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Biomedical subjects

G Cevenini

Publications and source records attributed to G Cevenini.

At least 19 recordsLinked to original sources

Rett syndrome and plasma leptin levels.

OBJECTIVE: To describe in patients with Rett syndrome (classic and preserved-speech variant) plasma leptin levels and their relationship to BMI (body mass index) and age. STUDY DESIGN: Female patients (n = 48; age range 3-20 years) affected by classic Rett syndrome were enrolled into the study. Eleven female patients, age range 3 to 20 years, with preserved-speech variant Rett syndrome were included in the study. Controls were 24 healthy female subjects, age range 3 to 20 years. Blood samples (3 mL) were withdrawn from an antecubital vein in the morning; plasma leptin concentrations were detected by enzyme-linked immunosorbent assay method. RESULTS: Patients with classic Rett syndrome and preserved-speech variant had leptin values significantly higher than controls. Leptin concentrations did not significantly differ between patients with classic Rett and preserved-speech variant. Leptin values positively correlated with age and BMI. CONCLUSIONS: Because in all patients the increased leptin concentrations were not associated to obesity, we hypothesize that in patients with Rett syndrome leptin might participate to clinical manifestations other than weight balance.

Adolescent↗

Standardized psychological evaluation pre- and posttransplantation: a new option.

A multicenter study was undertaken involving three teams in Italy to obtain a homogeneous psychological evaluation of patients needing organ transplantations. After a preliminary formulation of a common questionnaire individualizing 22 items, yielding a final score from 0 to 44, 294 forms were analyzed for correlations between variables. The sample responses were related to individual variables as well as by cluster analysis to aggregate typical profiles. Clustering of variables was observed in three areas that showed two variables (no. 6, "ongoing psychotic disturbances" and no. 10 "drugs") to be separate. Area 1 ("psychopathology") highlights psychic disturbances, cognitive disorders, and unhealthy behavioral styles; area 2 ("anxia") correlates anxious symptoms to pretransplant examinations and waiting time; area 3 ("depression") ties personal emotional resources and affective factors. Cluster analysis of the sample identified four groups: Group 1 (16.6%) "at risk;" mean score 25.2 (range 16-31); Group 2 (21.7%) "intermediate-at risk," mean score 32 (range 25-38); Group 3 (29.6%) "intermediate-ideal," mean score 35.3 (range 26-40); and Group 4 (31.9%) "ideal candidate," mean score 40.7 (range 36-44). The two "intermediate" groups were studied for mean values for area 1; namely, a cut-off value of 1.78 constituted a better or worse prognostic factor to assign the patient to either Group 2 or 3. Using a uniform method of psychological evaluation before transplantation reduced single operator subjectivity, obtaining comparable results in different transplant centers and allowing planning interventions for at-risk patients.

Cluster Analysis↗

Dysplastic naevus vs. in situ melanoma: digital dermoscopy analysis.

BACKGROUND: To date, much confusion exists about the biological significance of dysplastic naevi and about the relationship between melanocytic dysplasia and clinical atypia. OBJECTIVES: To use a digital dermoscopy analyser with a series of 'borderline' pigmented skin lesions (i.e. dysplastic naevi and in situ melanomas) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. METHODS: The pigmented skin lesions (n = 174) were histologically examined by three experienced dermatopathologists and identified as in situ melanomas (n = 38) and dysplastic naevi (n = 136). The system evaluated 48 parameters as possible discriminant variables, grouped into four categories: geometry, colours, textures and islands of colour. Once the lesions were analysed (stepwise discriminant analysis), sensitivity, specificity and accuracy were calculated. RESULTS: At the end of the stepwise procedure the percentage of cases classified correctly was 71.8%. Of 136 dysplastic naevi only 98 were classified correctly, while 27 of 38 in situ melanomas were recognized correctly. CONCLUSIONS: We conclude that there are so far no digital dermoscopic criteria that can clearly distinguish dysplastic naevi from in situ melanomas.

Dermoscopy↗

Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease.

