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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 307 records · Page 17Linked to original sources
PubMed1992

Chemoprevention of breast cancer with retinoids.

Fenretinide [N-(4-hydroxyphenyl)retinamide, 4-HPR] is an effective agent for the inhibition of N-nitroso-N-methylurea-induced breast cancer in rats. This compound has been studied extensively and proved to be safer and less teratogenic than many other retinoids. A major characteristic of 4-HPR is its ability to concentrate in the granular and fat tissue of the breast instead of in the liver. Between January and June 1986, we carried out a phase I study on 101 patients divided into four randomized groups receiving placebo and 100, 200, and 300 mg/day of 4-HPR. Patients received the drug for 6 months without any major toxic effect. This finding was confirmed by another 6-month study in which patients received a common dose of 200 mg/day. In March 1987, a phase III study was started to evaluate the effectiveness of 4-HPR in preventing contralateral primary tumors in women who had already been treated for breast cancer. If 4-HPR succeeds in preventing second primaries in breast cancer patients, it may be useful for a wider group of subjects at high risk for breast cancer. This randomized study was designed with two arms: an intervention group versus a group receiving no treatment. Patients in the intervention group will be treated with 200 mg/day 4-HPR for 5 years. Patients in the control group will not be treated. A further 2 years of follow-up is planned for both groups. Currently, 2450 patients have been recruited. We expect a total accrual of 3500 patients by the end of 1992.

Adult↗
PubMed1992

[A comparative study of intravenous diltiazem and nitroglycerin in the treatment of unstable angina].

To compare the efficacy of intravenous diltiazem vs nitroglycerin in patients with unstable angina, we conducted a prospective, single blinded study enrolling 45 patients, 24 of them received diltiazem and 21 nitroglycerin. We considered drug failure if the patient experienced two or more anginal episodes or if one of them was longer than 30 minutes. There was a good response in 19 of 24 patients (79%) of the diltiazem group and 17 of 21 (81%) in the nitroglycerin group. Only one of the 5 non-response patients in the diltiazem group that was crossed to nitroglycerin was controlled, in opposition to the 4 patients crossed to diltiazem that were controlled all of them (p less than 0.05). Both drugs significantly (p less than 0.01) reduced systolic and diastolic blood pressure, but there was not difference between the two groups. Heart rate and double product decreased only in the diltiazem group (p less than 0.05). We did not find notorious side effects. We concluded that diltiazem is an alternative to nitroglycerin in patients with unstable angina.

Angina, Unstable↗
PubMed1991

An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression.

Among 761 consecutive patients with chronic myeloproliferative disorders (CMD), it was found that 18 (nine men and nine women) did not fulfill at presentation the established diagnostic criteria for the typical forms. In seven patients, the diagnosis of CMD was made on the basis of an intense and persistent thrombocytosis that complicated splenectomy. The other 11 patients had various combinations of the following signs suggesting CMD: splenomegaly, bone marrow myeloid hyperplasia and/or slight myelofibrosis, mild thrombocytosis and/or leukocytosis, and rare immature myeloid cells in the peripheral blood. All patients were younger than 46 years of age (median age, 31.5 years; range, 20 to 45 years). A major thrombotic event was the most frequent presenting feature (eight of 18 cases), and thrombotic complications supervened in seven of the eight splenectomized patients (six in the portal system), raising the overall rate of patients with thrombotic events in their history to 11 of 18. At a median follow-up of 50 months (range, 24 to 241 months), three patients had died of thrombotic complications (two after splenectomy). The 15 surviving patients had stable disease, and 12 of them were not receiving cytoreductive therapy. Spontaneous growth of circulating burst-forming units erythroid was demonstrated in one patient, and erythroid responsiveness to erythropoietin appeared higher than in the normal controls in four. Spontaneous in vitro platelet aggregation in whole blood and/or platelet-rich plasma was seen in five of seven patients. It was concluded that a difficult to identify, slowly progressive form of CMD occurs in young people, that it carries a high risk of thrombosis, and that splenectomy is a high risk procedure in these cases.

Adult↗
PubMed1991

The risk of breast cancer subsequent to histologic diagnosis of benign intraductal papilloma follow-up study of 339 cases.

The risk of developing breast cancer was investigated in 339 patients in whom histologically confirmed intraductal papilloma had been surgically removed. Follow-up ranged from 2 to 14 years, (average, 6.62 years). Ten breast cancers were observed, whereas 3 were expected on the basis of age-specific incidence rates drawn from local cancer registries (relative risk = 3.33, 95% confidence interval = 1.60-6.13). No significant difference in the relative risk was observed as far as papilloma type (single or multiple) was concerned. All breast cancers observed occurred in the same breast as the papilloma. Women in whom a benign intraductal papilloma has been excised should be carefully followed since they at are higher risk for ipsilateral breast cancer.

