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Biomedical subjects

A Santinelli

Publications and source records attributed to A Santinelli.

46 records · Page 3Linked to original sources

Computer-aided S-phase fraction determination in DNA static cytometry in breast cancer. A preliminary methodologic study on cytologic material.

This methodologic study was performed on a single-cell-cycle breast carcinoma to evaluate the feasibility of computer-aided S-phase fraction determination in DNA static cytometry. The investigation was performed on Feulgen-stained cytologic material in which the total optical density values of 1,000 consecutive, randomly selected nuclei were analyzed (MultiCycle software). A good correlation in the S-phase fraction value with flow cytometry was obtained when the G2/G1 ratio was fixed at 1.95, when the histogram data points were smoothed at least once and the coefficient of variation of the G2 peak was the same as that of G0-G1 or when a first-order S-phase polynomial model was used. The percentages of nuclei in G0-G1 and G2 were somewhat similar to those obtained with flow cytometry. The greatest discrepancy with flow cytometry was observed in the value of the coefficient of variation of the G0-G1 peak of the static cytometric data: it was at least twice as great. It always remained high despite the software options used. As for the influence of the sample size in the S-phase calculation, the software was also run on samples of 600 and 200 nuclei. When the G2/G1 ratio was fixed at 1.95, the data obtained from 600 nuclei did not differ from those obtained with 1,000 nuclei, whereas an analysis on 200 nuclei showed a substantial variation. The software also allowed calculation of the ratio of the G0-G1 peak of the neoplastic population against that of the diploid reference (DNA index), the value of which in flow cytometry was 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Cytometric evidence that cervical intraepithelial neoplasia I and II are dysplasias rather than true neoplasias. An image analysis study of factors involved in the progression of cervical lesions.

Image analysis was performed on 40 Feulgen-stained histologic samples and 48 Feulgen-stained cytologic preparations representing normal squamous epithelium and all grades of cervical lesions (from mild dysplasia to invasive carcinoma) in order to characterize the evolutionary progressive changes in cervical epithelial proliferative disease toward malignancy. Quantitative studies included the analysis of proliferative features, differentiation features, nuclear morphology and DNA content. The data obtained on the histologic sections showed that the various features, to a different extent, detected a gradual increase in phenotypic cellular disarrangements related to the progression of the cervical lesions toward malignancy--that is, the modifications to nuclear area, perimeter, DNA content, percentage of nuclei with nucleoli, nuclear/cytoplasmic ratio and percentage of cells with no membrane positivity for soybean agglutinin lectin were progressively greater, moving from normal epithelium and mild dysplasia toward infiltrating carcinoma. In particular, all the morphologic and histochemical features appeared to parallel a diploid reduction and the appearance of aneuploidy. The simultaneous evaluation of proliferation- and differentiation-related features, together with those of nuclear DNA content, showed two main successive preneoplastic lesions: one characterized by an increase in cell turnover without alterations in its organization and another by a true neoplastic disorder. The data obtained on sequential cytologic examinations showed that individual cell changes are detectable and seem basically to be characterized by the appearance of clusters of cells with somatic characteristics not observed in previous cytologic checks. From the results of our study, the cervical intraepithelial neoplasia (CIN) concept appears to be inaccurate. In fact, only CIN III (severe dysplasia/carcinoma in situ) lesions have the morphologic and proliferative alterations of true neoplasia. In contrast, CIN I and some cases of CIN II lesions lack these characteristics and seem to be properly classified as dysplasia, thus avoiding the term neoplasia, implicit in CIN. Moreover, the multivariate study of data sets of features related to the progressive somatic changes, both in histologically and cytologically studied cases, allows us to detect the steps of progression; they are marked by the appearance of cell clusters with qualitatively different phenotypic characters when compared to the cell populations from which they presumably arise. These results seem to provide a further argument against the CIN theory, which stresses the concept that progression is related only to a gradual numerical increase in an initially established phenotype with the characteristics of malignancy.

Biopsy↗

Nerve regeneration through a combined autologous conduit (vein plus acellular muscle grafts).