Recent studies suggest that extracorporeal photochemotherapy (ECP) may be beneficial in patients with steroid-refractory chronic graft-versus-host disease (cGvHD). However, it is not yet clear whether certain conditions, such as age, mode of onset of cGvHD etc., influence clinical response and whether certain affected organs are more sensitive to ECP than others. We analysed the main clinical and laboratory parameters related to evolution of the disease in 32 steroid-refractory cGvHD patients, to identify any useful response predictors to ECP. ECP affected the course of the disease positively in 78% (25/32) of our cases.

Adult↗

Digital dermoscopy analysis of atypical pigmented skin lesions: a stepwise logistic discriminant analysis approach.

BACKGROUND: Digital microscopy is a non-invasive diagnostic technique enabling determination of characteristics that cannot be appreciated by direct observation. If correctly applied, this technique can be useful for the diagnosis of pigmented skin lesions. PURPOSE: To evaluate the utility of digital microscopy for analysing atypical benign and malignant pigmented skin lesions exploiting digital numerical filtering and automatic measurements. METHODS: Forty-eight parameters were identified as possible discriminating variables, and were grouped in four categories: geometries, colours, textures, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. RESULTS: The high quality of the digital image made it possible to observe diagnostic signs in pigmented skin lesion images, acquired by the present technique, in great detail. Specially designed filtering enhanced certain diagnostic patterns. Stepwise discriminant analysis selected only 10 variables (the means of these variables were higher in melanomas than in nevi). CONCLUSIONS: The combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing atypical nevi and early melanoma.

Diagnosis, Computer-Assisted↗

p53 mutation in breast cancer. Correlation with cell kinetics and cell of origin.

AIM: Several studies have investigated the expression of the cytokeratins (CKs), vimentin, the epithelial growth factor receptor (EGFR), the oestrogen receptor (ER), and the progesterone receptor (PgR), in breast cancer, but no study has directly compared p53 mutations with these phenotypic and differentiation markers in the same case. The present study was designed to provide some of this information. METHODS: The expression of the p53 and bcl-2 proteins was evaluated by immunohistochemistry in relation to phenotypic characteristics and cellular kinetic parameters (mitotic index and apoptotic index) in 37 cases of ductal carcinoma in situ (DCIS) and 27 cases of infiltrating ductal carcinoma (IDC) of the breast. In addition, p53 gene mutation was examined by polymerase chain reaction single strand conformation polymorphism analysis (SSCP). RESULTS: Thirteen cases (eight DCIS and five IDC) showed expression of CK8, CK14, CK18, vimentin, and EGFR, consistent with a stem cell phenotype, whereas 44 cases (27 DCIS and 17 IDC) showed expression of CK8 and CK1, weak or negative expression of CK18, but were negative for vimentin and EGFR, consistent with a luminal cell phenotype. DCIS and IDC cases with a stem cell phenotype were ER/PgR negative and intermediately or poorly differentiated. In contrast, the cases with luminal cell phenotype were ER/PgR positive and well or intermediately differentiated. In addition, intermediately or poorly differentiated cases with a stem cell phenotype showed higher proliferative activity (per cent of MIB-l positive cells) than did intermediately or well differentiated cases with a luminal cell phenotype. Both DCIS and IDC cases with a stem cell phenotype were p53 positive and bcl-2 negative by immunohistochemistry. In IDC, p53 expression was associated with a reduction of both mitotic index and apoptotic index compared with DCIS. Most of the tumours showing a more differentiated phenotype (luminal) were p53 negative and bcl-2 positive. In these cases, cell kinetic parameters increased from DCIS to IDC. These data suggest the existence of subsets of DCIS and IDC that, because of their phenotypic characteristics, could be derived from subpopulations of normal breast cells having different control mechanisms of cell proliferation and neoplastic progression. CONCLUSIONS: These results are compatible with the hypothesis that the phenotype of the cell of origin constrains both tumour phenotype and the choice of genetic events; however, the occurrence of p53 mutants by chance during neoplastic transformation cannot be excluded.

