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Biomedical subjects

F Villani

Publications and source records attributed to F Villani.

At least 109 records · Page 6Linked to original sources
PubMed1986

Phase II study of doxorubicin versus epirubicin in advanced breast cancer.

Doxorubicin and its epimerized analog epirubicin were tested at a dose of 75 mg/m2 given iv every 3 weeks to 42 patients with advanced breast cancer, 23 of whom were in relapse from prior cyclophosphamide, methotrexate, and 5-FU (CMF) chemotherapy. The median cumulative dose was 540 mg/m2 (range, 225-650) for doxorubicin and 565 mg/m2 (range, 150-600) for epirubicin. Complete plus partial response was documented in 11 of 21 patients (52%) following doxorubicin and in 13 of 21 patients (62%) following epirubicin. The median observation period was 22 months (range, 14-30); the median duration of response and the median survival were superimposable. Doxorubicin and epirubicin exhibited a superior response rate in previously untreated patients [six of eight (75%) vs eight of 11 (73%)] compared to those previously given CMF with or without endocrine therapy [five of 13 (38%) vs five of ten (50%)]. Vomiting, mucositis, and leukopenia were documented less frequently following administration of epirubicin as compared to doxorubicin. Regarding cardiac evaluation, no significant differences were evident between the two drugs. However, a significant fall in the left ventricular ejection fraction was documented in women who received doxorubicin following a cumulative dose greater than 550 mg/m2. Following completion of doxorubicin therapy at cumulative doses of 580 and 562 mg/m2, two women developed left ventricular failure at 6 and 14 months, respectively. Epirubicin appears to be an effective drug for the treatment of breast cancer and, given at equal doses, is less toxic than doxorubicin.

Adult↗
PubMed1986

Studies on insecticide susceptibility of Anopheles gambiae s.1. and Culex quinquefasciatus in the area of Ouagadougou, Burkina Faso (west Africa).

Tests to evaluate the susceptibility level in Anopheles gambiae s.1. and Culex quinquefasciatus from Ouagadougou and two nearby villages have been carried out. Anopheles gambiae s.1. larvae from Ouagadougou showed complete susceptibility to organophosphates and carbamates, and adults showed low level resistance to DDT. Nine percent survival of adult An. gambiae s.1. to one hour exposure of 4% DDT was observed in samples from Zaghtouli village while in those from Koubri village, where dieldrin also was tested, resistance to both organochlorine insecticides was detected. Culex quinquefasciatus showed susceptibility to fenthion, malathion, fenitrothion, and chlorpyrifos, whereas incipient resistance to temephos was detected. Electrophoretic analysis showed polymorphism of high and low active esterases (Est-2 + Est-3) confirming the association between OP resistance and enhanced esterase activity in this species.

Animals↗
PubMed1985

Adriamycin and epirubicin treatment monitored by radionuclide ejection fraction during therapy and follow-up.

Twenty-four patients with advanced breast cancer were studied with serial determinations of the radionuclide ejection fraction at rest (RST-LVEF) during anthracycline chemotherapy (CT) and with a mean follow-up (FU) of 8 months. We had 2 cases of anthracycline congestive heart failure (CHF) during FU, 3 and 12 months respectively after the end of CT. The RST-LVEF changes observed during CT were not able to predict which patients were to develop a symptomatic cardiomyopathy. The type of RST-LVEF change that is generally considered a worsening of cardiac performance is a decline greater than or equal to 15%. We had this type of RST-LVEF change, in addition to the 2 CHF, in 5 other patients without symptomatic cardiomyopathy. Nevertheless none of these 5 patients attained pathological values of RST-LVEF, while the 2 CHF showed symptomatic cardiomyopathy only when RST-LVEF became clearly pathologic (less than or equal to 46%). Therefore, although in our study the RST-LVEF changes during CT did not have predictive value for CHF, the method may give a notable clinical contribution all the same. In fact, by submitting the patients with a RST-LVEF fall greater than or equal to 15% to frequent sequential RST-LVEF determinations and stopping the CT if the RST-LVEF becomes pathologic it is possible to avoid severe and irreversible CHF.

