Variation of 4 MV X-ray dose rate strongly impacts biological response both in vitro and in vivo.

Whereas an RBE > 1 is described for very low-energy X-ray beams (in the range of 25-50 kV), there is a consensus that the RBE of X-rays (from 0.1 to 3 MeV) is equal to 1, whatever the energy or dose rate of the beam. Comparisons of X-ray beam dose rates are scarce even though these beams are widely used in medical diagnosis or radiotherapy. By using two dose rates (0.63 and 2.5 Gy.min-1) of high-energy X-rays on normal endothelial cells (HUVECs), we have studied the clonogenic assay, but also viability/mortality, cell cycle analysis and measured cellular senescence by flow cytometry, and have performed gene analysis on custom arrays. In order to consolidate these data, we performed localized irradiation of exteriorized small intestine at 0.63 and 2.5 Gy.min-1. Interestingly, in vivo validation has shown a significantly higher loss of weight at the higher dose when irradiating to 19 Gy a small fragment of exteriorized small intestine of C57Bl6J mice. Nevertheless, no significant differences were observed in lesioned scores between the two dose rates, while bordering epithelium staining indicated twofold greater severe damage at 2.5 Gy.min-1 compared to 0.63 Gy.min-1 at one week post-irradiation. Taken together, these experiments systematically show that the relative biological effectiveness of photons is different from 1 when varying the dose rate of high-energy X-rays. Moreover, these results strongly suggest that, in support of clonogenic assay, multiparametric analysis should be considered to provide an accurate evaluation of the outcome of irradiated cells.

Characteristics, medical management and outcomes of survivors of sexual gender-based violence, Nairobi, Kenya.

SETTING: Médecins Sans Frontières Clinic for sexual gender-based violence (SGBV), Nairobi, Kenya. OBJECTIVES: Among survivors of SGBV in 2011, to describe demographic characteristics and episodes of sexual violence, medical management, pregnancy and human immunodeficiency virus (HIV) related outcomes. DESIGN: Retrospective review of clinical records and SGBV register. RESULTS: Survivors attending the clinic increased from seven in 2007 to 866 in 2011. Of the 866 survivors included, 92% were female, 34% were children and 54% knew the aggressor; 73% of the assaults occurred inside a home and most commonly in the evening or at night. Post-exposure prophylaxis for HIV was given to 536 (94%), prophylaxis for sexually transmitted infections to 731 (96%) and emergency contraception to 358 (83%) eligible patients. Hepatitis B and tetanus toxoid vaccinations were given to 774 survivors, but respectively only 46% and 14% received a second injection. Eight (4.5%) of 174 women who underwent urine pregnancy testing were positive at 1 month. Of 851 survivors HIV-tested at baseline, 96 (11%) were HIV-positive. None of the 220 (29%) HIV-negative individuals who returned for repeat HIV testing after 3 months was positive. CONCLUSION: Acceptable, good quality SGBV medical care can be provided in large cities of sub-Saharan Africa, although further work is needed to improve follow-up interventions.

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy.

The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35+/-0.2 Gy) than the calculated equivalent whole-body dose (0.07+/-0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2+/-0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1+/-0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p = 0.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p = 0.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.

Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing.

OBJECTIVE: We hypothesized that adipose tissue may contain progenitors cells with cutaneous and angiogenic potential. METHODS AND RESULTS: Adipose tissue-derived stroma cells (ADSCs) were administrated to skin punched wounds of both nonirradiated and irradiated mice (20 Gy, locally). At day 14, ADSCs promoted dermal wound healing and enhanced wound closure, viscolesticity, and collagen tissue secretion in both irradiated and nonirradiated mice. Interestingly, GFP-positive ADSCs incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. Cultured ADSCs in keratinocyte medium have been shown to differentiate into K5- and K14-positive cells and produced high levels of KGF. At Day 7, ADSCs also improved skin blood perfusion assessed by laser Doppler imaging, capillary density, and VEGF plasma levels in both irradiated and nonirradiated animals. GFP-positive ADSCs incorporated into capillary structures in vivo and expressed the endothelial cell marker CD31. Finally, in situ interphase fluorescence hybridization showed that a small number of ADSCs have the potential to fuse with endogenous keratinocytes. CONCLUSIONS: ADSCs participate in dermal wound healing in physiological and pathological conditions by their ability to promote reepithelialization and angiogenesis. Hence, adipose lineage cells represent a new cell source for therapeutic dermal wound healing.

