Monitoring human exposure to urban air pollutants.

A multidisciplinary study on a general population exposed to vehicle exhaust was undertaken in Pisa in 1991. Environmental factors such as air pollution and those associated with lifestyle were studied. Meanwhile, biological and medical indicators of health condition were investigated. Chromosomal aberrations, sister chromatid exchanges (SCEs), and micronuclei in lymphocytes were included for the assessment of the genotoxic risk. Because of the large number (3800) of subjects being investigated, standardization of protocols was compulsory. The results on data reproducibility are reported. To assess the reliability of the protocol on a large scale, the population of Porto Tolle, a village located in northeast Italy, was studied and compared to a subset of the Pisa population. Preliminary results showed that probable differences between the two populations and individuals were present in terms of SCE frequencies. The study was potentially able to detect the effects of several factors such as age, smoking, genetics, and environment. The in vitro treatment of lymphocytes with diepoxybutane confirmed the presence of more responsive individuals and permitted us to investigate the genetic predisposition to genetic damage. The possible influence of environmental factors was studied by correlation analyses with external exposure to air pollutants as well as with several lifestyle factors.

Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: I. Contribution of methodological factors.

The influence of several methodological factors on mean values of sister chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes of 1,650 subjects was analyzed. Donors belonged to a general healthy population living in Pisa and in two nearby small cities: Cascina and Navacchio (Ca-Na). Blood samples were collected over a period of 29 months and processed in three different laboratories of the some institute. Slides were analyzed by several scorers. Our data showed that lymphocyte proliferation indexes (PIs) and baseline mean values of SCEs were affected mainly by sampling period. This factor accounted for a percentage ranging from roughly 10% (Pisa) to 20% (Ca-Na) of total SCE variance and from roughly 10% (Pisa) to 13% (Ca-Na) of total PIs variance. A marginal effect was attributable to the different laboratories involved (maximum 3% for SCEs and 7% for PIs). The sampling period variable included many sources of variability such as culture media batches, fetal calf serum, PHA, BrdUrd, and seasonality. MN counts revealed a more marked dependence on processing laboratories. This factor accounted for a percentage of roughly 10% (Pisa and Ca-Na) of total variance, while the sampling period was marginally effective (about 1-4% of total variability). Because laboratories were equipped and supplied with the same materials and consumables and technicians were rotated constantly, the only variable ascertained was represented by the three different models of CO2 incubators used for lymphocyte culturing. When "month" and "incubator" variables were considered jointly, experimental variability accounted for 15-20% of total variance, both for PIs and mean values SCEs and MN. The variability due to slide scoring was reduced by assigning each slide to five different scorers and matching low with high scorers in each group. Present data show that when the study is performed under these controlled conditions, about 20% of total interdonor variability can be explained by experimental or seasonal factors.

C-mitosis and numerical chromosome aberration analyses in human lymphocytes: 10 known or suspected spindle poisons.

As a part of a coordinated EEC project to validate suitable assays for chemically induced genomic mutations, numerical chromosomal aberrations and spindle effects were studied in human lymphocyte cultures exposed to cadmium chloride, chloral hydrate, colchicine, diazepam, econazole, hydroquinone, pyrimethamine, thiabendazole, thimerosal and vinblastine. Chromosome number analysis was carried out after treatment for 48 and 72 h; spindle effects, i.e., increases in the mitotic indices and c-mitoses, were analyzed in cultures treated 5 h before fixation. Dose-related numerical chromosomal aberrations are induced by colchicine and vinblastine, the only chemicals that also induce c-mitotic effects in a wide range of doses. Hyperdiploidy is induced by chloral hydrate, cadmium chloride and thimerosal without dose-effect relationship; chloral hydrate and thimerosal affect spindle functions while only a weak spindle effect is produced by cadmium chloride. Tetraploid and/or endoreduplicated cells are induced without dose-effect relationship by hydroquinone, thiabendazole and thimerosal, all of them able to produce c-mitotic effects. Diazepam and econazole induce only hypodiploidy; pyrimethamine does not induce numerical chromosomal aberrations.

Sistemática controlada de diagnóstico y tratamiento de infecciones en UCI Una estrategia efectiva para el uso racional de los antibióticos / Controlled systematics of diagnosis and treatment infections in the ICU An effective strategy for the use rational of antibiotics

Se han descrito varios programas para el uso racional de los antibióticos. Nosotros implementamos una sistemática de diagnóstico y tratamiento de infecciones en Unidad de Cuidados Intensivos (UCI) basados en el control como método estratégico de aplicación. La disminución del consumo total de antibióticos fue de 2454,87 DDD/100 pacientes/día (Dosis Diaria Definida/100 pac) en el 2003 a 1505,54 DDD/100 pacientes /día en el 2004 (61,32), (p < 0.0001). El ahorro en el gasto alcanzó 21.429 $ , de 69.958 $ en el 2003 a 48.529 $ en el 2004 (69,36%). No afectó el promedio de días de estada en UCI, que fue de 5.38 días en el 2003 y 4.89 días en el 2004 (p < 0.79 ), ni la mortalidad, que fue de 43.22% en el 2003 y 38.85% en el 2004 (p < 0,25). Los pacientes /día aumentaron de 1695 en el 2003 a 2059 en el 2004 (p 0.01). Se tomó a referencia la Tasa de Resistencia de P.Aeruginosa a Imipenem, que varió de 66% a 0% (p < 0.03) del 2003 al 2004 respectivamente, y la de A. Baumanni a Imipenem, que fue de 34% en el 2003 y de 36% en el 2004 (p 0.93). Las infecciones respiratorias fueron 18.70% en el 2003 y de 7,42% en el 2004 (p< 0.0001), sin cambio en el resto. La sistemática de diagnóstico y tratamiento de infecciones en la UCI disminuyó el consumo y costo de antibióticos. Sin embargo, otros estudios capaces de controlar mejor posibles variables confundidoras, son necesarios para obtener un mayor nivel de medicina basada en la evidencia y lograr así, que más médicos se sumen al uso apropiado de antibióticos(AU)

Diagnose and treatment of infections in ICU: An effective strategy for the rational use of antibiotics Several programes for the rational use of antibiotic have been described. We implemented a systematics of diagnosis and treatment of infections in the ICU, based on control as strategic method of application. The global consumption of antibiotics decreased from 2454.87 DDD/100 PTE/ DAY in 2003 to 1505.54 ddd/100 PTE DAY in 2004 (61,32), (P<0.0001). Savings in antibiotic expenditures reached $ 21.429, $ 69.958 in 2003 and $ 48.529 in 2004 (69.36%). It did not affect the staying days average which was 5.38 days in 2003 and 4.89 in 2004 (p<0.79), or mortality, wich was 43.22% in 2003 and 38.85% in 2004 (p<0.25).The patient/day increased form 1695 in 2003 to 2059 in 2004 (p 0.01).We chose as reference the Resistance Rate for P. Aeruginosa to Imipenem, that varied from 66% to 0% (p<0.03) in 2003 and 2004 respectively and the A.Baumanii to Imipenem, of 34% to 36% in the same períod (p0.93). The incidence of respiratory infections was 18.70% in 2003 and 7.42% in 2004 (p 0.0001), with no variation in other infections rates. Our sistematics of diagnosis and treatment for infections in ICU resulted in lower cost and consumption of antibiotics Nevertherless, other studies capable of controlling better possible confounder variables are necessary to obtain a greater evidence of the protocol we used and achieve more physician get involved in the appropiate use of antibiotics.(AU)