Introduction: Radioimmunotherapy (RIT) has been shown to be more effective against solid tumor micrometastases, possibly due to an inverse relationship between tumor size and radiolabeled antibody uptake. In this study, the accretion of radiolabeled antibody in intrahepatic micrometastases in an experimental model was investigated using quantitative digital autoradiography, enabling the analysis of antibody uptake in microscopic tumors.Methods: Mice bearing subcutaneous or intrahepatic metastatic models of LS174T colorectal cancer were injected with radiolabeled anti-carcinoembryonic antigen antibody ([I-125]A5B7). Tissues were taken to investigate distribution of radionuclide and tumor uptake. In a therapy Study, mice bearing intrahepatic metastatic tumors were injected with [I-131]A5B7.Results: Subcutaneous tumors and large metastatic deposits had similar uptake (e.g,, similar to 15%ID/g at 24 h). Small metastatic deposits had higher uptake (e.g., similar to 80%ID/g at 24 h) and prolonged retention at later time points. Small deposit uptake was significantly reduced by accompanying large deposits in the same liver. RIT resulted in increased survival time (untreated mean survival of 21.6 +/- 12.9 vs. treated mean Survival of 39.1 +/- 30.8 days), but there was a large range of response within groups, presumably due to variation in pattern and extent of tumor as observed in the biodistribution study. Liver function tests and body weight did not change with tumor growth or therapy response, strongly Supporting the use of in vivo imaging in metastatic tumor therapy studies.Conclusions: Radioimmunodetection and therapy might be greatly influenced by the size and distribution of intrahepatic tumor deposits. (C) 2009 Elsevier Inc. All rights reserved.
Classification problems with output class overlap create problems for standard neural network approaches. We present a modification of a simple feedforward neural network that is capable of learning problems with output overlap, including problems exhibiting hierarchical class structures in the output. Our method of applying weakened implicit negatives to address overlap and ambiguity allows the algorithm to learn a large portion of the hierarchical structure from very incomplete data. Our results show an improvement of approximately 58% over a standard backpropagation network on the hierarchical problem.
OBJECTIVE:To assess the role of carnitine in the skeletal myopathy present in anorexia nervosa.METHOD:Serum levels of free and total carnitine were measured in a group of severely underweight women with anorexia nervosa and skeletal myopathy before and after an inpatient refeeding program.RESULTS:Carnitine levels were within the reference range before refeeding and remained unchanged despite significant weight gain in all the subjects.CONCLUSION:These findings suggest that carnitine plays no part in the muscle weakness seen in severe anorexia nervosa.