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Biomedical subjects

S Zanardi

Publications and source records attributed to S Zanardi.

At least 37 records · Page 2Linked to original sources

The role of drugs, particularly oral contraceptives, in triggering thrombosis in congenital defects of coagulation inhibitors: a study of six patients.

It is well established that pregnancy and puerperium, surgery and trauma may often trigger thrombotic events even in the normal population. On the other hand, patients with congenital deficiency of clotting inhibitors may develop spontaneous thrombotic episodes, although they become often symptomatic when one of the above-mentioned triggering factors is present. We found this to be true in 40 out of 81 symptomatic patients with congenital defects of coagulation inhibitors. In six (15%) of these cases medications (mainly oral contraceptives) triggered the thrombotic event. The incidence of pharmacological factors as a cause of thrombosis is commonly maintained to be low. This study indicates that this is not so and underlines the potential importance of drugs, particularly oral contraceptives, in the pathogenesis of thrombotic events in patients with congenital defects of clotting inhibitors.

Adult↗

Evaluation of mucinous-like cancer antigen (MCA) in women with breast disease: preliminary results.

Mucinous-like cancer antigen (MCA) is a substance which is recognized by a novel monoclonal antibody, designated b12, when directed against a mixture of human breast cancer cell lines. The present study was carried out by means of a solid phase enzyme immuno assay to determine, prior to treatment, circulating levels of MCA in 131 women with malignant and in 99 with benign breast diseases (BBD). Statistical analysis did not reveal any significant difference between MCA values in healthy controls vs. BBD patients. By contrast, MCA levels were significantly higher in cancer patients as compared to the other groups (p less than 0.001). In particular, patients with metastatic disease had the highest MCA concentrations. The sensitivity and specificity of the test were 25.5 and 97.5%, respectively. The characteristics of MCA (low sensitivity, high specificity) encourage its evaluation as an indicator of tumor burden.

Adolescent↗

Identification of breast cyst subpopulations: biochemical and morphological features.

The concentration of insulin-like growth factor-I (IGF-I) and its relationship to other biochemical parameters of cyst fluids was investigated in 94 cyst fluids of 86 women with gross cystic breast disease. The relationship between the biochemical parameters and the cytological features of breast fluids (presence or absence of apocrine cells) was also studied. IGF-I was detected in all tested fluids, with a concentration 50 to 100 times lower than that found in plasma. IGF-I concentration was higher in cysts with a Na+/K+ ratio greater than 3 (greater than 3) and was inversely related to both dehydroepiandrosterone sulfate (DHEA-S) and epidermal growth factor (EGF) concentration (p less than 0.001). It is suggested that Na+/K+ greater than 3 cysts have a higher permeability to plasma and extracellular fluids compared to Na+/K+ less than 3 cysts. Apocrine cells were found in 78% of Na+/K+ less than 3 fluids as well as in 53% of Na+/K+ greater than 3 fluids. A well-defined relationship was found between the biochemical parameters of breast fluids, but the presence of either IGF-I or EGF was not related to the morphology of breast cysts as assessed by cytological examination.

Biopsy, Needle↗

Epidermal growth factor in breast cyst fluid: relationship with intracystic cation and androgen conjugate content.

In recent years, several studies focused on the biochemical analysis of breast cyst fluid composition. It has been shown that breast cysts lined by apocrine epithelium contain higher levels of potassium and dehydroepiandrosterone-sulphate as compared to cysts lined by flattened cells, and that women with apocrine cysts are more likely to develop breast cancer. In the present study, we measured the intracystic levels of sodium (Na+), potassium (K+), dehydroepiandrosterone-sulphate (DHEA-S), and epidermal growth factor (EGF), a factor which could play a role in the autocrine or paracrine control of breast cancer cell growth as recently proposed by some investigators. Breast cyst fluids obtained by fine-needle aspiration from 86 women with gross cystic breast disease were assayed. On the basis of the relative intracystic concentrations of Na+ and K+ two main classes of cysts were defined. An arbitrary cut-off value of 3 for the Na+/K+ ratio seemed adequate to separate these two types of cysts. An inverse relationship was found between the Na+/K+ ratio and DHEA-S concentration, median levels of the androgen conjugate being 3615 micrograms/dl in Na+/K+ less than 3 cysts and 480 micrograms/dl in Na+/K+ greater than 3 cysts (P less than 0.001). EGF levels were found to be significantly higher in Na+/K+ less than 3 cysts as compared to Na+/K+ greater than 3 cysts: 103.26 ng/ml versus 57.22 ng/ml, respectively (P less than 0.001). EGF appeared inversely correlated with total protein concentration in the Na+/K+ greater than 3 cysts, while in the Na+/K+ less than 3 cysts high EGF levels were observed independently of total protein content. In addition, a direct correlation was found between EGF and DHEA-S concentrations. On the basis of these results, the hypothesis can be made that EGF, which is measurable in all breast fluids tested and is nearly undetectable in plasma, is actually produced by the epithelium lining the cyst wall, particularly as far as the Na+/K+ less than 3 cysts are concerned. In view of our results this type of cyst, which has been shown to be lined by apocrine epithelium, appears to be characterized by high DHEA-S and EGF levels. It is suggested that the latter finding could provide a clue for understanding the increased risk of subsequent breast cancer in women bearing apocrine cysts.

Adult↗

Priming action on progesterone receptor synthesis by estradiol and tamoxifen in the 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma.

