Search PubMed⌕ Search

Biomedical subjects

G Milano

Publications and source records attributed to G Milano.

At least 199 records · Page 11Linked to original sources
PubMed1986

Altered pharmacokinetics and clinical consequences of low dose methotrexate plus cisplatin in the treatment of advanced head and neck cancer.

Thirty-two patients with head and neck carcinoma received a multidrug chemotherapy protocol including low dose methotrexate (LDMTX) (30 mg/m2) and cisplatin as their initial treatment. A sensitive immunoenzymatic technique was used for systematic MTX blood monitoring (0-56 hr) in all patients. The MTX-related side effects observed in 15 patients (47%) were significantly associated with an increase in systemic drug exposure occurring early during drug infusion. The average end-of-infusion concentration varied from 8 X 10(-7) M for nontoxic patients to 1.45 and 3.12 10(-6) M for moderately and severely toxic patients respectively. The area under the curve (AUC) (0-56 hr) was also directly related to the increase in side-effects. Total body clearance was reduced in an inverse manner. Volumes of distribution and terminal elimination half-lives were not related to the presence or intensity of MTX side-effects. Based on these data, the institution of folinic acid rescue adapted to the MTX blood concentration, a measure previously not suggested for LDMTX, completely prevented severe toxicity in a subsequent series of 26 patients without modification of the response rate.

Aged↗
PubMed1986

Hyper-induction of skin ornithine decarboxylase activity in psoriatic patients.

Ornithine decarboxylase activity was measured in skin from 14 normal and 24 psoriatic subjects (with stable plaque type psoriasis vulgaris) using punch biopsies carried out immediately (0 h) and 6 h after stimulation by cellotape stripping. At 0 h, no significant difference was found between normal and involved or uninvolved psoriatic skin, but a significant increase was measured 6 h after tape stripping. This increase was significantly greater in uninvolved and involved psoriatic skin compared with normal skin. Preliminary results indicated that these changes were localized in the epidermis.

Adolescent↗
PubMed1985

Continuous 5-day regional chemotherapy by 5-fluorouracil in colon carcinoma: pharmacokinetic evaluation.

Eighteen patients with liver metastasis or locoregional recurrence of colon carcinoma received locoregional treatment by continuous 5-day infusions of 5-FU. 5-FU blood levels were measured by HPLC every day of the cycle at 8 am and 5 pm for a total of 87 cycles. Twelve patients were given the drug by an intra-arterial hepatic (i.a.h.) route, 3 by the portal vein (i.p.v.) and 3 by an intra-arterial pelvic (i.a.p.) route. These three routes were compared in respect of their relative pre-systemic drug uptake and the effect of dose escalation. Both the i.a.h. and i.p.v. routes, but not the i.a.p. route, resulted in a significant reduction in AUC 0-105 h compared to the i.v. route at the same dose range. Increasing the dose led to a modification in circulating 5-FU levels proportional to the dose for the i.v. and i.a.p. routes. By contrast, for the i.a.h. and i.p.v. routes, systemic drug delivery was significantly elevated, out of proportion with the dose, indicating a saturable process. For the i.a.h. route, increasing the 5-FU dose from 780 to 1000 mg m-2 day-1 caused a drop in hepatic extraction from 0.93 (0.90-0.95) to 0.44 (0.21-0.66). Liver saturation mechanisms were also evidenced by a mean increase of 2.6 times for the circulating drug level during the second part of the cycle as compared to the first part (P less than 0.001). The evolution of 5-FU AUC 0-105 h as a function of the dose was exponential (r = 0.75, P less than 0.001). Local extraction consecutive to i.a.p. was non-existent, implying that this route of drug administration has no potential advantage over classical i.v. infusion.

Aged↗
PubMed1985

Distribution of polyamines in human epidermis.

Consecutive sections through the epidermis were cut parallel to its surface, and the polyamine (PA) concentration in each section was measured by liquid chromatography. There was a constant decrease in PA concentration (expressed as nmol/mg DNA) from the deepest layer to the more superficial layers. Putrescine showed the greatest increase (+83%) (P less than 0.02). The elevations of spermidine and spermine levels were less marked, respectively +30% (P less than 0.05) and +27% (NS). Proliferating cells in the basal layer possess high polyamine levels and as they mature in the superficial layers their polyamine content decreases.

