Global warming-related response after bacterial challenge in Astroides calycularis, a Mediterranean thermophilic coral.

A worldwide increase in the prevalence of coral diseases and mortality has been linked to ocean warming due to changes in coral-associated bacterial communities, pathogen virulence, and immune system function. In the Mediterranean basin, the worrying upward temperature trend has already caused recurrent mass mortality events in recent decades. To evaluate how elevated seawater temperatures affect the immune response of a thermophilic coral species, colonies of Astroides calycularis were exposed to environmental (23 °C) or elevated (28 °C) temperatures, and subsequently challenged with bacterial lipopolysaccharides (LPS). Using immunolabeling with specific antibodies, we detected the production of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB), molecules involved in coral immune responses, and heat shock protein 70 (HSP70) activity, involved in general responses to thermal stress. A histological approach allowed us to characterize the tissue sites of activation (epithelium and/or gastroderm) under different experimental conditions. The activity patterns of the examined markers after 6 h of LPS stimulation revealed an up-modulation at environmental temperature. Under warmer conditions plus LPS-challenge, TLR4-NF-kB activation was almost completely suppressed, while constituent elevated values were recorded under thermal stress only. An HSP70 up-regulation appeared in both treatments at elevated temperature, with a significantly higher activation in LPS-challenge colonies. Such an approach is useful for further understanding the molecular pathogen-defense mechanisms in corals in order to disentangle the complex interactive effects on the health of these ecologically relevant organisms related to global climate change.

Sea anemones, methylmercury, and bacterial infection: A closer look at multiple stressors.

Specimens of the Mediterranean sea anemone Anemonia viridis were exposed to methylmercury (MeHg) and bacterial infection to study their immune responses to a well-known toxic pollutant. Anemones were housed in laboratory conditions and divided into five experimental groups: 1. control (no microinjection); 2. filtered seawater + buffer injection; 3. filtered seawater + Escherichia coli injection; 4. MeHg + buffer injection; 5. MeHg + E. coli injection. Data showed an increase in antioxidant enzyme production compared to the constitutive condition, while methylmercury inhibited lysozyme production. The buffer inoculation had no statistically significant effects on the animals. In addition, electrophoretic and protease analyses revealed differences in the type of proteins produced, as well as a modulation of proteases depending on the treatment. The study demonstrated the immunomodulatory effect of the organic pollutant on A. viridis, validating its use as a model organism for marine coastal biomonitoring programmes and multiple stress studies.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

Self-assessed health status changes in a community cohort of people with multiple sclerosis: 11 years of follow-up.

BACKGROUND AND PURPOSE: Few data are available on the health status of people with multiple sclerosis (PwMS) in the community. We assessed changes in self-perceived health status and health related quality of life of a community-based cohort of PwMS over a decade, and identified predictors of such changes. METHODS: In 1999 we started the POSMOS study (Postal Survey of Self-Assessed Health of MS Adults and their Significant Others) on a random sample of 251 adults with MS from the Milan area (mean age 42 years, range 18-71 years), and prospectively assessed changes in self-perceived health status over 11 years. Participants completed the Multiple Sclerosis Quality-of-Life-54 (MSQOL-54) and a general/clinical questionnaire. We re-assessed the cohort in 2004 and 2010, sending the same questionnaires plus the Chicago Multiscale Depression Inventory. RESULTS: There were 205 (86%) respondents in 2004, 171 (74%) in 2010; 28 (11%) died during the study. Severely impaired [self-determined Expanded Disability Status Scale (EDSS) > 6.5] increased from 19% to 32%. One-fifth remained fully ambulatory (EDSS <4.0): 25% women (median age 44 years [interquartile range, IQR 39-53], median years from diagnosis 16 [IQR 12-19]); and 17% men (median age 40 years [IQR 38-45], median years from diagnosis 14 [IQR 12-17]). Changes in MSQOL-54 composite scores were negligible; but among individual scales, change in health, cognitive function and general health worsened, and social function and emotional wellbeing improved significantly. Depressive symptoms were high and stable. CONCLUSIONS: Multiple sclerosis had a pervasive but inhomogeneous impact on the lives of our MS sufferers. Notwithstanding overall clinical deterioration and aging, hospital admissions and medical consultations decreased, suggesting reduced use of health care resources. By contrast, housing adaptations and home care increased, psychological burden was high and self-perceived cognitive functioning worsened.

