Estimating the lifetime risk of cancer associated with multiple CT scans.

Multiple CT scans are often done on the same patient resulting in an increased risk of cancer. Prior publications have estimated risks on a population basis and often using an effective dose. Simply adding up the risks from single scans does not correctly account for the survival function. A methodology for estimating personal radiation risks attributed to multiple CT imaging using organ doses is presented in this article. The estimated magnitude of the attributable risk fraction for the possible development of radiation-induced cancer indicates the necessity for strong clinical justification when ordering multiple CT scans.

Stimulatory effect of volatile urinary components from intact mice on the proliferative activity of splenic lymphoid tissue in irradiated animals.

Immunohistochemical and morphometric analyses have demonstrated long-distance stimulatory effects of the natural volatile components of the urine of intact mice on the proliferation of splenic lymphocytes in mice exposed to a single total γ-irradiation in a dose of 1 Gy. These results are in line with the data on stimulation of the humoral immune response to thymus-dependent antigen in irradiated mice exposed to urine specimens of intact animals.

[Thyroid cancer: lessons of chernobyl and prognosis for Fukushima].

Results of epidemiological studies of thyroid cancer incidence in Russia following the Chernobyl accident are presented in the article. Child population in territories contaminated with radionuclides who got thyroid dose from incorporated (131)I above 100-150 mGy, should be referred to a group at radiation risk. Prognostic estimates of increase in thyroid cancer incidence among the population living in close vicinity of the Fukushima Daiichi NPP were made with account for the Chernobyl data and recommendations of the International Commission on Radiological Protection.

Estimation of risk from medical radiation exposure based on effective and organ dose: how much difference is there?

The authors compare radiation risks of potential cancer following diagnostic radiation exposure evaluated with the use of organ and effective doses. Lifetime attributable risk values of CT scanning are estimated with the use of ICRP (Publication 103) risk models and Russian national medical statistics data. For populations under the age of 50, the risk evaluated using organ doses usually differs from that using effective doses by <30 %. In older populations, the difference can be up to a factor of 3. Calculated values of lifetime attributable cancer risk for particular organs are presented as well.

[Therapy of patients with isolated metastasis in regional lymph nodes after primary treatment for skin melanoma].

The total of 186 metastatic skin melanoma patients with regional lymph nodes involvement (locoregional stage) received neoadjuvant chemotherapy and irradiation followed by extended lymphodissection. This therapy allowed obtaining favorable overall survival in most patients. Social aspect of the problem should also be noted - the tenacity in treatment of unfavorable prognosis patients using all treatment modalities available allows giving back the hope and extending the lifespan of many patients.

Radiation-epidemiological studies of thyroid cancer incidence in Russia after the Chernobyl accident (estimation of radiation risks, 1991-2008 follow-up period).

This study presents an analysis of the thyroid cancer incidence in the population of the most contaminated territories of Bryansk, Kaluga, Oryol and Tula oblasts affected by the Chernobyl accident. The follow-up period is 1991-2008, and the cohort size is 309 130 people. For that period 978 thyroid cancer cases were detected. The excess relative risk per 1 Gy (ERR/Gy) is found to be statistically significant for children and adolescents (0-17 y of age) at the time of the Chernobyl accident (ERR/Gy=3.22; 95 % confidence interval (1.56; 5.81). In boys, the ERR/Gy was higher than in girls -6.54 and 2.24, respectively. A statistically significant decrease in ERR/Gy with time since exposure, by a factor of 0.37 per 10 y, was observed for the whole cohort and for boys separately, but not for girls. No radiation risks of a thyroid cancer among people of 18 y of age at exposure and older were found.

Leukemia incidence in the Russian cohort of Chernobyl emergency workers.

