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Biomedical subjects

Linda Walsh

Publications and source records attributed to Linda Walsh.

8 recordsLinked to original sources
PubMed2006

Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line.

In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1muM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified.

Apoptosis↗
PubMed2006

Improving teamwork climate in operating theatres: the shift from multiprofessionalismto interprofessionalism.

A multi-faceted, longitudinal and prospective collaborative inquiry was initiated in December 2002 with one half of the cohort of operating theatre personnel in a large, acute UK hospital serving a mainly rural population. The same intervention was introduced in January 2004 to the other half of the cohort. The project aims to improve patient safety through a structured educational intervention focussed upon changing teamwork practices. This article reports one critical element of the larger project - changing teamwork climate as a necessary precursor to establishing an interprofessional teamwork culture. The aggregate of individual, unidirectional attitude changes across a large cohort constitutes a change in climate. This shift challenges the conventional culture of multiprofessionalism, where uniprofessional identification (the "silo" mentality) is traditionally strong.

Education, Medical, Continuing↗
PubMed2006

Indications of the neutron effect contribution in the solid cancer data of the A-bomb survivors.

Risk estimates for radiation-induced cancer are primarily based on the follow-up of the Japanese A-bomb survivors. Their exposures were due to gamma rays and neutrons, and, currently--with the assumed low RBE = 10 of neutrons and reference to the colon dose--the late radiation effects are almost fully attributed to the gamma rays. Solid cancer risk estimates for different organ sites are assessed here, and an inconspicuous but statistically highly significant trend of larger values is found for the organs closer to the body surface; i.e., the organs with less body shielding and, therefore, with larger neutron dose-fractions. Underestimation of the RBE of neutrons can explain this apparent correlation. The trend of ERR/Gy vs. depth ceases to be statistically significant for RBE values close to 100. The suggestion of high RBE values and the corresponding reduction of gamma-ray risk estimates is found to be in line with log-likelihood computations in terms of AMFIT, which provide for the solid cancer mortality of the A-bomb survivors the minimum deviance for RBE = 100 with a 95% confidence lower limit of 25. The present assessment had to use the data made publicly available by RERF. In this form they contain city-, sex-, age-, and dose-categories, but--instead of a separate neutron-dose category--only the mean neutron dose for each data cell. The tentative conclusions that are here obtained should, therefore, be examined by a more definitive analysis, either in terms of grouped data with a separate classification of neutron doses or, ideally, in terms of person by person calculations to be performed at RERF with individually estimated neutron doses.

Body Burden↗
PubMed2004

Cancer risk estimates for gamma-rays with regard to organ-specific doses Part II: site-specific solid cancers.

Part I of this study presented an analysis of the solid cancer mortality data for 1950-1997 from the Japanese life-span study of the A-bomb survivors to assess the cancer risk for gamma-rays in terms of the organ-specific dose for all solid cancers combined. Compared to earlier analyses, considerably more curvature in the dose-effect relation is indicated by these computations, which now suggests a dose and dose-rate effectiveness factor of about 2. The computations are extended here in order to explore the site-specific solid cancer risks for various organs. A computational method has been developed whereby the site-specific cancer risks are all simultaneously computed with global age and gender effect modifiers. This provides a more parsimonious representation with fewer parameters and avoids the large relative standard errors which would otherwise result. The sensitivity of site-specific risks to the choices of the neutron RBE is examined. The site-specific risk estimates are quite sensitive to the neutron RBE for the least shielded organs such as the breast, bladder and oesophagus. For the deeper lying organs, such as the gallbladder, pancreas and uterus, the impact of the neutrons is much lower. With an assumed neutron RBE of 35, which is in line with results on low neutron doses in major past studies on rodents and which corresponds approximately to the current ICRP radiation weighting factor for neutrons, the neutrons appear to contribute about 40% of the observed excess cancer risk in the breast, i.e. the organ that is closest to the body surface. However, this neutron contribution fraction is only about 10% for deeper lying organs, such as the colon.

Algorithms↗
PubMed2004

Cancer risk estimates for gamma-rays with regard to organ-specific doses. Part I: All solid cancers combined.

