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Biomedical subjects

M S Leaning

Publications and source records attributed to M S Leaning.

6 recordsLinked to original sources

Computer system for assisting with clinical interpretation of tumour marker data.

OBJECTIVE: To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN: A comparison of clinicians' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING: Department of medical oncology. PATIENTS: Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES: The system's accuracy in predicting need to change treatment compared with clinicians' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS: On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS: The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.

Biomarkers, Tumor

A data model for intensive care.

The paper describes a model of clinical management data in a typical general intensive care unit, intended as a generic database specification for advanced intensive care computer systems. The data model was developed as part of the INFORM project. The INFORM project is summarised and the relevance of the data model to the objectives of the project are discussed. An object oriented extension to the entity relationship diagram methodology is presented. The methodology is illustrated with reference to some specific aspects of the data model including: the principle clinical entities; classification of patient state related data and the homogeneous patient group system. It is suggested that such a model will contribute to the better understanding of the data in the system, to the better design of future intensive care computer systems and to the setting of standards for medical data.

Decision Support Systems, Management

A system for compartmental modelling and simulation.

The paper describes a software package for modelling and simulating compartmental systems based upon a generalisation of the equations of compartmental systems. The aim is a versatile package which can be used for rapid model development. Its use is first illustrated in a number of simple classical examples. The power of the software--and more generally the methodology--is demonstrated by showing its application in developing a model-based system for insulin planning for diabetic patients. The software has been written in Pascal and runs on IBM PC and compatible computers.

Algorithms

Uptake and processing of glycoproteins by isolated rat hepatic endothelial and Kupffer cells.

Mannose-(Man) and N-acetylglucosamine- (GlcNAc)-terminated glycoproteins are cleared from blood by carbohydrate-specific receptors present on both hepatic endothelial and Kupffer cells. It is not known whether the same receptors are present on each cell type or the relative contributions to glycoprotein metabolism made by Kupffer and endothelial cells. Here we report experiments where data from glycoprotein metabolism by purified populations of isolated rat hepatic endothelial and Kupffer cells have been analyzed by mathematical modelling and parameter estimation. Kupffer cells had significantly higher binding rate constants (k'21) than endothelial cells for agalactoorosomucoid (AGOR) and hyaluronidase, but lower k12 ('off-rate') indicating that Kupffer cells had higher affinities for Man/GlcNAc-terminated glycoproteins than endothelial receptors. Furthermore, although endothelial cells had similar affinities (k'21 and k12) for AGOR and hyaluronidase, the 'off-rate' of Kupffer cells was significantly greater for AGOR than for hyaluronidase, indicating that Kupffer cell receptors have lower affinity for AGOR. Internalization and ligand catabolic rates also differed between the two cell types. The data indicate that Kupffer and endothelial cells appear to have different Man/GlcNAc receptors and that the destination of a glycoprotein and its subsequent processing is determined by the structure of a glycoprotein's oligosaccharide.

Animals

Uptake and processing of glycoproteins by rat hepatic mannose receptor.

A linear compartmental model has been developed for the in vivo metabolism of glycoproteins. The model is applied to the interpretation of dynamic data from the rat on agalactoorosomucoid (AGOR), an N-acetylglucosamine (GlcNAc-)-terminated glycoprotein, and three neoglycoproteins terminating in mannose [mannose36-bovine serum albumin (Man-BSA)] or glucose [maltose29-BSA (Mal29-BSA) and maltose8-BSA (Mal8-BSA)]. All of these proteins are taken up by the Man/GlcNAc receptor on hepatic sinusoidal cells. The rate of uptake was found to be determined by sugar type (Man-BSA, 0.78 min-1 greater than Mal29-BSA, 0.13 min-1), sugar density (Mal29-BSA greater than Mal8-BSA), and the geometry of the sugar display (AGOR, 0.51 min-1 greater than Mal29-BSA). Intracellular transport from the cell membrane to the lysosomes was slower for Man-BSA (approximately 3 min) than for the other ligands (approximately 0 min), suggesting that receptor-ligand uncoupling was slower for Man-BSA for which the receptor had the highest affinity or that extralysosomal catabolism of the other ligands occurred. Catabolism was also determined by the carbohydrate moiety of the ligand; it was greater for Mal29-BSA and Mal8-BSA (greater than or equal to 0.8 min-1) than for Man-BSA (0.27 min-1), and AGOR, with a complex oligosaccharide, was most resistant to degradation (0.14 min-1). An understanding of these structural features of glycoproteins that influence hepatic uptake, transport, and catabolism will be of value in drug targeting and for enzyme replacement in lysosomal storage disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Decision support for patient management in oncology.

In this paper a novel approach to the development of the architecture of a knowledge-based decision support system for the management of patients with cancer of the breast is described. Its initial design and subsequent realization in a prototype version was facilitated by examining closely the overall clinical task and identifying its associated activities and related knowledge. Implementation in KEE highlights the value of rigorous conceptual modelling that leads to a design able to assess treatment response and disease progression as well as providing specific therapy advice. The approach is general and may be applied to the development of decision support systems for other areas of cancer and medicine.

Artificial Intelligence