[Role of some psycho-physiological factors on driving safety]. / Ruolo di alcuni fattori psico-fisiologici sulla sicurezza alla guida.

Within a research project on the role played by human factors on road accidents, the aim of the present study is to evaluate, in young adults, the relationships between driver behaviour and personality factors as well as to assess the neuroendocrine correlates of psychological and behavioural factors investigated. Another aim is to estimate in what measure the performance levels are affected by demographic, psychological and chronobiological variables. It has been found a positive relation between highway code violations, extroversion trait of personality and Sensation Seeking scores, so confirming that this component of personality can affect risky behaviour. Furthermore the subjects more oriented to morningness chronotype were found to be prone to adopt safe driving behaviour. Regarding the relations of the neuroendocrine parameters and driving behaviour a positive correlation was observed between dopamine levels and frequency of driving violations while a negative relationship was found between adrenaline levels and frequency of driving errors. In conclusion the identification of psycho-physiological variables related to driving risky behaviour might be a useful instrument to design traffic safety programs tailored to high risk subjects.

[Monitoring occupational exposure to volatile anaesthetics in the operating theatre: environmental and biological measurements]. / Monitoraggio dell'esposizione professionale ad anestetici volatili in sala operatoria: misurazioni ambientali e biologiche.

Concentrations of nitrous oxide (N2O) and isoflurane were measured in environmental and urinary samples from subjects occupationally exposed to volatile anaesthetics in operating theatres in a hospital in northern Italy. The aim was to establish whether: an automatic analyzer (Brüel & Kjaer 1302 spectrometer) can be used for fixed position sampling ("anaesthetist zone" and "surgeon/instrument nurse zone"); periodic monitoring of anaesthetics will reduce exposure; exposure to N2O and isoflurane is within legal limits; exposure differs between anaesthetists and surgeons/instrument nurses. Exposure to anaesthetics was monitored twice at six-month intervals. In the first test time spent in the operating theatre was noted and exposure levels were measured automatically. In the second test levels were monitored with passive personal sampling devices. Environmental concentrations of N2O determined by the spectrometer were correlated to urinary levels. Urinary levels of N2O calculated from the regression line were the same as those obtained with the personal samplers. Environmental and urinary levels of N2O decreased significantly from the first to second test. In the second sampling 70% of subjects had levels of exposure to N2O and isoflurane within prescribed environmental limits (50 ppm for N2O and 0.5 ppm for isoflurane). At the first test anaesthetists had significantly higher levels of exposure to N2O than surgeons/instrument nurses. The survey demonstrated that: fixed position sampling data related to time spent in the operating theatre can be used to gauge individual exposure levels; exposure levels decrease after tests following implementation of preventive measures; monitoring needs to be repeated because exposure levels often exceed legal limits; occupational exposure decreases when pollution in the anaesthetic zone is reduced.

Genetic polymorphisms influence variability in benzene metabolism in humans.

The role of genetic polymorphism in modulating urinary excretion of two benzene metabolites, i.e. trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (PMA), has been investigated in 59 non-smoking city bus drivers, professionally exposed to benzene via vehicle exhausts. Exposure to benzene was determined by personal passive samplers (mean +/- SD = 82.2 +/- 25.6 micrograms/m3), while internal dose and metabolic rate were evaluated by measuring urinary excretion of unmodified benzene (mean +/- SD = 361 +/- 246 ng/l), t,t-MA (mean +/- SD = 602 +/- 625 micrograms/g creatinine), and PMA (mean +/- SD = 5.88 +/- 4.76 micrograms/g creatinine). Genetic polymorphism at six loci encoding cytochrome-P450-dependent monooxygenases (CYP2E1 and CYP2D6), glutathione-S-transferases (GSTT1, GSTP1 and GSTM1) and NAD(P)H:quinone oxidoreductase (NQOR) was determined by polymerase chain reaction-based methods. No evidence emerged for a possible role of CYP2E1, GSTM1 and GSTP1 polymorphisms in determining the wide differences observed in the rate of benzene biotransformation. Conversely, a significantly higher t,t-MA urinary excretion was found to be correlated to, GSTT1 null genotype, and a significantly lower PMA excretion was detected in the subjects lacking NQOR activity and in the CYP2D6 extensive-metabolizers. Many biological (i.e. age and body burden) or lifestyle factors (i.e. rural or urban residence, use of paints and solvents, medication, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. These findings suggest that CYP2D6, GSTT1 and NQOR polymorphisms contribute in explaining the metabolic variability observed in our sample. Therefore, these polymorphisms should be regarded as potential risk factors for benzene-induced adverse health effects.

