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Biomedical subjects

R Navone

Publications and source records attributed to R Navone.

At least 19 recordsLinked to original sources
PubMed2004

Prognostic relevance of cell proliferation in head and neck tumors.

Cell proliferative activity has been extensively investigated in head and neck tumors. Ki67/MIB-1 immunostaining, tritiated thymidine or bromodeoxyuridine labeling indices, DNA S-phase fraction, proliferating cell nuclear antigen expression, potential doubling time and analysis of the nucleolar organizer region associated proteins (AgNORs) have shown significant correlation with prognosis in 4806 cases of tumors of the oral cavity, salivary glands, pharynx and larynx. However, this was not observed in 2968 other reported cases. Discrepancies may depend on various factors: the heterogeneity of the series, which include tumors from various anatomic sites and patients treated with different therapy, and the lack of standardization of methods for assessing cell proliferation. Furthermore, none of the methods currently applied can by themselves define the actual proliferative activity, as it depends both on the proportion of cells committed to the cycle (growth fraction) and the speed of the cell cycle. Indeed, the actual proliferative activity of a tumor could well be measured by the equation [PA = Ki67 or MIB-1 scores x AgNORs], as we did in pharyngeal carcinoma. Provided that large and homogeneous series are evaluated by standardized methods, cell proliferative activity can still be regarded as an inexpensive and reliable prognostic factor in head and neck tumors.

Carcinoma, Squamous Cell↗
PubMed2004

[Usefulness of oral exfoliative cytology for the diagnosis of oral squamous dysplasia and carcinoma].

AIM: It is well known that diagnostic oral exfoliative cytology, even if a useful, economical and practical tool in the diagnosis of oral dysplasia and carcinoma, is not yet used so extensively as is cervico-vaginal cytology. METHODS: Exfoliative cytology was used for the diagnosis of oral dysplasia and carcinoma, and the results compared to the histological examination. Cytological smears were taken from 89 patients with oral lesions suspicious for neoplasia (in particular erythro- and leukoplakia and lichen). All patients were also subjected to oral biopsy and histological examination. RESULTS: Out of 89 cases studied, histology showed the presence of an invasive squamous carcinoma in 32, dysplasia in 17, phlogosis in 15 and other types of lesions (2 of which malignant non-epithelial tumours) in 25. The cytological smear was inadequate for diagnosis in 11/89 cases (12.4%). In cytologically adequate and histologically positive cases, cytology confirmed the histological diagnosis of dysplasia and/or carcinoma in 38/45 cases (sensitivity 86.5%, accuracy 89.6%). Moreover, 1 case which was histologically negative at the onset, proved positive at cytology. There were 2 false-positive cytology results (specificity 94.3%, predictive positive value 95.7%). CONCLUSIONS: Despite the small number of cases in the cohort, oral cytology can improve the accuracy of histology, and may be a useful screening tool for the diagnosis of oral neoplasia/dysplasia.

Adult↗
PubMed2002

Papnet-assisted cytological diagnosis intensifies the already marked variability among cytological laboratories.

OBJECTIVE: The main objective was to assess the sensitivity, specificity and reliability of PAPNET-assisted diagnosis in comparison with conventional screening. SETTING: Seven Italian and one English University or Research Institutes, and a random sample of an other 20 Italian Laboratories of the Italian National Health Service (INHS) provided the cervical smears. METHODS: During the training phase every center examined in rotation four sets of slides for a total of 300 representative slides. Afterwards, 900 "positive" slides were added to the 3,100 slides which were collected consecutively without any selection or exclusion. The eight main centers were divided into four couples and each couple of centers examined 775 slides with the PAPNET system, "blindly" to the original diagnosis. An expert cytopathologist (M.A.) of the National Institute of Health (NIH) reassessed 40% of the slides with an original negative diagnosis to evaluate the false negative rate. Two expert NIH cytopathologists (M.A., G.M.) re-examined all slides where a disagreement had been observed between the original and one or both of the study diagnoses. The main analyses concerned the following three main categories: WNL and unsatisfactory for evaluation; ASCUS, AGUS and LSIL; HSIL and carcinoma. A special algorithm was devised to define the reference diagnosis for sensitivity and specificity assessment. RESULTS: Laboratories, even belonging to the same couple, classified as "no review" a very different proportion of slides ranging from 35% to 74%. The index of kappa agreement between the members of couples examining the same sets of slides was low or very low, ranging from 0.30 to 0.03. The sensitivity of the review classification was particularly low in some laboratories. Surprisingly, only a small correlation was observed between the sensitivity of the review classification and the proportion of slides classified as "review". The "tentative" diagnosis on PAPNET tiles of the "review" slides was almost as reliable as the microscopic diagnosis. In the overall performance, there were many significant differences among the eight laboratories. The best laboratory had a sensitivity of 95% and a specificity of 96%. At least three laboratories displayed unacceptably low sensitivity and one a very low specificity. CONCLUSION: Altogether these results seem to confirm that there are wide differences among cytological laboratories per se, and that these differences are intensified by the use of an instrument like PAPNET. The huge variation in performance may be explained by differences in basic skills and by different training, but it is difficult to understand exactly what could have been done to reduce it.

