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Biomedical subjects

P Barbini

Publications and source records attributed to P Barbini.

At least 19 recordsLinked to original sources

Relationship between skin color and sun exposure history: a statistical classification approach.

In this study our aim was to determine the biophysical values of constitutive skin color in Caucasians and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Constitutive skin color was measured on the buttock, with a Minolta CR-200 colorimeter, in a population-of 557 consecutive subjects belonging to phototype categories I, II, III and IV. The colorimeter expresses the results in five different color systems. We used the "Yxy" and L*a*b* systems, which are the most widespread in dermatology. Statistical analysis of the data showed that the "Yxy" system is even more discriminant than the L*a*b* system when the Fitzpatrick classification scheme is adopted as the reference and shows a poor ability to correctly classify the intermediate phototypes (II and III). On the contrary the "Yxy" system performs well in distinguishing phototypes I and IV. To establish whether this low discriminating capacity for phototypes II and III is related to a low discriminating capacity of the method suggested by Fitzpatrick or by our procedure, an objective technique (minimal erythemal dose) should be used to evaluate the percentage errors of classification of both the Fitzpatrick method and instrumental measurement of skin color. The results of such a study are extremely important because the evaluation of skin color is objective, simple and has potential applications in dermatology and cosmetology.

Adult

Nearest-neighbor analysis of spatial point patterns: application to biomedical image interpretation.

Analysis of the spatial distributions of objects is fundamental to biomedical image interpretation. Nearest-neighbor (NN) methods are generally used to assess whether objects are arranged at random or in a deterministic manner. Simple standard NN techniques, however, may fail to identify complex spatial organizations. To overcome this problem the present study proposes a NN iterative algorithm that enables deterministic spatial patterns to be detected by identifying the distances between objects for which there is the greatest deviation from randomness and hence the amplitude of the areas of maximum reciprocal influence between objects. The performance of the algorithm is evaluated by applying it to both manufactured and experimental data. The manufactured date example showed that the proposed procedure produced neither false positives or negatives. The method proved to be extremely sensitive, detecting even small deviations from randomness. The experimental analysis was applied to the study of the spatial distribution of apopototic structures in malignant neoplastic tissue. It showed that the apopototic cells and bodies are characterized by a complex spatial pattern, and aggregate closely.

Algorithms

Presence of the bcl-2 protein and apoptosis in non-Hodgkin lymphomas with diffuse growth pattern.

In an attempt to further clarify the role of the apoptosis-counteracting protein bcl-2, non-Hodgkin lymphomas (NHL, n = 170) were examined immunohistochemically, across the boundaries of histologic classification, for the presence of this oncoprotein, in comparison with apoptotic indices (AI) and percentages of Ki-67+ cells (growth fraction). The results of this retrospective study revealed a highly significant inverse relationship ("mirror image") between the proportion of bcl-2+ cells and the AI per case. Both these parameters, although variable, clearly distinguished low- from high-grade-malignancy lymphomas according to the Kiel classification. Cluster analysis detected 2 separate groups of high-grade NHL, one with rather high AI and low percentages of bcl-2+ cells, comprising most anaplastic large-cell lymphomas, the other group with reverse characteristics. We found no correlation between the percentage of bcl-2+ cells per case and overall survival.

Apoptosis

Two new algorithms for tracking arterial parameters in nonstationary noise conditions.

Two new algorithms with reduced sensitivity to the changing environment are applied to tracking arterial circulation parameters. They are variants of the Least-Squares (LS) algorithm with Variable Forgetting factor (LSVF), and of the Constant Forgetting factor-Covariance Modification (CFCM) LS algorithm, devised to overcome their main practical deficiencies related to noise level sensitivity and the high number of design variables, respectively. To this end, adaptive mechanisms are incorporated to estimate observation noise variance in LSVF and the rate of change for the different parameters in CFCM. Specific computer simulation experiments are presented to compare their effectiveness with the original counterparts and to provide guidelines for their optimal tuning at different noise levels. Moreover, algorithm performance degradation, consequent on changes in the noise level compared to that assumed during the tuning phase, is analyzed. In particular, it is shown that, when the noise level changes with respect to the tuning value, the new LSVF algorithm is much more robust than the original one, whose performance degrades rapidly. The new CFCM algorithm is characterized by a reduced number of design variables with respect to its original counterpart. Nevertheless, it can be preferred only when low noise signals are used for estimation.