Excess melanoma incidence in a cohort exposed to high levels of environmental selenium.

Epidemiological studies on the relation between selenium and human cancer have yielded strongly conflicting results. Prompted by the observation of a positive association between selenium intake and site-specific cancers, including melanoma, in a large cohort of nurses, we studied the 11-year melanoma incidence in an Italian cohort that consumed unusually high levels of inorganic selenium in tap water from 1975 to 1985. The setting was Reggio Emilia, an Italian municipality that provided a natural experiment relating to intake of high levels of inorganic selenium. We identified 2,065 individuals with high selenium exposure, who contributed a total of 20,179 person-years of follow-up, and we compared their experience with the 1,384,386 person-years of follow-up in the remaining population of Reggio Emilia. We included all cases of pathologically confirmed malignant melanoma, including intraocular melanoma, identified from the Reggio Emilia Hospital, the Bologna regional registry of hospital discharges, and the Milan National Cancer Institute. Eight cases of malignant melanoma occurred in the exposed cohort during the follow-up. Melanoma incidence was 3.9 times greater in the exposed than in the unexposed cohort (95% exact confidence limits, 1.8-7.4).

Heavy metals and experimental atherosclerosis. Effect of lead intoxication on rabbit plasma lipoproteins.

Previous studies have suggested that exposure to heavy metals may be a risk factor in coronary atherosclerotic heart disease in humans as well as in experimental animals. Little is known however on the mechanism underlying the effect of heavy metals on the development of atherosclerosis. In this study we tried to ascertain whether exposure to lead might: (a) alter plasma lipoprotein in normally fed rabbits; and (b) aggravate the hyperlipidemia usually found in cholesterol-fed animals. Rabbits were fed a normal diet or a diet containing 1% cholesterol in the presence or in the absence of 0.5% of lead subacetate for 45 days. This produced an accumulation of lead in plasma and bone. While in cholesterol-fed rabbits, lead exposure did not modify the plasma lipoprotein pattern, in normally fed animals it induced a striking elevation of cholesterol esters. This was associated with an increased concentration of VLDL (1.006 g/ml), LDL1 (1.006-1.020 g/ml), LDL2 (1.020-1.050 g/ml) and HDL1 (1.050-1.210 g/ml). These lipoproteins had an elevated content of cholesterol esters and apolipoprotein B. It is suggested that some of these lipoproteins may be important in the development of atherosclerosis in subjects chronically exposed to lead.

Emotional stability, anxiety, and natural killer activity under examination stress.

This study was performed to evaluate the relation between a stable personality trait, a mood state and immune response to an examination stress. A self-reported measure of emotional stability (BFQ-ES scale) was obtained in a sample (n = 39) randomly selected from 277 cadets; this personality trait was also investigated by completing a neuroticism scale (Eysenck personality inventory) and a trait-anxiety scale (STAI). Natural killer (NK) cell activity was measured at baseline, long before the examination time and the examination day. The state-anxiety scale evaluated the response to the stressful stimulus. Taking subjects all together, the academic task did not result in significant modification over baseline in NK cell activity. Subjects were then divided into three groups based on emotional stability and state-anxiety scores: high emotional stability/low anxiety, medium, and low emotional stability/high anxiety. Examination stress induced significant increases in NK cell activity in the high emotional stability/low anxiety group, no effect in the medium group, and significant decreases in the low emotional stability/high anxiety group. The repeated-measure ANOVA revealed a significant interaction of group x period (baseline vs. examination) for both lytic units and percent cytolysis. The results did not change after introducing coffee and smoking habits as covariates. Our findings suggest that the state-anxiety acts in concert with a stable personality trait to modulate NK response in healthy subjects exposed to a psychological naturalistic stress. The relation between anxiety and poor immune control has been already described, whereas the ability of emotional stability to associate with an immunoenhancement has not yet reported. The peculiarity of our population, a very homogeneous and healthy group for life style and habits, can have highlighted the role of emotional stability, and may account for the difference with other studies.

Cancer mortality in a residential cohort exposed to environmental selenium through drinking water.