Autoanalysis↗
PubMed2001

Biochemical and histological evaluation of human synovial-like membrane around failed total hip replacement prostheses during in vitro mechanical loading.

The biochemical role of the synovial-like membrane formed at the interface of eight aseptic failed total hip prosthesis has been investigated during in vitro mechanical loading. The study was carried out on four membranes from cemented prosthesis and four titanium alloy uncemented ones. Intermittent positive pressure leading to 20% deformation of the membrane (100 g/cm(2))was applied to the membrane fragments in cycles (300 cycles/15 min) repeated three times at thirty minutes intervals in which interleukin-6 (IL6), prostaglandin-E2 (PGE2) and interleukin-1beta (IL1beta) levels were quantified both in culture media and in tissue extracts. Histological, morphometrical and immunohistochemical studies were also carried out on the same membranes. Mechanical stress evidenced an increase in the release of the examined cytokines both in cemented and uncemented prosthesis tissues; particularly evident was IL6 trend of increase from cemented prosthesis and IL1beta result from uncemented ones. Histomorphological and immunohistochemical data revealed no differences between membranes obtained from cemented and uncemented prosthesis as to cell proliferation, fibrosis, macrophages lymphocytes B and T population, vessels and nervous fibers. The results indicate that mechanical stress plays a fundamental role in increasing membrane production and release of cytokines known as bone-resorbing agents. Furthermore, the histologic finding of synovial-like membrane with the same histomorphological and immunohistochemical findings but with different biochemical response to mechanical stimulation, suggests that cells involved in the production and release of the considered mediators might have different strain behavior by different development conditions (previous contact with PMMA).

Journal Article↗
PubMed2001

Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder.

We investigated the expression of oncogenes p53, c-erbB-2, and bcl-2 and cell proliferative activity in 62 newly diagnosed superficial pTa papillary bladder tumors. Based on the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications, 19 were urothelial neoplasias of low malignant potential (LMP) and 43 low-grade (grade 1) papillary carcinomas. All the patients underwent transurethral resection and were followed up to 97 months; 42 had recurrences. Initial biopsies were tested for p53, c-erbB-2, and bcl-2 proteins using DO7, CB11, and bcl-2 124 monoclonal antibodies. Cell proliferation was assessed by MIB-1 mAb and mitotic count. LMP had significantly lower MIB-1 (p = 0.002) and p53 immunopositivity (p = 0.03), mitotic count (p = 0.006), and recurrence rates (p = 0.04) than did grade 1 cases, whereas no difference was observed for c-erbB-2 and bcl-2 expression. The median disease-free survival for LMP was 76 months but only 15 months for grade 1 cases (p = 0.002). Although the cohort is small, the results indicate that the distinction between LMP and low-grade (grade 1) papillary urothelial neoplasias, as proposed by the 1998 WHO/ISUP and 1999 WHO classifications, reflects different biologic activity and clinical behavior; however, a long-term follow-up is advisable also for patients with LMP.

Adult↗
PubMed2000

Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells.

