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C Bartoli

Publications and source records attributed to C Bartoli.

At least 37 records · Page 2Linked to original sources

Effects of oral administration of heparan sulphate in the rat remnant kidney model.

Heparins are useful for the protection of residual renal function in several nephropathies, but the anticoagulant action and the need of parenteral administration are two main drawbacks limiting their use in chronic renal failure patients. Heparan sulphate (HS) is a heparin-like mucopolysaccharide devoid of anticoagulant action and active orally. In this study, the effects of HS oral administration have been evaluated in 18 subtotally nephrectomized rats;18 untreated remnant kidney rats served as control. No mortality was observed in the HS-treated rats, whereas in the control rats the survival rate was 72.2% at 18 weeks. At the end of the study, HS-treated rats showed lower urinary protein excretion (44 +/- 22 vs. 80 +/- 54 mg/24 h, p < 0.01), lower urea plasma levels (75 +/- 34 vs. 134 +/- 105 mg/dl, p < 0.01) and higher creatinine clearance (66 +/- 15 vs. 47 +/- 21 ml/min. 10(2), p < 0.05) than control rats. Remnant kidney weight (2.3 +/- 1.1 vs. 1.3 +/- 0.2 g, p < 0.01) and heart weight (1.3 +/- 0.2 vs. 1.1 +/- 0.1 g, p < 0.05) were greater in the control than in the HS-treated rats, as well as the systemic blood pressure values (167 +/- 19 vs. 115 +/- 32 mm Hg, respectively, p < 0.001). The remnant kidney histological examination in the HS-treated rats showed a lower prevalence of glomerular sclerosis, mesangial proliferation, and a much less evident tubulointerstitial damage than in controls. The antiproliferative and anti-inflammatory actions of HS together with its protective action on the endothelium are the putative mechanisms that could account for our findings. In conclusion, the present study supports evidence of an antiproteinuric and a renoprotective effect of orally administered HS in subtotally nephrectomized rats. This is in keeping with the well-known effects exerted also by other heparins, but the effectiveness of an orally available heparin-like product in this animal model could suggest the possibility of a clinical use also in progressing chronic renal failure patients.

Administration, Oral↗

Importance of the level of axillary involvement in relation to traditional variables in the prognosis of breast cancer.

Survival in breast cancer correlates with the presence of metastatic lymph nodes, so that removal and pathological examination of the axillary nodes provides the most important prognostic information and basis for planning subsequent therapy. However as the size of primary tumours at diagnosis is decreasing, the likelihood of axillary involvement is also declining, so that the indications for axillary dissection are undergoing radical revision. To definitively establish the value of removing all three axillary lymph node levels (as defined by Berg) in node positive breast cancer, retrospective analysis of a large series receiving complete dissection was carried out. consecutive breast cancer patients (n=1003) with positive axillary nodes were analyzed: all received identical axillary treatment and the three levels were tagged with metal disks to facilitate recognition and pathological examination. Follow-up (mean 97 months) was exceptionally complete. The length of disease-free and overall survival were taken as the primary endpoints. The variables considered in the statistical analysis were tumour size, number of metastatic nodes, axillary invasion by level (the three classic levels), perilymphnodal invasion and age. By univariate analysis, overall and disease-free survival decreased significantly as tumour diameter, number of involved lymph nodes, and involvement by axillary level increased. Multivariate analysis assessing the relative importance of these variables when all were considered together found that they were all important independent predictive factors for survival. This study confirms the importance of tumour size and number of metastatic axillary nodes as predictors of outcome in breast cancer. In addition, the level of axillary invasion as a third independent factor of equal importance to the established indicators was identified. When axillary dissection is performed it should be complete, and all three Berg levels tagged separately, so that involvement by level can be ascertained. This provides additional important prognostic information on which to base subsequent treatment decisions.

Adult↗

[Expression of adhesion molecules in idiopathic inflammatory myopathies. Immunohistochemical study of 17 cases].

