophoresis, as well as in isoelectric focusing. The molecular weight of the heavy band was estimated to be 65,000 with a value of p1 4.8 and the faint band was 57,000 with a value of pI 4.1.     

Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

BackgroundAnthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC.MethodsIntravenous pixantrone was administered at 180 mg/m² every 3 weeks (group A) versus 85 mg/m² on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population.ResultsForty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval [CI]: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%).ConclusionPixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT01086605","term_id":"NCT01086605"}}NCT01086605).     

Retrieving of Pups by Neonatally Stressed Mothers

Abstract

In the rat, perinatal food and maternal deprivation provoke long-lasting effects upon the retrieving responses of dams to displaced pups. In the current study, the retrieving latency and the disruption in the body area of pups chosen by the mother to transport them to a new location was investigated on days 4, 8 and 12 postpartum in lactating Wistar rats. Rats, neonatally underfed by daily (12 h) mother-litter separation in an incubator from days 1 to 23 postpartum, exhibited prolonged retrieving latencies and disruption in the body area of young ones chosen by the dam to transport them to the nest. Furthermore, neonatally underfed dams frequently transported pups in a rude manner eliciting sonic distress cries from them compared to control mothers. These findings are possibly relevant to understand the impact of epigenetic influences on offspring brain and physiological maturation partly mediated through maternal care.     

End-stage periventricular leukomalacia: MR evaluation

A prospective study was performed to assess the capabilities of magnetic resonance (MR) imaging in evaluation of end-stage periventricular leukomalacia (PVL) in six children, aged 31-54 months, in whom PVL had been documented by neurologic ultrasonography during the neonatal period. Eight children of similar age (four premature infants and four full-term infants) with normal neurologic development served as controls. A characteristic triad of PVL abnormalities was seen on MR images: (a) abnormally increased periventricular white-matter signal intensity on the first and second echo images of a T2-weighted sequence (repetition time = 2,000-2,400 msec, echo times = 20 or 30 and 80 msec), most commonly observed in the trigone regions of the lateral ventricles bilaterally; (b) marked loss of periventricular white matter in these regions of abnormal signal intensity, predominantly in the periatrial regions; and (c) compensatory focal ventricular enlargement adjacent to regions of abnormal signal intensity. In patients with the classic periatrial distribution of PVL lesions, general correlation between the degree of neurologic impairment and the severity of MR abnormalities was demonstrated. MR imaging was useful in detecting subtle forms of PVL in cases in which neurologic damage was subclinical.