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Biomedical subjects

M Stefanelli

Publications and source records attributed to M Stefanelli.

At least 91 records · Page 5Linked to original sources

Studies of ineffective erythropoiesis and peripheral haemolysis in congenital dyserythropoietic anaemia type II.

Erythrokinetic parameters were estimated in six patients suffering from congenital dyserythropoietic anaemia type II (CDA II) by means of a mathematical model of iron kinetics. A wide variation in effectiveness of erythroid activity was observed, and a significant negative correlation was found between ineffective erythropoiesis and peripheral haemolysis. In four patients with prominent peripheral haemolysis, splenectomy was carried out. Marked improvement in their clinical condition and in haemoglobin level resulted.

Adolescent↗

Quantitative evaluation of the mechanisms of the anaemia in heterozygous beta-thalassaemia.

Ferrokinetic studies were carried out in 8 patients with heterozygous beta-thalassaemia with anaemia of varying severity. Effective and ineffective erythropoiesis, mean red cell lifespan and non-erythroid iron turnover were estimated from the experimental data through a mathematical model of iron kinetics. Erythropoietic activity was markedly increased in all patients, but was variably ineffective (from 10 to 74%). A negative correlation (r = 0.855, P less than 0.01) was found between the amount of ineffective erythropoiesis and Hb level. Red cell lifespan was variably shortened and there was a negative correlation between the degree of daily peripheral haemolysis and Hb level (r = 0.733, P less than 0.05). Non-erythroid iron turnover was increased in most patients. The results provide quantitative measurements of the mechanisms responsible for the wide variation of the Hb level in heterozygous beta-thalaeeaemia. Ineffective erythropoiesis seems to be the major reason for the anaemia. Peripheral haemolysis contributes to it, especially in the most severely affected patients. The increased non-erythroid iron turnover may be responsible for the pathology which characterizes heterozygotes in the adult life.

Adolescent↗

Estimation of ferrokinetic parameters by a mathematical model in patients with primary acquired sideroblastic anaemia.

Ferrokinetic parameters were estimated in eight patients with primary acquired sideroblastic anaemia (PASA) by means of a mathematical model of iron kinetics. Both plasma 59Fe clearance and red cell utilization curves were used to identify the model parameters. The close agreement between experimental and theoretical data proved that the model can describe iron kinetics in sideroblastic anaemia. Ineffective erythropoiesis was found to be major factor in the production of the anaemia. Various degrees and patterns of peripheral haemolysis were observed. The storage iron was always markedly increased and a large non-erythroid iron turnover was calculated in the most severely affected patients. The results are compared with present knowledge of erythropoiesis in PASA.

Aged↗

Iron kinetics and erythropoiesis in Fanconi's anaemia.

Ferrokinetic studies were carried out in 4 patients with Fanconi's anaemia (FA). Experimental data were analysed by means of a mathematical model of iron kinetics in order to obtain a quantitative assessment of effective and ineffective erythropoietic activity, mean red cell lifespan, and non-erythroid iron turnover. The major pathogenetic mechanism of the anaemia appeared to be relative marrow failure, i.e. a reduction in the proliferative capacity of the erythroid marrow. The role of ineffective erythropoiesis was of minor importance. On the basis of the results obtained both the pathogenesis and the natural course of the disease are discussed.

Adolescent↗

Kinetics of D-histidine diffusion across rat intestine in vitro.

A five-compartment linear model for diffusion in vitro across rat jejunum has been proposed for the study of the kinetic constants of D-histidine transport. Once preliminary experiments using 2,4-dinitrophenol and L-methionine have proved that D-histidine gives rise to passive transport only, the validity of the model was tested and its parameters estimated through a best-fitting procedure by using experimental data concerning D-histidine transport. D-Histidine diffusion was studied in everted and unreverted loops mounted in an oxygenated bath system. Both mucosa to serosa and seroa to mucosa movements of D-histidine (3-30 mM) were evaluated by measuring chemically the amount of D-histidine transported into intestinal lumen every 5 min for 60 min. Results obtained proved that D-histidine transport in each direction (mucosa to seroa or seroa to mucosa) was dependent-concentration process. Nevertheless different values of gain and time constants were estimated for the transport in the two directions.

Animals↗

Numerical determination of intestinal membrane diffusing constants by a gradient method.

Optimisation problems arising in the identification of kinetic parameters of intestinal membranes are here considered. The dynamic behaviour of the membrane is described by means of a linear compartmental model. Using optimisation techniques of a gradient type, the intestinal kinetic parameters are identified, minimising a quadratic criterion between experimental data of D-histidine transport and model prediction. Numerical results are reported and their physiological implications discussed. The quantitative assessment of the asymmetry of diffusion constants with respect to diffusion direction seems to be an important result of this work.

Biological Transport↗

Qualitative models and fuzzy systems: an integrated approach for learning from data.

This paper presents a method for the identification of the dynamics of non-linear systems by learning from data. The key idea which underlies our approach consists of the integration of qualitative modeling techniques with fuzzy logic systems. The resulting hybrid method exploits the a priori structural knowledge on the system to initialize a fuzzy inference procedure which determines, from the available experimental data, a functional approximation of the system dynamics that can be used as a reasonable predictor of the patient's future state. The major advantage which results from such an integrated framework lies in a significant improvement of both efficiency and robustness of identification methods based on fuzzy models which learn an input output relation from data. As a benchmark of our method, we have considered the problem of identifying the response to the insulin therapy from insulin-dependent diabetic patients: the results obtained are presented and discussed in the paper.

Algorithms↗

Supporting tools for guideline development and dissemination.

This paper describes a methodology for representing clinical practice guidelines and facilitating their introduction into the medical routine. Since this methodology can be exploited in a www environment, it can represent the basis for sharing clinical guidelines both between different institutions and between human and software agents cooperating within a clinical context. In addition, the proposed guideline formalization is intended to deal with patient and organization preferences. This goal is achieved by augmenting the guideline with decision analytic models and by linking the guideline with an organizational model of the clinical setting. The designed framework allows guideline development, tailoring and implementation, real-time access to the guideline prescriptions and guideline validation.

Algorithms↗

An influence diagram for assessing GVHD prophylaxis after bone marrow transplantation in children.

Graft-versus-host disease (GVHD) represents one of the major complications of allogeneic bone marrow transplantation (BMT). Nevertheless, the occurrence of mild GVHD could be desirable in high-risk leukemic patients, due to a relapse-preventing effect known as the graft-versus-leukemia (GVL) effect. Given that different prophylactic interventions are available to prevent GVHD development, the decision problem consists in assessing both type and dosage of the drugs in order to avoid or induce GVHD, according to the specific patient's condition. The decision problem can be represented and solved by using an influence diagram. The choice of this formalism allows using new available methods for building and updating the model of the decision problem. The qualitative structure of the model and the conditional probabilities were first derived by combining literature results with a medical expert's judgement. More specifically, probabilities were initially assigned as ranges rather than as point values. Then, conditional probabilities were updated, by using a learning algorithm, as new cases became available. The authors analyzed 50 cases of pediatric patients affected by either malignant or nonmalignant diseases, undergoing BMT and receiving GVHD prophylaxis. They used the first 25 cases to adjust the initially assigned conditional probabilities, then checked the model obtained on the remaining patients. The overall performance for GVHD prediction was about 80%.

Algorithms↗