Of all potentially radiogenic cancers, leukemia, a type of cancer of the blood, has the highest risk attributable to ionizing radiation. Despite this, the quantitative estimation of radiation risk of a leukemia demands studying very large exposed cohorts, because of the very low level of this disease in unexposed populations and because of the tendency for its radiation risk to decrease with time. At present, the Japanese cohort of atomic bomb survivors is still the primary source of data that allows analysis of radiation-induced leukemia and the underlying dose-response relationship. The second large cohort that would allow to study radiation-induced leukemia is comprised of individuals who were exposed due to the accident of the Chernobyl nuclear power plant in 1986. The objective of the present study was to estimate radiation risks of leukemia incidence among the Russian cohort of Chernobyl emergency workers, for different time periods after the accident. Twenty-five years after the Chernobyl accident and based on the results of the present study, one can conclude that the radiation risk of leukemia incidence derived from the Russian cohort of Chernobyl emergency workers is similar to that derived from the cohort of atomic bomb survivors: The time-averaged excess relative risk per Gray (ERR Gy(-1)) equals 4.98 for the Russian cohort and 3.9 for the life span study (LSS) cohort; excess absolute risk decreases with time after exposure at an annual rate of 9% for the Russian cohort, and of 6.5% for the LSS cohort. Thus, the excess in risk of leukemia incidence in a population due to a single exposure is restricted in time after exposure by the period of about 15 years.

[Where intestinal epithelial stem cells are localized? About molecular markers].

Using stem cells as an example the review considers a new history and methodology of search for stem cells (SC), found in tissues of adult Homo sapiens and Drosophila melanogaster organisms. These studies of SC resulted in several original hypotheses explaining their unusual features. Impressive progress recently achieved in this direction (2008-2010) is associated with employment of new methods of somatic recombination for long-term registration of various strains of differentiated cells, early and distant SC progeny. 1) Although anatomic localization of intestinal epithelium cells lacking marked morphological and biochemical differentiation markers (the lower third of intestinal and colon crypts) is known for about 40 years results of their experimental identification, isolation and detection of their functional characteristics still represent the subject for discussions. Particularly, it remains unclear, which SC are involved in crypt regeneration: the same as those involved into homeostatic renewal or their various subpopulations or early SC progenies acquired stem features by reprogramming? 2) In addition, most detected biochemical markers of potential SC are common for SC from other tissues of embryonic and mature organisms so it is possible to apply method developed for intestinal epithelium for their isolation. 3) Data on induction of intestinal epithelium polyps and neoplasias by mutations in genes encoding SC markers and identification of biochemical characteristics of potential SC in these tumors support the hypothesis of stem tumor cell origination from normal SC or their earliest progeny. In general, facts considered in this review may be useful for both development of optimal methods for the use of SC in cell therapy (as the source of humoral factors), regenerative medicine (as the source of differentiated cells for restoration of injured tissue), and also for targeted search of antitumor drugs (SC as the target) and preparations modifying genetic and epigenetic reactions of SC to genotoxic and stress treatments.

[Mortality among the liquidators of the Chernobyl accident: dose dependences and groups of the potential risk].

Dynamics of the mortality and the mortality radiation risks among male emergency workers of 1986-1987 years of entrance to the Chernobyl zone is analyzed. The average dose of external gamma-exposure for this cohort equals 128 mGy. The size of the cohort at the beginning of the follow-up in 1992 was 47820 persons. For the follow-up period 1992-2006 statistically significant radiation risks of death rates have been estimated: for the mortality from all causes, the excess relative risk per Gy (ERR/Gy) equals 0.42 with 95% confidence interval (95% CI) (0.14-0.72); for the mortality from solid cancers ERR/Gy = 0.74, 95% CI (0.03-1.76); and for the mortality from the circulatory system diseases ERR/Gy = 1.01, 95% CI (0.51-1.57). Based on these estimates the risk groups were ranked among all Russian emergency workers (160 thousand persons): the group of the potential radiation risk with doses more than 150 mGy (33488 persons) and the group of the high radiation risk with doses more than 240 mGy (6054 persons).

[Methods of individual retrospective physical dosimetry in the problem of estimation of consequences of accidental irradiation].

The overview of the results of development, verification and application of the methods of individual retrospective physical dosimetry among population of settlements contaminated with radionuclides, which suffered from irradiation as a result of the accident in Chernobyl NPP, and among the population located in the vicinity of the Semipalatinsk nuclear test site is presented in the paper. The estimations of sensitivity of the methods of physical retrospective dosimetry are shown. The data on individual doses among population, which was irradiated as a result of accidental irradiation are presented as well.