Adult↗
PubMed1985

Cardiac function evaluation in AMSA-treated patients.

Cardiac function was monitored by means of ECG and systolic time intervals in 13 patients submitted to treatment with 4'-(9-acridinylamino) methanesulfon-m-aniside (AMSA) without the classical reconstitution vehicle N1N-dimethylacetamide. ECG changes were represented by flattening of T waves (100%), sporadic atrial extrasystoles (23%), and sporadic or coupled ventricular premature beats (7.6%). These alterations were transient and not dose related. The systolic time interval ratio, recorded at the end of infusion and 2 h after drug administration, did not change significantly from pretreatment values. Systolic time intervals recorded in 6 patients after the mean cumulative dose of 550 mg/m2, and in 3 patients after the mean cumulative dose of 1000 mg/m2, did not change from mean basal values. Present data failed to confirm the occurrence of a significantly cardiotoxic activity of AMSA.

Adult↗
PubMed1985

Possible enhancement of the cardiotoxicity of doxorubicin when combined with mitomycin C.

Forty-six patients with recurrent metastatic breast cancer were treated with a combination chemotherapy including doxorubicin and mitomycin C. Myocardial contractility was monitored by means of echocardiography. During therapy there was a progressive deterioration of myocardial function, and this phenomenon was found to be linearly correlated to the cumulative dose of doxorubicin. Six patients (13.8%) developed congestive heart failure during therapy; it occurred after the median cumulative dose of 322 mg/m2 (range 135-472). Possible risk factors of cardiomyopathy could be identified in only two patients. These results suggest that mitomycin C could enhance the cardiotoxicity of doxorubicin.

Adult↗
PubMed1985

Preliminary data on the genetic differentiation of Onchocerca volvulus in Africa (Nematoda: Filarioidea).

Data are reported on the genetic structure of three Onchocerca volvulus populations, respectively from Mali (savanna), Ivory Coast (forest), and Zaire (forest gallery in savanna). Electrophoretic analysis, carried out on 25 gene-enzyme systems, has shown a remarkable genetic heterogeneity existing within O.volvulus. Zaire and West Africa populations appear chiefly differentiated at Mdh-1 and 6Pgdh loci, their average Nei's genetic distance being 0.11. In West Africa Nei's D found between the savanna and forest samples is 0.04. The savanna population from Zaire is more similar to the savanna one from Mali (D = 0.09) than to the forest one from Ivory Coast (D = 0.13). This appears mainly due to the loci Ldh and Hbdh (possibly linked), some alleles of which seem to be selected for in forest populations (Ldh110, Hbdh108), while others in the savanna ones (Ldh100, Hbdh100). The hypothesis that the discrepant epidemiological patterns of human onchocerciasis are related to intrinsic differences in the parasite seems supported by the obtained data. The differences in allele frequencies found at the reported loci appear strong enough to allow biochemical identification of O. volvulus populations from different geographic regions and different habitats.

Alleles↗
PubMed1985

Preliminary evaluation of myocardial toxicity of 4'-deoxydoxorubicin: experimental and clinical results.

4'-deoxydoxorubicin (4'-deoxy-DXR), a new doxorubicin (DXR) analogue with interesting antineoplastic activity, was tested for its cardiotoxicity in guinea pigs and humans. In experiments on isolated guinea pig heart, which is considered a highly predictive model of acute anthracycline cardiotoxicity in humans, 4'-deoxy-DXR was found to be significantly less cardiotoxic than DXR. This effect was correlated with a lower degree of inhibition of the fast-exchanging calcium compartment and of the low affinity sarcolemmal calcium-binding sites. The preliminary study on 4'-deoxy-DXR in humans was conducted on 117 patients affected by advanced malignancies resistant to conventional chemotherapy. The drug was administered by bolus i.v. injection in doses ranging from 10 to 40 mg/m2 in the phase I study and in doses of 35 mg/m2 in the phase II study, which is still ongoing. Cardiologic evaluation consisted of recording of EKG, left ventricular systolic time intervals (STI), echocardiography and radionuclide ejection fraction. Preliminary data indicated a lower percentage of EKG abnormalities in comparison not only with DXR but also with other anthracycline analogues. Analysis of STI recorded 1 h after different doses of 4'-deoxy-DXR failed to show the dose-dependent effect on left ventricular function which has been described for DXR, thus confirming the lower acute cardiotoxic effect. Functional parameters serially measured to evaluate chronic cardiotoxicity in 15 patients who received more than 200 mg/m2 were not significantly different from basal values.

