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M Stefanelli

Publications and source records attributed to M Stefanelli.

At least 73 records · Page 4Linked to original sources

GAMEES: a probabilistic environment for expert systems.

This paper describes GAMEES (Graphical Modelling Environment for Expert Systems), an interactive graphical environment for building and processing Belief Networks and Influence Diagrams. We review the existing systems designed for analogous purposes, and, after a brief introduction to Belief Networks and Influence Diagrams, we describe the graphical interface, discuss algorithms for probabilistic inference on these networks and illustrate the current implementation of GAMEES. The system has been designed for being integrated within wider expert systems and actually it is part of the Therapy Advisor module within an expert system for the management of anemic patients.

Algorithms↗

A specialized framework for Medical Diagnostic Knowledge Based Systems.

To have a knowledge based system (KBS) exhibiting an intelligent behavior, it must be endowed even with knowledge able to represent the expert's strategies, other than with domain knowledge. The elicitation task is inherently difficult for strategic knowledge, because strategy is often tacit, and, even when it has been made explicit, it is not an easy task to describe it in a form that may be directly translated and implemented into a program. This paper describes a Specialized Framework for Medical Diagnostic Knowledge Based Systems able to help an expert in the process of building KBSs in a medical domain. The framework is based on an epistemological model of diagnostic reasoning which has proved to be helpful in describing the diagnostic process in terms of the tasks by which it is composed of.

Artificial Intelligence↗

NEOANEMIA: a knowledge-based system emulating diagnostic reasoning.

Medical diagnosis can be modeled in terms of the classical notions of abduction, deduction, and induction. Abduction is making a preliminary guess that allows one to establish a set of plausible diagnostic hypotheses, followed by deduction for exploring their consequences and induction for testing the hypotheses with available patient data or for planning the acquisition of new data. Such a description of diagnostic reasoning at a knowledge level helps the construction of an expert system by fashioning the adopted expert system building tool to reflect the structure of the problem rather than by fitting the problem to the tool. To this aim, reasoning strategies need to be represented abstractly, separate from medical facts and relations, to make the design more transparent and explainable.

Anemia↗

A performance evaluation of the expert system ANEMIA.

This paper reports the results of an evaluation study of the current level of performance given by ANEMIA, a knowledge-based consultation system addressing the clinical problem of managing anemic patients. ANEMIA was developed on a mainframe using the AI programming scheme EXPERT and then translated into a version running on a personal computer. At present the system is able to provide assistance in the diagnosis and management of 65 disease entities. After extensive local testing of accuracy, completeness, and consistency of the knowledge base included into ANEMIA, we designed a study to evaluate whether the system is able to appropriately mirror also the reasoning of well-known hematologists other than those who provided the knowledge. We were also interested in testing whether there were conflicting opinions among hematologists. Thus, we designed a validation study in which ANEMIA's performance could be compared with that of six hematologists and the interexpert consensus evaluated. ANEMIA's overall performance was judged acceptable in 87% (26/30) of the cases, while expert evaluators agreed with their colleagues in 90% (27/30) of them. A low interexpert consensus was found: considering the ratings given by different hematologists to the same ANEMIA performance, complete agreement occurred only 47% of the time.

Adult↗

ANEMIA: an expert consultation system.

Anemia is a knowledge-based consultation program for anemic states. It has been built using an artificial intelligence programming scheme, called EXPERT, which was developed at Rutgers University. At present, ANEMIA is able to provide assistance in the diagnosis and management of 64 disease entities. They include iron deficiency anemias, anemias due to chronic disorders, thalassemias, hemolytic anemias, arigenerative anemias, and a few other miscellaneous conditions. ANEMIA was tested against a data base of 220 retrospective and 100 new cases and the overall accuracy in the diagnostic performance was pretty good. Our intent is that ANEMIA ultimately will be able to serve as surrogate for the hematologist with the nonhematologist physician-user.

Anemia↗

Classification of anaemia on the basis of ferrokinetic parameters.

Quantitative information on abnormalities of erythropoiesis and mechanisms of anaemia has been obtained in 136 anaemic patients by means of ferrokinetic studies. To derive a functional classification of anaemia based on ferrokinetic parameters, agglomerative hierarchical cluster analysis and principal coordinate analysis were utilized as techniques for unsupervised classification. Two main clusters were found and named anaemia with low potential erythropoiesis and with high potential erythropoiesis, since the most discriminant parameter between them was total erythroid iron turnover, a measure of total erythropoietic activity. A value of total erythropoiesis equal to 4 times the normal was found to discriminate these two types of anaemia in 94% of cases. Within the group with low potential erythropoiesis, three clusters showing different qualitative disturbances of erythropoiesis were singled out. Among patients with high potential erythropoiesis, two clusters were found. A value of effective erythropoiesis equal to 2.5 times the normal was shown to have a high discriminant power between these clusters. This threshold level distinguished between patients having ineffective erythropoiesis or peripheral haemolysis as the major mechanism of anaemia. The present functional classification of anaemia provides a complete picture of the different pathogenetic mechanisms and may represent the basis for a more rational diagnostic approach to erythroid disorders.

