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Glyphosate is a non-selective systemic herbicide used in agriculture. For almost half a century, the International Agency for Research on Cancer has run a Monographs program, the conclusion in March 2015 that glyphosate is “probably carcinogenic to humans” in addition to being genotoxic and carcinogenic in animals, while the regulatory European Food Safety Authority have asserted that glyphosate poses no public risk. The scientific debate is still lively. We collected detailed socio-demographic, occupational exposures and health surveillance information for 26 winegrowers as aim to investigate exposure to glyphosate and other pesticide. Exposure was assessed through biological monitoring (24-hour urine collection), immune function (IL-4, IL-5, IL-8, IL-12, IL- 17, IL-33, IFN- γ), transcriptional and post transcriptional alterations (miRNA) and genotoxic effects (Comet assay). The exposure conditions in our winegrowers, as referred to the parameters so far analyzed, did not reveal a significant glyphosate absorption nor significant health concerns.

To ascertain whether the current risk of lung cancer in former asbestos workers was higher than in the general population, 1,557 past asbestos workers were recruited during statutory health examinations (from 2000 onward) and followed up for mortality. Standardized mortality ratios (SMRs) were calculated. Poisson regression was used to adjust the rate ratios (RRs) for confounders. SMR was about 1.00 in workers with or without pleural plaques and 4.62 (95% confidence interval: 0.61-18.1) in those with asbestosis. Adjusted RRs for lung cancer were 4.70 (0.99-22.5) for asbestosis, 4.35 (0.97-19.5) for former smokers, 6.82 (1.38-34.4) for current smokers. Currently, lung cancer mortality in past asbestos workers is similar to the general population, probably because workers more exposed /more susceptible could have died from lung cancer before the beginning of follow-up.

Background: In a district of Veneto (North-east Italy) where numerous females of childbearing age were occupationally exposed to organic solvents in nearly 400 shoe factories, a case–control study found significant associations between maternal exposures (from occupation and risky behavior) and spontaneous abortion (SAB). Thereafter, a health education campaign was undertaken to increase awareness of risk factors for pregnancy in the population. To evaluate the effects of this campaign maternal exposures and SAB risks were compared before and after the campaign. Methods: Hospital records were collected from a local hospital for SAB cases and age– residence-matched controls with normal deliveries. Information on solvent exposure, coffee and alcohol consumption, smoking and the use of medication was collected using a questionnaire. Before and after differences were tested through a modified Chi-square test and linear and logistic regressions for survey data. Odds ratios (ORs) with 95% confidence interval (CI) were estimated using logistic regression models. Results: The consumption of coffee ( P = 0.003) and alcohol ( P < 0.001) was lower after than before the campaign, controlling for age at pregnancy and level of education. There were no differences in reported solvent exposure or smoking (smokers were few). The previously detected increased risks of SAB in relation to solvent exposure and coffee consumption were no longer present. Conclusion: The results suggest that health education campaigns might reduce harmful maternal exposures and the risk of SAB.

Language phylogenesis is often presented as a matter of controversy between followers of continuity vs discontinuity theories of development. Both kinds of theory may be described as projects for mind naturalization. However, the latter seems better to agree with recent paleo-anthropological data, which hint at a non-linear evolution, with no sudden morphological change. The paper presents an account of G. H. Mead's theory which is surprisingly modern and of great relevance for present debates, as it describes the emergence of language as the joint action of adaptive skills already present in nature. Taking sociality as a biological universal, operating in different forms and degrees, Mead can trace the path from more elementary forms of social relation to the most complex and abstract tools of social thinking, typical of human communities.Keywords: Phylogeny of language, Mind, Society, Biology, Subject, Communication.Parole chiave: Filogenesi del linguaggio, Mente, Socialitŕ, Biologia, Soggettivitŕ, Comunicazione

BCG vaccine, vaccinia vaccine and certain pathogens that were shown in previous studies to protect against melanoma have antigenic determinants homologous in their amino acids sequence with the melanoma antigen HERV-K-Mel, encoded by a human endogenous retrovirus K (HERV-K), which is expressed in about 95% of malignant melanocytes. Yellow fever vaccine (YFV) likewise contains an antigenic determinant with a close homology to HERV-K-MEL and might therefore also confer protection against Melanoma. To investigate this possibility we carried out a cohort study (28,306 subjects) and a nested case-control study (37 melamona cases and 151 tumors not expressing HERV-K-MEL) in Veneto region (North-Eastern Italy). The standardized incidence ratio was 1.33 (95% confidence interval, 0.84-2.11), 1.59 (0.97-2.59) and 0.59 while the age- gender-adjusted odds ratios were 1.00, 0.96 (0.43-2.14) and 0.26 (0.07-0.96), (0.19-1.84), at 0-4, 5-9, and >= 10 years elapsed from YFV administration, respectively. The risk of melanoma may therefore be lowered 10 years after vaccination with yellow fever vaccine. (C) 2008 Elsevier Ltd. All rights reserved.

