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Biomedical subjects

F Giuliani

Publications and source records attributed to F Giuliani.

At least 55 records · Page 3Linked to original sources

[Comparison between one and two dimensional echocardiography in the study of segmentary kinetics of the left ventricle in post-infarct ischemic myocardiopathy].

Sixty two-dimensional M-mode echocardiograms of myocardial infarction patients, performed 3--6 months after acute attack, were compared with those of 30 normal subjects. In one-dimensional echocardiograms, the dimensions of the left ventricle and some segmentary signs of contractility such as diastolic thickness, excursion and systolic thickening of the septum and the posterior wall of the left ventricle were examined, in two-dimensional echocardiograms the contractility of single areas was compared to those adjacent. In heart attack patients parameters studied were changed in a statistically significant way (p less than 0,001); the degree of correlation between the site of hypo-akinesis and the ECG necrosis site was quite high; compensatory hyperkinesia was frequently found in the area diametrically opposite to dyskinetic areas. The two-dimensional examination was also very sensitive especially in the diagnosis of aneurysm, which is sometimes not noted in M-mode.

Cardiomyopathies↗

Anti-tumor activity of daunorubicin linked to poly-L-aspartic acid.

Daunorubicin was bound to poly-L-aspartic acid via the methylketone side chain of the drug to avoid reaction of the sugar amino group believed to be essential for optimal drug activity. Attachment of the drug to the polyamino acid by an ester linkage was achieved by nucleophylic substitution reaction of 14-bromo-daunorubicin. Compared with free daunorubicin, the polymeric derivative was less cytotoxic to HeLa cells in vitro, but more effective against all tumor models tested (P388 leukemia, Gross leukemia, MS-2 sarcoma). The binding to the polypeptide markedly reduced drug toxicity but only slightly decreased drug potency. The daunorubicin-poly-L-aspartic acid conjugate demonstrated antitumor activity comparable to that of doxorubicin in leukemia models, but superior to that of doxorubicin in a solid tumor model (MS-2 sarcoma).

Animals↗

Antileukemic activity of 4-demethoxydaunorubicin in mice.

4-demethoxydaunorubicin was tested against experimental mouse leukemias, in comparison with doxirubicin and daunorubicin. 4-demethoxydaunorubicin, administered ip to mice bearing ascitic L1210 or P388 leukemia was 5 times more potent than daunorubicin and 10 times more potent than doxorubicin (potency established in relation to optimal antitumor doses). At the optimal doses, 4-demethoxydaunorubicin was as active as daunorubicin and less active than doxorubicin. 4-demethoxydaunorubicin, administered iv was 8 times more potent than daunorubicin and 4-5 times more potent than doxorubicin. At the optimal doses, 4-demethoxydaunorubicin was markedly more active than daunorubicin or doxorubicin in mice injected iv with 10(5) L1210 leukemia cells (early or late leukemia) or with 10(2) Gross leukemia cells. In mice given 2 X 10(6) Gross leukemia cells iv, 4-demethoxydaunorubicin was as active as doxorubicin when treatment was given iv on days 1, 5 and 9 for 4-demethoxydaunorubicin, and on days 1, 3 and 6 for daunorubicin and doxorubicin. 4-demethoxydaunorubicin administered orally was highly active against ascitic P388 leukemia and against L1210 and Gross leukemia inoculated iv.

Administration, Oral↗

[Blood folates in chronic uremic patients in dialysis treatment].

The authors, after having reviewed folic acid and folates chemical and biochemical characteristics and their absorption and excretion modalities, determine serum folate levels by radioassay method on 30 patients with renal failure in chronic dialysis and on 24 normal controls. Low serum folate levels concerned 14 uremic patients (46.6% of th cases): 10 in hemodialysis and 4 in peritoneal dialysis. The mean serum folate values was 3.31 ng/ml (+/- 1.93) for the uremic patients' group and 4.29 ng/ml (+/- 1.21) for the control group. The difference between the mean level of these groups was statistically significant (p less than 0.05). No significant difference was observed among the mean serum folate levels of the uremic patients in peritoneal dialysis and of those in hemodialysis. Significantly low serum folate levels were finally found for the uremic HBsAg-positive patients, but in the same subjects the dialytic treatment period had been very prolonged. The authors conclude emphasizing the usefulness of folic acid treatment in uremic patients on dialysis, also without having an evident hematologic picture of megaloblastic anemia.

Adolescent↗

Enhancement of the antitumor activity of adriamycin by Tween 80.

This paper describes the effect of Tween 80 on the antitumor activity and on the distribution of adriamycin in mice. The dilution of adriamycin in a 10% water solution of Tween 80 produced a significant increase of the antitumor activity in mice against ascites tumors (L 1210 leukemia), disseminated leukemias (transplanted leukemias originally induced by Gross leukemai virus and Moloney leukemia virus), and solid tumors (Sarcoma 180, MS-2 sarcoma). In all these experiments the drug was administered i.v., according to different schedules. Higher antitumor activity at the optimal dose and an increase of activity at lower doses were observed in different experimental systems. Toxicity was also slightly enhanced. Tissue distribution was studied in normal mice and in tumor-bearing mice (Gross leukemia and MS-2 sarcoma). In animals give i.v. adriamycin diluted in 10% Tween 80 there was a higher drug concentration in spleen, lung and kidney than there was in mice given the drug in a water solution. In all the other organs examined (heart, liver, small intestine) and in the MS-2 tumor tissue, no significant increase was observed. In L1210 leukemia-bearing mice, i.p. treatment with adriamycin diluted in 10% Tween 80 resulted in a significantly higher toxicity than that which resulted from treatment with adriamycin in a wa ter solution; no increase of antitumor activity was observed.

