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Biomedical subjects

G Cevenini

Publications and source records attributed to G Cevenini.

43 records · Page 3Linked to original sources

Flow cytometric analysis of DNA ploidy pattern from deparaffinized formalin-fixed gastric cancer tissue.

Histologically processed tissue from gastric cancers has been analyzed by flow cytometry in an attempt to correlate DNA ploidy pattern and behavior of the tumor. Of the mucosal and submucosal cancers (so-called early, all stage I in the present series), 62.7% show a diploid DNA pattern and 37.3% show a single aneuploid pattern. Of the deeply infiltrating (beyond the submucosa) cancers (stage II and III), 52.1% are single aneuploid and 47.9% are multiploid. While stage-I patients are all alive at the end of the follow-up period (6 years), in stage II and III cases Cox's regression model shows that the hazard function depends on DNA pattern: survival is negatively influenced by multiploidy. On this basis, it may be assumed that the DNA pattern is a useful prognostic indicator of gastric cancer. As expected, in Cox's regression model an even more important negative correlation exists between survival and stage: single aneuploid cases in stage II have a better prognosis than those in stage III. Instead, no correlation is found between histological cancer subtype (Laurén and WHO classifications), grade and DNA pattern.

Adult↗

CADCS simulation of the closed-loop cardiovascular system.

A pulsatile simulator of the closed-loop cardiovascular system, designed to solve simulation, identification and control problems in a research and education context, is presented. Its implementation makes use of a command-driven interactive program for simulation of non-linear ordinary differential equations. The flexibility of the simulator is demonstrated by the results presented which refer to a basal steady-state circulatory condition as well as a transient induced by an abrupt change in peripheral resistance.

Blood Pressure↗

Three-element model for total systemic circulation: emphasis on the accuracy of parameter estimates.

In this study, the accuracy achievable in the parameter estimates of a three-element linear model for the systemic vascular bed is considered. The model neglects inertial effects and includes only three elements representing arterial compliance, peripheral resistance and venous compliance, in agreement with recent sensitivity investigations. Parameter estimation starts from arterial and right atrial pressure signals generated by a closed-loop simulator of the cardiovascular circulation and corrupted with normal noise to account for measurement errors. In this way, the influences of a wide variety of circulatory conditions were investigated. The results achieved give evidence that arterial compliance is generally well estimated, while venous compliance is more variable, particularly at high peripheral resistance when measured signals appear to be less sensitive to this parameter. However, presence of cardiac disease, such as heart failure and valvular stenosis has minimal influence on compliance estimates. These results suggest that this simple model can be conveniently applied even under noisy conditions.

Blood Circulation↗

Model selection for ventricular mechanics: a sensitivity analysis approach.

Quantitative characterization of left ventricle pump properties has been recognized as being of great significance for both physiological and clinical purposes. Several descriptions have been proposed in the past to this end, where the ventricle is viewed as an isovolumic pressure generator coupled to an internal impedance, considered as either only viscous, only elastic or viscoelastic. Though these models have been used widely, the respective advantages and limits have not been fully elucidated. In this paper, six models for the left ventricular pumping function, of the viscoelastic type, are compared using both simulated and experimental data in a typical parameter estimation approach. Elastic and viscous parameters are estimated starting from ventricular pressure and aortic flow, together with the isovolumic pressure at the same preload. The basis for the comparison is the well-established criterion relating the fit obtained from collected data and the covariance matrix of the parameter estimates. The latter allows evaluation of the so-called indifference region in the parameter space, which is represented by an ellipse if both elastic and viscous elements are present. The properties of the indifference region are synthetically represented by two indices linked to the area and the eccentricity of the ellipse: the first represents the mean accuracy of the parameter estimate, the second gives information about the different sensitivities to variation of single parameters. This comparison, in both simulated and experimental cases, generally leads to preference for a model where elastance and viscosity vary with time in linear proportion to the isovolumically developed ventricular pressure. Appropriate description of the elastic effect reveals it to be very crucial while the viscous effect, though improving the fitting of data, is less critical.

Animals↗

A new approach for tracking respiratory mechanical parameters in real-time.