Transcripts of human endogenous retrovirus K are expressed in most breast cancers (BCs). Yellow fever vaccine 17D (YFV) expresses a protein with a closely homologous epitope. Cross-reactive immunity could hypothetically inhibit BC growth at least in women aged around 50 years at diagnosis, in whom the prognosis of BC was found to be better than that in women younger or older. A cohort of 12 804 women who received YFV in the Veneto Region, Italy, was divided into two subcohorts according to age at vaccination and followed up through the Veneto Tumor Registry. The time since vaccination until cancer incidence was categorized (≤1.9; 2-3.9; 4-5.9; 6-7.9; 8-10.9; ≥11 years) and, using the lowest class as a reference, the incidence rate ratio for BC with a 95% confidence interval and P-value was estimated by Poisson regression in each time since vaccination class, adjusting for age and calendar period. In 3140 women vaccinated at 40-54 years of age, YFV administration resulted in a protective effect of long duration slowly fading over time with a U-shaped pattern of response. Overall, BC risk was reduced by about 50% (incidence rate ratio=0.46; 95% confidence interval=0.26-0.83; P=0.009) 2 years after vaccination. Cross-reactive antigens could not be the mechanism because no protection was observed in women vaccinated before 40 or after 54 years of age. BC cells in a microscopic stage of disease can be destroyed or severely damaged by YFV if BC is not very aggressive. To prove that treatment is truly effective, a placebo-controlled double-blind trial should be conducted.

Several reports indicate that the risk of lung cancer increases slightly for a short period of time after cessation of smoking while the risk of adverse cardiovascular events drops immediately. Recent studies on subjects occupationally exposed to organic dust-containing endotoxin have revealed lower than expected rates of lung cancer. There is experimental evidence that stimulation of the immune system by endotoxin has a protective effect against cancer. Tobacco smoke has been shown to contain high levels of endotoxin. We therefore postulate that cessation of smoking eliminates the protective effect of endotoxin. Any benefit conferred by endotoxin does not, however, justify smoking. As the inverse relationship between exposure to endotoxin and the risk of lung cancer is a strong one, endotoxin-like substances could form the basis of vaccination strategies.

Consistent with findings in other similarly exposed populations, lung cancer mortality was significantly reduced in 1,561 dairy farmers but not in 722 crop/ orchard farmers included in a cohort of Italian small farmers. Unlike previous investigations of this phenomenon, this study controlled for smoking. From the above cohort of 2,283 male farmers, 38 lung cancer cases and 353 referents were selected. The sources (and information collected) were clinical records (diagnosis, smoking habits), a mail questionnaire (smoking habits), and the historical files of self-employed small farmers in the Province of Padova (length of farm work, land area of the farm and number of dairy cattle). The risk of lung cancer was estimated by the odds ratio (OR) with the 95% confidence interval (CI) calculated using logistic regression models. In dairy farmers, the lung cancer OR decreased by 19% per head of cattle (OR = 0.81; CI = 0.68–0.97), when the influence of age and smoking habits was controlled. No relationship was found between lung cancer risk and size of farm or length of work, either in dairy farmers or in crop/orchard farmers. The increasing number of dairy cows, which probably increases the daily hours of exposure in cowsheds, is an indirect indicator of the suggested true protection factor: airborne biologic agents (delivered from bacteria proliferating on organic dusts), particularly endotoxin, which has been shown to be a potent stimulator of endogenous antineoplastic mediators.

Background: There have been few investigations of an association between poly(vinyl chloride) (PVC) dust exposure and an increase in lung cancer incidence, and their conclusions have been inconsistent. Aims: To determine whether PVC and/or vinyl chloride monomer (VCM) is the associated risk factor(s), by means of a nested case-referent study, in order to estimate lung cancer risk, avoiding selection, information, or confounding biases. Methods: Thirty eight cases of histologically verified lung cancer and 224 control subjects without a history of cancer were selected from an Italian cohort of 1658 vinyl chloride workers. Information sources included clinical records (diagnosis, smoking habits) and plant records (occupational history). The risk of lung cancer was estimated by odds ratios (OR) with 95% confidence intervals (CI), calculated using logistic regression models. Results: In PVC baggers exposed to high levels of respirable PVC particles in the workplace, the lung cancer OR increases by 20% for each extra year of work (OR = 1.2003; 95% CI 1.0772 to 1.3469; p = 0.0010), when the influence of age and smoking habits is controlled. No relation was found between lung cancer and cumulative VCM exposure. Conclusion: This nested case-control study showed, in the VCM/PVC industry, an increased risk of lung cancer associated with exposure to PVC dust; previous cohort studies failed to recognise such excess, probably because they used VCM exposure as the risk indicator.

Inhalation of polyaromatic hydrocarbons (PAHs) extracted from diesel exhaust particles (DEP) enhances local (nasal) production of IgE in humans. The aim of the present research is to investigate whether in humans dermal exposure to PAHs which are not extracted from DEPs increases serum IgE and whether host factors modify the immunologic effect. In thirty-two patients with acute psoriatic lesions, a cream containing 3% of coal tar (which holds a variety of PAHs) was applied to the skin for 24 hours. Serum IgE were measured before (IgE0) and four (IgE4) and eight (IgE8) days after application. Replicated means were compared by analysis of variance for repeated measures and by the Newman-Keuls' test. IgE0, IgE4 and IgE8 were 151.19, 159.69 (a 6% excess) and 170.90 kU/L (a 13% excess) respectively; pairwise comparison showed IgE8 was significantly higher than IgE0 (p