Health-related quality of life and depressive symptoms in significant others of people with multiple sclerosis: a community study.

BACKGROUND AND PURPOSE: Uncertain prognosis and modest treatment efficacy make multiple sclerosis (MS) a particularly difficult disease to adjust to for both patients and their significant others (SOs). Few studies have assessed health-related quality of life (HRQOL) and depressive symptoms in SOs of people with MS in the community. We assessed, and identified predictors of, HRQOL and depression in SOs of adults with MS. METHODS: POSMOS (postal survey of self-assessed health in MS adults and SOs) is a longitudinal survey on a random sample of 251 people with MS in the Milan area. In 2010, SOs and contemporaneous controls completed the SF-36 and Chicago Multiscale Depression Inventory (CMDI). RESULTS: Overall, 142 SOs (mean age 53.1 years; 50% women, 65% partners) and 120 controls (similar to SOs for sex and education, but older) participated. By multivariable modeling of the SO plus control population, SF-36 vitality was lower in SOs (proportional odds ratio 0.45; 95% confidence interval 0.28-0.70), women (0.41; 0.27-0.64), and older subjects (0.98; 0.97-0.99). SF-36 mental health was also lower in SOs (0.62; 0.40-0.96) and women (0.43; 0.28-0.67). Regarding MS characteristics associated with HRQOL and depression in SOs, severe disability [Expanded Disability Status Scale (EDSS > 6.5)] had no effect, whilst depressive symptoms (pathologic CMDI) negatively influenced most SF-36 and all CMDI scores in SOs. CONCLUSIONS: SOs had significantly lower vitality and psychological well-being than controls, identifying a burden in being the companion of a person with MS. This burden was unrelated to physical compromise but associated with depressive symptoms in MS.

The relationship between ambient particulate matter and respiratory mortality: a multi-city study in Italy.

The association of air pollutants with natural and respiratory mortality has been consistently reported. However, several aspects of the relationship between particulate matter with a 50% cut-off aerodynamic diameter of 10 µm (PM(10)) and respiratory mortality require further investigation. The aim of the present study was to assess the PM(10)-respiratory mortality association in Italy and examine potentially susceptible groups. All deaths from natural (n=276,205) and respiratory (n=19,629) causes among subjects aged ≥ 35 yrs in 10 northern, central and southern Italian cities in 2001-2005 were included in the study. Pollution data for PM(10), nitrogen dioxide and ozone were also obtained. A time-stratified case-crossover analysis was carried out. Different cumulative lags were selected to analyse immediate, delayed, prolonged and best-time effects of air pollution. The shape of the exposure-response curve was analysed. Age, sex, chronic conditions and death site were investigated as potential effect modifiers. We found a 2.29% (95% CI 1.03-3.58%) increase in respiratory mortality at 0-3 days lag. The increase in respiratory mortality was higher in summer (7.57%). The exposure-response curve had a linear shape without any threshold. Sex and chronic diseases modified the relationship between particular matter (PM) and respiratory mortality. The effect of PM on respiratory mortality was stronger and more persistent than that on natural mortality. Females and chronic disease sufferers were more likely to die of a respiratory disease caused by air pollution than males and healthy people.

Effects of cold weather on mortality: results from 15 European cities within the PHEWE project.

Weather-related health effects have attracted renewed interest because of the observed and predicted climate change. The authors studied the short-term effects of cold weather on mortality in 15 European cities. The effects of minimum apparent temperature on cause- and age-specific daily mortality were assessed for the cold season (October-March) by using data from 1990-2000. For city-specific analysis, the authors used Poisson regression and distributed lag models, controlling for potential confounders. Meta-regression models summarized the results and explored heterogeneity. A 1 degrees C decrease in temperature was associated with a 1.35% (95% confidence interval (CI): 1.16, 1.53) increase in the daily number of total natural deaths and a 1.72% (95% CI: 1.44, 2.01), 3.30% (95% CI: 2.61, 3.99), and 1.25% (95% CI: 0.77, 1.73) increase in cardiovascular, respiratory, and cerebrovascular deaths, respectively. The increase was greater for the older age groups. The cold effect was found to be greater in warmer (southern) cities and persisted up to 23 days, with no evidence of mortality displacement. Cold-related mortality is an important public health problem across Europe. It should not be underestimated by public health authorities because of the recent focus on heat-wave episodes.

