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Biomedical subjects

A Freschi

Publications and source records attributed to A Freschi.

12 recordsLinked to original sources
PubMed1998

[Computer-assisted image postprocessing in intraoral digital radiography].

INTRODUCTION: Computer-assisted postprocessing was performed on selected digital dental radiographs using a professional software for photographic retouching. MATERIALS AND METHODS: The optical characteristics of 22 digital intraoral images (radio-videographies) taken on 18 patients were modified as regards their density and contrast values. Three different kinds of densitometric curves, corresponding to particular changes in post-processing parameters, were preliminary defined as the most effective for the demonstration of root canals and of alveolar bone. They were then applied to each X-ray image and the pictures thus modified were subsequently printed and read on a blind basis by three observers who considered the conspicuity of each structure of interest (root canals and alveolar bone). RESULTS: The results, submitted to statistical analysis, demonstrate that computer-assisted postprocessing can improve the visual yield and the diagnostic effectiveness of digital dental images in 67% of cases for the periapical bone and in 86% of cases for the root canals. CONCLUSIONS: The most effective sets of post-processing parameters established for each structure of interest are proposed together with a pre-programmed function to be introduced into the software of digital radiographic equipments.

Adolescent↗
PubMed1997

Pharmacokinetics and tolerance of vinorelbine in elderly patients with metastatic breast cancer.

25 patients older than 65 years with metastatic breast cancer were treated with vinorelbine 30 mg/m2 i.v. days 1 and 8 every 3 weeks; the pharmacokinetics were studied in 10 of them. Vinorelbine showed a large apparent volume of distribution (mean 23.4 l/kg), a long terminal half-life (mean 26.2 h) and a large systemic clearance rate (mean 1.2 l/kg). These results are similar to those reported in younger patients. No correlation has been found between toxicity, age and drug exposure. We observed 6 partial responses out of 20 evaluable patients despite a relatively low mean dose intensity (67%). Severe neutropenia occurred in 37% of the patients; other side-effects were acceptable. This study does not provide a pharmacokinetic rationale for reducing the dosage of vinorelbine in selected elderly patients.

Age Factors↗
PubMed1996

Sensitive high-performance liquid chromatographic method with fluorescence detection for measurement of vinorelbine plasma concentrations.

A high-performance liquid chromatographic (HPLC) method with fluorescence detection for the determination of vinorelbine in plasma is described. The technique was derived from that published by Debal for an assay of vinorelbine in cell culture medium. The modifications concern the preparation procedure for plasma samples (a two-step liquid-liquid extraction from plasma is described), optimization of the mobile phase composition, and use of a single C18 column. These changes resulted in an improved sensitivity and reproducibility of the assay and led to its feasibility for clinical pharmacokinetic studies. The range of the assay is 2 to 1000 ng/ml.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Pharmacokinetics of vinorelbine in patients with liver metastases.

BACKGROUND: The main elimination pathway of vinorelbine is hepatic metabolism, and the clearance of vinorelbine could be reduced in patients with liver metastases. OBJECTIVES: To study the pharmacokinetics of vinorelbine in patients who have advanced breast cancer with or without liver metastases and to study the relationship between hepatic function and vinorelbine clearance. PATIENTS AND METHODS: We studied 29 patients with advanced breast cancer: 19 with liver metastases and 10 control patients with extrahepatic metastases (mean age, 61 years; age range, 38 to 81 years). The vinorelbine dose was 30 mg/m2 as a short intravenous infusion; the dose was reduced by 50% in patients with bilirubin > 2 mg/dl. Patients were classified by ultrasonographic estimation of the liver volume replaced by tumor (%LVRT). Standard liver function tests and a monoethylglycinexylidide test (a quantitative liver function test based on lidocaine metabolite formation) were performed. Vinorelbine was assayed in plasma by HPLC with fluorescence detection. Vinorelbine determination was impossible in two patients with more than 75% LVRT because of interferences. Pharmacokinetic parameters were calculated with a noncompartimental method and compared by means of the Kruskal-Wallis test. RESULTS: A lower vinorelbine clearance rate was observed in the five patients with more than 75% LVRT (22.9 L/hr/m2) compared with the 10 patients with no liver metastases (48.0 L/hr/m2) and the 12 patients with 25% to 75% LVRT (45.3 L/hr/m2). Terminal elimination half-life and apparent volume of distribution were not significantly different among groups. The monoethylglycinexylidide test had a significant correlation with vinorelbine clearance. (r2 = 0.70; p = 10(-4). CONCLUSIONS: These results support vinorelbine dose reduction in patients with severe liver failure but not in patients with moderate secondary liver involvement. The monoethylglycinexylidide test may prove to be useful for vinorelbine dose individualization.