Background: Despite the substantial amount of knowledge on effectiveness of worksite health promotion (WHP) in reducing cardiovascular disease (CVD) risk, WHP programs are not systematically applied in Italy. The aim was to design an intervention easy to integrate within the Italian organization of workplace health surveillance. Methods: We used the "pretest-posttest design". Workers were employed in multiple occupations and resident in Veneto region, Italy. Occupational physicians (OPs) performed all examinations, including laboratory evaluation (capillary blood sampling and measure of glycaemia and cholesterolemia with portable devices), during the normal health surveillance at worksite. CVD risk was computed based on sex, age, smoking habit, diabetes, systolic pressure and cholesterol level. After excluding those with 5%) as well as the exact McNemar significance probability or the exact test of table symmetry. Results: CVD risk decreased by 24% (McNemar p = 0.0000) after the intervention; in a sensitivity analysis assuming that all subjects lost to follow-up kept their pretest cardiovascular risk value, the effect (-18%) was still significant (symmetry p < 0.0000). Each prevented CVD case was expected to cost about 5,700 euro. Conclusions: The present worksite intervention promoted favorable changes of CVD risk that were reasonably priced and consistent across multiple occupations.

In a mesothelioma lawsuit, the Public Prosecutor commissioned an expert evidence on the legal accountability for the disease, because the patient experienced multiple exposures to asbestos in both occupational and environmental settings.To collect information on asbestos exposure from all available sources and to quantify the contribution of each source of exposure as a percentage of the total risk.We retrieved information on jobs done and asbestos exposure from a work colleague and a database maintained by the National Institute for Insurance of Occupational Accidents/Diseases, respectively. Information on environmental exposure was searched through the scientific literature. The contribution of each source of exposure was quantified with a method of risk apportionment, taking into account time elapsed since first and last exposure, intensity and frequency of exposure and carcinogenic potency of asbestos fiber mix.The subject worked in the maintenance of railway electrification system. The mechanical compression stress induced on the ballast during passage of trains released chrysotile (from fragmented stones) and crocidolite (through abrasive action of crushed gravel on the underbody of rolling stocks insulated with friable crocidolite). Despite the low cumulative exposure (about 2 ff×years/cc), 99% of the mesothelioma risk was attributable to the work done because of the high content of crocidolite of inhaled asbestos.The report of an uncommon source of occupational asbestos exposure and a scientifically based method to allocate mesothelioma risk among multiple exposure could help to recognize mesothelioma as occupational disease in the workers employed in maintenance of the railway electrification system under the Italian National Railways.

The aim of the present case-control study was to ascertain whether, in adults, yearly repeated anti-influenza vaccinations (AIV) enhance protection against cutaneous melanoma (CM), as do repeated febrile infections. Ninety-nine new cases of histologically confirmed CM and 104 healthy controls (matched to cases for sex, age, and skin colour) selected from the general population were examined in order to ascertain their skin type, the number of nevi on both arms, and the intensity of freckles on the face and the arms; in these subjects, a structured questionnaire was used to obtain information on age, sex, education, social class, exposure and susceptibility to sunlight, history of febrile infectious diseases, and vaccinations. The odds ratio (OR) and the 95% confidence interval (CI) were estimated by commonly used methods and by fitting models of logistic regression. The risk of CM was reduced in subjects with a history of febrile (temperature above 38.5 °C) infections in the 5 years prior to CM surgery (cases) or interview (controls), but was increased in those with voluntary exposure to sunlight in tropical countries. By holding the above factors constant at logistic regression analysis, it was found that a history of repeated AIV (3–5 times in the last 5 years) halved the risk (OR: 0.43; CI: 0.19–1.00; p < 0.05). With the variable `nevi on arms' included, the protective influence of repeated AIVs was observed in a similar magnitude. The inverse relationship found between melanoma and influenza vaccinations is unlikely to have depended on a bias, even if based on replies in a questionnaire, because neither the interviewers nor the interviewers were informed in advance of the working hypothesis.

Two rate ratios indicating the disappearance of infections and the growth of tumours, respectively, were simultaneously plotted against the calendar years of occurrence in a period during which mortality rates were reasonably comparable to incidences. The transformation used gave upward trend time variations for infectious diseases, providing strong evidence that in Italy during the first half of this century variations in infectious diseases preceded variations in cancer. While some bacteria and viruses are known to be cancer agents, sparse studies indicate that a host's immune response to infection may destroy cancer cells. With a decreasing mortality from infectious illnesses, there may have been a reduction in the activation of immunological mechanisms against transformed cells in early phases of carcinogenesis. If cancer growth is a consequence of a lower exposure to chronic sublethal doses of microbial agents, bacterial derivates could be potentially useful in cancer chemoprevention.

Various substances and industrial processes, surrogates of exposure to polycyclic aromatic hydrocarbons (PAHs), are currently classified as human carcinogens. This paper reviews recent epidemiological studies reporting direct evidence of the carcinogenic effects of PAHs in occupationally exposed subjects. Risks of lung and bladder cancer were dose dependent when PAHs were measured quantitatively and truly nonexposed groups were chosen for comparison. These new findings suggest that the current threshold limit value of 0.2 mg/m3 of benzene soluble matter (which indicates PAH exposure) is unacceptable because, after 40 years of exposure, it involves a relative risk of 1.2-1.4 for lung cancer and 2.2 for bladder cancer. Images p1166-a

Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL ® ) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL ® dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL ® against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL ® and those treated with a vaccine including the same allergoids but not MPL ® . The protective effect of MPL ® could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL ® could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer.