The priming action of estradiol and the antiestrogen tamoxifen (TMX) on progesterone receptor (PgR) synthesis has been investigated in the 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor model testing different priming times. Rats received either TMX or estradiol benzoate (E2B) for 3 or 7 days. Tumors were assayed before and after treatment to investigate the changes produced by each treatment on estrogen receptor (ER) and PgR concentration. As expected, ER concentration decreased in each treatment group. PgR concentration increased after 3 days of either E2B or TMX administration, but decreased when treatment was prolonged to 7 days. These findings point out the time dependency of PgR induction in this tumor model, similarly to what was observed in other experimental and clinical conditions.

9,10-Dimethyl-1,2-benzanthracene↗

Fibronectin concentration in the plasma of patients with malignant and benign breast disease.

Fibronectin concentration was determined in plasma from 97 patients with benign or malignant breast disease and from 62 controls. Median plasma fibronectin concentration (microgram FN/ml plasma) appeared to be significantly higher in patients with non-metastatic or metastatic breast cancer as compared to age-matched controls (P less than 0.01 and P less than 0.03, respectively); however, statistical significance disappeared when results were expressed as a function of total plasma protein content (microgram FN/mg total plasma protein). In patients with benign breast disease plasma fibronectin values were not significantly different from control levels. Our data indicate that the clinical usefulness of measuring FN in breast cancer patients appears to be very limited.

Adult↗

Effects of tamoxifen, estradiol benzoate and medroxyprogesterone acetate on the growth of DMBA-induced rat mammary carcinoma.

The potential synergism of sequential combinations of tamoxifen (TMX) or estradiol benzoate (E2B) with medroxyprogesterone acetate (MPA) in inhibiting the growth of 7.12-dimethylbenz(a)anthracene(DMBA) - induced rat mammary tumors has been investigated. In addition, the effect of TMX and E2B on estrogen and progesterone receptors' (ERs and PgRs) synthesis has been evaluated in the attempt to elucidate possible mechanisms involved. Previous treatment both with TMX and E2B has been shown to strongly enhance the antitumor activity of MPA. A priming on PgR synthesis has been observed only after E2B administration, TMX producing a sharp decrease in PgR levels. It is concluded that, while the priming action exerted by E2B on PgRs might explain the potentiating effect shown by E2B on MPA activity, the synergism observed between TMX and MPA should be explained on an extrareceptorial basis, an induction on PgR synthesis by TMX not being evident at the dosage and priming time employed in this study.

9,10-Dimethyl-1,2-benzanthracene↗

[Natural history and staging of brain metastases].

Intracranial metastases represent 7-17% of all brain tumours, their incidence at autopsy varying between 5.8 and 22% in different series. The neoplasms most commonly metastasizing to the brain are those of lung, breast, renal and skin (melanoma) origin. In two-thirds of cases, intracranial metastases are located within the brain parenchyma, while the remaining third involves the pachymeningeal envelopes. Leptomeningeal metastases are rare and develop mainly from leukemia, lymphomas and breast carcinoma. The route of spread to the central nervous system is usually hematogenous but occasionally direct involvement from adjacent bone or pachymeningeal metastases can occur. Median survival from clinical presentation usually doesn't exceed a few months. However brain metastases are the cause of death only in about 15% of patients. This is probably due because they occur late in the course of the natural history of the disease, when metastatic deposits in other viable organs have already developed. Due to this reason, systematic assessment of metastases to the brain is not advisable in all patients but it should be restricted to symptomatic patients and to asymptomatic patients affected by small cell carcinoma and adenocarcinoma of the lung, who could benefit from prophylactic brain irradiation. In symptomatic patients, plain skull X-ray, electroencephalography and computed tomography represent appropriate diagnostic tools to provide accurate informations about number, size, site and morphological characteristics of brain metastases.

Angiography↗

Endocrine effects of tamoxifen in postmenopausal breast cancer patients.

The effects of tamoxifen on plasma concentration of gonadotropins, prolactin (PRL), estrone (E1), estradiol-17 beta (E2), and sex hormone-binding globulin (SHBG) were studied in 40 postmenopausal breast cancer patients. In addition, the changes induced by the drug on endometrium and vaginal epithelium were investigated. After 6-8 weeks of tamoxifen treatment, a significant decrease in FSH, LH and PRL basal levels was observed, whereas the concentrations of E1 and E2 were not significantly affected. A significant increase in SHBG levels was induced by prolonged treatment with the drug. In addition, tamoxifen caused a partial estrogenization of vaginal smears, and a weak stimulatory effect on endometrium was also apparent. These findings indicate that tamoxifen produced agonistic effects on some targets and antagonistic effects on the others.

Aged↗

Preliminary study on serum levels of mucinous like cancer antigen (MCA) in patients with breast disease: comparison with CEA.

MCA (mucinous-like cancer antigen) can be measured in the biological fluids of patients by means of a solid phase enzyme immunoassay. This study describes the results of MCA determination in sera of 230 patients with benign (99) and malignant (131) breast diseases. MCA levels were significantly higher in breast cancer patients than in non cancer patients and in healthy subjects (p less than 0.001). MCA concentrations tended to increase as the stage of the disease advanced. The 95th percentile of MCA value distribution in normal subjects showed a diagnostic sensitivity in breast cancer patients of 16.3% at stage I, 26.2% at stages II-III and 52% at stage IV. In a group of 118 cancer patients, MCA and CEA were tested simultaneously. The diagnostic sensitivity and specificity of MCA and CEA assays was very similar; nevertheless the association of the two tests showed 11 cases with high levels of MCA and low levels of CEA and 9 patients with high levels of CEA and low levels of MCA. Seventy-four out of 118 patients were negative for both markers and in 22 out of 118 patients markers were positive. The new marker MCA appeared to correlate with breast cancer and gave different information complementary to CEA.

Adult↗