We investigated the immunohistochemical expression of endothelial cell adhesion molecules in 17 cases of idiopathic inflammatory myopathies. The present study revealed: 1) a constitutive expression of ICAM-1, ICAM-2 and PECAM-1, but not VCAM-1, LFA-3 and E-selectin, on endothelial cells in normal muscles; 2) a modification of cell adhesion molecules expression in idiopathic inflammatory myopathies with an increased expression of the expressed molecules constitutively; an expression of LFA-3 and VCAM-1 on capillary endothelial cells in polymyositis/inclusion body myositis, these molecules being only observed on endothelial cells of some arterioles in dermatomyositis; 3) an expression of all these molecules on inflammatory cells in inflammatory myopathies. In dermatomyositis, the expression of ICAM-1 and VCAM-1, predominated on mononuclear cells located near vessels. In polymyositis/inclusion body myositis, a strong expression of ICAM-1, VCAM-1 and LFA-3 was present on inflammatory cells invading non necrotic muscle fibers; 4) absence of E-selectin on endothelial and inflammatory cells in all cases.

Cell Adhesion Molecules↗

Small melanomas: a clinical study on 270 consecutive cases of cutaneous melanoma.

The ABCD (asymmetry, border, colour, dimension) criteria represent a commonly used clinical guide for the diagnosis of early cutaneous melanoma (CM). This guide stipulates that CMs usually are more than 6 mm in diameter. The purpose of this retrospective study was to establish the frequency of occurrence of small (< or =6 mm) melanomas in a clinical context. Our series consisted of 270 consecutive CMs (39 in situ and 231 invasive) in 267 patients. Of these 270 lesions, 47 (17%) were small lesions, ranging from 2 to 6 mm in maximum linear extent, with a median value of 5 mm. Of these small lesions, 14 were in situ and 33 Invasive CMs. The median thickness of the 33 small invasive lesions was 0.31 mm. The clinical features of CMs were sufficiently distinctive to suggest a diagnosis of CM in half of the cases, irrespective of the invasiveness or not of the lesions. Dermatoscopy was performed on 36 of the small lesions and achieved a correct diagnosis in 72% of the cases. The combination of simple visual examination with dermatoscopy allowed a higher rate of recognition (86%) than when the two methods were considered separately. Results of our study show that small CMs represent a considerable clinical subset of all CMs. Clinicians must be aware of this fact in their diagnostic activity.

Adult↗

Spectrophotometric imaging of cutaneous pigmented lesions: discriminant analysis, optical properties and histological characteristics.

Reflectance imaging spectroscopy at 17 selected wavelengths in the range 420-1040 nm has been applied as a method to discriminate melanoma from other pigmented cutaneous lesions. Reflectance images are acquired for 18 primary melanomas and 33 benign naevi in 44 patients. From each spectral image, four parameters related to lesion reflectance (mean value of reflectance, variegation, area and roundness of lesion) are derived at the corresponding wavelength. A discriminant function between the two groups of lesions is determined by using a stepwise discriminant analysis, resulting in a test with a sensitivity of 89% and a specificity of 88%. Since analyses are carried out on the same data set used to obtain the discriminant function, our results should be interpreted with caution. Moreover, in an attempt to assign a physical and/or physiological meaning to the lesion image descriptors, some histological features (i.e., lesion thickness, degree and uniformity of pigmentation) have also been analysed, and their correlations with the image descriptors investigated. Neither degree nor uniformity of pigmentation can fully explain the variations observed in the lesion image descriptors. It is hypothesized that the presence of pathologically related biological components such as lymphocytes and highly aggregated cells may play an important role. The actual performance of the spectrophotometric imaging system should be proven in an additional, unselected number of cases before being used as a diagnostic adjunct for physicians in the clinical detection of melanoma.