Adolescent↗

Quantitation of reticuloendothelial iron kinetics in humans.

Reticuloendothelial iron kinetics were investigated in a simultaneous dual-isotope study in 10 healthy adult subjects in whom 55Fe-ferric hydroxide phosphate colloid was used to label the reticuloendothelial iron pools, and 59Fe-transferrin was used to define plasma iron kinetics. The simultaneous clearance of 55Fe and 59Fe from plasma and the uptake of each into red blood cells were measured over 14 days. The 55Fe-colloid was cleared almost immediately, and its iron was rapidly released to bind to plasma transferrin. Red cell incorporation of 55Fe was, however, much slower than that of 59Fe bound to transferrin in vitro. The data were analyzed by a new model of reticuloendothelial iron metabolism that contained two reticuloendothelial iron pools; one had a rapid turnover and donated iron to transferrin, and the other, a storage pool, had a slower turnover. The transit pool contained a mean of 164 mumol iron with little variation between subjects, whereas the storage pool was somewhat larger (mean 873 mumol iron) and showed more marked variation between subjects. In general an equal proportion of the iron leaving the transit pool went to transferrin and to the storage pool. The distribution between the two routes did not appear to be related either to plasma iron concentration, latent iron-binding capacity, or transferrin saturation.

Adult↗

Immunoregulatory T cells in measles. The relationship between reduced lymphocyte proliferative response to PHA and increased proportion of circulating suppressor-cytotoxic T cells.

Viral infections are often associated with immunodeficiency states. Although T lymphocytes have been thought to suppress the host's immune response, the precise cellular basis for this phenomenon remains unclear. Therefore, we characterized peripheral blood mononuclear cells from 9 measles virus-infected children by means of monoclonal antibodies directed against surface antigens expressed on human T lymphocytes and T-cell subsets. In addition, the measles lymphocyte blast transformation response to the T-cell mitogen phytohaemagglutinin (PHA) was evaluated as an index of specific T-cell immunocompetence. During the course of measles, there was a slight reduction in the proportion of total circulating T cells, with a relative decrease in helper-inducer and a parallel increase in suppressor-cytotoxic T lymphocytes. The PHA lymphocyte blastogenic response was found to be defective in children with measles and, interestingly, there was a significant negative correlation between the reduced PHA blast transformation value and the increased proportion of suppressor-cytotoxic cells. The biological implications of these finding with respect to the underlying immunopathology of the measles virus infection are discussed.

Antibodies, Monoclonal↗

Competing models for the analysis of red cell survival obtained with 51Cr labelling technique.

A computer program for the analysis of 51Cr labelled red cell survival data was used in 84 patients and 8 normal subjects to estimate the parameters of 7 competing models derived from different hypotheses of the red cell destruction process. The purpose was to establish the optimal complexity of a red cell survival model to be used. Senescence or random destruction were the most common identified patterns of red cell death (79% of the cases). Models assuming different levels of death probability according to the age of cells, or 2 populations of cells with different death probabilities, were selected in 21% of the cases. These latter patients were characterized by the lowest values of MRCL. The conclusion of the work was that an automatic procedure for selecting the best model of red cell destruction is necessary when information concerning the mechanism of red cell death is required. For the more practical aim of obtaining an accurate measurement of the MRCL, the minimal set of competing models should account of at least 2 different populations of cells in addition to the random or senescence destruction models.

Anemia, Hemolytic↗

A mathematical model of iron metabolism.

A mathematical model of iron metabolism is presented. It comprises the following iron pools within the body: transferrin-bound iron in the plasma, iron in circulating red cells and their bone marrow precursors, iron in mucosal, parenchymal and reticuloendothelial cells. The control exerted by a hormone, called erythropoietin, on bone marrow utilization of iron for hemoglobin synthesis is taken into account. The model so obtained consists of a system of functional differential equations of retarded type. Most model parameters can be estimated from radiotracer experiments, others can be measured and numerical values can be assigned to the remaining ones making few reasonable assumptions according to the available physiological knowledge. Iron metabolism behavior under different therapeutical treatments was stimulated. Model predictions were compared to experimental data collected in clinical routine.

