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Biomedical subjects

T Mazzei

Publications and source records attributed to T Mazzei.

At least 91 records · Page 5Linked to original sources
PubMed1985

Enhancement of fluoropyrimidine cytotoxicity by 5-methyltetrahydrofolate in a human leukemia cell line, CCRF-CEM.

The inhibitory effects of combined 5-methyltetrahydrofolate (5-CH3-THF), the physiological circulating folate species, and fluoropyrimidines, 5-fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd), on growth of human leukemia cells, CCRF-CEM, were determined as a function of time, dose, and sequence of exposure. Exposure of CCRF-CEM cells in exponential growth to 5-CH3-THF (1-100 microM) for 4 h and to FUra (250 microM) or FdUrd (0.5 microM) during the last 2 h resulted in having synergistic inhibitory effects on cell growth. Synergy was dependent on 5-CH3-THF dose (100 greater than 10 greater than 1 microM) and did not occur at 0.1 microM. No clear dependency of synergy on sequence was observed with FUra and 5-CH3-THF combinations (4 h exposure, 5-CH3-THF----FUra, 5-CH3-THF + FUra, or FUra----5-CH3-THF). With 5-CH3-THF and FdUrd combinations, synergy was dependent on sequence of exposure (5-CH3-THF----FdUrd and 5-CH3-THF + FdUrd were synergistic, but FdUrd----5-CH3-THF was not). Thymidine (0.1 microM), added after drug treatment, substantially rescued CCRF-CEM cells from 5-CH3-THF-FUra cytotoxicity. L-Methionine (1500 mg/l) completely protected CCRF-CEM cells from the toxicity of the combination 5-CH3-THF-FdUrd. The results are consistent with the hypothesis that the mechanism by which 5-CH3-THF potentiated fluoropyrimidine cytotoxicity is the enhancement of ternary complex formation between thymidylate synthase and 5-fluorodeoxyuridylate, the active metabolite of fluoropyrimidines, as a consequence of an increase of intracellular levels of 5-10-methylenetetrahydrofolate generated from 5-CH3-THF.

Cell Division↗
PubMed1985

Infections in immunocompromised patients. II. Established therapy and its limitations.

Diseases affecting host defense mechanisms include neutropenia, aplastic anemia, leukemia, lymphocytopenia (B- and T-lymphocyte abnormalities), deficiencies of complement, splenectomy, diabetes mellitus, renal failure, and autoimmune diseases. Immunocompromised patients face frequent life-threatening complications of infections, particularly when they are hospitalized and receiving cytotoxic myelosuppressive drugs. Oral antimicrobial agents affect the flora of the host's alimentary tract, enhancing colonization by resistant, potentially pathogenic, strains and species, especially in a hospital environment. Nalidixic acid, oxolinic acid, pipemidic acid, polymyxins, co-trimoxazole, polyene antibiotics, and framycetin, which preserve anaerobic colon flora, do not affect the host's colonization resistance and can be given in oral doses high enough to suppress and clear susceptible potential pathogens from the intestinal tract. Such prophylactic treatment permits patients to stay hospitalized in ward conditions. In the compromised host who has fever and suspected septicemia, a decision concerning treatment should be made within an hour of notification of the patient's condition. In acute stages of life-threatening infection, the principal aim of antimicrobial chemotherapy is to provide the most potent treatment; at this stage, the accompanying side effects are less important. An essential component of therapy should be an aminoglycoside paired with a beta-lactam antibiotic. Because the incidence of staphylococcal resistance to antibiotics is high, preliminary sensitivity-testing is essential when staphylococcal sepsis threatens the life of a compromised host. Despite aggressive antibiotic therapy, more than half of immunocompromised patients and patients with severe underlying diseases die when gram-negative bacteria invade their blood. In these patients, medical or surgical removal of the septic focus is a major part of management, but plasma or plasma fractions should be given to correct hypovolemia, and an agent such as dopamine should be administered if volume replacement fails to restore adequate blood pressure. A high dose of corticosteroids should have a beneficial effect, and, for neutropenic patients with gram-negative bacteremia or fever, transfusion with functional neutrophils improves survival.

Aminoglycosides↗
PubMed1984

Chemistry and mechanism of action of bleomycin.

Bleomycin (BLM) is an antitumoral antibiotic active against various animal and human tumors. BLM causes a lot of biological effects characteristic of drugs which attack the DNA in cells. The nature of DNA damage consists of the release of bases and single and double-strand breaks. The Fe (II) is a necessary cofactor in the reaction of BLM with DNA. BLM is effective principally against non-dividing cells and against cells in mitotic phase, G2 and S. The various contents of BLM inactivating enzymes in tissues can explain the particular toxicity and therapeutic activity of this drug.

