Radioimmunotherapy (RIT) has demonstrated efficacy with acceptable toxicity leading to approval in non-Hodgkin’s lymphoma, but has been slower to develop for the treatment of advanced solid tumors. Prostate cancer (PC) represents a good candidate for RIT based upon high exposure to circulating antibodies at common disease sites with a specific, highly expressed cell-surface antigen of prostate-specific membrane antigen. Four phase I and II trials utilizing 177Lu- or 90Y-J591 have been reported. Long-term toxicity and chemotherapy administration was analyzed. As expected, the only serious toxicity observed was myelosuppression. Grade 4 thrombocytopenia occurred in 33.3% without significant hemorrhage and grade 4 neutropenia occurred in 17.3% with 0.07% febrile neutropenia. Nearly all subjects (97.3%) recovered to grade 0 or 1 platelets and all had complete neutrophil recovery. The majority (81.3%) received chemotherapy at any time, with 61.3% receiving chemotherapy following RIT. Ten subjects underwent bone marrow biopsies at some point in their disease course following RIT for low counts; all had diffuse PC infiltration without evidence of myelodysplasia or leukemia. As expected, myelosuppression occurs following therapeutic doses of RIT for men with metastatic castration-resistant PC. However, toxicity is predictable and self-limited, with the majority of patients who do not refuse able to receive cytotoxic chemotherapy following RIT.
AimsIn studying aetiological interactions of genetic, epigenetic and environmental factors in normal and abnormal developments of the dentition, methods of measurement have often been limited to maximum mesio-distal and bucco-lingual crown diameters, obtained with hand-held calipers. While this approach has led to many important findings, there are potentially many other informative measurements that can be made to describe dental crown morphology. Advances in digital imaging and computer technology now offer the opportunity to define and measure new dental phenotypes in 3-D that have the potential to provide better anatomical discrimination and clearer insights into the underlying biological processes in dental development. Over recent years, image analysis in 2-D has proved to be a valuable addition to hand-measurement methods but a reliable and rapid 3-D method would increase greatly the morphological information obtainable from natural teeth and dental models. Additional measurements such as crown heights, surface contours, actual surface perimeters and areas, and tooth volumes would maximise our ability to discriminate between samples and to explore more deeply genetic and environmental contributions to observed variation. The research objectives were to investigate the limitations of existing methodologies and to develop and validate new methods for obtaining true 3-D measurements, including curvatures and volumes, in order to enhance discrimination to allow increased differentiation in studies of dental morphology and development. The validity of a new methodology for the 3-D measurement of teeth is compared against an established 2-D system. The intra- and inter-observer reliability of some additional measurements, made possible with a 3-D approach, are also tested.Methods and resultsFrom each of 20 study models, the permanent upper right lateral and upper left central incisors were separated and imaged independently by two operators using 2-D image analysis and a 3-D image analysis system. The mesio-distal (MD), labio-lingual (LL) and inciso-gingival (IG) dimensions were recorded using our 2-D system and the same projected variables were also recorded using a newly developed 3-D system for comparison. Values of Pearson's correlation coefficient between measurements obtained using the two techniques were significant at the 0.01 probability level for variables mesio-distal and incisal-gingival with labio-lingual significant at the 0.05 level for the upper left side only, confirming their comparability. For both 2-D and 3-D systems the intra- and inter-operator reliability was substantial or excellent for variables mesio-distal, labio-lingual, incisal-gingival actual and projected and actual surface area. The reliability was good for inter-operator reliability measurement of the labio-lingual dimension using 3-D.ConclusionsWe have developed a new 3-D laser scanning system that enables additional dental phenotypes to be defined. It has been validated against an established 2-D system and shown to provide mea...
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