Correlation between eye lens doses and over apron doses in interventional procedures

Measurements of eye lens dose using over apron dosimeters with a geometric correction factor is an international accepted practice. However, further knowledge regarding geometric correction factors in different contexts is required. The authors studied the correlation between eye lens dose and over apron dosimetry for different medical specialties in eleven hospitals, using a standardized protocol, two independent over apron dosimeters (worn at chest and at neck levels) and a dedicated calibration procedure. The results show good correlation between subjects working on the same medical specialty for 5 specialties: Interventional Radiology, Vascular Surgery, Vascular Radiology, Hemodynamics and Neuroradiology. The geometric correction factors resulting from this study could be used to estimate eye lens dose using over apron dosimeters, which are more comfortable than eye lens dosimeters, as reported by the study subjects, as long as the increased uncertainty of the over apron dosimetry compared to the dedicated eye lens dosimetry is acceptable.     

Low doses of lead

The effects of exposure to high doses of lead on reproduction and development have been established, but not so those caused by low lead doses or the influence that life stage at which contact with the metal takes place might have. The aim of this work was to study the effects of 200 and 400 ppm lead acetate in drinking water on reproduction and development as well as on renal and hepatic parameters of rats at different life stages, from gestation to 3 mo postweaning. The results indicate a dose-dependent effect on reproduction, with variations in the number of births and in pups' weight. Development was mostly affected at the weaning stage, with hemoglobin levels and erythrocyte numbers significantly decreased. The lead levels in tissues, blood, urine, and feces along with selected renal and hepatic parameters (blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase) were determined. There were histological, blood urea nitrogen, alanine aminotransferase, and alkaline phosphatase changes in the first month postweaning. After 3 mo, these changes are no longer evident, possibly because of metabolic adaptation.     

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6(n=301) or 3 doses at months 0, 1 and 6(n=304). Girls aged 15–17 years(n=149) and women aged 18–26 years(n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration(GMC) ratio(95% CI, lower bound0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women(1.76(95% CI, 1.56, 1.99) for HPV-16 and 1.93(95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9–14 years receiving 2 doses compared with women(1.45(95% CI, 1.25, 1.62) for HPV-16 and 1.17(95% CI,1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.     

Patient doses from image-guided radiation therapy

Recent publications show that some patients receive high cumulative radiation doses from recurrent CT examinations. Most of these patients had a diagnosis of malignancy, meaning that there was a likelihood that they would receive radiation therapy, possibly with image guidance. Patients receiving X-ray-based image-guided radiation therapy (IGRT) receive even more imaging dose, including to volumes of tissue outside the tumor target volume. The benefits of IGRT must be considered in light of the additional dose received. Monitoring and recording of the imaging dose should be considered, as should techniques to reduce both the dose and volume irradiated.     

Errors in computing drug doses.

The 85 members of the pediatric and neonatal divisions of a medical centre were tested for their ability to calculate the appropriate volumes of drugs commonly administered to pediatric patients. Of a total of 680 computations 43 (6.3%) were wrong. Half the errors would have led to either a 10-fold overdose or a dose a 10th of that prescribed. Significantly more of the errors (p less than 0.01) were made by the nurses in the neonatal division (11.5%) than by those in the pediatric division (3.4%). A deficiency in the in-service training of the nurses in the neonatal division appeared to contribute to the higher proportion of errors in this group. There was also a trend towards a greater chance of error as the length of professional experience increased. All medical personnel involved in the ordering and administration of drugs should be taught computing skills and be evaluated routinely.     

Low doses and high doses of heparin have different effects on osteoblast-like Saos-2 cells in vitro

Long-term treatment with heparin has been associated with an increased risk of osteoporosis. Given the importance of heparan sulfate proteoglycans for bone metabolism, it can be anticipated that heparin due to its structural similarity with heparan sulfate chains somehow interferes with the biological activities of these cell surface- and extracellular matrix-associated molecules. Initially in order to study the effect(s) of heparin on osteoblasts that possibly contribute to the development of heparin-induced osteoporosis, we treated osteoblast-like Saos-2 cells in monolayer culture for different periods of time with different concentrations of heparin. None of the heparin concentrations tested led to an inhibition of osteoblast proliferation during the early proliferative phase. After longer incubation times, however, cultures treated with higher concentrations of heparin (>/=5 microg/ml) exhibited a reduction in cell number as well as an inhibition of matrix deposition and mineralization. These effects could not be observed with lower heparin concentrations. On the contrary, low concentrations of heparin (5-500 ng/ml) even promoted matrix deposition and its subsequent mineralization. Apparently, heparin has a biphasic effect on osteoblast-like Saos-2 cells, being inhibitory at high concentrations but stimulatory at low concentrations. These results imply that heparin at concentrations well below those used for antithrombotic therapy might eventually turn out to be beneficial for bone formation.     

DNA damage responses at low radiation doses

Increased cell killing after exposure to low acute doses of X rays (0-0.5 Gy) has been demonstrated in cells of a number of human tumor cell lines. The mechanisms underlying this effect have been assumed to be related to a threshold dose above which DNA repair efficiency or fidelity increases. We have used cells of two radioresistant human tumor cell lines, one that shows increased sensitivity to low radiation doses (T98G) and one that does not (U373), to investigate the DNA damage response at low doses in detail and to establish whether there is a discontinuous dose response or threshold in activation of any important mediators of this response. In the two cell lines studied, we found a sensitive, linear dose response in early signaling and transduction pathways between doses of 0.1 and 2 Gy with no evidence of a threshold dose. We demonstrate that ATM-dependent signaling events to downstream targets including TP53, CHK1 and CHK2 occur after doses as low as 0.2 Gy and that these events promote an effective damage response. Using chemical inhibition of specific DNA repair enzymes, we show that inhibition of DNA-PK-dependent end joining has relatively little effect at low (<1 Gy) doses in hyper-radiosensitive cells and that at these doses the influence of RAD51-mediated repair events may increase, based on high levels of RAD51/BRCA2 repair foci. These data do not support a threshold model for activation of DNA repair in hyper-radiosensitive cells but do suggest that the balance of repair enzyme activity may change at low doses.     

Thrombolytic therapy with ultra-high doses of streptokinase

Two pilot studies were carried out in patients suffering from acute myocardial infarction. They received high doses of streptokinase and acylated streptokinase-plasminogen activator complex intravenously as a bolus injection. Furthermore, the possibility of using streptokinase bolus therapy was examined in patients with acute vascular occlusion. Due to the limited number and the heterogenicity of cases the results obtained in patients with acute myocardial infarction are to evaluate with some reservation. In patients with acute vascular occlusion streptokinase bolus therapy at high doses proved to be a promising alternative to the conventional therapy.     

Uncertainties on lung doses from inhaled plutonium

In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.