Animals↗
PubMed1984

Single-dose ceftriaxone versus multi-dose cefotaxime as short-term antimicrobial prophylaxis in urologic surgery. Preliminary results of a multicenter prospective randomized study.

This controlled multicenter study on 407 evaluable patients demonstrates the equal efficacy of two short-term antimi crobial prophylactic regimens in urological surgery involving a single dose of a long-acting cephalosporin, ceftriaxone, in comparison with a multiple dose of cefotaxime. Fifty-three of the 196 patients (27%) on the cefotaxime regimen and 47 of the 211 patients (22.3%) who received ceftriaxone showed postoperative infectious complications. There were no differences in these results.

Adult↗
PubMed1984

Single-dose ceftriaxone versus multi-dose cefotaxime antimicrobial prophylaxis in gynecologic and obstetrical surgery. Preliminary results of a multicenter prospective randomized study.

This multicenter, prospective and randomized study on 355 patients demonstrates the equal efficacy of two short-term antimicrobial prophylactic regimens in gynecologic and obstetrical surgery involving a single dose of a long-acting cephalosporin, ceftriaxone, in comparison with a multiple cefotaxime dose. Among the cefotaxime and ceftriaxone groups which underwent abdominal hysteroctomy, 15 of 112 (13.4%) and 20 of 97 (20.6%) patients developed infections respectively. Four vaginal hysterectomy patients out of 20 (20%) on cefotaxime regimen and 4 of 25 (16%) who received ceftriaxone, became infected (febrile morbidity, wound infections, bacteriuria and infectious complications at a non-surgical site). Also among the cefotaxime and ceftriaxone groups of emergency or elective cesarean sections the differences on the incidence of infections are not statistically significant.

Adult↗
PubMed1984

Comparative pharmacokinetic evaluation of ceftriaxone and cefotaxime in coincidence for short-term antimicrobial prophylaxis in surgery.

In 48 patients undergoing elective gynecological, urological and otorhinolaryngological surgery a pharmacokinetic study after 1 g dose of ceftriaxone or cefotaxime was done. Concentrations of the two antibiotics were studied in interstitial fluid with the suction blister technique and in some tissues collected during the operation. The mean tissue levels were generally higher after ceftriaxone administration than after cefotaxime and for both drugs they were lower than the contemporary drug levels in interstitial fluid. However at the concentrations found almost all aerobic and anaerobic bacteria causing postoperative wound infections are inhibited.

Cefotaxime↗
PubMed1984

Cisplatin and etoposide combination in the treatment of bronchogenic carcinoma.

The authors investigated the activity of a combination of DDP 80 mg/m2 i.v. followed by VP16 50 mg/m2 on days 2-5 in bronchogenic carcinoma. Twenty-seven patients entered the study (10 small cell carcinoma, 9 squamous cell, 2 adenocarcinomas and 6 histologically undefined). Six patients evidenced partial response (22.3%); one patient (small cell) had complete remission. The toxicity of the regimen was scarce and well-tolerated by patients with an incidence of 88.8% alopecia, and 77.7% nausea and/or vomiting.

Adenocarcinoma↗
PubMed1984

Modulation of fluoropyrimidine cytotoxicity by methotrexate or 5-methyltetrahydrofolate in human leukemia cells in vitro.

The effects of methotrexate, 5-fluorouracil, 5-fluoro-2'-deoxyuridine on the growth of human leukemic T-lymphoblasts, CCRF-CEM, were determined as a function of drug concentration and exposure time. Substantial inhibition of cell growth (greater than or equal to 90%) was obtained with short duration of exposure (4 h) for MTX (ED90 = 4.3 microM). 5-fluorouracil was a relatively ineffective cytotoxic agent for exposure of short duration (4 h). Only exposure of 24 and 72 h resulted in cell growth inhibition greater than or equal to 90% with this drug. In terms of a ED90, 5-fluoro-2'-deoxyuridine was about 190- and 1300-fold more active than 5-fluorouracil for 24 and 72 h exposures, respectively (0.4 vs 75 microM and 0.01 vs 26 microM). Sequential exposure to methotrexate (4 h) and 5-fluorouracil during the last 2 h of methotrexate exposure resulted in synergistic inhibitory effects on cell growth. Antagonistic inhibitory effects on cell growth of methotrexate and 5-fluoro-2'-deoxyuridine combinations were observed independently of drug concentrations. Pretreatment (4h) with 5-methyltetrahydrofolate, the reduced folate to which leucovorin is rapidly converted in vivo, potentiated cell growth inhibitory effects of subsequently administered 5-fluorouracil or 5-fluoro-2'-deoxyuridine. These results provide information on scheduling of methotrexate or reduced folates and fluoropyrimidines that might have potential importance in the development of clinical trials designed for patients with leukemia and lymphoma.