BACKGROUND: The objectives of this study were to measure the incidence of sarcomas, including viscerally sited tumors that are not reported in cancer statistics, and to draw explanatory clues from a large and reliable sarcoma incidence data set. METHODS: Cases of sarcomas regardless of primary site (except bone and joints) were collected during 2 years in 3 European regions totaling approximately 26,000,000 person-years. The sources used were pathology reports and hospital discharges forms. Diagnoses were reviewed by expert sarcoma pathologists and were classified according to 2002 World Health Organization criteria. Soft tissue sarcomas (STS) were considered those located in arms, legs, trunk, head, neck, and retroperitoneum; visceral sarcomas (VS) were considered those that arose in internal organs. Rates were age standardized using the European (ASR-E) and the USA standard population. The rate of coexistence of VS and STS was calculated by dividing the 2 corresponding ASRs. RESULTS: There were 1558 sarcomas, 968 STS, and 590 VS. The ASRs-USA per 100,000 person-years was 5.12 × 105 among males and 4.58 × 105 among females for all sarcomas. For males and females, respectively, the ASR-E per 100,000 person-years was 3.58 × 105 and 2.55 × 105, respectively, for STS; 1.47 × 105 and 1.97 × 105, respectively, for VS; and 0.55 × 105 and 0.10 × 105, respectively, for Kaposi sarcoma. The coexistence rate of VS and STS was 0.41 for males and 0.77 for females. For dermatofibrosarcoma (both sexes), uterine sarcoma, liposarcoma (females), and leiomyosarcoma, including or excluding the uterus (females), the age-specific rates depicted a curve with a rapid increasing trend until ages 40 to 50 years and little variation thereafter. CONCLUSIONS: Compared with the incidence of STS, VS incidence made up an additional 41% in males and 77% in females. Because the shape of age-specific curves for some histotypes was similar to that of breast cancer, the authors concluded that sex hormones (plus many chemicals that act as endocrine disruptors) may be involved in carcinogenesis. This evidence could pave the way to investigate alternative treatments and to explore etiology. Cancer 2012. © 2012 American Cancer Society.

Various host-related factors have been reported as relevant risk factors for leprosy reactions. To support a new hypothesis that an antigenic load in local tissues that is sufficient to trigger the immune response may come from an external supply of Mycobacterium leprae organisms, the prevalence of reactional leprosy was assessed against the number of household contacts. The number of contacts was ascertained at diagnosis in leprosy patients coming from an endemic area of Brazil. The prevalence of reactions (patients with reactions/total patients) was fitted by binomial regression and the risk difference (RD) was estimated with a semi-robust estimation of variance as a measure of effect. Five regression models were fitted. Model 1 included only the main exposure variable "number of household contacts"; model 2 included all four explanatory variables ("contacts", "fertile age", "number of skin lesions" and "bacillary index") that were found to be associated with the outcome upon univariate analysis; models 3-5 contained various combinations of three predictors. Male and female patients were analyzed separately. In females, household contacts were a significant predictor for leprosy reactions in model 1 [crude RD = 0.06; 95% confidence interval (CI) = 0.01; 0.12] and model 5 (RD = 0.05; CI = 0.02; 0.09), which included contacts, bacillary index and skin lesions as predictors. Other models were unsatisfactory because the joint presence of fertile age and bacillary index was a likely source of multicollinearity. No significant results were obtained for males. The likely interpretation of our findings might suggest that in female patients, leprosy reactions may be triggered by an external spreading of M. leprae by healthy carrier family members. The small number of observations is an obvious limitation of our study which requires larger confirmatory studies.

The immunosuppressive macrolide FK-506 has been shown to protect neurons in culture against glutamate excitotoxicity. This effect was attributed to the binding of immunosuppressants to calcineurin-inhibiting immunophilins. We now report that also the non-immunosuppressive macrolide antibiotics protect neurons in culture against NMDA- but not kainate-mediated excitotoxicity. The effect was structure-dependent: larger macrolide rings were more active. Macrolides did not affect the 3-(2-carboxypiperazin-4yl)-propyl-1-phosphonic acid (CPP) binding or the NMDA-mediated calcium influx.

Brain-derived neurotrophic factor (BDNF) has recently been shown to enhance the survival of dopaminergic neurons in cultures derived from the embryonic rat mesencephalon. In the present study BDNF was found to protect cultured dopaminergic neurons from injury induced by acute exposure to the dopaminergic-selective neurotoxin 6-hydroxydopamine. The BDNF effect was concentration (ED50 approximately 10 ng/ml) and time-dependent, as determined by tyrosine hydroxylase immunocytochemistry. More importantly, subthreshold amounts of BDNF were rendered efficacious in the presence of ganglioside GM1: loss of tyrosine hydroxylase positive cells was reduced from 80% to only 20%. Thus GM1 may provide a fruitful treatment strategy for disorders of dopamine function such as Parkinson's disease.