The authors describe nerve regeneration obtained by using a combined autologous conduit, consisting of a vein plus acellular muscle grafts. The right sciatic nerve of seven Sprague Dawley rats was transected for a length of 2 cm and the gap was filled with 2 cm long femoral vein conduit in which two autologous acellular muscle grafts had been previously inserted. Clinical and electrophysiologic tests were carried out twelve weeks after the surgical procedure. The nerve was then removed and a morphological study, including histologic examination, immunohistochemistry and quantitative analysis, was performed. The left sciatic nerve was also removed and used as a control. Regeneration was observed in the middle and distal parts of the conduit in 5 rats. Nerve conduction velocity ranged between 0 and 14.9 ms(-1). In the distal part the nerves were enclosed by a perineurium thicker than their normal counterpart and in which groups of small axons were surrounded by thin myelin sheaths. Quantitative analysis showed that the operated nerve presented a wide variation of the area of the fascicle and the density of the fibres per area, while the diameter of the axons and myelinated fibres showed only small variation, independent of the size of the fascicle. In conclusion, by using this technique, the authors succeeded in obtaining regeneration of a well formed nerve fascicle.

Animals↗

Microvessel density (MVD) and vascular endothelial growth factor expression (VEGF) in human oral squamous cell carcinoma.

BACKGROUND: Carcinogenesis is thought to be dependent on neovascularization. Vascular endothelial growth factor (VEGF) is a glycoprotein that has the capability of increasing vascular proliferation and permeability. VEGF has been found to be expressed in several different types of tumours and it may contribute to the progression of malignant tumours. Increased microvessel density (MVD) has been described in oral squamous cell carcinoma (OSCC) and seems to be related to patient prognosis. MATERIALS AND METHODS: Fifty-two cases of OSCC were evaluated in the present study. Immunostaining for VEGF and Factor-VIII was performed. The MVD was evaluated in G1, G2 and G3 tumours. RESULTS: The differences between these 3 groups were statistically significant (p = 0.0331). MVD was also evaluated in lymph-node negative and lymph-node positive cases: the differences between these two groups were statistically significant (p < 0.0001). VEGF expression was evaluated in G1, G2 and G3 tumours. The differences between the 3 groups were not statistically significant (p = 0.289), even if an increasing trend in the VEGF positivity was evident from G1 to G3. The difference of VEGF expression between tumours with and without lymph node metastases was not significant (p = 0.196). No correlation was present between intensity of VEGF positivity and histological grading or lymph-node status and between VEGF and MVD. CONCLUSION: Our data showed that MVD was correlated with grading and lymph-node status, while no similar correlation was found for VEGF.

Adult↗

Urothelial papillary lesions. Development of a Bayesian Belief Network for diagnosis and grading.

The diagnosis and grading of urothelial papillary lesions are affected by uncertainties which arise from the fact that the knowledge of histopathology is expressed in descriptive linguistic terms, words and concepts. A Bayesian Belief Network (BBN) was used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependencies between elements in the reasoning sequence. A shallow network was designed and developed with an open-tree topology, consisting of a root node containing four diagnostic alternatives (papilloma, papillary carcinoma grade 1, papillary carcinoma grade 2 and papillary carcinoma grade 3) and eight first-level descendant nodes for the diagnostic features. Six of these nodes were based on cell features and two on the architecture. The results obtained with prototypes of relative likelihood ratios showed that belief in the diagnostic alternatives is very high and that the network can identify papilloma and papillary carcinoma, including their grade, with certainty. In conclusion, a BBN applied to the diagnosis and grading of urothelial papillary lesions is a descriptive classifier which is readily implemented and allows the use of linguistic, fuzzy variables and the accumulation of evidence presented by diagnostic clues.

Bayes Theorem↗

Vascular endothelial growth factor and microvessel density around healthy and failing dental implants.

Inflammatory infiltrate may be important in the evolution of inflammatory processes involving peri-implant tissues. Angiogenesis is an important feature of inflammation and healing, but its role in the development and progression or in the healing of periodontal lesions has not been elucidated. Vascular endothelial growth factor (VEGF) is a potent inducer of endothelial cell proliferation. The aim of the present study was to conduct a comparative immunohistochemical evaluation of VEGF and microvessel density (MVD) in normal keratinized gingiva and in peri-implant soft tissues surrounding failing implants. Fifteen patients participated in this study. Ten biopsies were taken from healthy keratinized gingiva, and 10 were taken from peri-implant soft tissues surrounding failing non-submerged implants. In healthy sites, the endothelial lining cells of the vessels always tested positive for VEGF; also, VEGF intensity was high in most cases. Stromal cells were positive for VEGF in 70% to 90% of samples. The MVD was 60.250 +/- 5.123. In peri-implantitis samples, the cells of the inflammatory infiltrate were positive for VEGF in 80% to 100% of cases, and the VEGF intensity was low in all cases. The stromal cells were positive for VEGF in 90% to 100% of cases, and in most cases the intensity was low. The MVD was 101.800 +/- 11.256. The difference in MVD between healthy sites and peri-implantitis was statistically significant (P = .0158). Expression of VEGF was lower in peri-implantitis samples, and this difference was statistically significant (P = .0373). Because of its extensive presence, VEGF is probably a factor in both the maintenance of periodontal physiology and in the progression of peri-implant inflammatory disease.