Adult↗
PubMed1985

Phase II study with amsacrines (m-AMSA and m-AMSA lactate) in refractory lymphomas.

A total of 70 patients with malignant lymphomas refractory to one or more chemotherapeutic regimens were treated with iv amsacrines (m-AMSA and m-AMSA lactate). Of 58 evaluable patients, 12 had Hodgkin's disease and 46 had non-Hodgkin's lymphoma. Twenty-nine of the evaluable patients received m-AMSA and 29 received m-AMSA lactate. The amsacrines were recycled every 3 weeks. The doses of m-AMSA were 90-120, 70, and 25-30 mg/m2/day for 3 days, respectively. All patients treated with m-AMSA lactate received a single dose of 225 mg/m2. In Hodgkin's disease, the response rate was 58.3% (one complete response among 12 patients), and in non-Hodgkin's lymphoma, the response rate was 30.4% (six complete responses among 46 patients). The median duration of response was 3 and 5 months, respectively. The response rate was unfavorably affected by the presence of extra-nodal disease and a Karnofsky performance status less than 80. There was no important difference in the incidence and duration of response between m-AMSA and m-AMSA lactate. After vomiting, myelosuppression was the most frequent observed toxic effect. One patient showed an unexpected fatal bone marrow aplasia following the first course of 90 mg/m2. This study indicates that m-AMSA and m-AMSA lactate are active and moderately toxic in previously treated malignant lymphomas. Thus, amsacrines could be effectively incorporated into salvage polydrug regimens.

Adult↗
PubMed1984

Relationship between pulmonary function tests and morphologic changes in the lung in bleomycin-treated patients.

The transfer factor of the lung for carbon monoxide (TLCO) and the respiratory response to moderate exercise were determined in 16 patients with pulmonary metastasis pretreated with bleomycin who underwent pulmonary partial resection. The results of pulmonary function tests were related to histologic findings. No significant correlation was found between pulmonary morphologic changes and the TLCO: this questions the usefulness of TLCO as a predictive method for detecting subclinical bleomycin pulmonary toxicity. No significant correlation was found between morphologic findings and cumulative dose of bleomycin: this confirms the limit of a dose limitation strategy. In contrast, evaluation of pulmonary response to exercise seemed to improve the sensitivity of monitoring such patients for clinical evidence of latent pulmonary toxicity; however, it seems that critical morphologic changes must occur before pulmonary performance begins to deteriorate.

Adolescent↗
PubMed1984

Phase I study with 4'-deoxydoxorubicin.

4'-Deoxydoxorubicin (dxDx), a new doxorubicin analogue, was administered intravenously on a 3-week schedule to 73 patients affected by advanced malignant neoplasms. Sixty-five patients, treated with eight dose levels ranging from 10 to 45 mg/m2, were evaluable. The dose-limiting toxicity was myelosuppression, mainly leukopenia. About one third of the patients complained of vomiting which was almost always mild. Minimal hair loss was also documented in about 40% of patients. No hepatic or renal toxicity was observed. Transient and aspecific electrocardiographic changes were recorded in 6% of patients after 1 h and in 3% after 24 h from drug injection. Left ventricular ejection fraction was decreased in two patients after a cumulative dose of 90 mg/m2. One patient died with cardiorespiratory insufficiency and his initial cardiovascular disease might have been aggravated by dxDx. No changes in myocardial function parameters were documented in 18 patients who reached higher cumulative doses, i.e. greater than or equal to 100 mg/m2 and greater than or equal to 200 mg/m2. The highest total dose administered in this study was 340 mg/m2. Therapeutic activity was observed with doses ranging from 25 to 45 mg/m2. Partial response was documented in pancreatic, colon, anal and breast carcinomas as well as in non-Hodgkin's lymphoma. Minor response was observed in prostatic, thyroid, and renal carcinomas as well as in chronic lymphocytic leukemia. The maximum tolerated dose was assessed to be between 40 and 45 mg/m2. A Phase II trial is ongoing utilizing the dose of 35 mg/m2 every 3 weeks.