Animals↗

Synthesis and antitumor activity of 4-demethoxyadriamycin and 4-demethoxy-4' -epiadriamycin.

Two new analogs of adriamycin have been obtained by chemical synthesis, 4-demethoxyadriamycin and 4-demethoxy-4' -epiadriamycin. Both compounds were highly effective against experimental mouse tumors at doses about ten times lower than those effective for adriamycin. At the optimal dose, 4-demethoxyadriamycin displayed antitumor activity similar to that of adriamycin in solid Sarcoma 180 (S180), L1210, P388, and Gross leukemias, and mammary carcinoma, while it did not markedly inhibit the growth of Moloney sarcoma virus-induced sarcoma in mice treated before the virus infection. At the optimal dose, 4-demethoxy-4' -epiadriamycin was as active as adriamycin against L1210, P388,and Gross leukemias, and less active against solid S180. The results show that anthracycline derivatives characterized by the absence of the methoxyl group at the C-4 position are markedly more potent than the parent compound, and may exhibit a differential antitumor effect on a number of mouse tumors.

Animals↗

Activation of K cells in mice with transplanted tumours differing in immunogenicity and metastasizing capacity.

The effector arm of antibody-dependent cellular cytotoxicity (ADCC) was evaluated using 51Cr-labelled chicken erythrocytes as targets in BALB/c mice transplanted with the Moloney sarcoma virus-induced tumours T-MSV and MS2, and in C57BL/6 mice transplanted with the chemically induced FS6 sarcoma, Lewis lung carcinoma and B16 melanoma. Tumour-bearing animals showed higher levels of ADCC than normal mice, a stimulation confirmed in MS2-bearing mice, using SL2 lymphoma cells as targets in a cytostasis assay. ADCC effector-cell capacity was higher in animals transplanted with the immunogenic, spontaneously regressing T-MSV than in mice bearing the poorly immunogenic metastasizing MS2 sarcoma. The increased ADCC activity detectable in the spleen of tumour-bearing hosts was not abolished by removal of phagocytic-adherent cells.

Animals↗

Epidoxorubicin and double biochemical 5-fluorouracil modulation with folinic acid and human lymphoblastoid interferon in advanced gastric carcinoma: a multicentric phase II study of the Southern Italy Oncology Group (GOIM).

In our previous randomized trial of advanced gastric cancer patients, the addition of epirubicin (EPI) to 5-fluorouracil (FU) with folinic acid (FA) resulted in an improved response rate and survival in the responder patients. Preclinical studies also showed an enhancement of FU and anthracyclines with interferon. To evaluate the possibility of human lymphoblastoid interferon (IFN) to enhance the therapeutic activity of the FA-FU + EPI combination regimen, 39 advanced gastric cancer patients received: FU at 375 mg/m2 i.v. immediately after FA (l-isomer form) at 100 mg/m2 i.v. for 5 consecutive days; EPI at 60 mg/m2 i.v. on day 1, and IFN 3 MU s.c. for 7 consecutive days, starting 2 days before the FA-FU administration. Thirty-seven patients were evaluable for response and toxicity. Twelve partial responses were observed with an overall response rate of 32% (95% CI, 17-48%). The median response duration was 6 months, and the median survival time was 8 months. Toxicity was mild and no grade 4 side effects or treatment-related deaths were observed. However, the addition of IFN to the FA-FU + EPI regimen did not improve response, duration of response or survival.

Adult↗

Biological properties of cell lines derived from Moloney virus-induced sarcoma.

Two cell lines derived from a primary MSV-M-induced tumor in a BALB/c mouse were studied. One line (MS-2) was subject only to continuous tissue culture transfer (tct). After 21 tct, MS-2 cells produced progressive tumors (MS-2 tumors) in syngeneic hosts. The second cell line (MS-2T) was established by cultivation of a MS-2 tumor. The ability to produce progressive tumors decreased with increased number of tct, in both cell lines. The virus content of MS-2 and MS-2T cells was very low, as shown by uridine incorporation and electron microscopy. Immmunofluorescence tests demonstrated that antigens different from the viral MSV-M antigens were present on the cell lines, and that antigenic changes occurred with increased number of tct. Serum of mice bearing progressive MS-2 tumors reacted with MS-2T cells when these cells produced progressive tumors and did not react with MS-2 cells when they produced regressing tumors. MS-2 cells producing regressing tumors reacted with serum from mice in which the MS-2 tumor had regressed and with serum from mice immunized with MS-2T cells at late tct when they were poorly oncogenic. The antigenic changes seemed, therefore, to parallel the decrease of malignancy. A chromosomal analysis carried out on MS-2 and MS-2T cells, when both produced progressive tumors, showed a modal number of 48 and 44, respectively. MS-2T cells showed a large acrocentric chromosome. In contrast, the MS-2 cells at late tct, when they gave regressing tumors, showed a modal number of 60 and a wide range of distribution of chromosome number.

Animals↗