The effect of intrahippocampal (i.h.) and intraocular (i.o.) administration of the selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) was studied in different rat strains. A massive hippocampal damage was observed in CD/SD and Fischer 344 but not in SD/Rij and Brown Norway rats 7 days following the i.h. injection of 1S,3R-ACPD, while no retinal damage was observed following its i.o. administration. Moreover, 1S,3R-ACPD reduced the N-methyl-D-aspartate (NMDA) toxicity in the retina of both CD/SD and SD/Rij rats. Regardless of its toxic action on hippocampal neurons the i.h. injection of 1S,3R-ACPD caused an acute stimulation of motor activity in both CD/SD and SD/Rij rats. This effect was blocked by the intracerebroventricular (i.c.v.) administration of the putative mGluR antagonist L-2-amino-3-phosphono-propionic acid (L-AP3). It is suggested that the differential expression of mGluR subtypes might determine their role in brain pathology.

Background The Italian Protective Maternity Legislation allows a woman to apply for early maternity leave from work during pregnancy if she is affected by health problems (option A) or if her working conditions are incompatible with pregnancy (option B). A community based health education program, implemented between 1995 to 1998 in North Eastern Italy, provided counseling (by a team of gynecologists, pediatricians, geneticists, psychologists and occupational physicians), and an information leaflet detailing the risks during pregnancy and the governmental benefits available to expectant mothers. This leaflet was distributed to women who were under occupational medical surveillance and to women attending any healthcare office and outpatient department and was also mailed to women working at home as shoemakers. The effectiveness of this intervention has been evaluated in this investigation using an evidence based approach. Methods A quasi-experimental design was adopted, applying several outcome measurements before (1989 to 1994) and after (1999 to 2005) the intervention. The outcome (ratio B/A) is the number of women receiving approval for B (circumstance where the pregnant woman is employed to undertake activities forbidden under the Article 7 of Law 151/2001, and it is impossible to change her duties) to those receiving approval for A (risky pregnancy due to personal medical conditions, Article 17 of the same Law). A linear regression coefficient (for B/A against years) was obtained separately for time periods "before" (1989-94) and "after" (1999-2005) the intervention program. The two regression coefficients were compared using a t-test. Results The trend over-time for the ratio B/A was steady before the initial intervention (y = 0.008x - 16.087; t = 2.09; p > 0.05) then increased considerably (y = 0.0426x - 84.89; t = 19.55; p < 0.001) in coincidence with the start of the education campaign. There was a significant difference between the two regression coefficients (t = 7.58; p < 0.001). Conclusion From a bureaucratic perspective Option B is far more complicated than A. In fact it implies an active approach involving an arrangement between the claimant and the employer, who has to certify to the relevant Authority that the woman's working conditions are incompatible with pregnancy. The increasing number of women availing of option B, as recommended, therefore suggests the suitability of such educational campaign(s).

Background Within the context of a European network dedicated to the study of sarcoma the relevant literature on sarcoma risk factors was collected by searching PubMed and Google Scholar, the two information storage and retrieval databases which can be accessed without charge. The present study aims to appraise the relative proficiency of PubMed and Google Scholar. Findings Unlike PubMed, Google Scholar does not allow a choice between "Human" and "Animal" studies, nor between "Classical" and other types of studies. As a result, searches with Google Scholar produced high numbers of citations that have to be filtered. Google Scholar resulted in a higher sensitivity (proportion of relevant articles, meeting the search criteria), while PubMed in a higher specificity (proportion of lower quality articles not meeting the criteria, that are not retrieved). Concordance between Google Scholar and PubMed was as low as 8%. Conclusions This study focused just on one topic. Although further studies are warranted, PM and GS appear to be complementary and their integration could greatly improve the search of references in medical research.

Background Sarcomas are rare tumors (1-2% of all cancers) of mesenchymal origin that may develop in soft tissues and viscera. Since the International Classification of Disease (ICD) attributes visceral sarcomas (VS) to the organ of origin, the incidence of sarcoma is grossly underestimated. The rarity of the disease and the variety of histological types (more than 70) or locations account for the difficulty in acquiring sufficient personal experience. In view of the above the European Commission funded the project called Connective Tissues Cancers Network (CONTICANET), to improve the prognosis of sarcoma patients by increasing the level of standardization of diagnostic and therapeutic procedures through a multicentre collaboration. Methods/Design Two protocols of epidemiological researches are here presented. The first investigation aims to build the population-based incidence of sarcoma in a two-year period, using the new 2002 WHO classification and the "second opinion" given by an expert regional pathologist on the initial diagnosis by a local pathologist. A three to five year survival rate will also be determined. Pathology reports and clinical records will be the sources of information. The second study aims to compare the effects on survival or relapse-free period - allowing for histological subtypes, clinical stage, primary site, age and gender - when the disease was treated or not according to the clinical practice guidelines (CPGs). Discussion Within CONTICANET, each group was asked to design a particular study on a specific objective, the partners of the network being free to accept or not the proposed protocol. The first protocol was accepted by the other researchers, therefore the incidence of sarcoma will be assessed in three European regions, Rhone-Alpes and Aquitaine (France) and Veneto (Italy), where the geographic distribution of sarcoma will be compared after taking into account age and gender. The conformity of the clinical practice with the recommended guidelines will be investigated in a French (Rhone Alps) and Italian (Veneto) region since the CPGs were similar in both areas.