A new recursive least-squares procedure for on-line tracking of changes in viscoelastic properties of respiratory mechanics is proposed and applied to artificially ventilated patients. Classical least-squares methods based on simple first-order linear models with time-constant parameters generally provide systematic residuals that hardly satisfy standard statistical tests for model validation in terms of residuals. On the other hand, high order and/or nonlinear models introduce parameters whose estimates are of difficult interpretation in a clinical context. The present procedure overcomes these limitations by using the well-known first-order model of respiratory mechanics, wherein variability of resistance and elastance during the breathing cycle is allowed to take into account nonlinear and high-order behavior. Mean and standard deviation of resistance and elastance estimates, relative to a respiratory cycle, are then determined recursively. Feasibility of the method is evaluated by applying it both to experimental and simulated pressure-airflow signals measured in an intensive care unit during mechanical ventilation of patients recovering from heart surgery. Results demonstrate that the proposed procedure provides data description satisfying statistical tests, such as residual whiteness, and reliable estimates of viscoelastic lung parameters even during substantial and fast variations in the respiratory status. In addition, unlike classical methods, the new technique provides the means for on-line evaluation of parameter variability during each respiratory cycle, by the estimate of their standard deviations. This is important in clinical practice, because only the knowledge of reliable parameter values and standard deviations enables significant changes in the respiratory viscoelastic characteristics, and thus in patient status, to be assessed.

Airway Resistance↗

Cellular kinetics and expression of bcl-2 and p53 in ductal carcinoma of the breast.

In this study, the expression of p53 (wild-type and mutated form) and bcl-2 in ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) of the breast was evaluated by immunohistochemistry and PCR-SSCP and correlated with cellular kinetic parameters, i.e., mitotic index (MI) and apoptotic index (AI). The results showed a significant inverse correlation between p53 and bcl-2 expression in all cases of DCIS and IDC. In the DCIS group, two subgroups with different kinetic characteristics were identified. The first group was characterized by p53 positivity, bcl-2 negativity and high values of MI and AI; the other group was characterized by p53 negativity, bcl-2 positivity and low values of MI and AI. Conversely, in IDC some cases were p53 negative, bcl-2 positive and with high values of AI and MI, other cases were p53 positive, bcl-2 negative and with low AI and MI. Molecular biological analysis showed that p53 was wild-type in DCIS, while it was in the mutated form in IDC. These results suggest that in IDC mutated p53 contributes to a change in cellular kinetics and the selection of genetically aberrant cells, thereby favouring neoplastic progression. The coexistence of bcl-2 positivity and high AI could be explained by the presence of of apoptosis that work independently of bcl-2.

Adult↗

Expression of the G2-M checkpoint regulators cyclin B1 and P34CDC2 in breast cancer: a correlation with cellular kinetics.

In this study, the expression of cyclin B1 and p34cdc2 in neoplastic and non-neoplastic breast lesions was evaluated by immunohistochemistry and quantitative analysis in relation to cellular kinetic parameters such as Mitotic Index (MI), Anatelophase Index (ATI), and Apoptotic Index (AI). The percentage of cyclin B1 and p34cdc2-positive cells was significantly higher in neoplastic glands than in their normal counterparts. This finding was paralleled by significantly higher values of MI, ATI, and AI in breast cancer than in normal glands. Furthermore, two groups with different cytokinetic characteristics were identified among infiltrating ductal carcinomas by an unsupervised learning technique of cluster analysis using the percentages of cyclin B1 and p34cdc2 positive cells and the cellular kinetic parameters (MI, ATI and AI) as variables. The final clusters, groups I and II, consisted of 42 and 13 cases respectively. The first cluster (group I) was characterized by a significantly linear correlation between the percentages of cyclin B1 and p34cdc2-positive cells. On the contrary, the second cluster (group II) revealed no correlation between these two proteins and was characterized by values of p34cdc2 largely exceeding those of cyclin B1. A positive correlation between the expression of these two proteins and the cellular kinetic parameters (MI, ATI and AI) was also found in group I but not in group II. These observations suggest that a disturbed nuclear translocation of Mitosis Promoting Factor (MPF) components is present in group II cases, resulting in a defective cellular division cycle. In fact, group I cases showed lymph node metastasis more frequently than group II cases. Our results suggest that the analysis of the cell cycle "machinery" components, such as the cyclins and their dependent kinases, can identify tumors with different levels of aggressiveness.

Adult↗