Adult↗

Effect of compliant intermediate airways on total respiratory resistance and elastance in mechanical ventilation.

Total respiratory resistance and elastance were estimated off-line in a sample of 60 patients undergoing mechanical ventilation by means of two regression models in order to analyse and understand a possible physiological mechanism determining differences in inspiration and expiration. The first model considered a single value for resistance and elastance over a whole breathing cycle, whereas the second model considered separate values for inspiratory and expiratory resistance and a single value for elastance. Inspiratory resistance was found to be lower than expiratory resistance, and intermediate values were obtained for resistance estimated over the whole breathing cycle. Student's t-test showed a highly significant difference between these resistance estimates, and principal components analysis demonstrated a significant increase in information when both inspiratory and expiratory resistances were used. Minor differences were found between values of elastance calculated with the two approaches. In an attempt to interpret these experimental results, a lung model incorporating the non-linear viscoelastic properties of the intermediate airways was considered. This model suggested that changes in intermediate airway volume play a significant role in breathing mechanics during artificial ventilation and indicated that inspiratory and expiratory resistance could be useful parameters for locating airway obstruction.

Airway Resistance↗

Differentiation between pigmented Spitz naevus and melanoma by digital dermoscopy and stepwise logistic discriminant analysis.

Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.

Dermatology↗

Role of the mechanical properties of tracheobronchial airways in determining the respiratory resistance time course.

A physiologically based simulation model of breathing mechanics was considered in an attempt to interpret and explain the time course of input respiratory resistance during the breathing cycle, observed in recent studies on ventilated patients. The model assumes a flow-dependent Rohrer resistance for the upper extrathoracic airways and volume-dependent resistance and elastance for the intermediate airways. A volume-dependent resistance describes the dissipative pressure loss in the lower airways, and two constant elastances represent lung and chest wall elasticity. Simulated mouth flow and pressure signals obtained in a variety of well-controlled conditions were used to analyze total respiratory resistance and elastance estimated by an on-line algorithm based on a time-varying parameter model. These estimates were compared with those provided by classical estimation algorithms based on time-invariant models with two, three, and four parameters. The results show that the four-parameter model is difficult to identify, while the three-parameter one offers no substantial advantage for estimating input resistance with respect to the more simple two-parameter model. In contrast, the time-varying approach provides good on-line estimates of the simulated end-expiration and end-inspiration resistances. These values provide further information of potential clinical utility, with respect to time-invariant models. For example, the results show that the difference between the end-expiration and end-inspiration resistance increases when obstructions shift from the upper to the lower airways. The similarity of the results obtained with measured and simulated data indicates that, in spite of its simplicity, the simulation model describes important physiological mechanisms underlying changes in respiratory input resistance, specifically the mechanical properties of intermediate airways.

Airway Resistance↗

Expression of the ALK protein by anaplastic large-cell lymphomas correlates with high proliferative activity.

A variable fraction of anaplastic large-cell lymphomas (ALCLs) exhibits a t(2;5)(p23;q35) translocation that results in expression of the chimeric hyperphosphorylated protein NPM-ALK (p80). Tumor cells expressing NPM-ALK exhibit markedly enhanced proliferative activity, but comparative cellular kinetic studies on ALK(+) (ALK lymphomas) and ALK(-) lymphomas are lacking. The present study showed that ALK(+) lymphomas, detected with the monoclonal antibody ALKc (n = 17), had significantly higher average values for the proliferation-associated parameters mitotic index, ana/telophase index, growth index (x x mitotic index - apoptotic index, assuming x = 3), percentages of Ki-67(+) cells and fraction of cells expressing cyclin A or B or the cell cycle-regulatory protein p34(cdc2) than did ALK(-) ALCLs (n = 15). Whether this intense proliferative activity contributes to the good response to chemotherapy and favorable outcome of ALK(+) ALCLs remains to be assessed in a larger series of patients. Our findings support the notion that ALK(+) and ALK(-) ALCLs are 2 distinct disease entities.

