Comparison of internal radiation doses estimated by MIRD and voxel techniques for a "family" of phantoms

The aim of this study was to use a new system of realistic voxel phantoms, based on computed tomography scanning of humans, to assess its ability to specify the internal dosimetry of selected human examples in comparison with the well-established MIRD system of mathematical anthropomorphic phantoms. Differences in specific absorbed fractions between the two systems were inferred by using organ dose estimates as the end point for comparison. A "family" of voxel phantoms, comprising an 8-week-old baby, a 7-year-old child and a 38-year-old adult, was used and a close match to these was made by interpolating between organ doses estimated for pairs of the series of six MIRD phantoms. Using both systems, doses were calculated for up to 22 organs for four radiopharmaceuticals with widely differing biodistribution and emission characteristics (technetium-99m pertechnetate, administered without thyroid blocking; iodine-123 iodide; indium-111 antimyosin; oxygen-15 water). Organ dose estimates under the MIRD system were derived using the software MIRDOSE 3, which incorporates specific absorbed fraction (SAF) values for the MIRD phantom series. The voxel system uses software based on the same dose calculation formula in conjunction with SAF values determined by Monte Carlo analysis at the GSF of the three voxel phantoms. Effective doses were also compared. Substantial differences in organ weights were observed between the two systems, 18% differing by more than a factor of 2. Out of a total of 238 organ dose comparisons, 5% differed by more than a factor of 2 between the systems; these included some doses to walls of the GI tract, a significant result in relation to their high tissue weighting factors. Some of the largest differences in dose were associated with organs of lower significance in terms of radiosensitivity (e.g. thymus). In this small series, voxel organ doses tended to exceed MIRD values, on average, and a 10% difference was significant when all 238 organ doses were considered as a single group. In 12 comparisons of effective dose, the mean voxel to MIRD ratio was 1.07 (range 0.72-1.32). It was shown for the majority of cases that, whereas some large differences in SAF values exist, differences in source organ and effective dose values between the MIRD and voxel methods were largely accounted for by the respective organ mass differences. The reasons for various organ dose differences with the selected radiopharmaceuticals are discussed. Taking biological variation into account, there is reasonable agreement between the two methods but some significant differences exist that warrant further investigation. More extensive comparisons involving a wide variety of voxel phantoms are required to establish whether realistic voxel phantoms should eventually replace the MIRD system.     

Arginine: mediator or modulator of sepsis?

Arginine is a conditionally essential amino acid that plays pivotal roles in maintaining body homeostasis. Arginine is a substrate for protein synthesis but can also be metabolized to various bioactive compounds that include nitric oxide, ornithine, polyamines, creatine phosphate, agmatine, and dimethylarginines. Arginine produces physiologic effects via nitric oxide dependent and independent pathways. Nitric oxide is important for the modulation of vascular tone, inflammation, immune function, endothelial function, platelet and leukocyte adherence, and neurotransmission. Nitric oxide modulates many biochemical processes important for the response to sepsis. Arginine, independent of nitric oxide, is important for growth, wound healing, cardiovascular function, immune function, inflammatory responses, energy metabolism, urea cycle function, and other metabolic processes. Arginine supplementation improves outcomes in animals with sepsis, wounds, ischemia-reperfusion injury, and following thermal injury. Enteral administration of arginine improves endothelial function but has little effect upon hemodynamics during human sepsis. An analysis of clinical studies using enteral formulas with supplemental arginine suggests benefits upon outcome, with no evidence of significant detrimental effects.     

Predicting abdominal adipose tissue in overweight Latino youth.

OBJECTIVES: 1) Examine associations between visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and anthropometric and demographic variables; 2) generate and cross-validate prediction equations for estimating VAT and SAAT in overweight Latino children. STUDY DESIGN: Cross-sectional. PARTICIPANTS: 196 overweight 8-13-year-old Latino youth. Two-thirds (n = 131) were randomly assigned to a development group to generate prediction equations for VAT and SAAT; one-third (n = 65) was used as a cross-validation group. METHODS AND PROCEDURES: Anthropometric measurements (height, weight, skinfold thicknesses, and circumferences) were performed. VAT and SAAT were measured using magnetic resonance imaging (MRI). RESULTS: The strongest univariate correlate for VAT was waist circumference (WC) (r = 0.65, p < 0.01) while the strongest correlate for SAAT was hip circumference (r = 0.88, p < 0.001). Regression analyses showed approximately 50% of the variance in VAT was explained by WC (43.8%), Tanner stage (4.2%) and calf skinfold (1.7%). Variance in the SAAT model was explained by WC (77.8%), triceps skinfold (4.2%) and gender (2.3%). Residual analyses showed no bias in either equation. Though mean differences between measured and predicted VAT and SAAT were small, there was a large degree of variability at the individual level especially for VAT. CONCLUSIONS: Both VAT and SAAT prediction equations performed well at the group level, but the relatively high degree of variability suggests limited clinical utility of the VAT equation. MRI is currently required to derive an accurate measure of VAT at the individual level.     

