We evaluated the predictive value of interim positon emission tomography (I-PET) after one course of chemoimmunotherapy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). One hundred and twelve patients with DLBCL were enrolled. All patients had PET/computed tomography (CT) scans performed after one course of chemotherapy (PET-1). I-PET scans were categorized according to International Harmonization Project criteria (IHP), Deauville 5-point scale (D 5PS) with scores 1-3 considered negative (D 5PS > 3) and D 5PS with scores 1-4 considered negative (D 5PS = 5). Ratios of tumor maximum standardized uptake value (SUVmax) to liver SUVmax were also analyzed. We found no difference in progression-free survival (PFS) between PET-negative and PET-positive patients according to IHP and D 5PS > 3. The 2-year PFS using D 5PS = 5 was 50.9% in the PET-positive group and 84.8% in the PET-negative group (p = 0.002). A tumor/liver SUVmax cut-off of 3.1 to distinguish D 5PS scores of 4 and 5 provided the best prognostic value. PET after one course of chemotherapy was not able to safely discriminate PET-positive and PET-negative patients in different prognostic groups.
The alpha spectrometry measurements of specific activity of 238Pu and 239Pu in urine from bioassay examinations of 1,013 workers employed at the radiochemical and plutonium production facilities of the Mayak Production Association and in autopsy specimens of lung, liver, and skeleton from 85 former nuclear workers who died between 1974-2009, are summarized.The accumulation fraction of 238Pu in the body and excreta has not changed with time in workers involved in production of weapons-grade plutonium production (e.g., the plutonium production facility and the former radiochemical facility). The accumulation fraction of 238Pu in individuals exposed to plutonium isotopes at the newer Spent Nuclear Fuel Reprocessing Plant ranged from 0.13% up to 27.5% based on the autopsy data. No statistically significant differences between 238Pu and 239Pu in distribution by the main organs of plutonium deposition were found in the Mayak workers. Based on the bioassay data,the fraction of 238Pu activity in urine is on average 38-69% of the total activity of 238Pu and 239Pu, which correlates with the isotopic composition in workplace air sampled at the Spent Nuclear Fuel Reprocessing Plant. In view of the higher specific activity of 238Pu, the contribution of 238Pu to the total internal dose, particularly in the skeleton and liver, might be expected to continue to increase, and continued surveillance is recommended.
Laboratory experiments were carried out to study bioaccumulation and determine a concentration factor (CF) for technetium (95mTc) in the homarid crustacean Nephrops norvegicus L. The steady state CF for accumulation from seawater was estimated to be about 2,000 and the biological half-time was about 50 days. The highest tissue Tc concentrations were found in the green gland and the digestive gland. Depuration following accumulation from water was slow with a half-time of about 165 days. Tc accumulation from labelled food followed a biphasic model with one compartment containing about 94 percent of the ingested activity and with a half-time of about 1 day and the second compartment containing about 6 percent of the ingested activity with a half-time of about 56 days. Most retained activity was found in the digestive gland.
Bank voles (Clethrionomys glareolus) and laboratory strains of house mice (Mus musculus BALB and C57BL) were relocated into enclosures in a highly contaminated area of the Red Forest near the Chornobyl (Ukraine) Reactor 4 to evaluate the uptake rates of 137Cs and 90Sr from abiotic sources. Mice were provided with uncontaminated food supplies, ensuring that uptake of radionuclides was through soil ingestion, inhalation, or water. Mice were sampled before introduction and were reanalyzed every 10 d for 137Cs uptake. Levels of 90Sr were assessed in subsamples from the native populations and in experimental animals at the termination of the study. Uptake rates in house mice were greater than those in voles for both 137Cs and 90Sr. Daily uptake rates in house mice were estimated at 2.72 x 10(12) unstable atoms per gram (whole body) for 137Cs and 4.04 x 10(10) unstable atoms per gram for 90Sr. Comparable rates in voles were 2.26 x 10(11) unstable atoms per gram for 137Cs and 1.94 x 10(10) unstable atoms per gram for 90Sr. By comparing values from voles in the enclosures to those from wild voles caught within 50 m of the enclosures, it was estimated that only 8.5% of 137Cs was incorporated from abiotic sources, leaving 91.5% being incorporated by uptake from biotic materials. The fraction of 90Sr uptake from abiotic sources was at least 66.7% (and was probably much higher). Accumulated whole-body doses during the enclosure periods were estimated as 174 mGy from intramuscular 137Cs and 68 mGy by skeletal 90Sr in house mice over 40 d and 98 mGy from 137Cs and 19 mGy from 90Sr in voles over 30 d. Thus, uptake of radionuclides from abiotic materials in the Red Forest at Chornobyl is an important source of internal contamination.