Algorithms

Influence of flow pattern on the parameter estimates of a simple breathing mechanics model.

The first-order model of breathing mechanics is widely used in clinical practice to assess the viscoelastic properties of the respiratory system. Although simple, this model takes the predominant features of the pressure-flow relationship into account but gives highly systematic residuals between measured and model-predicted variables. To achieve a better fit of the entire data set, an approach hypothesizing deterministic time-variations of model parameters, summarized by information-weighted histograms was recently proposed by Bates and Lauzon. The present study uses flow and pressure data measured in intensive care patients to evaluate the real potential of this approach in clinical practice. Information-weighted histograms of the model parameters, estimated by an on-line identification algorithm, were first constructed by taking into account the parameter percentage standard deviations. Then, the influence of the respiratory flow pattern on the calculated histograms was evaluated by the Kolmogorov-Smirnov statistical test. The results show that the method gives good reproducibility under stable experimental conditions. In addition, for a given airflow waveform, an increase in respiratory frequency shifts the histograms representing time-varying viscous properties strongly versus lower values, whereas it shifts the histograms representing time-varying elastic properties slightly versus higher values. On the other hand, the same histograms were highly dependent on the airflow waveform, especially for the viscous properties. Even in a limited experimental work, in all the conditions considered, the method provides results which agree well with the physiological knowledge of nonlinear and multicompartment behavior of respiratory mechanics.

Algorithms

Spatial distribution of mitosis, apoptosis and small blood vessels in malignant diffuse follicular-center-cell lymphomas: a nearest-neighbor analysis.

To better comprehend the relationships between cell birth and cell death in neoplastic disorders, the topography of these events needs to be considered. We applied a computerized nearest-neighbor analysis to malignant, diffuse follicular-center-cell lymphomas in order to examine the spatial distribution of pyknotic (apoptotic) cells/bodies (A) and mitotic figures (M) in relation to capillaries (C) and venules (V). The results revealed a complex dispersion pattern, with significant aggregations of A and M, in addition to an even greater random distribution component. The greatest clustering displayed by A was around capillaries (A-C, 42% reduction of object frequency between the first and second distance class), followed by A-A (33%), A-V (24%) and A-M (12%). Additional values for mitotic figures were: M-M (45%), M-V (33%) and M-C (22%). These findings may reflect the relative importance of inherent properties of the neoplastic and host factors, respectively, in the regulation of cell birth and cell death rates.

Adult

Estimating respiratory mechanical parameters of ventilated patients: a critical study in the routine intensive-care unit.

Airflow and pressure were measured post-operatively in eight mechanically ventilated patients in the routine intensive care unit. Analysis of the input impedance spectra versus frequency suggested that respiratory data cannot be adequately reproduced using the classic two-element R-C model, as the real part of input impedance decreases with frequency. To fit in with this behaviour, we adopted a three-element model with an additional parallel compliance. The three parameters of this model were estimated separately in the frequency and time domains by minimising suitable least-square criterion functions. The results demonstrate a good agreement between the parameter estimates in the frequency and time domains, and show that the three-element model reproduces the input impedance frequency pattern in the range 0.2-8 Hz. Comparison of different linear models in the time domain demonstrated that the precision of parameter estimates and the quality of best fitting sharply increase from the two-element to the three-element model. The addition of a fourth resistive parameter, like in the Mead model, does not lead to appreciable improvement and makes the model almost unidentifiable. The possible contribution of a ventilator-patient circuit of the upper airway shunting and of the peripheral airway obstruction are also discussed.

Airway Resistance

A four-parameter linear model for analysing cardiorespiratory data in post-operative cardiac patients.

This paper investigates the possibility of characterizing the differences between normal- and high-risk postoperative cardiac patients on the basis of four parameters related to a simple linear model of cardiorespiratory performances. The model comprises three subsystems representing cardiac, vascular and respiratory functions, respectively. These parameters, determined from physiological variables measured in the Intensive Care Unit, seem useful for clinical evaluation of patient status. In fact, their values quantify the improved cardiovascular and respiratory response that normal-risk patients exhibit to increasing metabolic needs after hypothermic treatment, with less utilization of blood oxygen reserve. In addition, a set of three parameters derived from the proposed four allows a prediction of patient class membership with an error lower than 7% when used with a Bayes quadratic classifier.