Background Statistics on occupational accidents are based on data from registered employees. With the increasing number of immigrants employed illegally and/or without regular working visas in many developed countries, it is of interest to estimate the injury rate among such unregistered workers. Findings The current study was conducted in an area of North-Eastern Italy. The sources of information employed in the present study were the Accidents and Emergencies records of a hospital; the population data on foreign-born residents in the hospital catchment area (Health Care District 4, Primary Care Trust 20, Province of Verona, Veneto Region, North-Eastern Italy); and the estimated proportion of illegally employed workers in representative samples from the Province of Verona and the Veneto Region. Of the 419 A&E records collected between January and December 2004 among non European Union (non-EU) immigrants, 146 aroused suspicion by reporting the home, rather than the workplace, as the site of the accident. These cases were the numerator of the rate. The number of illegally employed non-EU workers, denominator of the rate, was estimated according to different assumptions and ranged from between 537 to 1,338 individuals. The corresponding rates varied from 109.1 to 271.8 per 1,000 non-EU illegal employees, against 65 per 1,000 reported in Italy in 2004. Conclusions The results of this study suggest that there is an unrecorded burden of illegally employed immigrants suffering from work related injuries. Additional efforts for prevention of injuries in the workplace are required to decrease this number. It can be concluded that the Italian National Institute for the Insurance of Work Related Injuries (INAIL) probably underestimates the incidence of these accidents in Italy.

In an endemic area of North-East Brazil (the town of Picos, State of Piauí), a nongovernmental organization (NGO) supported the activity against leprosy in connection with governmental health organizations and local agents. The indicators of leprosy elimination were compared over time (within Picos) and across space (Picos versus Piauí). The case detection rate, above 8 per 10,000 people in the last two years of observation, increased over time in Picos (p=0.010). This finding could be due to active detection activities rather than expanding endemicity, as suggested by the reduction in leprosy in children (p=0.053) and the decrease in the proportion of new cases with grade 2 disability (p

Objectives: Two cross-sectional studies were undertaken on workers in a beverage processing plant to investigate the association between low H2O2 exposure and symptoms of irritation (2005 study) and to investigate the effect of wearing respiratory protection (2006 study). Methods: The study comprised 69 workers exposed to H2O2 in sterile chambers and 65 unexposed controls. The exposure was assessed from measurements and work task information from employment records. The severity of work-related symptoms was evaluated using questionnaires. Data were analyzed by the Student’s t-test, multiple linear regression and analysis of variance for repeated measures of symptoms. Results: Symptoms of eye, nose and throat irritation were significantly (P < 0.001) more severe among exposed workers compared to controls. Exposure values were occasionally above American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value–time-weighted average (TLV-TWA) in the sterile chambers. The relationship between the severity of symptoms and the number of entrances in the chambers was significant (P < 0.0001) in 2005 but not in 2006, when respirators were used during work in the sterile chamber. No differences were found between exposed who entered a sterile chamber in 2005 but not in 2006 and exposed who entered a sterile chamber both in 2005 and 2006. This suggests that respirators provided an efficient protection and that the irritative effects of exposure to H2O2 in 2005 did not disappear after 1 year. Conclusions: The source of risk was exposure in the sterile chamber, even though the time of exposure was generally only � 30 min. To ensure complete worker protection, there is a need for a short-term exposure limit for H2O2 in addition to the existing ACGIH TLV–TWA value.

A survey was carried out in 2000 by the European Foundation for the Improvement of Living and Working Conditions in a random sample of workers from 15 countries of the European Union in order to obtain information on occupational exposure, health problems and preventive measures taken at the workplaces.To obtain similar information in workers in the Veneto Region and compare the results with those of the third European Survey on Working Conditions (ESWC). The results of the survey on Veneto Region workers were further analyzed, investigating the distribution by risk factors in each work sector, and the association between risk factors and reported health problems.The ESWC questionnaire was adapted to the requirements of a telephone interview and a sample of 5000 workers (size based on the budget) between 15 and 64 years of age was randomly extracted from the regional list of telephone subscribers. The questionnaire was administered by trained interviewers. No statistical tests were used in the comparison between ESWC and Veneto Region results due to the lack of a priori hypotheses. Odds ratio (OR) was calculated in estimating the association between risk factors and symptoms; and p-value for OR trend across the increasing level of exposure was also obtained.Workers reported to be exposed for more than a quarter of their work time to: vibrations (20%), noise (19%), dusts, fumes vapours, chemicals (18%), repetitive hand/arm movements (50%), tiring/painful positions (46%); working at very high speed or tight deadlines (60%). 54.4% of the subjects reported working with computers. Taking as a reference the third ESWC in 2000, among Veneto Region workers in 2005 exposure was lower as regards physical, chemical and ergonomic risk factors, and similar as regards working at very high speed. The more frequently reported work-related health problems were: stress (26.9%), backache (17.8%), overall fatigue (11.9%), muscular pains in upper limbs (6.8%), headache (6.1%), sight problems (5.4%), anxiety (5.5%), muscular pain in lower limbs (4.3%), irritability (4.0%), hearing problems (2.3%). Except for stress, all symptoms/health problems were two-three times more frequently reported in the ESWC than in the Veneto Region survey where, conversely, the number of persons with at least one new sick- leave spell was higher. Lastly, there was no difference as regards preventive measures taken at the workplace: information on risks (78.2%), wearing personal protective equipment (28.7%), training paid by employer (28.7%). Among the Veneto Region workers, the most often reported risk factors were exposure to physical and chemical risk factors in industry/agriculture, and shift-work and working at very high speed in the services. The most commonly adopted preventive measures were information on risks and wearing of personal protective equipment in industry, and training in services. Moreover, among the Veneto Region workers, a significant exposure-dependent increase was reported for respiratory problems, allergies, dermatitis, hearing loss, accidents, back pain, pain in the upper and lower limbs, and headache. The risk of stress, anxiety, sleeping problems, stomach pain and headache increased when skills were not adequate to cope with job demand. In contrast, the perception of improved health conditions increased with increasing skill discretion, decision authority, social support (which are dimensions of control of job demand), but not with information on risk, training, or use of personal protective equipment.Data from the present survey provide useful insights on working and health conditions of workers in the Veneto Region, revealing problems that were subsequently investigated using other sources of information, as reported in the studies published elsewhere in this volume.