Diagnosis, Differential↗

Detection of TP53 mutation, loss of heterozygosity and DNA content in fine-needle aspirates of breast carcinoma.

Recent preclinical and clinical data suggest that TP53 status and TP53 mutations may be important in determining tumour aggressiveness and therapy response. In this study we investigate the feasibility of a structural and quantitative analysis of TP53 on fine-needle aspiration (FNA) material obtained from 31 consecutive female patients with breast carcinoma, enrolled in a primary chemotherapy protocol. Tumours were screened for p53 protein overexpression and TP53 mutations (exons 5-8) using immunocytochemistry, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing analyses, and finally using fluorescence in situ hybridization (FISH) analysis. Positive nuclear staining was identified in six cases whereas mutations were detected in nine. Although the immunoreactive pattern fitted fully with the characterized TP53 mutation type, the considerable number of null p53 mutations (i.e. four) coupled with the lack of information regarding the localization of TP53 mutations make immunocytochemistry an inadequate indicator of TP53 function deregulation. Combining molecular and FISH analyses, we detected three cases with TP53 deletion and one case with deletion and mutation. Finally, DNA static-image analysis performed on 29 cases showed aneuploidy in 26 cases, which included all TP53-mutated cases. The present results show that FNA may assist clinical decisions by allowing the evaluation of a variety of biological parameters relevant for prognosis and treatment planning.

Adult↗

Local expression of cytokines in idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), and inclusion body myositis (IBM), are regarded as autoimmune diseases. They are characterized by chronic lymphocytic and macrophagic infiltration in muscle tissue. Of particular importance in understanding the immune response to IIM is the specific pattern of locally produced cytokines. Frozen muscle tissues from IIM (5 DM, 3 PM, and 1 IBM) were used to investigate the cytokine responses. The RT-PCR technique was instrumental to determine the pattern of expression of pro-inflammatory (IL-1 beta, IL-6, TNF-alpha), Th1 (IFN-gamma IL-2), and Th2 (IL-4) cytokines. Immunohistochemistry was also used to localize morphologically IFN-gamma and IL-4. Our results show that pro-inflammatory cytokines and Th1 cytokines are mainly expressed in IIM. The accumulation of mononuclear inflammatory cells and the inflammatory syndrome in IIM are probably related in part to the production of pro-inflammatory cytokines. Moreover, the pattern of local cytokine expression is consistent with a Th1 immune response related to autoimmune diseases.

Cytokines↗

Estrogen-receptor status of patients who underwent mastectomy for breast cancer with a disease-free interval of not less than 8 years.

The authors present a series of 1,226 patients who underwent total or partial mastectomy for breast cancer, who for a period of no less than 8 years from surgery did not have a relapse or relapsed only after 8 years. The patients were evaluated for estrogen-receptor (ER) content of the primary tumor. In the group of 237 patients who relapsed, only 8.8% (21 of 237) were ER negative; in the group of 989 patients without a relapse, 24.1% (239 of 989) were ER negative. The difference was significant (p < 0.001). Therefore, the absence of hormone receptors (ER negative) indicates a favorable prognosis after a period of 8 years. For comparison, ER content in the group of patients who relapsed before 8 years was evaluated; the results showed a different prognosis from the ER-negative patients in this group. Because the behavior of ER-negative tumors in the cancer-affected breast is similar to that of non-hormone-dependent carcinomas arising in other parts of the body (which generally are considered cured after a long disease-free interval from surgery), we conclude that this repudiates the theory that confers to breast cancer the character of a systemic disease.

Breast Neoplasms↗

Expression of peptide-23/pancreatitis-associated protein and Reg genes in human pituitary and adenomas: comparison with other fetal and adult human tissues.