Cancer mortality from 1986 to 1992 was examined in a cohort of 4419 individuals who had been residing in an area of the municipality of Reggio Emilia, northern Italy, where tap water with unusually high selenium content was accidentally supplied. Mortality for all cancers was not significantly different, both in males and in females, from that expected using death rates in the remaining municipal population as standard rates. No significant difference in mortality for site-specific cancers was observed in males, while in females a higher mortality for malignancies of the lymphatic-hematopoietic tissue overall considered and for non-Hodgkin's lymphoma was detected. Even if evaluation of the results is hampered by the low number of cancer deaths on which the analysis is based, findings of the study do not support the hypothesis of a strong inverse independent relationship between dietary intake of selenium and cancer mortality in humans.

Hypertension in newly diagnosed non-insulin-dependent diabetic subjects.

Medical records of newly diagnosed non-insulin-dependent diabetic patients attending a Diabetic Centre in Modena, northern Italy, during the period 1985-88 were reviewed to analyze the prevalence of hypertension at age of diagnosis of diabetes and its association with selected risk factors. The prevalence of hypertension was also determined in a representative sample of control subjects. In the multivariate analysis, greater body mass index and older age, but not smoking, were strongly associated with increased rates of hypertension both in control and in diabetic subjects. In diabetic patients, family history of diabetes, defined as presence of diabetes in close relatives, was not significantly associated with hypertension, while rates of hypertension were significantly lower in patients who reported at least one parent affected by diabetes. After adjustment for age and body mass index, newly diagnosed non-insulin-dependent diabetes was not an independent risk factor for hypertension. These findings seem to be consistent with the hypothesis that diabetes and hypertension are not linked by a common genetic background.

Rising melanoma incidence in an Italian community from 1986 to 1997.

We examined the incidence of primary invasive melanoma in the municipality of Reggio Emilia, northern Italy, in the period from 1986 to 1997. We identified 169 cases, five of which were intraocular. After adjustment for confounders, the risk of having a thick melanoma (Breslow > or = 1 mm) did not decrease over time, except in older females. The age-standardized incidence of cutaneous melanoma during the entire study period was 7.57 in males and 11 in females; from 1986-1991 to 1992-1997, it rose from 5.04 to 10.04 cases/100,000 person-years in males and from 8.96 to 13.09 cases/100,000 person-years in females. In males, the increase in incidence was almost entirely confined to subjects aged 30 or more, suggesting a possible cohort effect. We noted rising age-standardized incidences over time both in males with thin tumours (Breslow < 1 mm) (from 2.05 to 4.38 cases/100,000 person-years) and thick tumours (from 2.73 to 5.51 cases/100,000 person-years), while in females the increase was limited to thin melanomas (from 3.14 to 6.93 cases/100,000 person-years), mainly due to an increase in the older age groups (50 69 years and > or =70 years). The increase in thick melanomas among males and the expected cohort effects suggests antecedent exposure to environmental risk factors.

Relationship between low lead exposure and somatic growth in adolescents.

The possible effects of moderate lead exposure on human growth and development are not well defined. This study was carried out in order to evaluate the relationship between somatic growth and lead exposure. 418 subjects (202 males and 216 females) aged 11-13 years in good health and living in an area of the northern region of Italy were submitted to the following determinations: blood lead levels (PbB), serum concentrations of gonadotropins (LH, FSH) and sex-steroid hormones (DHA-S, T, E2) and anthropometric measurements (stature and weight). The mean blood levels were 85.39 and 70.08 micrograms/1, respectively, for males and females. Significant and negative relationships were found between blood lead levels and stature in 13 years old males and 12 years old females (p = 0.009 and p = 0.006, respectively). Negative relationships between lead in blood and LH and FSH were found only in males with lead levels higher than 90 micrograms/1. Our findings seem to suggest that even for low lead exposure this metal may affect stature growth and gonadotropins levels.

Adverse health effects of selenium in humans.

Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.

Zinc and copper status and blood pressure.

In order to elucidate the relationships between Zn and Cu and blood pressure, the present case-control study was carried out. Zn and Cu status was evaluated in 60 subjects, pharmacologically untreated, affected by mild stable hypertension and in 60 normotensives matched for sex, age and smoking habits. Different markers of Zn and Cu status, including serum, erythrocyte and urine levels of the two trace elements and activities of some Zn- or Cu-dependent enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase and lysyl oxidase) were evaluated. No significant difference between hypertensives and normotensives was observed in the mean levels of Zn and Cu as well as in Zn- or Cu-dependent enzymes, though higher levels of serum copper were associated with increased risk of hypertension. Interesting relationships between the biological parameters investigated were observed in the hypertensive subjects. Inverse correlations between blood pressures and serum Zn were observed. Furthermore, blood pressure was inversely related to lysyl oxidase activity. These findings give further support to the hypothesis that an imbalance of Zn and Cu bioavailability may be associated to hypertensive condition.

