Measuring Recent Thymic Emigrants in Blood of Normal and HIV-1–Infected Individuals before and after Effective Therapy

The role of the thymus in HIV-1 pathogenesis remains unclear. We developed an assay to quantify the number of recent thymic emigrants in blood based on the detection of a major excisional DNA byproduct (termed α1 circle) of T cell receptor rearrangement. By studying 532 normal individuals, we found that α1 circle numbers in blood remain high for the first 10–15 yr of life, a sharp drop is seen in the late teen years, and a gradual decline occurs thereafter. Compared with age-matched uninfected control individuals, α1 circle numbers in HIV-1–infected adults were significantly reduced; however, there were many individuals with normal α1 circle numbers. In 74 individuals receiving highly active antiretroviral therapy, we found no appreciable effect on α1 circle numbers in those whose baseline values were already within the normal range, but significant increases were observed in those with a preexisting impairment. The increases in α1 circle numbers were, however, numerically insufficient to account for the rise in levels of naive T lymphocytes. Overall, it is difficult to invoke thymic regenerative failure as a generalized mechanism for CD4 lymphocyte depletion in HIV-1 infection, as α1 circle numbers are normal in a substantial subset of HIV-1–infected individuals

A minor role of asparaginase in predisposing to cerebral venous thromboses in adult acute lymphoblastic leukemia patients

Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients

External and internal irradiation of a Rural Bryansk (Russia) population from 1990 to 2000, following high deposition of radioactive caesium from the chernobyl accident.

In 1990, a joint Nordic-Russian project was initiated in order to make independent estimations of the effective dose to selected groups of inhabitants in a highly contaminated area around the city of Novozybkov In the western Bryansk region of Russia. The inhabitants were living in six villages with initial contamination levels of Cs-137 between 0.9 and 2.7 MBq m(-2). Some villages had been decontaminated, others not. Both school children and adults participated in the study. The external irradiation of 100-130 inhabitants was determined during 1 month in September-October each year from 1990 to 2000 (except 1999), using individual thermoluminescent dosemeters. The body burden of (137,) (CS)-C-134 was determined by in vivo measurements in about 500 inhabitants annually from 1991 to 2000, and for a subgroup also with analysis of the (CS)-C-137 concentration in urine. The mean effective dose (E) from external and internal irradiation due to Cs-137,Cs- 134 deposition varied between 2.5 and 1.2 mSv per year between 1990 and 2000. The total mean E decreased, on average, by 9% per year, while the mean external dose decreased by 16% per year. The dose rate from internal radiation decreased more slowly than the dose rate from external radiation, and also showed an irregular time variation. The contribution from the internal dose to the total E was 30-50%, depending on the village. Predictions for the long-term changes in the effective dose to people living in the areas are presented. The cumulated E for the 70 years following the accident was estimated to be about 90 mSv with the assumption that both internal and external dose decrease by 2% per year after year 2000. The highest E during a life-time received by single individuals living in the area may amount to around 500 mSv considering the individual variations in E

Transfer of (137)Cs from Chernobyl debris and nuclear weapons fallout to different Swedish population groups.

Data from measurements on the body burden Of (CS)-C-134, Cs-137 and K-40 in various Swedish populations between 1959 and 2001 has been compiled into a national database. The compilation is a co-operation between the Departments of Radiation Physics in Malmo and Goteborg, the National Radiation Protection Authority (SSI) and the Swedish Defense Research Agency (FOI). In a previous study the effective ecological half time and the associated effective dose to various Swedish populations due to internal contamination of Cs-134 and Cs-137 have been assessed using the database. In this study values of human body burden have been combined with data on the local and regional ground deposition of fallout from nuclear weapons tests (only Cs-137) and Chernobyl debris (both Cs-134 and (CS)-C-137), which have enabled estimates of the radioecological transfer in the studied populations. The assessment of the database shows that the transfer of radiocesium from Chernobyl fallout to humans varies considerably between various populations in Sweden. In terms of committed effective dose over a 70 y period from internal contamination per unit activity deposition, the general (predominantly urban) Swedish population obtains 20-30 mu Sv/kBq m(-2). Four categories of populations exhibit higher radioecological transfer than the general population; i.) reindeer herders (similar to 700 mu Sv/kBq m(-2)), ii.) hunters in the counties dominated by forest vegetation (similar to 100 mu Sv/kBq m(-2)), iii.) rural non-farming populations living in sub-arctic areas (40-150 mu Sv/kBq m(-2)), and iv.) farmers (similar to 50 mu Sv/kBq m(-2)). Two important factors determine the aggregate transfer from ground deposition to man; i.) dietary habits (intakes of foodstuff originating from natural and semi-natural ecosystems), and ii.) inclination to follow the recommended food restriction by the authorities. The transfer to the general population is considerably lower (similar to a factor of 3) for the Chernobyl fallout than during the 1960s and 70s, which is partly explained by a higher awareness of the pathways of radiocaesium to man both by the public and by the regulating authorities, and by the time-pattern of the nuclear weapons fallout during the growth season in Sweden. (c) 2005 Elsevier B.V. All rights reserved