Cardiac Surgical Procedures

Gastric intestinal metaplasia type III cases are classified as low-grade dysplasia on the basis of morphometry.

The aim of this study was to try to place gastric intestinal metaplasia, type III (type III IM) in the stepwise chain of events from atrophic gastritis to cancer. A number of dysplastic, periulcer regenerative, and type III IM lesions were qualitatively diagnosed (and graded) blindly and independently by several pathologists. These lesions were further analysed by means of quantitative parameters, with the aim of differentiating dysplastic from regenerative changes. Inconsistencies between the qualitative and quantitative classification (about 7 per cent of cases) were eliminated and homogeneous groups (low-grade dysplasia, high-grade dysplasia, regenerative changes) were obtained. These cases were taken as the gold standard against which type III IM was compared. The results indicate that the great majority (91.4 per cent) of cases of type III IM fulfil the nuclear and architectural criteria for low-grade dysplasia.

Adult

Low-frequency respiratory mechanics using ventilator-driven forced oscillations.

We evaluated the potential for using a fast Fourier transform (FFT) analysis applied to a standard ventilator waveform to estimate (< 2 Hz) frequency dependence of respiratory or lung resistance (R) and elastance (E). In four healthy humans we measured pressure and flow at the airway opening while applying sine wave forcing from 0.2 to 0.6 Hz at two tidal volumes (VT; 250 and 500 ml). We then applied a step inspiratory ventilator flow wave with relaxed expiration at the same VT and only 0.2 Hz. Step waveform data were also acquired from nine mechanically ventilated patients under intensive care unit conditions. Finally, we simultaneously measured total respiratory (rs), lung (L), and chest wall (cw) impedance data from two dogs (0.156-2 Hz) before and after severe pulmonary edema. Rrs and Ers were estimated by the FFT approach. Humans displayed a small frequency dependence in Rrs and Ers from 0.2 to 0.6 Hz, and both Rrs and Ers decreased at the higher VT. The spectral estimates of Rrs and Ers with the step ventilator wave were often qualitatively comparable to sine wave results below 0.6 Hz but became extremely erratic above the third harmonic. Conversely, in dogs the step wave produced reliable and stable estimates up to 2 Hz in all conditions. Nevertheless, Ecw and Ers still displayed clear and correlated oscillations with increasing frequency, whereas EL showed none. This suggests that nonlinear processes, most likely at the chest wall, contribute to periodic-like fluctuations in respiratory mechanical properties when estimated by applying FFT to a step ventilator wave. Moreover, in humans, but not dogs, a ventilator flow cycle contains insufficient signal energy beyond the third harmonic. We show that the amount of energy available at higher frequencies is largely governed by the mechanical time constant contributing to passive expiratory flow. In dogs the shorter time constant contributes to increased energy. In essence, the frequency content of the flow is subject dependent, and this is not a desirable situation for controlling the quality of the impedance spectra available from a standard ventilator wave.

Adult

Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas.

Cell production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one hand and histological malignancy grades on the other hand. The cellular protein BCL-2, which counteracts apoptosis, was significantly (P < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade.

Apoptosis

A simple computational approach to model parameter estimation.

The desire to describe biological data using mathematical models has led to the rapid development of various analytical techniques for model identification and parameter estimation. The procedures used may be non-linear and complex, and require long calculation periods. Thus, the aid of a personal computer renders efficient the application of these rather complicated procedures. In this study we developed a simple identification programme for heparan sulfate pharmacodynamics which can be easily and rapidly implemented on a personal computer. The programme is based on an iterative algorithm performing a non-linear regression analysis by the least-square method. This programme was applied to a clinical measured variables with which it was possible to quantify the pharmacodynamic effect of heparan sulfate.

Aged

Phenotypic overlaps between pleomorphic malignant T-cell lymphomas and mixed-cellularity Hodgkin's disease.

