Current knowledge on tumour induction by computed tomography should be carefully used

Risks associated to ionising radiation from medical imaging techniques have focused the attention of the medical society and general population. This risk is aimed to determine the probability that a tumour is induced as a result of a computed tomography (CT) examination since it makes nowadays the biggest contribution to the collective dose. Several models of cancer induction have been reported in the literature, with diametrically different implications. This article reviews those models, focusing on the ones used by the scientific community to estimate CT detriments. Current estimates of the probability that a CT examination induces cancer are reported, highlighting its low magnitude (near the background level) and large sources of uncertainty. From this objective review, it is concluded that epidemiological data with more accurate dosimetric estimates are needed. Prediction of the number of tumours that will be induced in population exposed to ionising radiation should be avoided or, if given, it should be accompanied by a realistic evaluation of its uncertainty and of the advantages of CTs. Otherwise they may have a negative impact in both the medical community and the patients. Reducing doses even more is not justified if that compromises clinical image quality in a necessary investigation. Key Points ? Predictions of radiation-induced cancer should be discussed alongside benefits of imaging. ? Estimates of induced cancers have noticeable uncertainties that should always be highlighted. ? There is controversy about the acceptance of the linear no-threshold model. ? Estimated extra risks of cancer are close to the background level. ? Patients should not be alarmed by potential cancer induction by CT examinations.     

Ultra-Violet Light Emission from HPV-G Cells Irradiated with Low Let Radiation From 90Y; Consequences for Radiation Induced Bystander Effects

In this study, we aimed to establish the emission of UV photons when HPV-G cells and associated materials (such as the cell substrate and cell growth media) are exposed to low LET radiation. The potential role of UV photons in the secondary triggering of biological processes led us to hypothesize that the emission and absorption of photons at this wavelength explain some radiation induced “bystander effects” that have previously been thought to be chemically mediated. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate, and were exposed to β-radiation from ⁹⁰Y produced by the McMaster Nuclear Reactor. UV measurements were performed using a single photon counting system employing an interference-type filter for selection of a narrow wavelength range, 340±5 nm, of photons. Exposure of the cell substrates (which were made of polystyrene) determined that UV photons were being emitted as a consequence of β particle irradiation of the Petri-dishes. For a tightly collimated β-particle beam exposure, we observed 167 photons in the detector per unit μCi in the shielded source for a 1.76 mm thick substrate and 158 photons/μCi for a 0.878 mm thick substrate. A unit μCi source activity was equivalent to an exposure to the substrate of 18 β-particles/cm² in this case. The presence of cells and medium in a Petri-dish was found to significantly increase (up to a maximum of 250%) the measured number of photons in a narrow band of wavelengths of 340±5 nm (i.e. UVA) as compared to the signal from an empty control Petri-dish. When coloured growth medium was added to the cells, it reduced the measured count rate, while the addition of transparent medium in equal volume increased the count rate, compared to cells alone. We attribute this to the fact that emission, scattering and absorption of light by cells and media are all variables in the experiment. Under collimated irradiation conditions, it was observed that increasing cell density in medium of fixed volume resulted in a decrease in the observed light output. This followed a roughly exponential decline. We suggest that this may be due to increased scattering at the cell boundary and absorption of the UV in the cells. We conclude that we have measured UVA emitted by cells, cell medium and cell substrates as a consequence of their irradiation by low LET β-particle radiation. We suggest that these secondary UV photons could lead to effects in non-targetted cells. Some effects that had previously been attributed to a chemically mediated “bystander effect” may in fact be due to secondary UV emission. Some radiation bystander effect studies may require re-interpretation as this phenomenon of UV emission is further investigated.     

Effects of early and late adverse experiences on morpho-quantitative characteristics of Sprague-Dawley rat spleen subjected to stress during adulthood

Morpho-quantitative studies of the spleen indicate that the proportions of the compartments and sub-compartments are stable in normal conditions. However, disorders due to stress can influence the number and function of the immune cells in this organ. The aim of this study was to determine, through the model of altering the early mother-infant bond and altering the late social bond through isolation, the effect on the morpho-quantitative characteristics of the spleen in adult Sprague-Dawley rats subjected to intermittent chronic stress in adulthood. Twenty-five newborn female rats were used, kept under the standardized lactation and feeding conditions. The rats were assigned randomly to 2 control groups (C1 and C2) and 3 experimental groups, exposed to early (E1), late (E2) or early-late (E3) adverse experiences and then subjected to intermittent chronic stress in adulthood (C2, E1, E2 and E3). The spleen of each animal was isolated and its morphometric characteristics were determined: volume density (Vv) of the red pulp, white pulp, marginal zone, splenic lymph nodule, periarterial lymphatic sheath and germinal center; areal number density (Na), surface density (Sv), number density (Nv), diameter (D) and total number of splenic lymph nodules. The mass of each compartment was also determined. A one-way analysis of variance (ANOVA) and Scheffé’s post hoc test were used for the statistical analysis. The p values were considered significant when they were less than 0.05 (*) and very significant at less than 0.025 (**). There were significant differences in the Vv of the red pulp, white pulp and their sub-compartments between the control and experimental groups. The white pulp increased significantly (P = 0.000) in E1, E2 and E3 compared to C1 and C2. The average Na and D values of the splenic lymph nodules were also higher in the experimental groups. The ANOVA for the mass of the spleen and the red pulp revealed no differences between the groups. The mass of the white pulp and its subcompartments was greater in the experimental groups. A higher proportion of white pulp in the experimental groups could be associated with an increase in spleen immune activity, with alterations depending on certain cell subsets. The chronic stress produced morpho-quantitative changes in the rat spleen, and these depended on the animal’s history of stress, whether it had been previously stressed or not, with further exposure to stress in adulthood.     