Systemic sclerosis is an autoimmune disease characterized by immunological and vascular abnormalities. Autoantibodies against intracellular antigens are associated with particular clinical features of the disease, whereas autoantibodies against cell surface antigens may be pathogenic by inducing endothelial cell damage, considered the primary event in the pathogenesis of the disease. Latent human cytomegalovirus infection may contribute to progression of systemic sclerosis through its ability to infect endothelial cells; however, direct links between human cytomegalovirus infection and systemic sclerosis are still lacking. Molecular mimicry is one of the mechanisms that account for the link between infection and autoimmunity. Here we have identified an immunodominant peptide using systemic sclerosis serum screening of a random peptide library; such peptide shares homology with autoantigens and with the human cytomegalovirus late protein UL94 (ref. 9). Immunoglobulin G antibodies against the peptide affinity-purified from the sera of patients with systemic sclerosis specifically recognized the viral product and autoantigens; moreover, such antibodies induced endothelial cell apoptosis through specific interaction with the cell surface integrin-NAG-2 protein complex. Our results provide evidence that antibodies against human cytomegalovirus cause apoptosis of endothelial cells, considered the initial pathogenic event of systemic sclerosis, and indicate a previously unknown mechanism for the etiological link between human cytomegalovirus infection and autoimmunity.

Apoptosis↗
PubMed1999

Defective recovery and severe renal damage after acute hemolysis in hemopexin-deficient mice.

Hemopexin (Hx) is a plasma glycoprotein mainly expressed in liver and, less abundantly, in the central and peripheral nervous systems. Hx has a high binding affinity with heme and is considered to be a major transport vehicle of heme into the liver, thus preventing both heme-catalyzed oxidative damage and heme-bound iron loss. To determine the physiologic relevance of heme-Hx complex formation, Hx-deficient mice were generated by homologous recombination in embryonic stem (ES) cells. The Hx-deficient mice were viable and fertile. Their plasma iron level and blood parameters were comparable to those of control mice and they showed no evidence of tissue lesions caused by oxidative damage or abnormal iron deposits. Moreover, they were sensitive to acute hemolysis, as are wild-type mice. Nevertheless, Hx-null mice recovered more slowly after hemolysis and were seen to have more severe renal damage than controls. After hemolytic stimulus, Hx-deficient mice presented prolonged hemoglobinuria with a higher kidney iron load and higher lipid peroxidation than control mice. Moreover, Hx-null mice showed altered posthemolysis haptoglobin (Hp) turnover in as much as Hp persisted in the circulation after hemolytic stimulus. These data indicate that, although Hx is not crucial either for iron metabolism or as a protection against oxidative stress under physiologic conditions, it does play an important protective role after hemolytic processes.

Animals↗
PubMed1998

Histochemical and morphometric observations on the new tissue formed around mammary expanders coated with pyrolytic carbon.

The authors investigated tissue reaction around implanted silicone expanders, focusing on clinical morphological and morphometrical aspects. For use in breast reconstruction in post mastectomy patients, the surface of a medical-grade silicone elastomer was modified, without changing its bulk properties, by the addition of a pyrolytic carbon film. The presence of lipophagy, the number of foreign-body giant cells of histiocytic origin, and the number of MIB-1 positive nuclei (an index of proliferation for the reactive stromal population) were all seen to be influenced by the pyrolytic carbon coating. Indeed, all these parameters were lower in the membrane formed around Carbofilm TM-coated expanders, thus demonstrating the effective protective properties of pyrolytic carbon coating.

Adult↗
PubMed1997

Risk groups of myeloma patients by histologic pattern and proliferative activity.

We investigated the histologic pattern and the cell proliferative activity of myeloma cells by the analysis of the nucleolar organizer regions (AgNORs) in bone marrow biopsy specimens from 150 multiple myelomas at diagnosis. The objective was an attempt to define risk groups of myeloma patients. On univariate analysis, the percentage of bone marrow plasma cells (BMPC%), the pattern of infiltration, the degree of plasma cell (PC) atypia, the marrow fibrosis, and the number of AgNOR/PC were correlated with survival time. On multivariate analysis, only AgNOR counts and pattern of infiltration retained independent prognostic significance. At 4-year followup, all patients with BMPC% < or = 20, interstitial pattern of invasion, and well-differentiated (G1) PC plus AgNOR/cell < or = 3.32 were alive, while no patient with BMPC% >50, diffuse pattern of infiltration, and poorly differentiated (G3) PC plus AgNOR/cell >5.15 survived (p < 0.0001). In conclusion, the histologic pattern and proliferative activity of myeloma cells, evaluated by AgNOR counts, are reliable predictors of survival in myeloma. Both parameters can be easily assessed in the same biopsy specimen, are reproducible, and permit identification of a group of patients with favourable outcome at 4-year followup. Thus, bone marrow biopsy should always be included in the diagnostic procedures for myeloma patients.

Adult↗
PubMed1995

A method for histomorphometric characterization of a peri-implantar new formed tissue to biomaterials.