Adult↗
PubMed1991

Zinc and copper in breast cancer. A joint study in northern Italy and southern France.

The relationship between breast cancer and two trace elements, zinc (Zn) and copper (Cu), was investigated by means of an hospital based case-control study at Milan (Italy) and Montpellier (France). Variables concerning dietary intake of Zn and Cu (in Milan) and their blood levels (both in Milan and Montpellier) were measured. Dietary intake, evaluated through a questionnaire of the dietary history type, and blood levels of Zn and Cu were measured in 261 cases and 261 controls. Cu blood level showed a contradictory tendency in the two samples (higher in controls in Milan, higher in cases in Montpellier), which tended to lessen after adjustment for related variables. No odds ratios (OR) in the different quantiles, nor X2 for trend reached statistical significance. A sharp difference was evidenced on the opposite with regard to Zn blood values in cases and controls. In both samples Zn mean values are significantly higher in cases than in controls, and the difference remains significant in the two samples even after adjustment for related variables. The pooled OR computed from the two samples, after adjustment for known risk factors and related variables, reaches in the fourth quartile a value of 9.5 (CI: 4.9-18.2). Dietary intake of the two minerals (measured only in Milan sample) showed no difference between cases and controls, but a stronger relationship between dietary and blood Zn was evidenced in cases with respect to controls. The authors suggest that the higher Zn level in cases might be related with an higher incorporation of Zn in cancer cases and that the same mineral might play a possible role in tumor growth promotion.

Adult↗
PubMed1991

Long-term tolerability of fenretinide (4-HPR) in breast cancer patients.

A group of 53 patients initially participating in a phase I trial with the synthetic retinoid fenretinide was assessed for the long-term tolerability of this compound. The patients were evaluated after 42 months of drug intake at a dose of 200 mg/day, including a 3-day drug interruption at the end of each month, by the following examinations: a dermatological visit; an ophthalmological evaluation including an ophthalmological questionnaire and an electroretinogram (ERG); a study on blood chemistry and plasma retinol levels; a study on bone densities and on skeletal X-rays; and finally a psychological evaluation including various tests for anxiety, depression and overall mood. The results show that prolonged administration of fenretinide is well tolerated. No acute nor severe toxicity was observed and thus this compound can be considered a good candidate for chemoprevention trials in a variety of patient populations.

Affective Symptoms↗
PubMed1991

Distribution of fenretinide in the mammary gland of breast cancer patients.

Fenretinide has been used orally as a chemopreventive retinoid in a trial for women at risk of developing contralateral breast cancer. The levels of fenretinide and its metabolites were measured in the breast tissue obtained at surgery from women in the trial. Fenretinide was concentrated by breast tissue. Two major metabolites were detected in the tissue extract, one co-eluting with N-(4-methoxyphenyl)retinamide (4-MPR), and the other, more polar, eluting at 17 min under the conditions used. This metabolite remains unidentified. Division of the breast tissue into epithelial cells and fat fractions revealed that fenretinide and the metabolite at the 17 min peak were concentrated in the epithelial cells, whereas 4-MPR was principally localised in the fat compartment. Thus fat may serve as a storage compartment for the retinoid.

Adipose Tissue↗
PubMed1991

Small-dose iron tolerance test and body iron content in normal subjects.

The small-dose iron tolerance test (SD-ITT) was performed in 37 healthy subjects (20 females and 17 males). The area under the curve (AUC) of serum iron variations after the test dose (10 mg of iron as iron sulphate) was corrected by the expected plasma iron disappearance rate, the expected subject's plasma volume and the measured spontaneous time-dependent serum iron variations, and was used as a summary measure of the outcome, Q-ITT. Q-ITT correlated strictly with the maximum serum iron increase (SImax). Q-ITT gave positive (greater than zero) values in only 14 out of the 37 subjects (11 females and 3 males). Serum ferritin proved to be the best discriminating parameter between positive and non-positive subjects, and was inversely correlated with Q-ITT in the positive ones. In 2 male subjects, aged 43 and 34 years, SD-ITT proved to be highly sensitive to the progressive decrease of mobilizable body iron content during repeated venesections. In these patients the threshold for a positive test result was obtained at values lower than 1050 and 950 mg of body iron content, respectively. The threshold-dependent sensitivity, simplicity, and repeatability of this method favor its becoming a useful technique for studying the up-regulation of iron absorption in normal subjects and in pathological conditions.