Treatment in the pediatric emergency department is evidence based: a retrospective analysis

Background  

Our goal was to quantify the evidence that is available to the physicians of a pediatric emergency department (PED) in making treatment decisions. Further, we wished to ascertain what percentage of evidence for treatment provided in the PED comes from pediatric studies.     

Induction of apoptosis and cell cycle arrest by imexon in human pancreatic cancer cell lines

Imexon is an aziridine-containing small molecule currently in Phase I clinical trials. This agent has been shown to bind to thiols and increase intracellular oxidants, inducing apoptosis in hematologic cancer cells. Pancreatic cancers are known to be sensitive to oxidation, suggesting this disease may be an appropriate target for this agent. The current report examines the activity of imexon in pancreatic cells. Imexon induced concentration-dependent and time-dependent apoptosis in a panel of six human pancreatic carcinoma cell (PCC) lines. The mean IC₅₀ (SD) for growth inhibition by the SRB assay was 200 (101) µM for a 48 h exposure with a range of 64–358 µM. Cell killing was schedule-dependent, favoring exposure times ≥48 h. Imexon-treated MiaPaCa-2 cells underwent non-lethal growth arrest following exposure to concentrations ≤200 µM for 48 h. When concentrations were increased to 300 µM for ≥48 h, the MiaPaCa-2 cells arrested in G₂ phase and activated caspases 3, 8, and 9 were detected. After a 72 h exposure to the IC₈₀ concentration of imexon, cells exhibited a loss of mitochondrial membrane potential detected by CMXRos staining. However, there was no loss of reduced cellular thiols unless very high concentrations of ≥400 µM were used. In contrast, reactive oxygen species (ROS) were elevated in a dose-dependent fashion, starting at very low imexon concentrations. Imexon also significantly inhibited MiaPaCa-2 tumor growth in SCID mice at 100 mg/kg/d for 9 d. The tumor growth inhibition (% T/C) was 27% of control, and the tumor growth delay was 21 d, indicating an active agent by NCI standards. The levels of imexon that are cytotoxic in human PCC’s are achievable based on the preliminary results of the ongoing Phase I trial. Imexon appears to be active against PCCs in vitro and has an entirely novel mechanism of action involving G₂ arrest, accumulation of ROS, and the induction of apoptosis.     

Long-term PM2.5 exposure before diagnosis is associated with worse outcome in breast cancer

Breast Cancer Research and Treatment - Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing...     

Self-reported yeast symptoms compared with clinical wet mount analysis and vaginal yeast culture in a specialty clinic setting

OBJECTIVE: To determine the validity of patients' self-reported symptoms of vulvovaginal candidiasis and the accuracy of clinical wet mount examinations compared with vulvovaginal yeast culture results in a specialty clinic. STUDY DESIGN: A retrospective chart review of new patients seen at the Saint Louis University Vulvar and Vaginal Disease Clinic from January 2005 to March 2006 was performed. Patients' age, medication use, symptom scores on a rating scale for vaginal/vulvar pain, burning, itching, dyspareunia and wet mount analyses were compared with yeast culture results. RESULTS: Of 153 patients, 40 had positive yeast cultures (prevalence rate 26.1%). Compared with yeast cultures, self-reported symptom scores >4 resulted in high sensitivity (90%) and low specificity (7%). Positive wet mount result showed low sensitivity (18%) and high specificity (99%). Patient symptom scores were a poor predictor of yeast infections based on yeast culture results. No correlation was found among wet mount, self-reported symptoms and yeast culture results. No significant difference between age or symptom scores to culture result was found. CONCLUSION: Wet mount analysis for recurrent or persistent patient symptoms should be reevaluated. Self-reported symptoms are not reliable for diagnosis. Wet mount analysis resulted in low sensitivity. Yeast cultures should be considered the gold standard for identification of vulvovaginal candidiasis in persistent or recurrent cases.     

Patterns of injuries: accident or abuse

This study uses two types of independent variables, age and the location of the physical wound, to develop a model of injury patterning that identifies violent behavior without direct observation of the assault. In this research, domestic violence injuries are compared to accidental injuries. The results indicate that there are specific and predictable injury patterns that separate abuse from other kinds of wounds. A logistic regression model was developed to identify the regions of the body most susceptible to injury from domestic assault. Using the age of the victim and the injury regions, probabilities were calculated to determine which wounds were caused by abuse.