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Biomedical subjects

V Leoni

Publications and source records attributed to V Leoni.

At least 19 recordsLinked to original sources

A phase I trial of fixed dose rate gemcitabine plus capecitabine in metastatic cancer patients.

BACKGROUND: Capecitabine and gemcitabine given as fixed dose rate (FDR) has not been demonstrated to be well tolerated in phase I previous studies. The goals of this phase I study were to determine the maximum-tolerated dose of this combination and to describe the dose-limiting toxic effects (DLT) and the safety profile of this way of administration. PATIENTS AND METHODS: Patients with advanced solid tumors were eligible for this study. Capecitabine was administered orally at a dose of 650 mg/m(2) bis in die (b.i.d.) for 14 consecutive days. Gemcitabine was administered at FDR of 10 mg/m(2) per min in escalating durations of infusion on days 1 and 8. The cycles were repeated every 21 days. RESULTS: All 20 patients enrolled into the study were assessable for toxicity. Only one out of the first six patients treated at FDR gemcitabine dose of 800 mg/m(2) met protocol-specified DLT criteria (grade 4 neutropenia lasting >or=7 days) during the first two cycles. At these doses the majority of cycles of therapy were, however, delivered without dose reduction or delay. Another similar episode of DLT was observed at the same dose step among the following eight included patients. The dose of FDR gemcitabine 800 mg/m(2) in 80 min on days 1 and 8 plus capecitabine 650 mg/m(2) b.i.d., for 14 consecutive days followed by 1 week of rest is recommended for further study. CONCLUSION: The combination of FDR gemcitabine plus capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies.

Adult↗

Oxysterols and Alzheimer's disease.

There is a clear link between cholesterol turnover and neurodegenerative diseases and hypercholesterolemia is an established risk factor for Alzheimer's disease (AD). The failure to demonstrate a transfer of cholesterol from the circulation into the brain in humans and experimental animals makes it difficult to explain the link between hypercholesterolemia and AD. In contrast to cholesterol itself, side-chain oxidized cholesterol metabolites such as 24S-hydroxycholesterol and 27-hydroxycholesterol are able to pass the blood-brain barrier (BBB). Formation of 24S-hydroxycholesterol is the quantitatively most important mechanism for elimination of cholesterol from the brain and we recently demonstrated a significant net uptake of 27-hydroxycholesterol by the brain from the circulation. We have also shown that patients with AD have increased brain levels of 27-hydroxycholesterol, which may affect the production of beta-amyloid in the brain. The levels of 27-hydroxycholesterol in the circulation are correlated with the levels of cholesterol and the possibility must be considered that the flux of 27-hydroxycholesterol into the brain is the missing link between hypercholesterolemia and Alzheimer's disease. Current knowledge about the role of the two oxysterols for cholesterol homeostasis in the brain as well as their diagnostic potential are reviewed.

Alzheimer Disease↗

Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection.

Assessment of minimal residual disease (MRD) by flow cytometry is considered to be based on the reproducibility of the leukemic immunophenotype detected at diagnosis. However, we previously noticed modulation of surface antigen expression in acute lymphoblastic leukemia (ALL) during the early treatment. Hence, we investigated this in 30 children with B-cell precursor ALL consecutively enrolled in the AIEOP-BFM ALL 2000 protocol. Quantitative expression of seven antigens useful in MRD monitoring was studied at diagnosis and compared to that measured at different time points of remission induction therapy. Downmodulation in the expression of CD10 and CD34 occurred at follow-up. By contrast, upmodulation of CD19, CD20, CD45RA, and CD11a was observed, while the expression of CD58 remained stable. Despite this, we could unambiguously discriminate leukemic cells from normal residual B cells. This holds true when bone marrow (BM) samples from similarly treated T-ALL patients, but not from healthy donors, were used as reference. Our results indicate that immunophenotypic modulation occurs in ALL during the early phases of BFM-type protocols. However, the accuracy of MRD detection by flow cytometry seems not negatively affected if adequate analysis protocols are employed. Investigators should take this phenomenon into account in order to avoid pitfalls in flow cytometric MRD studies.

Antigens, CD↗

Cytogenetic biomonitoring of workers from laboratories of clinical analyses occupationally exposed to chemicals.

A cytogenetic monitoring study was carried out on a group of workers in clinical analysis laboratories to investigate the risk of occupational exposure to chronic low levels of chemicals.Thirty-four clinical laboratories have been involved in the study. In these laboratories, toxicants and analytical procedures utilized have been characterized. The individual occupational exposure of workers was assessed by use of a questionnaire concerning the chemical substances utilized. About 300 different chemicals have been identified. Cytogenetic analyses (chromosomal aberration and micronucleus tests) were carried out on a strictly selected group of 50 workers enrolled from these laboratories and compared to 53 controls (healthy blood donors) matched for gender and age. The exposed group shows a significantly higher frequency of genetic damage than the control group. Both chromatid and chromosome aberration frequencies in workers appear significantly higher than in controls. Similarly, comparison between micronucleated cells rates of exposed and unexposed groups show significantly higher frequencies of binucleated cells with micronucleus (BNMN) and of total micronuclei (MN tot) in workers than in controls.