The association of socioeconomic disadvantage with postoperative complications after major elective cardiovascular surgery.

BACKGROUND: Understanding the mechanism by which both patient- and hospital level factors act in generating disparities has important implications for clinicians and policy-makers. OBJECTIVE: To measure the association between socioeconomic position (SEP) and postoperative complications after major elective cardiovascular procedures. DESIGN: Multicity hospital-based study. SUBJECTS: Using Hospital Discharge Registries (ICD-9-CM codes), 19 310 patients were identified undergoing five cardiovascular operations (coronary artery bypass grafting (CABG), valve replacement, carotid endarterectomy, major vascular bypass, repair of unruptured abdominal aorta aneurysm (AAA repair)) in four Italian cities, 1997-2000. MEASURES: For each patient, a five-level median income index by census block of residence was calculated. In-hospital 30-day mortality, cardiovascular complications (CCs) and non-cardiovascular complications (NCCs) were the outcomes. Odds ratios (ORs) were estimated with multilevel logistic regression adjusting for city of residence, gender, age and comorbidities taking into account hospital and individual dependencies. MAIN RESULTS: In-hospital 30-day mortality varied by type of surgery (CABG 3.7%, valve replacement 5.7%, carotid endarterectomy 0.9%, major vascular bypass 8.8%, AAA repair 4.0%). Disadvantaged people were more likely to die after CABG (lowest vs highest income OR 1.93, p trend 0.023). For other surgeries, the relationship between SEP and mortality was less clear. For cardiac surgery, SEP differences in mortality were higher for publicly funded patients in low-volume hospitals (lowest vs highest income OR 3.90, p trend 0.039) than for privately funded patients (OR 1.46, p trend 0.444); however, the difference in the SEP gradients was not statistically significant. CONCLUSIONS: Disadvantaged people seem particularly vulnerable to mortality after cardiovascular surgery. Efforts are needed to identify structural factors that may enlarge SEP disparities within hospitals.

Airport and city-centre temperatures in the evaluation of the association between heat and mortality.

A variety of ambient exposure indicators have been used to evaluate the impact of high temperature on mortality and in the identification of susceptible population sub-groups, but no study has evaluated how airport and city centre temperatures differ in their association with mortality during summer. This study considers the differences in temperatures measured at the airport and in the city centre of three Italian cities (Milan, Rome and Turin) and investigates the impact of these measures on daily mortality. The case-crossover design was applied to evaluate the association between daily mean apparent temperature (MAT) and daily total mortality. The analysis was conducted for the entire population and for subgroups defined by demographic characteristics, socioeconomic status and chronic comorbidity (based on hospitalisation during the preceding 2 years). The percentage risk of dying, with 95% confidence intervals (95% CI), on a day with MAT at the 95th percentile with respect to the 25th percentile of the June-September daily distribution was estimated. Airport and city-centre temperature distributions, which vary among cities and between stations, have a heterogeneous impact on mortality. Milan was the city with the greatest differences in mean MAT between airport and city stations, and the overall risk of dying was greater when airport MAT (+47% increase, 95%CI 38-57) was considered in comparison to city MAT (+37% increase, 95%CI 30-45). In Rome and Turin, the results were very similar for both apparent temperature measures. In all cities, the elderly, women and subjects with previous psychiatric conditions, depression, heart and circulation disorders and cerebrovascular disease were at higher risk of dying during hot days, and the degree of effect modification was similar using airport or city-centre MAT. Studies on the impact of meteorological variables on mortality, or other health indicators, need to account for the possible differences between airport and city centre meteorological variables in order to give more accurate estimates of health effects.

Prevalence of respiratory symptoms in migrant children to Italy: the results of SIDRIA-2 study.