Peptide 23, the rat homolog of the human pancreatitis-associated protein (PAP)/hepatocarcinoma-intestine-pancreas (HIP) protein, has been identified in primary culture of rat pituitary cells. Its secretion was shown to be stimulated by GH-releasing factor and inhibited by somatostatin in a similar fashion to GH. This observation led the researchers to speculate that peptide 23 does have a physiological hormonal role. We tested this hypothesis by screening by RT-PCR reactions the expression of the PAP/HIP gene in several human pituitary adenomas, especially GH-producing adenomas. Our results show a weak expression of the PAP/HIP gene in the pituitary gland and in most of the tumors, but independent of their origin. The significant homology of the PAP/HIP gene to the Reg gene family prompted us to study in the same pituitary adenomas the presence of the related Reg genes. Reg expression was never observed in the adenomas tested or in the pituitary gland. In contrast, the RegL transcript was observed in pituitary gland and in some subtypes of adenomas. We then extended our work to normal adults and developing human tissues to compare the expression patterns of the PAP/Reg gene family. We observed the presence of the PAP/HIP transcript in each tissue tested. In contrast, the Reg gene was expressed only in fetal pancreas and in some adult tissues, whereas the RegL gene was expressed not only in fetal pancreas but also in fetal colon and brain as well as some adult tissues. In conclusion, our results show that all of the human fetal and adult tissues examined express at least one of the different transcripts of the PAP/Reg family, suggesting that the regulation of these homologous genes is coordinately controlled.

Acute-Phase Proteins↗

Effects of short-term pre-operative tamoxifen on steroid receptor and Ki-67 expression in primary breast cancer: an immunocytochemical study.

The effects of the short-term pre-operative administration of tamoxifen (TAM, 20 mg once daily) on the tumor levels of steroid receptors and the nuclear proliferation Ki-67 antigen, were investigated in 32 elderly patients with hormone-sensitive, operable primary breast cancer by means of fine-needle aspiration biopsy (FNAB). The FNAB smears before (pre-TAM) and after six weeks of treatment (post-TAM) were stained immunocytochemically in order to obtain an H-score for steroid receptors, and the percentage of cellular nuclei containing Ki-67. The mean oestrogen receptor (ER) score between the pre- and post-TAM specimens fell from 181.2 9.7 ( SEM) to 148.1 7.9 (Wilcoxon's matched-pairs signed-rank test, p=0. 01) and there was also a significant decrease in both the mean progesterone receptor (PgR) score (178.4 10.6 vs 148.5 10.6; p=0.01) and mean Ki-67 index (8.2% 1.2 vs 4.9% 0.9; p=0.0002). The reliability of FNAB as a sampling method was checked by comparing the results of the immunocytochemical assay (ICA) of the post-TAM biopsies with those of the immunohistochemical assay (IHA) of the corresponding excised tumors. There was a positive correlation between the ICA and IHA scores: ER (Spearman's correlation coefficient, rho=0.66, p<0.001), PgR (rho=0.84, p<0.001) and Ki-67 (rho=0.96, p<0.001). We conclude that the sequential use of FNAB is a reliable means of assessing the behaviour of within-tumor biomarkers during endocrine therapy.

Aged↗

Breast infection due to Dirofilaria repens: report of two new Italian cases and revision of the literature.

Two new cases of human dirofilariasis, occurred in women aged 46 and 52 years, respectively, both living in Lombardy (Northern Italy) are reported. Dirofilaria repens nematodes were localised in the breast in both cases. In one of them the parasite was accidentally extracted while the patient underwent a fine needle aspirate. The international literature records 30 cases of breast Dirofilariasis. Except in rare cases, the parasite was located subcutaneously in the breast, and nested in a nodule. The clinical diagnoses were consistently wrong, the nodule being diagnosed as a suspected tumor of the breast.

Animals↗

Hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine. Synthesis of the carrier and pharmacological properties of the conjugate.