Adolescent↗
PubMed1983

Role of the fast-exchanging calcium compartment in the early cardiotoxicity of anthracycline analogs.

Two new anthracycline analogs, 4'-epi-doxorubicin and 4'-deoxydoxorubicin, were tested for their cardiotoxicity and their activity on calcium turnover in guinea pig heart. The df/dt was used as an index of contractile force; calcium turnover was studied by means of a radioisotopic technique. 4'-Epi-doxorubicin was found less cardiotoxic than doxorubicin, whereas 4'-deoxydoxorubicin was found almost completely devoid of cardiotoxicity. The different cardiotoxic activity was found to be linearly correlated with the relative capacity to inhibit the fast-exchanging calcium compartment in cardiac muscle: doxorubicin greater than 4'-epi-doxorubicin greater than 4'-deoxydoxorubicin. This result supports that the inhibition of calcium exchange is involved in development of the early cardiotoxicity of anthracyclines.

Animals↗
PubMed1983

Interaction between doxorubicin and mitomycin C on mortality and myocardial contractility in guinea pig.

The present investigations were carried out in guinea pig to ascertain whether mitomycin C has a direct cardiotoxic effect or interacts with doxorubicin-induced cardiotoxicity. I.p. administration of mitomycin C did not modify the survival rate up to 30 days, whereas the combined administration of doxorubicin and mitomycin C significantly decreased the survival time in comparison to the doxorubicin-treated group. On isolated atria, mitomycin C did not cause significant inhibition of the contractile force or an enhancement of the doxorubicin-induced negative inotropic effect. These results do not support the possibility that mitomycin C potentiates the acute cardiotoxic effects produced by doxorubicin.

Animals↗
PubMed1983

Phase I study of 4-demethoxydaunorubicin.

4-demethoxydaunorubicin (4-dm DNR), a new analog of daunorubicin, was tested at an every 3-week dose schedule in 63 evaluable patients with various forms of disseminated malignancy. Utilizing the intravenous (i.v.) route of administration, the maximum tolerated dose (MTD) was 15-18 mg/m2; with the oral route the MTD was 60 mg/m2. Myelosuppression represented the dose-limiting factor, and leukopenia was more often observed than thrombocytopenia. However, leukopenia was more frequently detected following i.v. administration while vomiting represented the most frequent toxic sign after oral administration. Loss of hair was moderate with either route of administration and comparatively less frequent and pronounced than that observed after doxorubicin (DX) and its analog 4'-epi-doxorubicin (4'-epi-DX). Aside from transient aspecific electrocardiographic changes recorded in 30% of patients, no cardiac toxicity was documented. Tumor response was documented in seven patients with malignant lymphomas, breast cancer, melanoma and carcinoma of uterine cervix. Two out of the seven responders achieved prolonged complete remission and four were resistant to doxorubicin. 4-dm DNR appears to be an analog worth further clinical trials.

Administration, Oral↗
PubMed1983

[Electrophoretic study of gene-enzyme systems in oysters classified as Crassostrea gigas (Thunberg, 1793) and Crassostrea angulata (Lamarck, 1819) (Mollusca: Ostreidae)].

As a further contribution to the systematics of species belonging to the genus Crassostrea, electrophoretic studies of gene-enzyme system have been carried out on five populations of oysters regarded as either Crassostrea gigas or Crassostrea angulata species. Two populations of C. gigas from Japan (Karakawa and Hiroshima), one of C. gigas from France (Fouras), one of C. angulata from Portugal (Sado) and one of Crassostrea sp. from Italy (Chioggia) have been examined. The electrophoretic study of 20 enzyme loci and the genetic distance value showed no significant genetic divergence among the Crassostrea sp. populations. Thus the results of this study seem to confirm and extend to other populations what obtained by Buroker et al. (1979), that is a remarkable genetical identity between the two species Crassostrea gigas and Crassostrea angulata.

Animals↗