Zinc and copper levels in serum, urine, and hair of humans in relation to blood pressure.

Zinc and copper status was evaluated in 63 early hypertensives and compared with that of 63 normotensives matched for sex, age, smoking habits and body mass index. Zinc and copper in serum, urine and hair were measured, and the serum activity of two zinc-dependent enzymes (AP and LDH) were analysed. Mean urinary copper concentration in patients was 14.11 micrograms g-1 creatinine compared with 9.16 micrograms g-1 creatinine in normotensive subjects (paired "t" = 3.94, p less than 0.001). Serum AP and LDH were significantly decreased (16 and 36%, respectively) in the patients compared with controls, although almost all values fell within the normal range of activities. Systolic and diastolic pressures were significantly and positively correlated to urinary copper excretion. These correlations were still apparent after correcting blood pressure values for other urinary measurements. Blood pressure levels (both systolic and diastolic) were also negatively correlated with the two zinc-dependent enzymes.

Relationship between zinc in serum and hair and some hormones during sexual maturation in humans.

We have measured the levels of zinc in serum (Zn-S) and in hair (Zn-H) in 391 adolescents, in good health, aged between 11 and 14 years. To evaluate the relationship between zinc status and sexual maturation we have analyzed, in the same subjects, the serum concentrations of the following hormones: luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrosterone-sulphate (DHA-S), testosterone (T) and estradiol (E2). No significant relationship between zinc in the biological samples and the hormones measured in all subjects was observed; only in prepuberal females was a positive correlation found between Zn-S and E2. A significant relationship between Zn-S and LH was observed only for males with short stature or low weight (less than 25th percentile) (r = 0.359, p = 0.010; r = 0.47, p = 0.008, respectively). When prepuberal males with short stature were considered, a significant association between Zn-S and T appeared (r = 0.399, p = 0.006). In females with short stature (less than 25th percentile), partial correlation coefficients showed a significant association between FSH and zinc in hair (r = 0.435, p = 0.004), while in girls with low weight, FSH appeared positively related to zinc in hair (r = 0.470, p = 0.003) and negatively related to zinc in serum (r = -0.320, p = 0.050). Our results suggest that zinc plays an important role in the metabolism of hormones linked to sexual maturation.

Inter-individual variability of benzene metabolism to trans,trans-muconic acid and its implications in the biological monitoring of occupational exposure.

Unmodified benzene (UBz) and trans,trans-muconic acid (t,t-MA) were measured in urine samples collected at the end of the first half-shift in 80 bus drivers from a large city in Northern Italy. Mean UBz was 1155 ng/l (S.D. = 494), range 85-1980 ng/l; these values roughly correspond to 10-1000 micrograms/m3 of benzene in air. Mean t,t-MA was 297 micrograms/g creatinine; the range was large (20-1295 micrograms/g creatinine), and the distribution of values was bimodal. At further analysis of t,t-MA data, two subgroups of 59 and 18 subjects were identified (3 outliers were excluded): mean values of the index were 108 (S.D. = 65) and 916 (S.D. = 264) micrograms/g creatinine respectively, and the values within each subgroup were normally distributed. The mean ratio between t,t-MA and UBz in the subgroups were 0.15 and 0.85, respectively; the difference was significant. The first subgroup was defined as 'poor t,t-MA metabolizers', the other as 'efficient t,t-MA metabolizers'. No inter-subgroup differences were observed regarding the main characteristics (age, dietary and smoking habits, etc.). As the parent compound of t,t-MA, trans,trans-muconaldehyde is myelotoxic, and its production has been implicated in benzene-induced leukemia. 'efficient' t,t-MA metabolizers may be at higher risk of developing benzene toxicity. If confirmed in further studies, the inter-individual variability rate of metabolizing benzene to t,t-MA may introduce some limitations in the application of this metabolite as an exposure index of low benzene exposure. Nevertheless, the t,t-MA/UBz ratio may be an important index of susceptibility to benzene toxicity.

Risk of birth defects in a population exposed to environmental lead pollution.

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.

The epidemiology of selenium and human cancer.