Animals↗

Quantitative evaluation of erythropoietic activity in dysmyelopoietic syndromes.

Based on the morphological appearances of the bone marrow and peripheral blood, 43 patients with dysmyelopoietic syndromes were categorized into four types: refractory anaemia with excess of blasts, chronic myelomonocytic leukaemia, primary acquired sideroblastic anaemia and refractory anaemia with cellular marrow, without excess of blasts and/or ring sideroblasts. Ferrokinetics allowed three distinct groups of patients to be defined. All cases of refractory anaemia with excess of blasts and chronic myelomonocytic leukaemia were classified in the same group. They were characterized by relative marrow failure and had a high likelihood of developing acute leukaemia. At the other end of the spectrum, individuals with primary acquired sideroblastic anaemia had high erythropoietic activity which was largely ineffective. They had a benign clinical course without evidence of leukaemic transformation. In the middle group, in terms of erythropoietic activity, lay patients with refractory anaemia with cellular marrow and a few individuals with primary acquired sideroblastic anaemia. Their clinical course and risk of developing acute leukaemia were intermediate between the other two groups. These findings indicate that separate entities may exist within the spectrum of dysmyelopoietic syndromes. In clinical practice, they may be recognized by morphological studies and other simple laboratory means.

Adolescent↗

Erythropoiesis in myelofibrosis with myeloid metaplasia: recognition of different classes of patients by erythrokinetics.

A quantitative assessment of erythropoiesis was performed by means of a mathematical model of iron kinetics in 26 patients with myelofibrosis with myeloid metaplasia (MMM). A direct relationship between total erythropoiesis and red cell volume was revealed. This 'inverse' characteristic of erythropoietic control was the best marker of the proliferative nature of the disease. Three classes of patients were singled out by means of a cluster analysis of the erythrokinetic parameters. In class I (11 patients) the red cell volume was above the predicted normal in all but two patients. Erythropoiesis was sustained at 5--10 times the normal levels with a high degree of ineffective erythropoiesis. A fairly constant absence of erythroid activity over the sacral marrow was demonstrated. In class II most of the 12 patients had a decreased red cell volume. Erythropoiesis was sustained at 2--4 times the normal level with a high degree of peripheral haemolysis. Erythroid activity was recognized over the sacral area in all but two patients. The three patients of class III showed a pattern of erythroid failure and had the worst prognosis. It is suggested that these classes represent separate disease forms of MMM.

Adult↗

[The plasma 59Fe clearance curve in man. An evaluation of methods of measurement and analysis].

Studies of 59Fe clearance from the plasma are used for obtaining a quantitative measure of erythropoiesis. However, there are many difficulties associated with a good definition and a valid analysis of the plasma 59Fe clearance curve. The low plasma activity, plasma iron variation, and traces of haemolysis are factors which make the measurement of the curve difficult. All these problems were examined in the present work. Liquid scintillation counting allows a more accurate assay of plasma 59Fe activity than conventional gamma counting. Plasma iron fluctuations may affect tracer kinetics but adjustment of plasma activity for plasma iron variation (expressing 59Fe activity per unit mass of iron) does not appear a satisfactory procedure for overcoming this difficulty. The removal of haemoglobin from plasma samples is a necessary procedure to avoid contamination by [59Fe] haemoglobin. Fitting three exponentials to the plasma 59Fe clearance curve does not yield satisfactory results in some cases. A better prediction of the clearance curve in most cases can be obtained by means of a more refined mathematical model.

Erythropoiesis↗

REDCE: a computer program for the analysis of red cell survival data.

A computer program for the analysis of red cell survival data is described. Experimental data are used to estimate the parameters of seven models of derived from different hypotheses on the red cell destruction process. The program includes statistical tests for the reliability of the estimated parameter values and the bias due to the poor model. A set of criteria for selecting between models is given. The results obtained from simulated and red data are reported and discussed.

Computers↗

Quantitative assessment of erythropoiesis in haemolytic disease.

Erythrokinetic parameters were estimated in 21 patients suffering from haemolytic disease using a mathematical model of iron kinetics. A proper definition of radioiron reflux from red cells to the plasma proved to be essential for an accurate estimate of effective and ineffective erythropoiesis in severe haemolytic conditions. Erythropoietic activity was increased in all the patients, with the marrow capable of sustaining erythropoiesis at about 6 times normal in hereditary spherocytosis and 3 times normal in autoimmune haemolytic anaemia. This proliferative effort was countered by an increase in ineffective erythropoiesis which was especially marked in hereditary spherocytosis.

Adolescent↗