Effects of body composition on the procoagulant imbalance in obese patients.

Obesity is associated with increased thrombotic risk and hypercoagulability whose main driver is an excess of coagulation factor VIII relative to protein C. The aims of this study were to evaluate the association between factor VIII, protein C, factor VIII-to-protein C ratio and bioimpedance parameters of body composition in obese patients. We analysed blood from 69 obese patients and 23 non-obese healthy controls. Plasma levels of factor VIII, protein C, and factor VIII-to-protein C ratio were correlated with total fat, visceral fat, and muscle mass. Compared to controls, obese patients had significantly higher factor VIII (110.5% vs 78.05%, p < 0.001), protein C (120.99% versus 110.51%, p = 0.014), and factor VIII-to-protein C ratio (0.93 versus 0.73, p = 0.002). In obese patients, factor VIII correlated with body-mass index, body fat percentage, muscle mass percentage, and fat-to-muscle ratio, whereas protein C had significant relationships with body fat percentage, muscle mass percentage and fat-to-muscle ratio, but not with body-mass index. Factor VIII-to-protein C ratio > 1 was significantly associated with body-mass index (odds ratio 1.08, 95% CI 1.02 to 1.14) and fat-to-muscle ratio (odds ratio 2.47, 95% CI 1.10 to 5.55). Factor VIII-to-protein C ratio strongly correlated with D-dimer levels in the overall population (rho 0.44, p < 0.001) and obese patients (rho 0.41, p < 0.001). In obese patients, bioimpedance measures of body fat and muscle mass percentage were associated with factor VIII and protein C. Factor VIII-to-protein C ratio was strongly associated with fat-to-muscle ratio and only modestly related to BMI.

Circulating asymmetric dimethylarginine and lipid profile in pre-pubertal children with growth hormone deficiency: effect of 12-month growth hormone replacement therapy.

OBJECTIVE: Growth hormone deficiency (GHD) in adults is associated with cardiovascular complications, which lead to reduced life expectancy. At present, data on cardiovascular risk factors in GHD children are limited. The aim of this study was to evaluate whether pre-pubertal GHD children have increased cardiovascular risk factors, and whether 12-month growth hormone (GH) treatment can reverse them. DESIGN: Twenty pre-pubertal GHD children (6 boys, mean (±SD) age: 9.5±1.8 years) were matched for sex and age with 20 healthy controls (6 boys, mean (±SD) age: 8.8±1.5 years). Asymmetric dimethylarginine (ADMA), lipid profile, glucose metabolism parameters, IGF-1, blood pressure and anthropometric parameters were assessed at baseline and after 12 months of GH treatment. RESULTS: At baseline, GHD patients showed significantly higher ADMA levels (median [interquartile range]: 78.5 [69.6-123.5] vs 54.0 [38.3-60.8] ng/ml, p<0.001), total cholesterol (mean±SD: 177.5±30.4 vs 150.1±21.4 mg/dl; p=0.004) and LDL-cholesterol (mean±SD: 111.2±22.2 vs 84.9±15.9 mg/dl; p<0.001) than controls. After 12-month GH treatment, ADMA (median [interquartile range]: 55.4 [51.2-73.8] ng/ml), total cholesterol (mean±SD: 155.6±43.2 mg/dl), and LDL-cholesterol (mean±SD: 95.4±32.1 mg/dl) significantly decreased in GHD children, reaching values comparable to those in controls. CONCLUSIONS: This study showed that, as in adults, pre-pubertal GHD children manifest increased cardiovascular risk markers and that 12-month GH treatment can improve them.

Morphometric discrimination between syndromic (Gorlin) and nonsyndromic keratocysts.