Absorption↗
PubMed1991

Cell kinetics and response to primary intra-arterial chemotherapy in patients with advanced oral cavity tumors.

The relationship was analyzed between cell kinetics, defined as 3H-thymidine labeling index (3H-TdR LI), and clinical responses for 35 previously untreated patients with locally advanced oral cavity squamous cell carcinomas. Patients were treated with three cycles of vincristine and bleomycin (VB) or of VB plus methotrexate (VBM), given by intra-arterial infusion followed by surgery. The objective clinical response rate was higher after VBM treatment than after VB, whereas overall clinical response rates were similar for patients with slowly or rapidly proliferating tumors. The probability of relapse-free survival at 4 yr and overall survival was significantly higher for patients with high 3H-TdR LI tumors given VBM than for those given VB. For patients with slowly proliferating tumors, there were no differences in relapse-free survival and overall survival between the two treatments. These data suggest that patients with rapidly proliferating tumors benefit from primary intensive chemotherapy treatment including methotrexate and that cell kinetics can be used to formulate rational clinical protocols for oral cavity cancers.

Adult↗
PubMed1991

Adverse events with droxicam in the early clinical trials.

This study analyses the results of 8 randomized, controlled clinical trials and one open study carried out with droxicam (a new NSAID, pro-drug of piroxicam), comparing the adverse events and gastrointestinal tolerance of this compound against those of the control drugs used in these trials. The frequency of adverse events was lower in the droxicam treated patients. Adverse events concerning the gastrointestinal area were also lower. No differences were found in the distribution of adverse events by age of sex among the drugs compared. The pattern of side effects found was that expected in all non-steroidal anti-inflammatory agents. These results seem to sustain the hypothesis of a better tolerance of droxicam than that of piroxicam, indomethacin or diclofenac, especially in the gastrointestinal area.

Aged↗
PubMed1991

Reliability of 3H-thymidine labeling index: cell proliferation of colorectal carcinoma in three different centers.

Although the 3H-thymidine labeling index (TLI) has been used extensively as a biologic marker of increased susceptibility to neoplasms or as a prognostic indicator of the clinical outcome in cancer patients, there is still some concern regarding its accuracy and reliability as a marker of cell replication. A study on the prognostic value of TLI in colorectal cancer gave us the ability to evaluate how such a measurement may vary in different laboratories. A total of 150 malignant tumors of the large bowel were studied in the period from 1988 to 1989. Microautoradiography was carried out in tumor fragments taken at surgery. There were only slight differences among the three centers involved in the investigation, mainly as regards the culture medium, exposure time, and the addition of O2 + CO2 during the incubation. No significant difference was observed among TLI values recorded in the three centers (18.3 +/- 0.9; 17.4 +/- 0.9; 15.7 +/- 1.0 mean +/- SE), and the ranges of values were almost identical. Similarly, the numbers of total and of labeled cells counted for each patient were comparable among the three centers. The frequency distribution of TLI showed a peak value between 10 and 19.9% in all three centers. Moreover, more than 80% of the observed values were within the range of 10 to 29.9%. In addition, the neoplastic areas with the highest proliferative activity ("high" TLI) showed a frequency distribution once again rather similar among the three centers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Non-Hodgkin's lymphoma with hepatosplenic involvement. The importance of imaging diagnosis using magnetic resonance tomography].

This study evaluates the importance of magnetic resonance imaging (MR) in the exploration of the abdomen in a case of non-Hodgkin lymphoma diagnosed in a 14-year-old boy. Results are compared with those obtained using two widely used diagnostic methods: CT and ultrasonography (US). US revealed a prevalent involvement of the spleen, whereas CT showed a marked hepatic infiltration. The role of MR seems important because it allowed the contemporary and careful evaluation of hepatolienal involvement. The main advantages and drawbacks of using MR in pediatrics, and in particular in the study of the metastatic involvement of hypochondriac organs are discussed.

Adolescent↗
PubMed1990

[Study of cellular kinetics in oral leukoplakia].

The Authors aim was to study the Labeling Indices (LI) of 12 subjects with oral leukoplakia, using an in vitro labeling technique with tritiated thymidine (Silvestrini-Kit, Ribbon spa, Milan). Twelve volunteers of our Dental Clinic were enrolled in this study as a control group. The kinetic parameter was investigated by counting cells from autoradiographs on histological selections of the biopsies. By a Wilcoxon test, significant differences were found between the LI of the two groups: p = 0.00003. Finally, a comparison has also been made between LI of these lesions and the LI of oral squamous cell carcinomas.

Adult↗