Dental enamel EPR dosimetry: comparative testing of the spectra processing methods for determination of radiation-induced signal amplitude.

The aim of this investigation is to find out the optimal algorithm for mathematical processing of the EPR spectra of irradiated tooth enamel for estimating the amplitude of the radiation-induced signal, which is used for determination of the absorbed dose in enamel for retrospective individual dosimetry. A recently developed analytical model, which takes into account the line shape variation of the enamel EPR spectral components registered at different microwave power, was applied to spectra processing in various operation modes to simulate spectra processing techniques differing by the number of fitted parameters. The precision of dose determination at spectra processing was assessed by the root mean square deviation between experimental and nominal doses for sets of spectra of enamel samples irradiated in different doses and measured at different microwave power. It is shown that in the case of pooled enamel samples prepared as a mixture from different teeth, the higher precision of spectra processing is obtained using a model with fixed native background signal line shape (characterized by width and asymmetry parameters). In case of individual samples prepared each from a different tooth, better results are obtained using a model with variable background signal line shape.

The neutron dose conversion coefficients calculation in human tooth enamel in an anthropomorphic phantom.

In the present study, MCNP4B simulation code is used to simulate neutron and photon transport. It gives the conversion coefficients that relate neutron fluence to the dose in tooth enamel (molars and pre-molars only) for 20 energy groups of monoenergetic neutrons with energies from 10-9 to 20 MeV for five different irradiation geometries. The data presented are intended to provide the basis for connection between EPR dose values and standard protection quantities defined in ICRP Publication 74. The results of the calculations for critical organs were found to be consistent with ICRP data, with discrepancies generally less than 10% for the fast neutrons. The absorbed dose in enamel was found to depend strongly on the incident neutron energy for neutrons over 10 keV. The dependence of the data on the irradiation geometry is also shown. Lower bound estimates of enamel radiation sensitivity to neutrons were made using obtained coefficients for the secondary photons. Depending on neutron energy, tooth enamel was shown to register 10-120% of the total neutron dose in the human body in the case of pure neutron exposure and AP irradiation geometry.

[Pharmacokinetic and dosimetric characteristics of new radiopharmaceutical based on complexes of 103Pd and albumin microspheres].

Results of the study of absorbed dose formed in organs and tissues of mice after administration of new therapeutic radiopharmaceutical on the base of 103Pd and albumin microspheres (MSA) are presented. Pharmacokinetic parameters of preparation distribution in the body of animals were experimentally determined and then absorbed doses were calculated using MCNP code for the developed mathematical model of mouse. It was shown that absorption of 103Pd-MSA in tumor, physical properties of 103Pd and daughter radionuclide 103mRh provide a targeted irradiation of tumor as compared with the adjusting tissues and critical organs. In administration to tumor muscle tissue of the leg of experimental animals after 15 days following the injection of 103Pd-MSA the accumulated absorbed dose was 15 times less than corresponding one in tumor. In a critical organ (kidneys) the accumulated absorbed dose was 20 times less than in tumor. The work performed as a stage of pre-clinical testing of the radiopharmaceutical.

Morphofunctional study of the therapeutic efficacy of human mesenchymal and neural stem cells in rats with diffuse brain injury.

We studied the effect of transplantation of human stem cells from various tissues on reparative processes in the brain of rats with closed craniocerebral injury. Combined treatment with standard drugs and systemic administration of xenogeneic stem cells had a neuroprotective effect. The morphology of neurons rapidly returned to normal after administration of fetal neural stem cells. Fetal mesenchymal stem cells produced a prolonged effect on proliferative activity of progenitor cells in the subventricular zone of neurogenesis. Adult mesenchymal stem cells had a strong effect on recovery of the vascular bed in ischemic regions.

Possible involvement of NO in the stimulating effect of pifithrins on survival of hemopoietic clonogenic cells.