Interventricular delay interval optimization in cardiac resynchronization therapy guided by echocardiography versus guided by electrocardiographic QRS interval width

Present devices for cardiac resynchronization therapy offer the possibility of tailoring the hemodynamic effect of biventricular pacing by optimization of the interventricular delay (VV) beyond atrioventricular (AV)-interval optimization. It was not yet defined whether a QRS width-based strategy may be a helpful tool for echocardiography for device programming. The aim of the study was to investigate the relation between VV-interval optimization guided by echocardiography and guided by QRS interval width. One hundred six patients with a cardiac resynchronization therapy device for > or =3 months were enrolled. All patients underwent echocardiographic AV and VV delay optimization. The AV interval was optimized according to the E wave-A wave (EA) interval and left ventricular filling time. At the optimal AV delay, VV optimization was performed by measuring the aortic velocity time integral at 5 different settings: simultaneous right and left ventricle output, left ventricle pre-excitation (left ventricle + 40 and 80 ms, respectively), and right ventricle pre-excitation (right ventricle + 40 and 80 ms, respectively). A 12-lead electrocardiogram was recorded and QRS duration was measured in the lead with the greatest QRS width. The electrocardiographic (ECG)-optimized VV interval was defined according to the narrowest achievable QRS interval among 5 VV intervals. The echocardiographic-optimized VV interval was left ventricle + 40 ms in 28 patients, left ventricle + 80 ms in 15 patients, simultaneous in 46 patients, right ventricle + 40 ms in 14 patients, and right ventricle + 80 ms in 3 patients. Significant concordance (kappa = 0.69, p <0.001) was found between the echocardiographic- and ECG-optimized VV interval. In conclusion, significant concordance appeared to exist during biventricular pacing between VV programming based on the shortest QRS interval at 12-lead ECG pacing and echocardiographic-guided VV-interval optimization. A combined ECG- and echocardiographic approach could be a less time-consuming solution in performing this operation.     

Contribution of vasoconstriction to the origin of atherosclerosis: a conceptual study

Research during the past century has clearly shown that endothelial injury (EI) and/or endothelial dysfunction (ED) are among the major events determining the onset of atherosclerosis. Included in the events that may elicit endothelial damage, vasoconstriction (VC) has received relatively little attention. This conceptual review attempts to show that in elastic and conduit arteries, VC is not only capable of producing EI/ED, but is also closely associated with many recognized proatherogenic stimuli. Of related interest is the observation that a number of suspected antiatherogenic stimuli oppose VC by their vasodilatory effects, lending further support to this relationship. In addition, recent developments in the knowledge of the molecular basis of VC (including the role of specific inhibitors) are discussed, and their potential for preventing lesion formation and thus becoming novel therapeutic alternatives against the onset of atherosclerosis are highlighted.     

Primary aldosteronism and hypertensive disease

Recent studies in hypertensive populations that have used the serum aldosterone (SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a high prevalence of primary aldosteronism (PA). This frequency is higher than that previously described when hypokalemia was used as a screening tool. However, other factors, such as the characteristics of hypertensive disease, could also influence the prevalence of PA. We studied 609 essential hypertensive patients, classified according to the Joint National Committee VI (JNC VI), in 3 different stages depending on the severity of their hypertensive disease. We measured SA and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio >25 was detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA diagnoses in 37 of 609 (6.1%) cases. PA prevalence according to hypertension stage was as follows: stage 1, 6 of 301 cases (1.99%); stage 2, 15 of 187 cases (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger than the other hypertensive patients (48.4+/-10.5 vs 53.6+/-10.2 years; P<0.05). Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of PA in essential hypertensives classified in stages 2 and 3 according to the JNC VI. The low frequency of computed tomography scan abnormalities and hypokalemia suggests that the diagnosis for most PA patients corresponds to attenuated forms of the disease.