BACKGROUND: Epidemiological studies have documented large international variations in the prevalence of asthma, and 'westernization' seems to play an important role in the development of the disease. The aims of this study were to compare the prevalence of respiratory symptoms in migrant and nonmigrant children resident in Italy, and to examine the effect of length of time living in Italy. METHODS: Data were collected in a large cross-sectional study (SIDRIA-2) performed in 12 Italian centres, using standardized parental questionnaires. For the 29 305 subjects included in the analysis (6-7 and 13-14 years old), information about place of birth and parental nationality was available. RESULTS: There were 1012 children (3%) born outside of Italy, mainly in East Europe. Lifetime asthma and current wheeze were generally significantly less common among children born abroad than among children born in Italy (lifetime asthma: 5.4% and 9.7% respectively, P < 0.001; current wheeze: 5.2% and 6.9%, respectively, P = 0.04). Lower risks for lifetime asthma (prevalence odds ratio, POR = 0.39; 95% CI: 0.23-0.66) and current wheeze (POR = 0.72; 95% CI: 0.47-1.10) were found for children who had lived in Italy <5 years, while migrant children who had lived in Italy for 5 years or more had risks very similar to Italian children. CONCLUSIONS: Migrant children have a lower prevalence of asthma symptoms than children born in Italy. Prevalence increased with the number of years of living in Italy, suggesting that exposure to environmental factors may play an important role in the development of asthma in childhood.

The impact of the summer 2003 heat waves on mortality in four Italian cities.

This study evaluates the impact of the 2003 heat wave on cause-specific mortality and the role of demographic characteristics and socioeconomic conditions that may have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome and Turin. Daily mortality counts, for the resident population by age, sex and cause of death were considered. Daily excess mortality was calculated as the difference between the number of deaths observed and the smoothed average. The impact of heat on health is measured in terms of maximum apparent temperature. The greatest excess in mortality was observed in the north west of Italy (Turin, +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were the age groups most affected, and when stratifying by sex, the increase in mortality seemed to be greater among females. The greatest excess in mortality was registered in those with low socioeconomic status in Rome (+17.8%) and in those with lower education levels in Turin (+43%). The analysis of cause-specific mortality not only confirms results from previous studies of an increase in heat-related mortality by respiratory and cardiovascular diseases, but also shows a significant excess in mortality for diseases of the central nervous system and for metabolic/endocrine disorders. Results from 2003 highlight the necessity of targeting future prevention programmes at the susceptible sub-groups identified. The introduction of warning systems alongside efficient preventive plans and the monitoring of mortality during heat waves may represent a valid tool for the reduction of heat-related deaths.

The impact of the summer 2003 heat waves on mortality in four Italian cities.

This study evaluates the impact of the 2003 heat wave on cause-specific mortality and the role of demographic characteristics and socioeconomic conditions that may have increased the risk of mortality in four Italian cities: Bologna, Milan, Rome and Turin. Daily mortality counts, for the resident population by age, sex and cause of death were considered. Daily excess mortality was calculated as the difference between the number of deaths observed and the smoothed average. The impact of heat on health is measured in terms of maximum apparent temperature. The greatest excess in mortality was observed in the north west of Italy (Turin, +23% and Milan, +23%). The old (75-84 years) and the very old (85+ years) were the age groups most affected, and when stratifying by sex, the increase in mortality seemed to be greater among females. The greatest excess in mortality was registered in those with low socioeconomic status in Rome (+17.8%) and in those with lower education levels in Turin (+43%). The analysis of cause-specific mortality not only confirms results from previous studies of an increase in heat-related mortality by respiratory and cardiovascular diseases, but also shows a significant excess in mortality for diseases of the central nervous system and for metabolic/endocrine disorders. Results from 2003 highlight the necessity of targeting future prevention programmes at the susceptible sub-groups identified. The introduction of warning systems alongside efficient preventive plans and the monitoring of mortality during heat waves may represent a valid tool for the reduction of heat-related deaths.

Time To Pregnancy and occupational lead exposure.