Monitoring translocations by M-FISH and three-color FISH painting techniques: a study of two radiotherapy patients.

PURPOSE: To compare translocation rate using either M-FISH or FISH-3 in two patients treated for head and neck cancer, with a view to retrospective dosimetry. MATERIALS AND METHODS: Translocation analysis was performed on peripheral blood lymphocyte cultures from blood samples taken at different times during the radiotherapy (0 Gy, 12 Gy and 50 Gy) and a few months after the end of the treatment (follow-up). RESULTS: Estimated translocation yield varied according to the FISH technique used. At 50 Gy and follow-up points, the translocation yields were higher with FISH-3 than with M-FISH. This difference can be attributed to three events. First, an increase in complex aberrations was observed for 50 Gy and follow-up points compared with 0 Gy and 12 Gy points. Second, at the end of treatment for patient A, involvement of chromosomes 2, 4, 12 in translocations was less than expected according to the Lucas formula. Third, a clone bearing a translocation involving a FISH-3 painted chromosome was detected. CONCLUSIONS: More translocations were detected with M-FISH than with FISH-3, and so M-FISH is expected to improve the accuracy of chromosome aberration analyses in some situations.

Study of the tools available in biological dosimetry to estimate the dose in cases of accidental complex overexposure to ionizing radiation: the Lilo accident.

PURPOSE: To compare the efficiency of different cytogenetic tools in estimating the doses received by four people involved in the Lilo accident and to monitor the dose estimate over 4.5 years. MATERIALS AND METHODS: Several young Georgian frontier guards handled at least one of the 12 Caesium sources found in a former Russian military camp. Overexposure lasted from July 1996 to May 1997. The Institute for Radiological Protection and Nuclear Safety (IRSN) obtained blood samples taken at several intervals post-exposure from the four most highly-exposed people. Dose estimation was performed using dicentric and translocation scoring. RESULTS: The first dose estimations performed by dicentric scoring gave whole-body doses ranging from 0.4 to 1.3 Gy. Overexposure was complex and several mathematical models were used to take this complexity into account. This could provide information concerning the circumstances of overexposure. Concerning follow-up, the yield of dicentrics decreased by about 50% in the first 4 months following the end of overexposure whereas translocations were stable over the period of analysis. CONCLUSION: It has been useful to compare cytogenetic results with clinical results. The results presented here reveal good stability of translocations. However the first dose estimation was not attempted until 6 months after the last exposure.

International intercomparison for criticality dosimetry: the case of biological dosimetry.

The Institute of Radiation Protection and Nuclear Safety (IRSN) organized a biological dosimetry international intercomparison with the purpose of comparing (i) dicentrics yield produced in human lymphocytes; (ii) the gamma and neutron dose estimate according to the corresponding laboratory calibration curve. The experimental reactor SILENE was used with different configurations: bare source 4 Gy, lead shield 1 and 2 Gy and a 60Co source 2 Gy. An increasing variation of dicentric yield per cell was observed between participants when there were more damages in the samples. Doses were derived from the observed dicentric rates according to the dose-effect relationship provided by each laboratory. Differences in dicentric rate values are more important than those in the corresponding dose values. The doses obtained by the participants were found to be in agreement with the given physical dose within 20%. The evaluation of the respective gamma and neutron dose was achieved only by four laboratories, with some small variations among them.