The spatial distribution and concentration of distinct cellular elements are of interest in the evaluation of the biological reaction to implant materials, the so called biomaterials. We present a method, based on a computer assisted cell-counting program, developed to quantify the soft tissue reaction to implanted material. Five pseudomembranes formed around silicone skin expanders were studied; they were subjected to histological immunohistochemical and histomorphometrical investigation. This quantitative approach overcomes weakness due to the subjectivity of the observers and offers new possibilities when assaying the local tissue compatibility; moreover, it shows a good applicability to a wide variety of implant materials.

Adult↗
PubMed1994

Cell proliferation indices, morphometry and DNA flow cytometry provide objective criteria for distinguishing low and high grade bladder carcinomas.

Argyrophilic nucleolar organizer region (Ag-NOR) analysis, proliferating cell nuclear antigen (PC-NA/PC10) and MIB-1 immunohistochemistry, nuclear morphometry and DNA flow cytometry have been performed on formalin-fixed, paraffin-embedded biopsies from 50 patients with transitional cell carcinoma of the urinary bladder. The mean AgNOR count was 6.01 for the 17 grade 1 (G1), 7.59 for the 21 G2 and 13.33 for the 12 G3 carcinomas (p < 0.001). The mean PCNA score was 15.03% for G1, 24.04% for G2 and 40.01% for G3 cases (p < 0.001). The mean MIB-1 score was 11.31% for G1, 17.09% for G2 and 34.47% for G3 carcinomas (p < 0.001). The mean nuclear area was 35.53 microns2 for G1, 38.65 microns2 for G2 and 83.62 microns2 for G3 cases (p < 0.001). Aneuploidy rates were significantly higher (91.7%) in G3 than in G2 (42.9%, p < 0.01) or G1 cases (47.1%, p < 0.05) but not different for G1 versus G2 cases (p = 0.94). While many overlaps of values were seen between G1 and G2 tumours, no overlaps were found between G3 and G1/G2 tumours. Significant differences of values were also found between pTa and invasive tumours (p < 0.0001 for AgNOR count and PCNA score; p < 0.001 for MIB-1 score and mean nuclear area; p < 0.01 for DNA ploidy); however many overlaps were seen. Our findings indicate that the quantitative parameters obtained with different methods are associated with histological grade of bladder urotheliomas and may improve the grading reproducibility. In addition, the absence of overlaps between G3 and G2/G1 carcinomas supports the tendency to classify bladder urotheliomas in only two categories of malignancy.

Aneuploidy↗
PubMed1993

Antineoblastic activity of antioxidant vitamins: the role of folic acid in the prevention of cervical dysplasia.

The authors made a study on 90 patients affected by various degrees of uterine cervix dysplasia searching for folic acid plasmatic concentrations. The team members affected by CIN have been compared with a test team consisting of women with normal pap-test and vaginoscopy. The study proved that the average levels of folic acids have significantly decreased in cases of dysplasia compared with the test team. These results allow stating that low folic acid plasmatic concentrations may be associated with cervix neoplasms development.

Adult↗
PubMed1993

Danazol in the treatment of endometrial hyperplasia.

The paper reports the results of a study performed in 62 menorrhagic women with endometrial hyperplasia treated with Danazol. The efficacy and tolerability of the above drug was found to be satisfactory.

Danazol↗
PubMed1992

Bone marrow histopathology and prognosis in malignant lymphomas.

Bone marrow trephine biopsies of patients with non-Hodgkin's malignant lymphomas (ML), followed for at least 4 years, were investigated using univariate and multivariate survival analyses to detect which anagraphic data and histomorphologic medullary patterns before therapy were related to the prognosis. In 234 ML (146 low grade, 88 high grade), univariate analysis showed that survival was reduced by bone marrow involvement, absence of reactive lymphoid nodules, and low marrow cellularity. Moreover, in low-grade ML, patients 50 years or older and showing absence of myeloid hyperplasia, excess of hemosiderin and mast cell hyperplasia had significantly lower-survival rates. The prognostic relevance of these parameters did not change when cases without marrow involvement were separately analyzed. Multivariate analysis showed that, besides marrow involvement, age and myeloid hyperplasia had significant prognostic importance in low-grade ML, and lymphoid nodules in high-grade ML. Our data confirm the value of bone marrow histopathology in ML and indicate that the prognosis is related not only to medullary involvement but also to the morphology of the uninvolved marrow.

Adult↗