In 2005, 52% of workers in the Veneto Region reported one or more sick leave spells in the previous 12 months, compared with 16% reported in the European Survey on Working Condition in 2000 (ESWC), although health conditions were better in the Veneto Region than in the ESWC.Since the above findings were based on answers to a questionnaire, we used an objective source of information in order to further investigate the problem.The source of data consisted of the sick leave records of workers in the Veneto Region, 1997-2002, which were obtained from the Italian National Social Security Institute (INPS). Four measurements were used: (1) frequency = number of sick-leave spells during the study period/number of insured persons at risk for sickness absence during the study period; (2) cumulative incidence = number of persons with at least one new sick-leave spell during the study period/number of insured persons at risk for sickness absence during the study period; (3) sick-leave rate = number of sick-leave days during the study period/number of insured persons at risk for sickness absence during the study period; (4) duration of absence = number of sick-leave days in new sick leave spells during the study period/number of new sick-leave spells during the study period. Cumulative incidence could only be analyzed by statistical methods (binomial regression).The first three measurements gave overlapping results. The values were highest in industry, lowest in agriculture, and intermediate in crafts and services; they were highest in middle-aged subjects and lowest in younger and older individuals; the time trend increased up to 1999 and then decreased slowly. Cumulative incidence was 52.0%, 38.0%, 36.4% and 22.9%, in industry, services, crafts, and agriculture, respectively, and 42.8% in the total population. The results of binomial regression confirmed the above pattern, as well as an excess in women, in white collar workers, and in various occupational categories which, however, were probably not due to occupational exposures since in each occupational category the risk was always higher in industry than in crafts. By contrast, the sick-leave rate was higher in crafts and agriculture and lower in services and industry; it increased exponentially with age and did not show real differences between males and females.The choice of measurements influences the results; duration of absence could be used to detect areas of suspected work-related diseases, while cumulative incidence might be more helpful to detect areas of suspected absenteeism/presenteeism.

Stress was the most frequent (26,9%) health problem reported in a survey on the perception of working and health conditions in 5000 workers in the Veneto Region.The aim of the study was to investigate in the Veneto Region the association between occupational stress and events occurred in the previous 12 months: occupational accidents, or sickness absence for 10 or more consecutive days.Perceived occupational stress is correlated, according to Karasek's model, to high job demand (JD) and low decision latitude (DL). Using Karasek's questionnaire (to which questions on smoking and alcohol consumption were added), we examined 2174 subjects working in 30 companies with between 10 and 500 employees, who belonged to the occupational categories of industry and services that are more prevalent in the Veneto Region. The questionnaire was administered by the occupational physician during health surveillance. The subjects were classified on the basis of current exposure to psychosocial factors or, for subjects reporting an event, their exposure at that time. We identified the tertiles of JD and DL; data were submitted to the analysis of multiple logistic regression, estimating odds ratio (OR) and 95% confidence interval (CI). The population attributable risk (PAR) was calculated using the formula (pc (OR-1)/OR), where pc is the fraction of exposed cases.An elevated risk of occupational accidents was found in subjects with regular consumption of alcohol (OR = 2.0; IC = 1.2-3.5), in smokers smoking 10-20 (2.3; 1.3-3.8) or20 cigarettes/day (3.8; 1.8-7.9), in the highest tertile of JD (2.29; 1.35-3.89) and in the lowest tertile of DL (1.6; 1.0-2.6). PAR was 37.6% for occupational factors (high JD and low DL), 44.5%for non-occupational factors (cigarette smoking and alcohol consumption), and 82.1% overall. The risk of sickness absence increased in subjects smoking 10-20 cigarettes (1.63 = 1.1-2.40), in the highest tertile of JD (1.5; 1.0-2.2) and in the lowest tertile of DL (1.6; 1.1-2.2). PAR was 26.1% for occupational factors (high JD and low DL), 7.6% for non-occupational factors (smoking), and 30.4% overall. While the risk of sick absence increased mainly with the reduction of DL, the risk of occupational accidents increased with increasing JD and, to a lesser extent, with decreasing DL. The current approach to accident prevention is based only on technical and administrative aspects, in spite of the fact that 80% of accidents are not attributable to malfunctioning of machinery. Injury prevention should address technical, personal and psychosocial risk factors together as a whole.

