A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential.

Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.

First bacteraemic human infection with Escherichia albertii.

The facultative anaerobic Gram-negative species Escherichia albertii has been isolated from human faeces in gastrointestinal infection and from a range of wild bird species. Here we report the first case of a febrile infection associated with E. albertii bacteraemia in a 76-year-old woman with gastric dysplasia.

SU-E-T-153: Detector-Grade CVD Diamond for Radiotherapy Dosimetry.

PURPOSE: To evaluate the use of commercially available detector-grade synthetic diamond films made via chemical vapor deposition (CVD) as x- ray detectors for radiotherapy dosimetry. METHODS: A detector was fabricated using high-quality single crystal CVD diamond films (0.5 × 3 × 3 mm̂3) with 0.4 mm̂3 sensitive volumes, which were encapsulated with PMMA. The detector was placed in a (30 × 30 × 30 cm̂3) PTW water phantom. Six- and ten-MV photons from an Elekta Synergy linac were measured using an SSD of 90 cm and typically a 10-cm phantom depth with a 10 × 10 cm̂2 field size in the central axis of the beam. Data acquisition was performed using a PTW UNIDOS E electrometer with a 100-V bias. The detector was evaluated by measuring leakage current, priming dose, response dynamics, dose linearity, dependence on dose rate, percent depth dose (6 and 10 MV photons) and output factors. Some measurements were compared with a Si diode detector, 0.04 and/or 0.13-cc ion chamber(s). RESULTS: Leakage currents were negligible (∼1 pA) given the overall average sensitivity of the material (680 nC/Gy at 100 V). Detector current rise and fall times were < 2 s. Dose measurements up to 5 Gy were linear. A slight dependence on nominal dose rates up to 500 MU/min was seen with Fowler fitting parameter delta = 0.981. Percent depth dose profiles compared well to a 0.13-cc ion chamber up to 25 cm depths for 10-MV photons. Output factors measured well for field widths 5-15 cm; below 5 cm, differences are seen between all four different detectors as expected. CONCLUSIONS: The type of diamond tested has potential to be used for small field dosimetry due to its small sensitive volume and high sensitivity. Further experiments are ongoing and detector packaging is yet to be optimized.

SU-E-T-157: Reproducibility of CVD Diamond Detectors for Radiotherapy Dosimetry.

PURPOSE: Three diamond x-ray detectors fabricated in-house using films from the same batch of commercially-available chemical vapor deposition (CVD) diamond were investigated for performance inter-comparability under clinically relevant conditions. METHODS: Detectors were based on single-crystal CVD diamond films (0.5 × 3 × 3 mm̂3) with 0.4 mm^3 sensitive volumes, which were encapsulated with PMMA. Detectors were placed in a (30 × 30 × 30 cm̂3) PTW water phantom. Six-MV photons from an Elekta Synergy linac were measured using an SSD of 90 cm and 10 cm phantom depth with a 10 × 10 cm̂2 field size in the central axis of the beam. Data acquisition was performed using a PTW UNIDOS E electrometer. Leakage current, priming dose, response dynamics, dose linearity, dependence on dose rate and angular dependence were used to evaluate differences between diamond detectors. RESULTS: Differences were seen in leakage currents before (< 1.5 pA) and after (< 12 pA) irradiation. A priming dose of ∼7 Gy and rise and fall times of 2 s were found for all three detectors. Sensitivities differed by up to 10%. Dependence on dose rate was similar (Fowler fitting parameter, delta = 0.92-0.94). Angular dependence was minimal (97-102% average). Differences in detector performance appeared to be primarily due to film thickness, which can significantly change sensitivities and applied fields for detectors with small sensitive volumes. CONCLUSIONS: Although films were sourced from the same manufactured batch, small deviations were seen between detectors such that correction factors may be required much like natural diamonds used in existing commercial detectors. Differences in sensitivity and dependence on dose rate most likely originate from variation in film thickness due to manufactured tolerances. Preselecting films by thickness is important to help eliminate variability in detector response where small sensitive volumes are used.