BACKGROUND/AIMS: The hepatotropic conjugate of adenine arabinoside monophosphate with lactosaminated poly-L-lysine (L-Poly(Lys)) must have a high solubility in order to be injected in a small volume compatible with the intramuscular route. In this paper the molecular weights of Poly(Lys) which allowed the synthesis of conjugates with the properties of high solubility and limited loss by the kidney were determined and a procedure for obtaining Poly(Lys) preparations with the required range of polymerization has been described. METHODS: Conjugates were prepared using Poly(Lys) of different molecular weights obtained by the procedure described here or purchased from a commercial source. Their solubility and renal loss in mice was determined. RESULTS: Poly(Lys) with molecular weights ranging from 45,000 and 65,000 Da guarantees high solubility and low renal elimination of the conjugates. Conjugate preparations with these properties, intramuscularly administered to woodchuck hepatitis virus-infected woodchucks for 37 days at a daily dose of 5.8 mg/kg exerted a strong antiviral activity. These preparations were devoid of acute toxicity in rat and caused no toxic effects when injected intramuscularly daily for 28 days at a dose ten times higher than that active in woodchucks. CONCLUSIONS: The results support the possibility of a clinical use of L-Poly(Lys) to obtain liver targeting of adenine arabinoside monophosphate for the treatment of chronic hepatitis B virus infection.

Amino Sugars↗

The minimal effective exemestane dose for endocrine activity in advanced breast cancer.

Phase I studies have demonstrated that exemestane, an irreversible oral aromatase inhibitor, is able to suppress circulating oestrogen levels. In our previous experience, doses ranging from 2.5 to 25 mg induced a similar suppression of oestrogens. The aim of this study was to identify the minimum effective exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5 mg, in double-blind conditions. Oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate serum levels were evaluated from the first day of treatment to the 7th, 14th, 28th and 56th day. Serum E1, E2 and E1S levels were suppressed by all doses starting from day 7; the degree of inhibition versus baseline was 25 up to 72% for E1, 30 up to 62% for E2 and 16 up to 52% for E1S, with higher doses achieving greater suppression; these changes were maintained over time. A significant increase in FSH and LH levels was observed for all doses. Treatment tolerability was satisfactory. The endocrine effects of exemestane appear to be dose related and 0.5 and 1 mg are ineffective for adequately suppressing circulating oestrogens.

Aged↗

Ambulatory narrow excision for thin melanoma (< or = 2 mm): results of a prospective study.

Although narrow surgical excision may be sufficient for thin melanoma, questions remain concerning how narrow the excision should be and how it should be related to tumour thickness. To address these issues, a group of 168 consecutive patients with primary invasive melanoma up to 2 mm thick underwent ambulatory surgery with excision margins of 1 cm. 40 (24%) of these patients had lesions thicker than 1 mm. In a median follow-up of 5 years, 11 patients relapsed and 3 developed second malignancies. The crude cumulative incidence of regional and distant metastases were, respectively, 5.6% and 1.5%. No local isolated recurrence was observed, indicating that ambulatory narrow excision is justified for melanoma up to 2 mm thick.

Ambulatory Surgical Procedures↗

PCR analysis of IgH and BCL2 gene rearrangement in the diagnosis of follicular lymphoma in lymph node fine-needle aspiration. A critical appraisal.