Adolescent↗

Genetic alterations of the retinoblastoma-related gene RB2/p130 identify different pathogenetic mechanisms in and among Burkitt's lymphoma subtypes.

Alterations of cell cycle-associated genes probably contribute to the pathogenesis of Burkitt's Lymphoma (BL), in addition to c-myc translocation. Mutations disrupting the nuclear localization signal of the retinoblastoma-related gene RB2/p130 have been documented recently in BL cell lines and primary tumors. Given the importance of the RB2/p130 gene in controlling cell growth, mutations of this gene may result in uncontrolled cell proliferation. We tested the expression and genomic organization of the RB2/p130 gene in relation to the proliferative features of a series of BL samples collected from the endemic and sporadic regions, regardless of whether the samples were acquired immune deficiency syndrome (AIDS)-related. The expression of the Rb2/p130, p107, and cell proliferation-related proteins (cyclin A and B) was determined by immunohistochemistry. The structures of exons 19 through 22 of the RB2/p130 gene, encoding for the B domain and C terminus, were analyzed by polymerase chain reaction (PCR) analysis and single-strand conformation polymorphism (SSCP) technique. The direct PCR products were sequenced to identify the actual mutations. Our results suggest that BL is composed of a mixture of molecular types with distinct genetic and phenotypic patterns, probably resulting from different pathogenetic mechanisms. In endemic BL, the RB2/p130 gene is mutated in most of the cases, and the protein is restricted to the cytoplasm. In AIDS-related BL, high levels of nuclear expression of the wild-type pRb2/p130, p107, and cell proliferation-related proteins were detected. This finding is in line with the molecular mechanisms observed in virus-linked oncogenesis. Sporadic BLs were mainly characterized by the low nuclear values of the wild-type pRb2/p130 and, conversely, the high values of p107. The increased cell proliferation due to different alterations of cell growth control by Rb-related proteins may be the first step in lymphomagenesis, during which additional genetic changes, including missense mutations of c-myc, may subsequently occur.

Adolescent↗

Modified Karhunen-Loéve expansion for evaluating skin-colour-associated melanoma risk factors.

An approach based on the modified Karhunen-Loéve expansion (MKLE) of constitutive and facultative skin colour data acquired by colorimeters in melanoma patients and healthy control subjects, was used to identify two colour features defining skin-colour-associated risk of melanoma. None of four common statistical classifiers trained on colour features were sufficiently accurate for allowing skin colour alone to be used for classification purposes, though a Bayesian quadratic classifier matched the transformed data well. This study supersedes the indeterminate character of most common clinical criteria based on qualitative factors and, irrespective of the results of classification, provides objective skin colour information for the prevention of melanoma.

Algorithms↗

Expression of p34(cdc2) and cyclins A and B compared to other proliferative features of non-Hodgkin's lymphomas: a multivariate cluster analysis.

In view of recent knowledge on proteins regulating the cell cycle, we re-evaluated proliferative features of 98 diffusely growing non-Hodgkin's lymphomas. The combined use of 5 proliferation-associated variables (mitotic indices and percentages of Ki-67(+), p34(cdc2+), cyclin A(+) and cyclin B(+) cells) and their entry into a multivariate cluster analysis separated, without overlaps, the entire cohort into 3 groups (clusters) with (1) low, (2) intermediate and (3) high proliferative activity. Conversely, bivariate plots exposed considerable cluster overlaps. Multivariate stepwise discriminant analysis of all cases revealed a decreasing order of discriminant power for % Ki-67(+) cells > % p34(cdc2+) cells > mitotic index > % cyclin A(+) cells > % cyclin B(+) cells. The combined use of 2 variables only, mitotic index and % p34(cdc2+) cells, allowed a clear-cut separation of clusters 2 and 3. In bivariate plots, correlations were best between % Ki-67(+) cells and % cyclin A(+) cells and between mitotic indices and % cyclin B(+) cells. Except for chronic lymphocytic leukemias, immunocytomas and marginal zone lymphomas (all in cluster 1), individual lymphoma entities were distributed among at least 2 clusters. There was, however, a marked preponderance of mantle cell lymphomas and diffuse follicular center lymphomas in cluster 1 and of diffuse large B-cell lymphomas and peripheral T-cell lymphomas in cluster 2. Anaplastic large-cell lymphomas predominated in cluster 3 and responded best to therapy.