Adult↗
PubMed1995

Effect of cyclosporine on teniposide pharmacokinetics and pharmacodynamics in patients with renal cell cancer.

Five patients with metastatic renal cell cancer (RCC) entered this study. The patients received two courses of teniposide (VM26) (200 mg/m2/24 h i.v.) after which no objective response was observed: three patients had stable disease (SD) and two had progressive disease. Cyclosporine (CsA) (5 mg/kg/2 h followed by 30 mg/kg/48 h i.v.) was then added (VM26/CsA) and at least another two courses were administered. Pharmacokinetic and pharmacodynamic parameters were analyzed. CsA increased the area under curve (AUC) of VM26 in four out of five patients; on average, the variation in the paired AUC of VM26 was 41%. Nadir granulocyte count was lower (average 650/mm3, ranging from < 100 to 1800/mm3) after VM26/CsA than after VM26 (average 1260/mm3, ranging from 200 to 2100/mm3) (p < 0.01). Bilirubin concentration in the serum was increased after VM26/CsA compared with VM26 (p < 0.05). Finally, after two courses of VM26/CsA, four patients had stable disease and one patient had a minor response. In conclusion, the ongoing pilot study indicates that CsA affects both the pharmacokinetics and the pharmacodynamics of VM26.

Aged↗
PubMed1995

Induction and maintenance of monocyte cytotoxicity during treatment with liposomes containing muramyl tripeptide despite tachyphylaxis to the cytokine response.

Monocyte-mediated cytotoxicity (determined in a 72-h111In release assay) and the circulating levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, IFN-gamma, C-reactive protein, and beta2-microglobulin were determined in 14 melanoma patients treated with multilamellar vesicle liposomes containing muramyl tripeptide phosphatidylethanolamine, 4 mg twice a week for 12 weeks. Monocyte-mediated cytotoxicity increased 24 h after the first infusion in 9 of 14 patients and had reached maximum levels (mean, 44% +/- 8) in all patients by the sixth week; similar values were observed at the 12th week. Once increased in vivo, peripheral blood monocyte cytotoxicity was not susceptible to any further increase after a subsequent in vitro incubation of the monocytes with liposomes. However, the peripheral blood monocytes which were not cytotoxic in vivo were activated by in vitro incubation with liposomes and not by medium. TNF-alpha and IL-6 peaked 2 h after the first infusion and returned to baseline values at 24 h; they were not significantly increased by subsequent treatments. The induction of fever in patients, observed 2 h after the first infusion, correlated with TNF-alpha and IL-6 levels. Similarly, C-reactive protein levels also increased at 24 h, but only after the first dose. No increase in beta2-microglobulin and IL-1beta levels was observed, and IFN-gamma was never detected in serum. Two patients experienced stable disease lasting 7 and 12 months, and 12 patients progressed. These results show that multilamellar vesicle muramyl tripeptide phosphatidylethanolamine administration activates monocyte cytotoxicity and cytokine production (TNF-alpha, IL-6). Chronic treatment with multilamellar vesicle muramyl tripeptide phosphatidylethanolamine results in tachyphylaxis in terms of cytokine secretion but not cytotoxicity. There was no difference between the maximum cytotoxicity levels obtained in vivo and those obtained in vitro using the same agent. A better understanding of immunoregulation is required for a rational application of this and related immunotherapies.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Feasibility and efficacy of arginine 2-mercaptoethanesulfonate (ARGIMESNA) in the prevention of hemorragic cystitis from ifosfamide (IFO).

Tolerability and efficacy of the new uroprotective agent ARGIMESNA was assessed within a randomized cross-over study comparing it to sodiummercaptoethanesulfonate (MESNA), in patients treated with IFO. MESNA i.v., 20% of IFO dose, was given to all patients before chemotherapy; 4 h later, at random, they received ARGIMESNA p.o., 20% of IFO dose every 2 h x 4, or MESNA p.o., 40% of IFO dose every 4 h x 2. Overall, 78 cycles of oral uroprotection were administered: 37 for ARGIMESNA capsules; 41 for MESNA vials p.o. ARGIMESNA was subjectively better tolerated, determining gastro-intestinal discomfort in only 12 out of 37 cycles versus 34/41 of MESNA p.o. (p less than 0.001). Both preparations were equivalent for subjective and objective efficacy since no cycles were complicated by urinary symptoms (dysuria, stranguria, or hematuria). Nevertheless, 2 patients (7.7%) refused further oral assumption of both uroprotectors, whereas MESNA i.v. was added in other 7 patients because of nausea and vomiting caused by chemotherapy. In conclusion, this new oral preparation of mercaptoethanesulfonate turned out to be well tolerated, safe and active in the prevention of haemorrhagic cystitis from IFO.