In order to improve the cytomorphologic diagnosis of malignant lymphoma on lymph node fine-needle aspiration (FNA), and to make a confident discrimination between low-grade follicular non-Hodgkin's lymphoma (NHL) and lymphoid hyperplasia, polymerase chain reaction (PCR) analysis was performed of the Ig CDR3 region and BCL2 breakpoint region in 25 nonselected cases of malignant lymphoma (17 NHL and 8 Hodgkin's disease [HD]) with histologic control, and 22 cases of lymph nodal hyperplasia with histologic and/or clinical control. Among lymphomas, IgH monoclonality was detected in 7 (77%) of 9 NHLs and BCL2 rearrangement in 3 (17.6%) of 17 NHLs, all of which were follicular centroblastic-centrocytic (FCBCC). Three BCL2/JH negative FCBCC cases were monoclonal for CDR3. Neither IgH monoclonality nor BCL2 rearrangement were found in HD. Among cytologically diagnosed lymphoid hyperplasias, one IgH polyclonal case was considered false-negative, being histologically diagnosed as lymphoplasmacytic NHL on the subsequent excisional biopsy. Another 4 cases (2 BCL2 rearranged and 2 monoclonal for IgH) were considered false-positive on the basis of histologic features or clinical control. These data indicate that the combined PCR analysis of IgH and BCL2 rearrangements can confirm a cytologic diagnosis of lymphoma in FNAs while, due to the occurrence of both false-positive and false-negative results, it is of limited value in the distinction between follicular lymphoma and lymphoid hyperplasia without morphologic or clinical support.

Biopsy, Needle↗

Sequential Adriamycin and CMF in Metastatic Breast Cancer.

PURPOSE: To evaluate the clinical activity of a sequential treatment with Adriamycin followed by CMF (cyclophosphamide, methotrexate, fluorouracil) and the relative therapeutic contribution of the two drug regimens given at full conventional doses in metastatic breast cancer. PATIENTS AND METHODS: From August 1990 to February 1993, 44 patients with advanced breast cancer previously untreated with chemotherapy entered the study. Treatment consisted of the intravenous administration of Adriamycin (75 mg/m&sup2; on day 1 every three weeks) for four cycles followed by intravenous CMF (cyclophosphamide, 600 mg/m&sup2;; methotrexate, 40 mg/m&sup2;; fluorouracil 600 mg/m&sup2;) on days 1 and 8 every four weeks for four total courses. RESULTS: In 41 evaluable patients, four cycles of full-dose Adriamycin were able to achieve an overall response rate of 75%, including 17% complete remissions. Four cycles of CMF administered after Adriamycin were able to increase tumor response in 64% of evaluable cases. At the end of the sequential treatment program, 78% of 41 patients achieved an objective remission and in 30% of them a clinical complete response was documented. Main side effects, i.e., leukopenia and gastrointestinal disturbances, were moderate and short-lasting. One patient died because of acute myocardial infarction. CONCLUSION: In untreated metastatic breast cancer patients, the sequential administration of Adriamycin and CMF is highly effective at the expense of a moderate toxicity profile that allows high-dose intensity of both drug regimens. CMF treatment after upfront Adriamycin is able to exert a further therapeutic advantage.

Journal Article↗

Clinical diagnosis and therapy of cutaneous melanoma in situ.

BACKGROUND: The frequency of in situ melanoma is increasing, and it is often diagnosed fortuitously by histology. METHODS: We retrospectively reviewed 121 melanomas in situ in 113 patients with the aim of identifying the clinical features of, and optimal surgical treatment for this cutaneous malignancy. Treatment was limited surgery with 3 mm margins of excision in 69 cases (57%) and wider margins of excision (more than 3 mm) in 52 cases (43%). The lesions had a median diameter of 1 cm (range, 2-35 mm) and were generally macular (92% of cases) asymmetric (87%), with an irregular border (88%) and nonuniform pigmentation (98%), usually in shades of brown (41%) and black (48%). These features had permitted a clinical diagnosis of melanoma or suspected melanoma in 62% of cases and of doubtful nevus in an additional 18% of cases. RESULTS: At a median follow-up of 4 years, there were six local recurrences (three treated by limited surgery and three by wider excision), all in situ melanomas. CONCLUSIONS: The typical clinical features of melanoma in situ, which are similar to those of early invasive melanoma, are usually sufficiently distinctive to suggest the clinical diagnosis of melanoma or suspected melanoma. Except for large size and superficially extended lesions (larger than 2 cm), adequate treatment is excision with 3 mm margins, although larger lesions (larger then 2 cm) may have an appreciable incidence of local recurrence.

Aged↗