Adolescent↗

Digital dermoscopy analysis for the differentiation of atypical nevi and early melanoma: a new quantitative semiology.

OBJECTIVES: To use a digital dermoscopy analyzer with a series of "borderline" pigmentary skin lesions (ie, clinically atypical nevi and early melanoma) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. DESIGN: A total of 147 pigmentary skin lesions were histologically examined by 3 experienced dermatopathologists and identified as nevi (n = 90) and melanomas (n = 57). The system evaluated 36 variables to be studied as possible discriminant variables, grouped into 4 categories: geometries, colors, textures, and islands of color. SETTING: University medical department. PATIENTS: A sample of patients with excised pigmentary skin lesions (nevi and melanomas). MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the model for evaluating "borderline" pigmentary skin lesions. RESULTS: After multivariate stepwise discriminant analysis, only 13 variables were selected to compute the canonical discriminant function. CONCLUSION: The present method made it possible to determine which objective variables are important for distinguishing atypical benign pigmentary skin lesions and early melanoma.

Adult↗

Quantitative characterization and study of the relationship between constitutive-facultative skin color and phototype in Caucasians.

In this study constitutive and facultative colorimetric values were quantified to determine the physiologic changes in Caucasian skin color and to define the correlation between skin color and phototype assessed according to the Fitzpatrick method. Our population consisted of 401 subjects ranging in age from 24 to 28 years with similar life styles. Skin color was measured with a Minolta CR-200 colorimeter on the upper medial quarter of the buttock (constitutive color) and on the cheek (facultative color). Advanced multivariate statistical analysis allowed differentiation between constitutive and facultative skin color in relation to the phototype to be quantified. Moreover, Kullback divergence showed that the probability of correctly determining a subject's phototype is high when the variables of constitutive and facultative skin color are considered together. This interesting result makes it possible, in the future, to use colorimetric values of exposed and nonexposed skin, together with determination of Fitzpatrick phototype and of other phenotypic characters, to better predict cutaneous sun reactivity.

Adult↗

Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: distinct mechanisms of cell growth control.

pRb/p105, p107, and pRb2/p130 compose the retinoblastoma (RB) family of proteins and regulate cellular growth and differentiation. Because recent functional studies have indicated that the expression of the RB-related proteins p107 and pRb2/p130 are tightly cell cycle regulated, we were interested in investigating their expression along with cellular kinetic characteristics and proliferative features of non-Hodgkin's lymphomas (NHLs). p107 and pRb2/ p130 expression was determined immunohistochemically in biopsy specimens from 83 untreated patients with NHLs of various histiotypes. The expression of these two RB-related proteins was correlated with the mitotic index, apoptotic index, and percentages of Ki-67(+), cyclin A(+), p34(+), and cyclin B(+) cells. The overall survival rate was evaluated according to the Kaplan-Meier method and the log-rank test. We found a positive correlation between the percentages of cells positive for p107 and proliferative features such as mitotic index and percentage of Ki-67(+) and cyclin A(+) cells, whereas such correlation could not be demonstrated for the percentages of pRb2/p130 positive cells. Low immunohistochemical levels of pRb2/p130 detected in untreated patients with NHLs of various histiotypes inversely correlated with a large fraction of cells expressing high levels of p107 and proliferation-associated proteins. Such a pattern of protein expression is normally observed in continuously cycling cells. Interestingly, such cases showed the highest survival percentage (82.5%) after the observation period of 10 years. Thus, down-regulation of the RB-related pRb2/p130 protein could be one of the reasons why these cases display such a high rate of proliferation and why they respond so well to therapy.