Pifithrin alpha (PFTalpha), one of the first known low molecular weight modulators of activity of tumor suppressor p53, increases survival of hemopoietic clonogenic cells (evaluated by the criterion of formation of endogenous spleen CFU-C8 colonies in irradiated animals). This effect appeared when PFTalpha was administered either before or after irradiation. Increase in CFU-C8 was also observed after administration of two PFTalpha analogs, derivatives of 2-amino-4,5,6,7-tetrahydrobenzothiazole. These included a parent compound, 2-ATBT (2-amino-4,5,6,7-tetrahydrobenzothiazole), which is used for synthesis of PFTalpha, and a product of its intramolecular cyclization under physiological conditions, cyclo-PFT (2-(4-methylphenyl)imidazo[2,1-b]-5,6,7,8-tetrahydrobenzothiazole). Earlier we found that many low molecular weight compounds increasing number of CFU-C8 (e.g. isothiourea derivatives) demonstrate NO inhibitory activity. Such activity was also found in 2-ATBT and cyclo-PFT by means of EPR spectroscopy of NO. These compounds caused more than twofold inhibition of NO production in vivo. Thus, it has been demonstrated that PFTalpha and its structural analogs increase survival of hemopoietic clonogenic cells in vivo, and NO may play a role in the mechanism of this effect.

[Systemic transplantation of autologous mesenchymal stem cells of the bone marrow in the treatment of patients with multidrug-resistant pulmonary tuberculosis].

The study undertaken 3 years ago examined the effect of systemic transplantation of autologous mesenchymal stem cells (MSC) in the complex therapy of 27 patients with pulmonary tuberculosis, including 15 patients with multidrug-resistant pulmonary tuberculosis and 12 with extensive drug resistance of Mycobacterium tuberculosis. All the patients were bacteria-discharging persons with disseminated destructive processes in lung tissue, most (n=17) of them had chronic fibrocavernous tuberculosis. In all the patients, previous long specific antituberculous treatment was ineffective or inadequately effective. After systemic MSC transplantation, 16 patients were followed up for 1.5-2 years or more and the remaining 11 patients for at least 6 months. After MSC administration, a positive clinical effect was observed in all 27 cases; bacterial discharge stopped in 20 patients after 3-4 months; resolution of sustained lung tissue cavities further occurred in 11 patients. At present, a persistent remission of a tuberculous process may be stated in 9 of the 16 patients in whom MSCs were transplanted 1.5-2 years, significant positive bacteriological and morphological changes are observed in 6 patients. Thus, inclusion of transplantation of the autologous MSCs propagated in the culture into a course of antituberculous therapy may be a promising procedure for enhancing the efficiency of therapy in patients with resistant forms of pulmonary tuberculosis.

Effects of gram-positive microorganisms and their products on in vivo survival of hemopoietic clonogenic cells.

The effects of gram-positive bacterial strains (Lactobacillus acidophilus and Lactobacillus rhamnosus) and their subcellular components on the survival of hemopoietic clonogenic cells were evaluated by the formation of endogenous splenic colonies. The effects of these preparations on NO production were studied by the spin-trap paramagnetic resonance spectroscopy. Bacterial preparations from gram-positive bacteria stimulated survival of hemopoietic clonogenic cells, but did not induce NO production in contrast to E. coli LPS.

Role of cyclooxygenases in the stimulatory effect of carcinogen 1,2-dimethylhydrazine on stem cell survival in the intestinal epithelium and bone marrow.

In vivo experimental studies showed that 1,2-dimethylhydrazine and product of its metabolism in the body azoximethane improve postradiation survival of two types of stem cells in the adult organism: hemopoietic stem cells and intestinal epithelial stem cells. This effect similar to the well-known radioprotective effect of E. coli lipopolysaccharide was observed, when the carcinogen was administered 1 day before gamma-irradiation. Treatment with 1,2-dimethylhydrazine prolonged the mean life-span of mice irradiated in supralethal doses inducing death of the majority of intestinal epithelial stem cells. Nonspecific cyclooxygenase inhibitor indometacin weakened this radioprotective effect of 1,2-dimethylhydrazine. We also found that carcinogen 1,2-dimethylhydrazine improved survival of hemopoietic stem cells. However, in contrast to intestinal epithelial stem cells, indometacin did not inhibit the radioprotective effect of the carcinogen. The radioprotective effect of 1,2-dimethylhydrazine and lipopolysaccharide on stem cells in the presence of indometacin was a sum of individual effects of these preparations and indometacin.