Female↗
PubMed1984

Response of epidermal polyamines to orally administered aromatic retinoid RO 10-9359.

Polyamine levels were measured in skin (pure epidermis) and 24-h urine before and 15 days after the start of continuous oral treatment with Etretinate (1 mg/kg/day) in 20 patients with various dermatoses. In uninvolved epidermis, treatment modified levels of spermidine (45% increase, P less than 0.05) and spermine (30% increase, P less than 0.05). In urine, the putrescine concentration was significantly altered, increasing from 1.96 to 2.60 micrograms/mg creat (P less than 0.05). During the time interval considered, variations in polyamine levels did not reflect the inhibiting mechanism of retinoids on ornithine decarboxylase, the key enzyme in the regulation of polyamine synthesis.

Adult↗
PubMed1984

[Interventional radiology in chemotherapy. Percutaneous arterial route and and embolization with microspheres].

The authors present their experience with interventional radiological techniques employed for chemotherapy: 205 intra-arterial chemotherapy (IAC) cycles were administered to 67 patients (lesion sites were: liver 20, pelvis 35, unknown 12). Catheters were left in place for 5 days in 89% of cases. The positions of the end of the catheter was checked by CT scan, with concomitant arterial opacification in the case of pelvic pathologies; this allowed evaluation of the tumor volume treated. Serious radiological complications of IAC included: 2 surgical thrombectomies and 2 surgical removals of broken catheters (2% complication rate for IAC). 15 embolizations with microcapsules of mitomycin were performed for 11 patients, using the technique of Kato. Venous blood samples revealed the persistence of mitomycinemia for up to four hours. three instances of pain were noted in the 24 hours following embolization. These two techniques have a low rate of serious complications; the therapeutic efficacy observed in certain cases warrants the use of these methods for cancers impossible to treat by radical procedures.

Adult↗
PubMed1983

An enzyme immunoassay design using labelled antibodies for the determination of haptens. Application to methotrexate assay.

A competitive enzyme immunoassay with labelled antibodies has been developed for methotrexate (MTX). Methotrexate in the sample and a constant quantity of this hapten physically absorbed to polystyrene spheres through a methylated bovine albumin carrier were allowed to compete for a limiting amount of peroxidase labelled antibody. After washing, the residual enzyme activity bound to the solid phase was measured. This test was able to detect 10 fm of MTX per sample. A comparative study of this test with a commercial radioimmunoassay kit using the same antiserum and a high pressure liquid chromatography method showed that the sensitivity, specificity and precision of this test were as good as of the radioimmunoassay. The high pressure liquid chromatography method was 500 times less sensitive. Good agreement was found among the 3 methods on 83 serum samples from patients receiving methotrexate therapy.

Animals↗
PubMed1983

Plasma levels of 7-hydroxymethotrexate after high-dose methotrexate treatment.

Thirteen patients with cancer being treated with high-dose methotrexate (MTX) chemotherapy (350-5,000 mg/6 h IV were entered in this study. Plasma levels of MTX and 7-OHMTX, its main circulating metabolite, were measured by an HPLC technique. 7-OHMTX appears rapidly in the blood, reaching a maximum 6-12 h after the beginning of treatment. The elimination of 7-OHMTX is slower than that of MTX, but the elimination half-lives (24-48 h) are not significantly different: 25.2 h for 7-OHMTX versus 20.3 h for MTX. In all cases, 24 h after starting infusion plasma levels of 7-OHMTX exceeded those of MTX. There was a positive and significant correlation between the dose administered and peak plasma 7-OHMTX. Finally, 7-OHMTX formation was shown to be relatively stable throughout the treatment.

Adolescent↗
PubMed1983

Polyamine levels in normal human skin. A comparative study of pure epidermis, pure dermis, and suction blister fluid.

The polyamines putrescine, spermidine, and spermine were detected and measured in both free and total forms in man in pure epidermis, pure dermis, suction blister fluid, blood, and 24-h urines. The technique employed for polyamine measurement consisted in liquid chromatography by ion exchange using an automatic amino acid analyzer and a fluorescence detection system. Polyamine concentrations were found to vary significantly between the dermis and the epidermis, both quantitatively and qualitatively: spermidine and spermine levels were much higher in the epidermis than in the dermis, and putrescine&spermidine and spermidine/spermine ratios were much lower in the epidermis. These differences reflect the known differences in cellularity, proliferative activity, and differentiation between these two cutaneous regions. The high spermidine and spermine concentrations in the epidermis suggest that these substances play a special role in this tissue.