OBJECTIVE: To search for morphologic nuclear features in the epithelial lining of odontogenic keratocysts to differentiate simple from Gorlin syndrome cysts. STUDY DESIGN: Five cases of syndrome-associated keratocysts and five of simple ones were studied. Thirty nuclei from the epithelial basal layer for each case were analyzed by the shape analytical morphometry (SAM) software system to quantitatively evaluate nuclear dimensions (area, perimeter, diameter), contour irregularities and nuclear shape asymmetries. Results were subjected to Student's t test and cluster analysis. RESULTS: Values of nuclear dimensions were very close in both groups of keratocysts, without any significant statistical differences. The variables related to nuclear profile irregularities, as well as those describing nuclear asymmetry, showed significantly higher values (P < .001) in syndromic cysts. Cluster analysis produced two different clusters by using variables related to nuclear contour irregularities. CONCLUSION: Preliminary results indicate the existence of nuclear morphologic differences between simple and syndromic cysts.

[Atypical meningioma: morphometric analysis of nuclear pleomorphism]. / Meningioma Atipico: un'analisi morfometrica del polimorfismo nucleare.

The revised edition of the WHO classification of brain tumours now includes the "atypical" meningioma (grade II) which should be placed between the common type (grade I) and anaplastic type (grade III) according to histomorphological features and prognosis. However, diagnostic criteria for atypical meningioma are vague and the significance of brain invasion in the determination of malignancy is controversial. Nuclear pleomorphism and mitoses are usually considered the most important parameters to distinguish atypical and malignant meningiomas. According to WHO classification we selected eight cases of meningioma diagnosed as atypical (3 cases) and malignant (5 cases). All the tumours were supratentorially located. Nine cases of benign meningiomas were also studied as a control group. Morphometrical analysis was carried out by S.A.M. (Shape Analytical Morphometry) system. S.A.M. logical architecture assumes that each irregular shape contains elements of two distinct logical domains: gross distortions that interest the contour and its local perturbations. These features were investigated separately by analytical procedures to acquire independent parameters both on the logical and the numerical level. The results, statistically evaluated, show that nuclear pleomorphism is not a satisfactory criterion, if used alone, to distinguish atypical from malignant meningioma (Discriminant Analysis: 19% of minimum error).

[Malignant mesothelioma of the pleura. Morphometric study]. / Il mesotelioma maligno della pleura. Studio morfometrico.

Malignant mesothelioma is difficult to distinguish from other pleural malignancies and also from benign mesothelial lesions. A morphometric study has been performed to distinguish between them using quantitative size and shape parameters. Seven cases of malignant mesothelioma, 5 cases of pleural metastatic adenocarcinoma and 4 cases of benign mesothelial lesions were selected and subjected to S.A.M. (Shape Analytical Morphometry). The results, statistically evaluated, showed that morphometric parameters can be proposed for diagnostic purposes being useful in the discrimination among the three populations. In fact, multivariate discriminant analysis (MDA) of the quantitative parameters obtained by morphometrical study distinguished the three groups of lesions with only 2% of error between BML/MM, 7% of error between BML/MA and 25% between MM/MA.

Nuclear morphometry in node-negative breast carcinoma.

OBJECTIVE: To determine whether nuclear morphometry can confirm or add useful information to classic clinicopathological prognosticators to identify the subpopulation of breast carcinoma patients with node-negative (N-) disease, at high risk of disease relapse. STUDY DESIGN: On the basis of results obtained by clinicopathologic evaluation of a group of patients with N- breast cancer, on a test group of 56 cases (32 patients disease free and 24 with relapse), we performed a morphometric analytical study of nuclei using the Shape Analytical Morphometry (SAM) software system; 20 nuclei for each case and 17 morphometric parameters for each nucleus were analyzed. RESULTS: The SAM system allowed us to quantify shape differences in nuclei in terms of contour irregularities and asymmetries along with evaluation of nuclear dimensions. Dimensional and analytic parameters were subjected to univariate (Student's t test) and multivariate (Hotelling's test) analysis. Multivariate discriminant analysis showed that an exact forecast of disease relapse could be made in 77% of patients with N- breast cancer by using a set of six both analytic and dimensional parameters. CONCLUSION: These results confirm that nuclear pleomorphism is the result of both contour irregularities and shape asymmetries and that even though they should be considered preliminary results, they stress the importance of quantitative shape evaluation.