Aged↗

Cellular kinetic differences between Hodgkin's and anaplastic large cell lymphomas: relation to the expression of p34cdc2 and cyclin B-1.

Our study was designed to compare cellular kinetic parameters of classical Hodgkin's disease (HD) with those of anaplastic large cell lymphomas (ALCL-C, common type; and ALCL-HL, Hodgkin's like), with a particular focus on the G2/M transition. These disorders share some phenotypic properties, e.g., CD30 positivity of putative neoplastic cells. The percentages of cells expressing p34cdc2 (p34) and cyclin B-1 (cyclin-B), which form a complex (maturation/mitosis promoting factor, MPF) regulating the G2-M phases of the cell cycle, were also registered. Highly significant differences between HD and ALCL-C were recognized: a) in HD, evidence for abortive mitosis (i.e., difficulty to proceed beyond the metaphase stage) and consequent multinucleation and/or deletion of CD30+ cells was prominent, in contrast to ALCL-C. This was associated with a markedly lower fraction of large atypical cells (LAC) expressing cyclin-B in the cytoplasm and the nucleus (C + N) in HD than in ALCL-C; b) the extent of multinucleation of CD30+ cells in HD, but not in ALCL-C, was correlated with the %p34+ LAC; c) the proportions of LAC expressing p34 and/or cyclin-B (C) were positively related to the percentages of cyclin-B (C + N)+ LAC in ALCL-C but not in HD; d) in HD, in contrast to ALCL-C, the size of the fraction of cyclin-B (C + N)+ LAC did not correlate with the ana/telophase indices (ATI, reflecting successful completion of mitosis) and the magnitude of cell loss; e) in ALCL-C, the percentages of p34+ LAC were positively correlated with ATI or the degree of CD30+ cell deletion, but inversely in HD. With regard to all parameters mentioned above, ALCL-HL tended to take an intermediate position between HD and ALCL-C, but sided more with the latter. In conclusion, our present results suggest a derangement of MPF kinetics and functions that is more profound in HD than in ALCL-C.

CDC2 Protein Kinase↗

DNA ploidy pattern in papillary renal cell carcinoma. Correlation with clinicopathological parameters and survival.

Papillary renal cell carcinoma (PRCC) is a less frequent histomorphologic variant of renal cortical carcinoma (RCC). Morphologically, PRCC differs from other forms of RCC in that it is associated with frequent tumor infiltration by macrophages and lymphocytes, and a tendency for central necrosis and cystic change. Follow-up data revealed that survival rates are higher among patients with PRCC than among patients with other forms of RCC. The authors explore the DNA content in a series of PRCC and correlate the findings with nuclear grade, pathological stage and survival. Using Flow Cytometry, we analysed the DNA ploidy pattern of 37 paraffin-embedded PRCC. At least 3 tumor fragments were analysed in each case. To obtain the reference diploid standard, the non-tumor renal tissue from the same case was added to the solution. Tumor ploidy was classified as diploid and aneuploid. The degree of DNA content abnormalities was given by the DNA Index (DI). An aneuploid DNA profile was found in 65% of the tumors. 25% of the aneuploid tumors presented near diploid peaks (1.10 < DI < 1.30; low degree aneuploidy), 25% were hyperdiploid, while 22% had a hypodiploid profile (DI < 0.90). A homogeneous DNA ploidy pattern was observed in 25 tumors (68%), while there was intratumoral heterogeneity in 12 tumors (32%). Patients with aneuploid DNA patterns had high grade/stage tumors and died at the end of the follow-up period, while patients with diploid/near diploid profiles had low grade/stage tumors and survived. However, the multi-way analysis of variance performed in order to investigate the prognostic significance of ploidy pattern against tumor stage and grade showed a highly significant main effect of ploidy pattern. Moreover, the patients with hypodiploid DNA profile presented the worst prognosis. These results suggest that the DNA profile of PRCC is a highly significant prognostic index.

Aged↗