The relation between the trace element selenium and the etiology of cancer in humans remains elusive and intriguing, despite the number of epidemiologic studies published on the topic. We address some methodologic issues, such as misclassification of exposure, particularly to single selenium compounds, effect modification, confounding, and other sources of bias, which may explain the inconsistencies in the literature. We also review the results of cohort studies, which have yielded either inverse or null or direct associations between selenium exposure and subsequent cancer risk. To date, no beneficial effect on cancer incidence at major sites, including prostate cancer, has emerged from the Finnish program begun in 1984 to increase the average selenium intake in its population. Populations exposed to unusually high or low levels of environmental selenium might offer unique opportunities to investigate if selenium exposure is related to the etiology of human cancer.

Zinc, copper, and zinc- or copper-dependent enzymes in human hypertension.

Imbalance of zinc and copper status has been hypothesized in human hypertension. A case-control study was carried out to elucidate the possible relationship between zinc and copper status and essential hypertension. Thirty-one subjects affected by mild stable hypertension, pharmacologically untreated, were investigated together with 31 normotensive controls individually matched for sex, age, and smoking habits. Zinc and copper in serum and urine wee measured, and serum activities of alkaline phosphatase (AP), lactic dehydrogenase (LDH), copper-zinc superoxide dismutase (Cu-Zn SOD), lysyl oxidase (LOX), and monoamine oxidase (MAO) were evaluated. No significant difference in serum and urine zinc and copper content as far as in serum activity of zinc (AP and LDH) or copper (Cu-Zn SOD, LOX, and MAO)-dependent enzymes was found between hypertensives and normotensives. Positive relationships were found in normotensives between serum and urine levels of zinc (r = 0.577; p = 0.001) and copper (r = 0.394; p = 0.028), and between serum copper and Cu-Zn SOD (r = 0.534; p = 0.002). In normotensives, diastolic blood pressure and serum zinc were positively related (r = 0.370; p = 0.041). In hypertensives, inverse correlations were observed between diastolic blood pressure and AP (r = -0.498; p = 0.004) and Cu-Zn SOD (r = 0.452; p = 0.011), and between systolic blood pressure and LOX (r = -0.385; p = 0.033). Diastolic blood pressure was related to LDH inversely in hypertensives (r = -0.357; p = 0.049) and positively in normotensives (r = 0.457; p = 0.010). In normotensives, diastolic blood pressure was inversely related with MAO (r = -0.360; p = 0.046). These findings support the hypothesis that an imbalance of zinc and copper status might be involved in human hypertension.

Changes in drinking water selenium and mortality for coronary disease in a residential cohort.

In a part of the municipal territory of Reggio Emilia, northern Italy, selenium in drinking water decreased from 7 micrograms/L to less than 1 micrograms/L. In a cohort of 4419 individuals, previously exposed for at least 5 yr to the drinking water with higher selenium content, the 7-yr temporal distribution of deaths for coronary disease and for stroke was analyzed to examine a possible relationship with changes in drinking water selenium. From January 1986 until August 1988, when tap water selenium was 7 micrograms/L, deaths for coronary disease were one in males and two in females. After the decrease in drinking water selenium, 21 and 10 coronary deaths were observed, respectively, in males and in females from September 1988 to December 1992. No significant difference in the temporal distribution of stroke deaths was observed both in males and in females. Even if an effect of chance and aging in the temporal distribution of coronary deaths may not be excluded, findings of the study seem to be consistent with the hypothesis of a beneficial effect of selenium on coronary disease mortality.

[Evaluation of the risk of neuropsychological damage from lead exposure in childhood]. / Valutazione del rischio di danno neuropsicologico per esposizione al piombo nell'infanzia.

Potential neurotoxicity of lead in children has been explored in many recent epidemiological studies carried out all over the world. Within a multicentric European study, an investigation was carried out also in Italy on children living in an industrial area and characterised by a non steady-state exposure condition with higher exposure at the early stages of life. This peculiar feature allowed to observe interesting associations between neurobehavioural functions and the levels of Pb measured in teeth, but not in blood. Indeed, Pb in teeth was associated with the results of psychometric tests which evaluate the discriminant ability and the attention. Other associations, like those found between the intelligence quotient (IQ) scores and Pb in teeth disappeared after correction for the socioeconomical status of parents. In general, in children exposed to environmental Pb, more consistent associations were found with visual-motor integration and attention than with IQ measurements. In agreement with literature data from other countries, we suggest that the relevance of neurotoxic effects of Pb is limited, at least at the current exposure levels, but also that a threshold Pb level associated with no effect cannot be identified.