Cells, Cultured↗
PubMed1984

Preliminary research on the evaluation of some prognostic factors in a randomized study of adjuvant immunochemotherapy in colorectal adenocarcinoma.

In a randomized, multicenter study, 168 evaluable patients with colorectal adenocarcinoma at B2, C1 or C2 stages of the Dukes, Astler and Coller classification, were treated after radical surgery with BCG and 5-fluorouracil alone (regimen A) or in combination with hydroxyurea, methyl-CCNU and mitomycin C (regimen B). Radiation therapy was mandatory after surgery for rectal cancer. Response to therapy was evaluated for length of disease-free interval after surgery and was analyzed in comparison to the data obtained upon entrance to the study. The results are reported as life curves of the duration of the disease-free interval for treatment in comparison to the presence or absence of various signs or symptoms of disease. Also reported are responses obtained using the Cox method for linear regression analysis on non-parametric data, that gave information on the importance of various prognostic factors.

Adenocarcinoma↗
PubMed1984

Polychemotherapy in ovarian cancer: treatment with Adriamycin, BCNU and cyclophosphamide vs. Adriamycin and cyclophosphamide.

The authors compared both therapeutic efficacy and toxicity of two different treatment regimens: ABC = adriamycin, nitrogen mustard (BCNU) and cyclophosphamide (CTX) vs. AC = adriamycin and cyclophosphamide in ovarian cancer. Thirty-one patients were entered under treatment plan ABC and 26 under treatment plan AC simultaneously. Therapeutic evaluation was subdivided into different risk groups (adjuvant therapy, residual disease less than or greater than 2 cm). A similar result could be noted in the two different treatment regimens. Toxicity was more severe and frequent in the group treated with BCNU. The AC regimen was preferred because of its lower incidence of side-effects and for its easier mode of administration.

Adenocarcinoma↗
PubMed1982

Estradiol and progestin receptors, 17-beta-hydroxysteroid-dehydrogenase and histopathologic grade in endometrial carcinoma.

The possible correlation between steroid receptor systems, 17-beta-HSD and histopathologic examinations were investigated. The well-differentiated tumors showed higher steroid receptor and 17-beta-HSD values than undifferentiated carcinomas. The steroid receptors did not present a statistically significant correlation with 17-beta-HSD. Nevertheless, some neoplastic endometria (29%) show higher values of progestin receptors and 17-beta-HSD, with a progestin:estrogen receptor ratio greater than one.

17-Hydroxysteroid Dehydrogenases↗
PubMed1976

Amikacin in obstetric, gynecologic, and neonatal infections: laboratory and clinical studies.

Based on the proportion of resistant, moderately sensitive, and sensitive strains, the descending order of activity of amikacin against clinical isolates of urinary pathogens was Salmonella, Klebsiella, Enterobacter, Escherichia coli, Staphylococcus aureus, Citrobacter, Proteus species, and Pseudomonas aeruginosa. However, amikacin was the most active of the antibiotics tested (including gentamicin and tobramycin) against 100 strains of P. aeruginosa. The calculated half-life of amikacin was substantially longer in patients with compromised renal function than in normal subjects. Immaturity of renal function, characteristic of the newborn, similarly slowed the rate of excretion of amikacin. The cure rate (complete clinical remission and eradication of the pathogen) was 91% in 22 patients with urinary tract infection (including 16 with chronic pyelonephritis) treated with 500 mg of amikacin every 8 or 12 hr for eight to 17 days. After single injections of 7.5 mg/kg 2-3 hr before delivery, appreciable amounts of the drug were recovered from the cord blood. No local or systemic intolerance or laboratory abnormalities were observed in a total of 42 patients (including eight infants) treated for a maximum of two weeks. No ototoxicity was demonstrable in any of the 12 patients subjected to audiometry; nystagmography revealed slight vestibular dysfunction in two elderly patients.

Amikacin↗
PubMedDate not supplied

[Chemotherapy of gestational chorionepithelioma].

The department of Gynecology and Obstetrics of Florence University reports the following findings for the chemotherapy of gestational choriocarcinoma during the period 1962-74. Sixteen cases, 11 of which were rated high risk cases, were given chemotherapy with MTX alone or in association with other cytotoxic agents. In the 12 surviving cases that may be considered the incidence of complete remission (from 4 to 13 years) is 67%. Of the 8 cases rated as cured 3 were high risk cases at the beginning of treatment. Intermittent chemotherapy with MTX only was given by slow intravenous injection at doses of 3 to 4 mg/kg for 24-48 h followed from the 48th h by folinic acid treatment for 1-2 days. This schedule is recommended because of its negligible toxicity as a replacemen for intramuscular MTX in 5-day courses, which carries a fairly high risk of toxicity.

Adult↗