Recurring intracranial meningiomas. Morphometrical evaluation of nuclear pleomorphism by S.A.M. (shape analytical morphometry) system.

Meningiomas are the most common neoplasms of the central nervous system and their biological behavior is not always predictable from the histologic appearance of the tumors. The nuclear pleomorphism seems to be one of the most important morphological features in the prediction of recurrence. By using analytical morphometric methods it is possible to quantify nuclear atypias and to obtain parameters describing nuclear contour irregularities and distortions of the figure. Moreover the amount of information obtained from analytical procedure allowed to discriminate, by multivariate discriminant analysis recurrent or no-recurrent meningiomas (5% of error).

Nuclear morphometry in squamous cell carcinoma (SCC) of the tongue.

In the histological grading of oral squamous cell carcinoma (OSCC) nuclear features are very important. Nevertheless evaluation is usually performed in a subjective and not highly reproducible way. The aim of this work was to investigate the relationship between nuclear shape and survival in 30 cases of carcinoma of the tongue. All the patients were divided into two groups: short-term survival and long-term survival. Twenty nuclei for each tumour were submitted to a morphometrical study by the shape analytical morphometry (SAM) software system. It was thus possible to evaluate not only nuclear dimensions but also nuclear contour irregularities and nuclear shape asymmetries. Multivariate discriminant analysis (MDA) of the quantitative parameters obtained by the morphometrical study distinguished the patients of the two groups with only a 10% error; moreover successful cluster analysis was performed by using Fourier parameters. Both these sets of results were achieved mainly owing to the parameters for contour irregularities.

Size and shape evaluation of astrocytoma nuclei with the shape analytical morphometry software system.

Eighteen cases of astrocytomas diagnosed as grades 1-3 of malignancy were studied with analytical morphometry to determine if different grades can be discriminated by size and shape parameters related to the nuclei. The shape analytical morphometry system was used to calculate dimensional measurements and express shape irregularities through quantitative parameters. With the shape asymmetry evaluator procedure, nuclear symmetry was evaluated. All parameters subjected to univariate and multivariate strategies were the same in easily distinguishing grade 1 from the others. Grades 2 and 3 could not be discriminated completely by either dimensional or with analytical parameters revealing strong similarities of nuclear shape and dimensions.

Nuclear morphology and histological grading of oral squamous cell carcinoma (OSCC). A morphometric study.

Histological grading of oral squamous cell carcinoma (OSCC) is usually evaluated in a semiquantitative way and this causes a low grade of reproducibility of this prognostic evaluation. The aim in this preliminary phase is to investigate the relation between nuclear shape (studied by an analytical procedure) and histological grading to evaluate the weight of nuclear shape and dimension in grading formulation. Nine cases of OSCC were studied (3 cases of G1, G2 and G3 respectively) with 20 nuclei for each case. All the tumors were localized on the lip. Histologic grading according to the Bryne system was performed. Each nucleus was submitted to a morphometrical study by the SAM (Shape Analytical Morphometry) system which, apart from dimensions allows us to evaluate nuclear contour irregularities and nuclear shape asymmetry. Nuclei of squamous cell carcinoma show a progressive increase in dimensions (area, perimeter and diameter) from G1 to G3. Nuclei of G3 carcinoma are characterized by the most irregular shape. Size differences (mean value) are significant to differentiate G1 nuclei from G2 and G3 nuclei while shape parameters are useful in distinguishing G3 nuclei from G1 and G2. Multivariate discriminant analysis showed that by using only nuclear parameters it is possible to correctly classify about 80% of nuclei. This study, using quantitative methods, confirmed nuclear pleomorphism to be the most important feature in grading evaluation.