BACKGROUND: Lead exposure is known to be harmful to the male reproductive system, including impairment of fertility. However, it is unclear whether currently existing low levels of exposure have this effect. AIMS: To study retrospectively current workers in lead using industries (battery manufacture, smelting, etc), and in non-lead using control industries, in four European countries, with Time To Pregnancy as the outcome variable, as part of the EU funded Asclepios Project. METHODS: Exposure assessment was mainly by blood lead values, which were available from the late 1970s, supplemented by imputed values where necessary. Three exposure models were studied: (1) short term (recent) exposure; (2) total duration of work in a lead using industry; and (3) cumulative exposure. A Cox proportional hazards model with discrete ties was used for the statistical analysis, with covariates for both partners. RESULTS: A total of 1104 subjects took part, of whom 638 were occupationally exposed to lead at the relevant time. Blood lead levels were mainly less than 50 microg/dl. No consistent association of Time To Pregnancy with lead exposure was found in any of the exposure models, although reduced fertility was observed in one category each in models (2) and (3). CONCLUSIONS: This basically negative result is unlikely to be due to the misclassification of key variables, to insufficient statistical power, or to bias, for example, response bias. If any impairment of male reproductive function exists at the levels of occupational lead exposure now current, it does not appear to reduce biological fertility.

Respiratory effects of sulphur dioxide: a hierarchical multicity analysis in the APHEA 2 study.

BACKGROUND: Sulphur dioxide (SO(2)) was associated with hospital admissions for asthma in children in the original APHEA study, but not with other respiratory admissions. AIMS: To assess the association between daily levels of SO(2) and daily levels of respiratory admissions in a larger and more recent study. METHODS: Time series of daily counts of hospital emergency admissions were constructed for asthma at ages 0-14 years and 15-64 years, COPD and asthma, and all respiratory admissions at ages 65+ years in the cities of Birmingham, London, Milan, Paris, Rome, Stockholm, and in the Netherlands for periods of varying duration between the years 1988 and 1997. A two stage hierarchical modelling approach was used. In the first stage generalised additive Poisson regression models were fitted in each city controlling for weather and season. These results were then combined across cities in a second stage ecological regression that looked at potential effect modifiers. RESULTS: For an increase of 10 micro g/m(3) of SO(2) the daily number of admissions for asthma in children increased 1.3% (95% CI 0.4% to 2.2%). Effect modification among cities by levels of other air pollutants or temperature was not found. The SO(2) effect disappeared after controlling for PM(10) or CO, but correlation among these pollutants was very high. Other respiratory admissions were not associated with SO(2). CONCLUSION: SO(2) is associated with asthma admissions in children, indicating that reduction in current air pollution levels could lead to a decrease in the number of asthma admissions in children in Europe.

Sperm count and chromatin structure in men exposed to inorganic lead: lowest adverse effect levels.

OBJECTIVES: To obtain knowledge on male reproductive toxicity of inorganic lead at current European exposure levels and to establish lowest adverse effect levels, if any. METHODS: A cross sectional survey of the semen of 503 men employed by 10 companies was conducted in the United Kingdom, Italy, and Belgium. The mean blood lead concentration was 31.0 microg/dl (range 4.6-64.5) in 362 workers exposed to lead and 4.4 microg/dl (range below the detection limit of 19.8) in 141 reference workers. Semen volume and sperm concentration were determined in a fresh semen sample according to an agreed protocol subject to quality assurance. The sperm chromatin structure assay (SCSA) was performed at a centralised laboratory. Extraneous determinants including centre, period of sexual abstinence, and age were taken into account in the statistical analysis. If appropriate, possible thresholds were examined by iterative threshold slope linear regression. RESULTS: The median sperm concentration was reduced by 49% in men with blood lead concentration above 50 microg/dl. There was no indication of a linear trend of lower sperm concentration with increasing blood lead values, but threshold slope least square regression identified a blood lead concentration of 44 microg/dl (beta=-0.037, F=4.35, p=0.038) as a likely threshold. Abnormal sperm chromatin structure was not related to blood lead concentration, but some indications of deterioration of sperm chromatin was found in men with the highest concentrations of lead within spermatozoa. Biological monitoring data did not indicate long term effects of lead on semen quantity or sperm chromatin. CONCLUSION: Adverse effects of lead on sperm concentration and susceptibility to acid induced denaturation of sperm chromatin are unlikely at blood lead concentrations below 45 microg/dl. Effects of low level exposure to lead on other measures of testicular function cannot be ruled out.