Clinical investigations of a CVD diamond detector for radiotherapy dosimetry.

X-ray detectors based on single crystal diamond film made via chemical vapor deposition were investigated to evaluate their performance under clinically relevant conditions for radiotherapy dosimetry. Studies focused on repeatability, dose rate dependence, tissue phantom ratios, output factors and beam profiling. Repeatability experiments revealed a temporary loss in sensitivity due to charge detrapping effects following irradiation, which was modeled to make corrections that improved short-term precision. Dose rate dependence was observed (Fowler fitting parameter Δ = 0.96 ± 0.2) using dose rates up to ~2 Gy min(-1). The detector statistically distinguished (n = 5, P < 0.05) between dose values separated by 7.7 × 10(-3) Gy (1 MU). Depth dose measurements from 1 to 15 cm and output factors using 3 × 3 to 10 × 10 cm2 field sizes compared well with a Farmer ion chamber (<1.3% difference). Output factor measurements indicate encouraging results for fields sizes <4 × 4 cm2. Off-axis measurements showed that perturbation of the beam could be reduced when the detector is used in the edge-on orientation due to its thin-film sandwich configuration and ~200 nm thick Ag contacts. This relatively inexpensive detector has potential to be used for routine dosimetry using conventional radiotherapy instrumentation.

Comparison of natural and synthetic diamond X-ray detectors.

Diamond detectors are particularly well suited for dosimetry applications in radiotherapy for reasons including near-tissue equivalence and high-spatial resolution resulting from small sensitive volumes. However, these detectors have not become commonplace due to high cost and poor availability arising from the need for high-quality diamond. We have fabricated relatively cheap detectors from commercially-available synthetic diamond fabricated using chemical vapour deposition. Here, we present a comparison of one of these detectors with the only commercially-available diamond-based detector (which uses a natural diamond crystal). Parameters such as the energy dependence and linearity of charge with dose were investigated at orthovoltage energies (50-250 kV), and dose-rate dependence of charge at linear accelerator energy (6 MV). The energy dependence of a synthetic diamond detector was similar to that of the natural diamond detector, albeit with slightly less variation across the energy range. Both detectors displayed a linear response with dose (at 100 kV) over the limited dose range used. The sensitivity of the synthetic diamond detector was 302 nC/Gy, compared to 294 nC/Gy measured for the natural diamond detector; however, this was obtained with a bias of 246.50 V compared to a bias of 61.75 V used for the natural diamond detector. The natural diamond detector exhibited a greater dependency on dose-rate than the synthetic diamond detector. Overall, the synthetic diamond detector performed well in comparison to the natural diamond detector.

Empyema thoracis: new insights into an old disease.

Pleural infection is a disease of historical importance and is still a modern menace, with incidences rising in adults and children, and a significant mortality in adults. Basic research is hampered by limitations with in vivo models, and the bacteriology of empyema is complex. The role of thoracic ultrasound in guiding investigation and drainage of empyema is clear. Prompt treatment with appropriate systemic antibiotics and chest tube drainage are the key; in cases of failure of these measures, thoracic surgery is of proven efficacy in the treatment of this age-old disease.

The origin of regenerating mesothelium: a historical perspective.

Bichat first described the mesothelium in 1827 but despite its early discovery, it has only been in recent years that its importance both in health and disease has been realised. One area still poorly understood is that of the mechanisms regulating mesothelial repair. Mesothelial cells are derived from the mesoderm but express many epithelial characteristics. However, mesothelium does not heal in the same way as other epithelial-like cells. Epithelium heals by centripetal migration, with cells at the edge of the wound proliferating and migrating into the injured area. Hertzler in 1919 noted that both large and small peritoneal injuries healed within the same time frame, concluding that the mesothelium could not heal solely by centripetal migration. The exact mechanisms involved in mesothelial regeneration following injury are controversial with a number of proposals suggested to explain the origin of the regenerating cells. This review will examine these proposals and give some insights into the likely mechanisms involved.