Adult↗

[Survey of disinfectant usage in a polyclinic in Rome: preliminary results].

The authors describe the survey that was conducted in the largest hospital in Rome. The aim was to estimate the disinfectants and chemical sterilizers employed and asses possible hazards for patients and workers arising from the use of disinfectants, together with the problem of waste disposal. The study was conducted by means of a survey form that was distributed to 39 departments/institute in the whole hospital of which 24 (61%) responded. Overall 635 charts were collected listing 886 usage procedures and 110 formulations with 40 different active ingredients. The disinfection fields of use were: skin(52.4%) environment (28.8%) and hospital equipment (20.8%) This study shows that a modern hospital should select very few disinfectants and prepare a handbook that can explain disinfectant usage procedures and concentrations. In the guidelines the problem of waste disposal and employee safety should also be considered.

Containment of Biohazards↗

Bone-fracture incidence rate in two Italian regions with different fluoride concentration levels in drinking water.

The effect of the fluoride concentration in drinking water on the prevention of fractures related to osteoporosis has been questioned or contradicted in several recent studies. These studies have been mostly performed using water with artificially added fluoride, at the optimum level of about 1 mg/l. In the present study authors have investigated the effect of equal or greater fluoride concentrations (mean 1.45 mg/l) naturally present in waters supplied for human consumption to a population of 72.756 (Bracciano county), in comparison with a population of 126.189 (Avezzano county), supplied with low fluoride concentration water (mean 0.05 mg/l). The incidence of fractures in the years 1990 and 1991 was evaluated in the two areas (Bracciano and Avezzano), which are located in central Italy and where population have a similar life style, economic and social level and employment structure. The incidence data were obtained from the registers of the public hospital taken as a reference in each district. The authors noticed a significantly greater rate of fracture incidence at several parts of the body, in particular femur fractures (relative risks for males 4.28 and for females 2.64), in the population of the district of Avezzano than in the population of Bracciano. The greater concentration of fluoride in waters distributed for human consumption in Bracciano district seems to have the effect of protecting its inhabitants against fractures.

Fluorides↗

PCB and other organochlorine compounds in blood of women with or without miscarriage: a hypothesis of correlation.

Polychlorobiphenyls (PCBs) have been shown to affect reproduction in experimental animals and in human beings following intoxication. The concentrations of PCBs and other organochlorine compounds were determined in blood samples from 120 women hospitalized for miscarriages and 120 full-term pregnancy controls. The average PCB hematic level (reported as Fenclor 54) was higher in women with miscarriages than in control women. No differences were detected as far as the hematic concentrations of hexachlorobenzene and DDT compounds were concerned. The reproductive history of each woman was assessed together with confounding variables on the phenomenon of miscarriage and the factors regarding environmental exposure and food intake. Food consumption did not indicate diet as the main source of PCB intake.

Abortion, Spontaneous↗

Spontaneous abortion in relation to the presence of hexachlorobenzene in the Italian environment.

This study determined hexachlorobenzene (HCB) levels in the blood of women who had suffered spontaneous abortions (120 cases) and women with healthy reproductive functions (120 controls). Samples were collected in 1984 during an epidemiological investigation into the relation between polychlorobiphenyl levels in the blood and spontaneous abortion in the women. Evaluation of the HCB data showed no significant differences between the groups, the blood of the group with spontaneous abortion containing 1.6 +/- 1.6 ppb HCB compared with 1.5 +/- 1.1 ppb for the control group.

Abortion, Spontaneous↗

Application of a simplified method for recovery of Yersinia enterocolitica from surface waters.

Yersinia enterocolitica was recovered from surface water by a simplified method: samples were taken by means of the Moore tampon and, after a short, warm preincubation in peptone-sorbitol-bile salts broth, were quickly passed to an alkali solution. Immediately after this, samples were directly plated on MacConkey agar. Y. enterocolitica was isolated from 60% of the water samples, and the identification confirmation of the strains chosen was 100%.

Bacteriological Techniques↗

[Polychlorinated diphenyls (PCB) : industrial hygiene and environmental toxicology].

The industrialized countries have been producing, every year from 1929, thousands of tons of polychlorinated biphenyls (PCB). Although it was known from that period the toxic activity of PCB (chlorancne), only from 1966 their presence and persistence in the environment has been detected and their mechanism of bioconcentration studied. Systematic researches to evaluate the mechanism of their toxicity, expecially for long period, have been carried out. The Italian environmental contamination of PCB is quite well defined, but only recently in Italy we have been specifically studying the industrial environment and the professionally exposed workers, to evaluate the exposure levels of PCB, the long term health effects and the possible preventive measures. In particular we are carrying out a research program in a transformer plant in the Roma area in which PCB are used as dielectrics. The methodological approach and the initial results are described.

Air Pollutants↗