Americium-241 (²4¹Am) is the second most significant radiation hazard after ²³?Pu at some of the Mayak Production Association facilities. This study summarizes current data on the accumulation, distribution, and excretion of americium compared with plutonium in different organs from former Mayak PA workers. Americium and plutonium were measured in autopsy and bioassay samples and correlated with the presence or absence of chronic disease and with biological transportability of the aerosols encountered at different workplaces. The relative accumulation of ²4¹Am was found to be increasing in the workers over time. This is likely from ²4¹Pu that increases with time in reprocessed fuel and from the increased concentrations of ²4¹Am and ²4¹Pu in inhaled alpha-active aerosols. While differences were observed in lung retention with exposures to different industrial compounds with different transportabilities (i.e., dioxide and nitrates), there were no significant differences in lung retention between americium and plutonium within each transportability group. In the non-pulmonary organs, the highest ratios of ²4¹Am/²4¹Am + SPu were observed in the skeleton. The relative ratios of americium in the skeleton versus liver were significantly greater than for plutonium. The relative amounts of americium and plutonium found in the skeleton compared with the liver were even greater in workers with documented chronic liver diseases. Excretion rates of ²4¹Am in ‘‘healthy’’ workers were estimated using bioassay and autopsy data. The data suggest that impaired liver function leads to reduced hepatic ²4¹Am retention, leading to increased ²4¹Am excretion.
Polychlorinated biphenyls (PCBs), including coplanar congeners, hexachlorocyclohexane isomers, chlordane-related compounds, and hexachlorobenzene, were found in the breast muscle of Steller's sea eagles (SSE) and white-tailed sea eagles (WSE) threatened species, collected in Hokkaido, Japan, during the two years from 1998 to 1999. Both PCBs and DDTs were the most notable compounds, with concentrations one to two orders of magnitude higher than the other compounds, that is, from 120 to 39,000 and from 68 to 15,000 ng/g wet weight, respectively. Non-ortho (International Union of Pure and Applied Chemistry [IUPAC] 77, 126, and 169) and mono-ortho (IUPAC 105, 118, and 156)-substituted coplanar PCB congeners amounted to 9.2 to 740 pg/g of 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalents derived from the World Health Organization, Paris, France (WHO), toxic equivalent factors. The atmospheric PCBs and DDTs in eastern Siberian cities, such as Khabarovsk and Magadan, have been reported to be much higher than Hokkaido and the North Pacific. Thus, we speculated that the eagles might have been contaminated in these areas, where they spend most of the year except winter, which they spend in eastern Siberia. Adult eagles accumulated more PCBs and DDTs than younger ones. The patterns of PCB congeners were also found to change, depending on the age of the eagle examined; adult eagles showed relatively higher proportions of highly chlorinated PCBs thanjuvenile eagles did. This difference would be related to the efficiency of the excretion and the metabolism of each PCB congener in the eagles.
Dental amalgam restorations are a significant source of mercury exposure in the human population, but their potential to cause systemic health effects is highly disputed. We examined effects on the immune system by giving genetically mercury-susceptible Brown Norway (BN) rats and mercury-resistant Lewis (LE) rats silver amalgam restorations in 4 molars of the upper jaw, causing a body burden similar to that described in human amalgam-bearers (from 250 to 375 mg amalgam/kg body weight). BN rats with amalgam restorations, compared with control rats given composite resinous restorations, developed a rapid activation of the immune system, with a maximum 12-fold increase of the plasma IgE concentration after 3 wks (p 0.05). After 12 wks, BN rats with amalgam restorations showed significantly increased (p spleen > cerebrum occipital lobe > cerebellum > liver > thymus, and the tissue silver concentration was significantly (p
We studied the relationship between increasing age and blood concentrations of four persistent organochlorines (OCs), hexachlorbenzene (HCB), oxychlordane, p,p'-dichlorodiphenyldichloroethylene (DDE), and 2,2',4,4',5,5'-hexachlorbiphenyl (PCB-153), in arctic-breeding glaucous gulls (Larus hyperboreus). We measured OC concentrations in 31 individuals of known age and took repeated blood samples of 64 individuals in different years, either one year apart or three or four years apart. The age of individuals was not related to the blood concentrations for any of the four compounds, and in birds whose values were measured repeatedly, there was no effect of the length of time (number of years) between sampling events on the relative change in OC concentration. This indicates that steady-state levels were reached before the age of first breeding. However, breeding area significantly influenced the changes in OC concentration between sampling events. In areas in which birds fed on prey from higher trophic levels, the OC concentrations showed large increases between sampling events; in areas in which birds fed at lower trophic levels, OC concentrations increased relatively little or not at all. This indicates that individual birds had different equilibrium concentrations, which are reached at different ages depending on the intake of OCs through the food. It also indicates that some individuals had not reached steady-state concentrations at the onset of reproduction. Changes in body condition and amount of blood lipids were of lesser importance than trophic level and influenced the concentrations of HCB and oxychlordane more strongly than DDE and PCB-153. In conclusion, this study indicates that steady-state concentrations of persistent OCs are reached early in life in most glaucous gulls, considering the long life span of the species.
Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition.
Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion.
After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues.
This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.