Adult↗
PubMed1983

Simultaneous micro measurement of steroid receptors in breast cancer.

The oestradiol (RE) and progesterone (RP) receptor levels were analyzed in 26 tumour fragments (200-500 mg) from breast cancer patients. After pulverization of tissue, one part was analyzed by the routine dextran-coated charcoal (DCC) method and the other by a micromethod as follows: (i) cytosol incubation using the DCC method but in the simultaneous presence of [3H]oestradiol and [3H]R5020 (ii) extraction of the steroids bound to the receptor by precipitation with ethanol/TCA (iii) high pressure liquid chromatography (HPLC) on a modular system, with a C185 microns column and an elution by gradient mixture methanol/water. The fractions were collected and the radioactivity counted. The separation of oestradiol from R 5020 was rapid and complete. In addition dexamethasone was separated by this system making possible triple measures of RE, RP and glucocorticoid receptors. A highly significant correlation was obtained between the 2 methods: RE = 0.996, P less than 0.001; RP r = 0.975, P less than 0.001, implying that the thresholds of positivity, i.e. for therapeutic decisions, remain unchanged. Simultaneous measurement of RE and RP in a single needle biopsy is possible with this micromethod.

Breast Neoplasms↗
PubMed1983

[Host-tumor relationship as a function of the orosomucoid-prealbumin ratio].

Of the various prognostic factors for cancer, biological parameters of the Host/Tumour relationship allow objective evaluation of the conflict between the organism and the disease. Alpha 1-acid glycoprotein (Orosomucoïd), which belongs to the Acute Phase Reactant's Proteins, and prealbumin, a highly sensitive nutritional protein, are two compounds whose blood levels vary in inverse proportion during perceptible-stage cancers: alpha 1-acid glycoprotein concentrations increase while prealbumin values drop. The ratio of the blood levels of these two parameters provides a more sensitive index than either parameter taken alone. Study of the orosomucoïd/prealbumin ratio (ROP) in a population of 132 patients and 63 controls revealed a good association between the ratio values and the different stages of the disease. The highest values corresponded to patients with active disease; normal levels were obtained for patients in partial or complete remission. During the course of disease, the orosomucoïd/prealbumin ratio is more reliable than the sedimentation rate. Furthermore, when measured at the onset of the disease, this ratio is an undeniable prognostic element, independent of the stage of disease extension.

Adolescent↗
PubMed1982

Polyamines as biological markers in malignant lymphomas.

The urinary polyamines putrescine (PU) and spermidine (SPD) were measured for 67 patients with lymphomas: 48 non-Hodgkin (NHL) and 18 Hodgkin's disease (HD). Monthly repeat measurements were obtained over an average follow-up period of 12.5 months. For NHL, a good association was observed between polyamine levels and the severity of the the stage; the distribution of values between nodular and diffuse forms was also significantly different. No such correlations were seen for HD. The evolution of PU values in time has been shown to reflect disease activity for NHL. Non-specific fluctuating Pu values were found in the case of HD. In the case of 20 patients with NHL undergoing chemotherapy, comparison of polyamine levels before and after chemotherapy allowed differentiation between the population of complete responders to treatment and those with only partial or no response.

Adolescent↗
PubMed1981

The diagnostic and prognostic value of urinary polyamine measurement in bladder cancer.

This study concerns a group of 54 patients with bladder cancer aged from 51 to 80 years (50 males, 4 females). Polyamines (putrescine -PU, spermidine - SPD) were measured on 24 h urine collections prior to surgery by an automatic ion exchange analyzer. Both polyamines, and especially PU, correlated well with the degree of tumor infiltration (JEWETT - MARSHALL stage) and mitotic activity (BROD -ER'S grade). Retrospectively, 28 patients for whom follow-up after surgery was 6 months to one year were classified into two groups: R+ (21) patients with disease recurrence or progression, and R0 (8) patients remaining tumour free. Twenty patients with high preoperative PU levels were in the R+ group. By contrast, 6 patients with normal preoperative PU levels were in the R0 group.

Follow-Up Studies↗