A previous analysis of the solid cancer mortality data for 1950-1990 from the Japanese life-span study of the A-bomb survivors has assessed the solid cancer risk coefficients for gamma-rays in terms of the low dose risk coefficient ERR/Gy, i.e. the initial slope of the ERR vs. dose relation, and also in terms of the more precisely estimated intermediate dose risk coefficient, ERR(D1)/D1, for a reference dose, D1, which was chosen to be 1 Gy. The computations were performed for tentatively assumed values 20-50 of the neutron RBE against the reference dose and in terms of organ-averaged doses, rather than the traditionally applied colon doses. The resulting risk estimate for a dose of 1 Gy was about half as large as the most recent UNSCEAR estimate. The present assessment repeats the earlier analysis with two major extensions. It parallels computations based on organ-average doses with computations based on organ-specific doses and it updates the previous results by using the cancer mortality data for 1950-1997 which have recently been made available. With an assumed neutron RBE of 35, the resulting intermediate dose estimate of the lifetime attributable risk (LAR) for solid cancer mortality for a working population (ages 25-65 years) is 0.059/Gy with the attained-age model, and 0.044/Gy with the age-at-exposure model. For a population of all ages, 0.055/Gy is obtained with the attained-age model and 0.073/Gy with the age-at-exposure model. These values are up to about 20% higher than those obtained in the previous analysis with the 1950-1990 data. However, considerably more curvature in the dose-effect relation is now supported by the computations. A dose and dose-rate reduction factor DDREF=2 is now much more in line with the data than before. With this factor the LAR for a working population is--averaged over the age-at-exposure and the age-attained model--equal to 0.026/Gy. This is only half as large as the current ICRP estimate which is also based on the assumption DDREF=2.

Algorithms↗
PubMed2002

Risk coefficient for gamma-rays with regard to solid cancer.

A previous investigation has uncoupled the solid cancer risk coefficient for neutrons from the low dose estimates of the relative biological effectiveness (RBE) of neutrons and the photon risk coefficient, and has related it to two more tangible quantities, the excess relative risk (ERR1) due to an intermediate reference dose D1 = 1 Gy of gamma-rays and the RBE of neutrons, R1, against this reference dose. With tentatively assumed RBE values between 20 and 50 and in terms of organ-averaged doses--rather than the usually invoked colon doses--the neutron risk factor was seen to be in general agreement with the current risk estimate of the International Commission on Radiation Protection (ICRP). The present assessment of the risk coefficient for gamma-rays incorporates--in terms of the unchanged A-bomb dosimetry system, DS86--this treatment of the neutrons, but is otherwise largely analogous to the evaluation of the A-bomb data for the ICRP report and for the recent report of the United Nations Scientific Committee on the effects of ionizing radiation, UNSCEAR. The resulting central estimate of the lifetime attributable risk (LAR) for solid cancer mortality is 0.043/Gy for a working population (ages 25-65), and is nearly the same whether the age at exposure or the attained age model is used for risk projection. For a population of all ages 0.042/Gy is obtained with the attained age model and 0.068/Gy with the age at exposure model. The values do not include a dose and dose rate effectiveness factor (DDREF), and they are only half as large as the new UNSCEAR estimates of 0.082/Gy (attained age model and all ages) and 0.13/Gy (age at exposure model and all ages). The difference is only partly due to the more explicit treatment of the neutrons. It reflects also the fact that UNSCEAR has converted ERR into LAR in a way that differs from the ICRP procedure, and that it has summed the overall risk coefficient for solid tumor mortality and incidence from separate estimates for eight solid tumor categories, whereas the present study employs a combined computation for all solid tumors and uses the ICRP procedure for the conversion of ERR into LAR. The appendix gives results for the solid cancer incidence data.

Adult↗
PubMed2002

Solid cancer risk coefficient for fast neutrons in terms of effective dose.

Cancer mortality risk coefficients for neutrons have recently been assessed by a procedure that postulates for the neutrons a linear dose dependence, invokes the excess risk of the A-bomb survivors at a gamma-ray dose D(1) of 1 Gy, and assumes a neutron RBE as a function of D(1) between 20 and 50. The excess relative risk (ERR) of 0.008/mGy has been obtained for R(1) = 20 and 0.016/mGy for R(1) = 50. To compare these results to the current ICRP nominal risk coefficient for solid cancer mortality (0.045/Sv for a population of all ages; 0.036/Sv for a working population), the ERR is translated into lifetime attributable risk and is then related to effective dose. The conversion is not trivial, because the neutron effective dose has been defined by ICRP not as a weighted genuine neutron dose (neutron kerma), but as a weighted dose that includes the dose from gamma rays that are induced by neutrons in the body. If this is accounted for, the solid cancer mortality risk for a working population is found to agree with the ICRP nominal risk coefficient for neutrons in their most effective energy range, 0.2 MeV to 0.5 MeV. In radiation protection practice, there is an added level of safety, because the effective dose, E, is-for monitoring purposes-assessed in terms of the operational quantity H*, which overestimates E substantially for neutrons between 0.01 MeV and 2 MeV.

Dose-Response Relationship, Radiation↗