Histologically diagnosed, or in part questionable, malignant pleomorphic peripheral T-cell lymphomas (pPTCLs, n = 16) and mixed-cellularity Hodgkin's disease (MCHD, n = 12) were objectively compared by the use of combined immunohistochemistry on paraffin sections, test-point analysis of tissue components, and semi-automated nuclear morphometry on semi-thin resin sections. Classical, qualitative histomorphological distinction of these sub-types of lymphomas proved to be valid and is probably still the best method. Quantitative discriminant features, in order of decreasing significance, were: (i) expression by large atypical cells (LACs) of CD45R0, CD43 and CD45 in pPTCLs, and of CD30 and CD15 in MCHD; (ii) means and standard deviations (SDs) of LAC nuclear-profile areas (greater in MCHD than in pPTCLs); (iii) expression of CD3 by LACs in pPTCLs; (iv) prominence of small lymphoid cells in MCHD; (v) higher percentage of medium-sized lymphoid cells in pPTCLs; and (vi) higher SDs of nuclear-profile circularity factor of small lymphoid cells in MCHD. The medians of the largest nucleolar profile areas in LACs per field did not differ in pPTCLs and MCHD, but dispersion of individual values towards higher levels was significantly greater in the latter. Stepwise discriminant analysis of test point and nucleometric variables that best distinguished pPTCLs from MCHD revealed considerable overlaps, and questionable cases tended to be intermediate between the two. In conclusion, our results confirm and expand the notion of intra-group heterogeneity, with indistinct borders and the existence of intermediate phenotypes between these two taxonomic categories of malignant lymphomas.

Adolescent

Bronchiolo-alveolar carcinoma: an analysis of survival predictors.

Macroscopic and microscopic features of tumours have been analysed in 37 bronchiolo-alveolar carcinomas. Lymphocytes, Langerhans cells, collagen (mature and/or myofibroblastic), were quantitatively or semiquantitatively evaluated. Histology, stage, type of fibrosis, nuclear profile features (area and shape factors), amount and type of mucin secreted, number of mitoses, Langerhans cells, myofibroblasts and LeuM1+ cells were not related to survival. Gross morphology of the tumour and, to a lesser extent, lymphoid infiltrates (in particular UCHL1+ and L26+ peritumoral lymphoid cells) were the only variables significantly related to survival. Estimated survival functions were computed according to Cox's model: well demarcated tumours behaved significantly better than poorly demarcated tumours and even more so than diffuse or multiple mass. Lymphoid infiltrates were significantly more represented in and around well demarcated tumours: however, their survival predicting value was less than that of the gross type.

Adenocarcinoma, Bronchiolo-Alveolar

Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression.

As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Comparison of algorithms for tracking short-term changes in arterial circulation parameters.

Three recursive methods especially suited for identification of systems with rapidly changing parameters are applied to tracking of the viscoelastic properties of the systemic arterial bed. These methods include two least squares (LS) algorithms with constant or variable forgetting factor (RLS and LSVF) and a LS algorithm incorporating both a constant forgetting factor and covariance modification (CFCM). The methods are presented in a unified framework and their sensitivity with respect to the design variables is investigated using noisy data from computer simulations. All analysed methods have shown themselves to be able to satisfactory track rapid changes in peripheral resistance. The LSVF method, which offers slightly better performances than the classical RLS, may be preferred when calculation efficiency is the prime requirement. The CFCM algorithm, although maintaining reasonable simplicity, shows the best tracking ability also on varying of the noise sequence.

Algorithms

Diffuse centrocytic and/or centroblastic malignant non-Hodgkin's lymphomas: comparison of mitotic and pyknotic (apoptotic) indices.

Mitotic indices (MIs) and pyknotic (apoptotic) indices (PIs) were assessed in diffuse centrocytic (CC, n = 10), centroblastic/centrocytic (CB/CC, n = 18) and centroblastic (CB, n = 20) malignant non-Hodgkin's lymphomas (NHL). Significant differences were observed. MIs were lowest in CC (median: 0.07%), intermediate in CB/CC (0.18%) and highest in CB (0.43%) NHLs. The PIs exhibited a similar pattern. The PIs of CC (0.11%) and CB/CC (0.17%) NHLs were significantly different from those of CB lymphoma (0.62%). The ratios MI/PI per case, as well as MIs and PIs per case, varied greatly and showed considerable overlapping, thus documenting a marked inter-case and inter-group heterogeneity. MIs tended to loosely correlate with PIs in a non-linear fashion, which raises the question of feedback mechanisms. More information is needed on mitotic time (TM) and apoptotic time (TA), in order to estimate cell doubling time from data on MIs and PIs.

Adult