Adult↗

Surgical pathology examination of radical prostatectomy specimens. Updated protocol based on the Italian TAP study.

Between January 1996 and June 2000, 192 men with prostate cancer underwent radical retropubic prostatectomy (RP) and bilateral pelvic node dissection in 26 centers participating in the Italian randomized prospective TAP study. The reviewing pathologist evaluated 145 RP specimens. Seventy-five cases had not been treated with total androgen ablation before RP was performed, whereas 70 had been treated for three months. Whole-mount sectioning of the complete radical prostatectomy specimens was adopted in each center for accurately evaluating the pathological stage of prostate cancer and resection limit status. The results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage T2 because of the significant pathological down-staging and decrease in the number of positive margins in the RP specimens. On the basis of the experience acquired through the Italian TAP study and recent publications on prognostic factors in prostate cancer, the original practice protocol for examination of RP specimens removed from patients with carcinoma of the prostate glands was updated.

Androgen Antagonists↗

Evolution of the changes of the ileal pouch mucosa over a long follow-up period.

BACKGROUND/AIMS: The mucosa of the ileal pouch after restorative proctocolectomy develops relevant adaptative changes but the real mechanisms and the evolution over time of these alterations are still unclear. The aims of the present work were to study the distribution of the mucosal changes at different levels in the reservoir and to evaluate the evolution of these alterations over a long follow-up period. METHODOLOGY: The severity of chronic and acute inflammation, villous atrophy, colonic-type mucins production and proliferative index were evaluated in the bioptical specimens from 46 patients (30 males, 16 females, mean age 38 years) with functioning pouch. We compared the histology of the upper pouch mucosa with the lower one. Then we divided the 46 patients into Group A-24 patients with a median follow-up of 11 years (range 9-16); Group B-22 patients with a median follow-up of 4 years (range 2-8), comparing the results from the two groups. Finally we performed a prospective evaluation in the 24 patients who were controlled in 3 subsequent follow-ups (1993-1994, 1996-97, 1999-2000). RESULTS: At the topographic evaluation only the acute inflammation was significantly more pronounced in the lower pouch area (p = 0.031). All the morphological changes showed a trend of greater severity in the group A patients, in particular villous atrophy (p = 0.005) and colonic-like mucins secretion (p = 0.006). At the prospective evaluation, the chronic inflammation showed a significant progressive worsening over time (p = 0.011). CONCLUSIONS: Our experience showed that the transformation of the mucosa represents an "organ" response to the luminal environment and may progress over time.

Adult↗

Proliferating cell nuclear antigen (PCNA) evaluation in the diagnostic quantitative pathology of cribriform adenocarcinoma of the prostate.

The aim of this study was to emphasise the importance of the measurement sites in tumours from the biological point of view. In particular, two distinct aspects regarding locations were investigated for Proliferating Cell Nuclear Antigen (PCNA) expression in the cribriform adenocarcinoma of the prostate as an example. The first aspect was the identification of the most suitable part of the tumour nodule to be analysed, that is, periphery or marginal zone vs central. The second aspect consisted of the precise location of the objects in relation to the histologic pattern and its components, such as the different cell layers in the cribriform pattern. The results obtained showed that the proportion of PCNA-immunostained nuclei in the marginal zone of the tumour decreased from the basal position, or adjacent to the stroma, towards the lumen: 14.40% (standard error, SE, 0.61%) in the basal position, 11.84% (SE 1.30%) in the intermediate and 9.26% (SE 0.66%) in the lumenal position. In the central zone of the tumour the trend of value changes was similar to that obtained in the marginal zone. However, the proportions were lower and the differences statistically significant. In conclusion, the degree of PCNA expression is related to both locations. Thus, adequate information on the biology of the lesions can only be obtained when the precise site of the objects to be evaluated is identified. Otherwise, misleading results about the lesions being measured can be derived.

Adenocarcinoma↗