Estimate of population coverage with the prostate specific antigen (PSA) test to screen for prostate cancer in a metropolitan area of northern Italy.

The use of the prostate specific antigen (PSA) test in the period 1999-2000 in a population of 311 822 men, aged 40 years or more, resident in Milan, Italy, was examined. Data were drawn from the outpatient database of the local health information system. A total of 139 350 PSA tests were used in 83 943 subjects. Overall, 26.9% of the male population aged 40 or older, with no history of prostate cancer, received a PSA test in the 2 year study period. For subjects older than 50 the rate rose to 34%. Results show a high coverage of the male population in northern Italy with screening using the PSA test for prostate cancer.

Time to pregnancy among male workers of the reinforced plastics industry in Denmark, Italy and The Netherlands. ASCLEPIOS.

OBJECTIVES: The relationship between occupational styrene exposure and male fecundity was examined. METHODS: Among 1560 Danish, Italian, and Dutch reinforced plastics workers, 220 styrene-exposed workers and 382 unexposed referents who had fathered a child were identified. A total of 768 historical styrene measurements conducted in 1970-1996 in the study companies formed the basis for semiquantitative exposure assessment in combination with measurements of urinary styrene metabolite levels. All the subjects were interviewed about work conditions and other factors potentially related to reduced fecundity. Fecundity was measured as the reported time to pregnancy (number of months a couple needed to conceive their youngest child). RESULTS: A statistically nonsignificantly reduced fecundity was observed for the styrene-exposed workers [fecundity ratio 0.79, 95% confidence interval (95% CI) 0.59-1.05]. But no consistent pattern of a detrimental effect on fecundity was found when time to pregnancy was related to worktasks indicating higher styrene exposure levels or semiquantitative or quantitative measures of styrene exposure. The workers with high exposure showed a fecundity ratio of 1.09 (95% CI 0.69-1.72). CONCLUSIONS: It is unlikely that styrene exposure has a strong effect on male fecundity.

The effect of lead on male fertility: a time to pregnancy (TTP) study.

BACKGROUND: Growing attention has been paid in recent decades to the effects on male reproduction of occupational exposures to toxic agents. There is strong evidence that high level exposure to lead, i. e. blood lead level (PbB) > 70 microg/dl, is associated with male infertility and some reports suggest an effect even at lower PbB (i. e. < 50 microg/dl). The aim of this study is to shed more light on the postulated association between occupational exposure to relatively low levels of inorganic lead and reduced fertility in men estimated by the length of time taken to conceive: time to pregnancy (TTP). METHODS: A survival analysis of TTP of the last pregnancy was performed adopting the Kaplan Meier methodology. The target population included 782 lead-exposed workers and 165 controls. 251 lead workers and 119 controls were finally eligible and interviewed. Lead-exposed subjects were distributed into four exposure levels according to their blood lead concentration (i.e. < 20; 20-29; 30-39, and >/= 40 microg/dl). The Cox model was adopted to estimate the Relative Risk of unsuccessful waiting time to pregnancy associated to the exposure to lead. RESULTS: A statistically significant difference in fecundability (shorter TTP) in favor of exposed subjects was detected. Nevertheless, longer TTP was associated within the exposed group to higher levels of PbB, even though the gradient is not statistically significant. The exposed workers revealed an average number of children larger than those not exposed, and a clear gradient of the same variable was evident from the lowest to the highest PbB level. Focusing on subjects with one child only, the Cox model confirmed no significant difference in fecundability between exposed and not exposed, whereas a statistically significant longer TTP was associated to the exposure level >/= 40 microg/dl. CONCLUSIONS: It is not easy to assert or to deny the effect of inorganic lead on male fecundity, quantitatively estimated by TTP, with the data available for this study. In fact, while the general data seem to exclude effects of Pb on male fecundability a more detailed analysis suggests an unfavorable effect at relatively high levels of exposure but some confounding attributable to personal and social conditions of the workers cannot be ruled out. Further investigations with a better control of confounding are needed.