Adolescent↗
PubMed1990

Flavone acetic acid distribution in human malignant tumors.

The pharmacokinetics of flavone acetic acid (FAA) after a dose of 4.8 mg/m2 given i.v. over 1 h was investigated in 13 patients with different solid tumors. The mean volume of distribution and clearance were 52 +/- 4 l/m2 and 2.6 +/- 0.2 l/h x m2, respectively. A tumor or metastasis biopsy was obtained from six patients 2 h after the end of infusion. Tumor FAA levels ranged from 39.6 to 148.8 micrograms/g and were similar to those obtained after a therapeutic i.v. dose of 200 mg/kg FAA in animals bearing Pan/03 tumor, which is very sensitive to the drug. Although FAA tumor concentration could be detected only during one interval and we therefore cannot draw a definitive conclusion, differences in the agent's antitumor activity in mice and patients (i.e. very active in the former and inactive in the latter) are apparently not due to discrepancies in drug distribution and pharmacokinetics.

Adult↗
PubMedDate not supplied

Occult small cell lung cancer associated with paraneoplastic neurologic syndrome: case report.

Cancer is often associated with paraneoplastic syndromes, which may be misinterpreted. We report a case of a patient with occult small cell lung cancer that was initially compounded by clinical features of a paraneoplastic neurologic syndrome. The presence of antineuronal antibodies and positron emission tomography scan guided the search for the underlying tumor. Following chemo-radiotherapy the patient showed no evidence of disease for the next 18 months, whereas only a slight improvement in the neurologic disorders was observed. The course of the small cell lung cancer was very indolent and the paraneoplastic neurologic syndrome did not worsen with the use of cisplatin.

Ataxia↗
PubMedDate not supplied

Soluble intercellular adhesion molecule-1 and serum cytokines in melanoma patients treated with liposomes containing muramyl tripeptide.

AIMS AND BACKGROUND: A soluble form of intercellular adhesion molecule-1 (sICAM-1) has been recently identified in patients with malignant melanoma. It has been demonstrated that inflammatory cytokines can modulate the cellular expression of ICAM-1 and the shedding of this molecule by cells. To our knowledge, few data exist on serum sICAM-1 levels in cancer patients treated with immunomodulators. Liposomes containing muramyl tripeptide (MLV MTP-PE) can activate monocytes from cancer patients in vitro and in vivo, making them cytotoxic such as tumor necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). The purpose of the present study was to evaluate the levels of sICAM-1 and their possible correlation with serum inflammatory cytokine levels in melanoma patients treated with MLV MTP-PE. METHODS: The sera from 9 patients with metastatic melanoma treated with MLV MTP-PE, 4 mg i.v. twice a week for 12 weeks, were tested in ELISA system to detect sICAM-1, TNF-alpha, IL-6, Interleukin-1 beta (IL-1 beta) and Interferon-gamma (IFN-gamma) before, and 2 and 24 h after the 1st, 12th and 24th infusion of MLV MTP-PE. RESULTS: Baseline levels of sICAM-1 were elevated in all patients (median 540 ng/ml: range 400-1030 ng/ml). Twenty-four h after the 1st infusion of MLV MTP-PE, we observed 6 increases in sICAM-1 levels, 1 decrease and 2 stable values (median 720 ng/ml: range 410-1820; P = 0.060). Twenty-four h after the 12th infusion, sICAM-1 increased in 3 patients and did not change in 4 (median 790 ng/ml: range 495-1650 ng/ml; P = 0.069). At the 24th infusion, sICAM-1 increased in 4 of 6 evaluable patients and remained stable in 2 (median 802 ng/ml: range 510-1450 ng/ml; P = 0.045). To better analyze the variations in sICAM-1, the patients were arbitrarily divided into two groups according to their clinical behavior: 4 presented stabilization (all lesions, n = 2; some lesions, n = 2) (Group A); 5 presented progressive disease (Group B). In Group A, sICAM-1 levels remained stable or showed a modest increase during treatment (except in 1 patient, who exhibited a substantial variation after the 12th infusion). In contrast, in Group B very high levels of sICAM-1 were observed at the beginning of the study therapy in 1 patient and after the 1st infusion in 3 patients; these values remained high until the 24th infusion. In most of the patients, TNF-alpha and IL-6 increased after the 1st infusion, but not thereafter. IFN-gamma was never detected; IL-1 beta was detectable in a few cases, but only before the infusions. CONCLUSIONS: baseline levels of sICAM-1 were elevated in all patients and further increased during treatment only in patients with more aggressive disease. No correlation was found between sICAM-1 and inflammatory cytokines. It would therefore seem that in patients with advanced disease, higher levels and a progressive increase in sICAM-1 may be unfavorable prognostic factors.

Acetylmuramyl-Alanyl-Isoglutamine↗