According to Italian law, workers are insured against disability through the National Social Security Institute (INPS), whose records contain information on diseases causing disability and occupational histories.Using the INPS data, our objective was to identify any excess risk of disabling diseases in relation to the occupational categories.Insurance covers all private sector employees, a small proportion of public sector employees, agricultural labourers, domestic workers, self-employed workers (craftsmen, commercial dealers,farmers), and few other occupational categories. For each insured worker, a database was created containing registry data, occupational history and, for compensated workers, the disease code, for each year from 1994 to 2002. A cohort study design was adopted, in which references were self-employed workers (with mixed exposure) to whom different categories of employees in agriculture, industry, crafts, and services were compared. Data were analyzed by means of Poisson regression, estimating the Incidence Rate Ratio (IRR) and confidence interval (CI) at 99.99%, instead of 95%, in order to set the threshold of error for the entire study at 0.05.In the construction industry there were significantly high risks of disability in both industry and crafts for tumours (industry: IRR = 2.07; IC = 1. 67-2.57; crafts: 2.57; 1.89-3.18), circulatory disorders (industry: IRR = 2.24; IC = 1.65-3.04; crafts.: 3.06; 2.16-4.32), and bone and joint diseases (industry. IRR = 5.0; IC = 3.15-7.94; crafts: 6.58; 5.04-8.59).The advantage of this approach is to recruit a large number of subjects at limited cost. The procedure here proposed is a mainly exploratory approach aimed at establishing new study hypotheses: disability, in fact, is acknowledged by INPS when its cause is not occupational according to the current literature.

Several studies report a lower than expected mortality in lung cancer among workers exposed to organic dust. Recent studies also reported a decreased risk for cancer at other sites.To evaluate the mortality from lung and other cancer sites in cotton mill workers.A cohort of 3961 Italian cotton mill workers was divided into those working with carding (exposed to high levels of endotoxin-containing cotton dust) and other tasks, which generally have lower exposure. Standardised mortality ratios (SMRs), with 95% confidence intervals (CI), were calculated using death rates of the regional general population as a reference. Cancer mortality was analysed in relation to the length of employment in the two task groups. An internal analysis was also performed through Poisson regression.Among workers in carding departments, lung cancer SMRs were 1.88 (CI: 0.69 to 4.08), 1.01 (CI: 0.20 to 2.94) and 0.22 (CI: 0.00 to 1.24), respectively, for6, 6-12 and12 years of employment (chi(2) for trend = 5.45; p0.05). A significant (p = 0.04) trend was confirmed by Poisson regression. No reduced risks were found for other forms of cancer, nor for those working with other tasks.The results support previous reports that a high and prolonged exposure to cotton dust and other endotoxin-containing organic dusts is related to a lower risk of lung cancer. There was no indication of a reduced risk for other forms of cancer.

Summary The basis of World Health Organization strategy for leprosy elimination is that the only source and reservoir for infection are patients with the disease. It was assumed that multi drug therapy (MDT) would reduce transmission of Mycobacterium leprae , but there is no convincing evidence for this. Furthermore, even if MDT has been proved to be extremely effective against the infectious disease, a noticeable proportion of leprosy patients can suffer from immunologic hypersensitivity reactions which are now the most significant issue in the managements of the disease. In endemic areas it was found that: M. leprae survives outside human body; healthy individuals harbor M. leprae bacilli in nasal cavity and shed micro-organisms in environment; there is widespread subclinical transmission of M. leprae with transient infection of the nose resulting in the development of a mucosal immune response. This disparate clinical, epidemiologic, and microbiologic evidence leads to the first hypothesis: that antigenic load in local tissues, sufficient to trigger the immune response, comes from external supply of M. leprae organisms. The hypothiocyanite anion (OSCN − ) is generated in vivo by the reaction of thiocyanate with hydrogen peroxide catalyzed by lactoperoxidase. OSCN − is an antimicrobial oxidizing agent that prevents growth of bacteria, fungi, and viruses. OSNC − exists in lower airway secretions and lung has never been reported to be affected by leprosy. There is a sufficient concentration of OSCN − in the saliva, and accordingly mouth is rarely affected by leprosy. By contrast, the concentration of this compound is low or nil in nasal and lacrimal secretions and leprosy very often affects nose and eyes. The second hypothesis is that OSCN − may also protect from leprosy. Recently a method of OSCN − production, not involving enzymatic steps or use of toxic heavy-metal salts, has been patented. Studies on the susceptibility of M. leprae to hypothiocyanite could be carried out and, in case of positive results, the substance might be used in order to sterilize the nasal cavity of healthy carriers and prevent transmission of M. leprae to healthy subjects and to leprosy patients in whom it may trigger an immune response.

Background Five cancer cases over 7 years were reported in a small orthopaedic hospital where radiation protection practice was poor. Aim To investigate whether workers subject to routine radiation dosimetric assessment in that hospital had an increased cancer risk. Methods One hundred and fifty-eight workers subject to routine dose assessment and 158 age-sex-matched unexposed workers were questioned about cancer occurrence. All tumours were analysed as a single diagnostic category. Results Cumulative 1976-2000 cancer incidence was 29 (9/31), 6 (8/125) and 4% (7/158) in orthopaedics, exposed other than orthopaedics, and unexposed workers, respectively. At logistic regression analysis, working as orthopaedic surgeon significantly (P < 0.002) increased the risk of tumours. Conclusion These findings caution against surgeons' underestimation of the potential radiation risk and insufficient promotion of safe work practices by their health care institutions.

In old subjects exposed to extreme high temperature during a heat wave, studies have consistently reported an excess of death from cardio- or cerebro-vascular disease. By contrast, dehydration, heat stroke, acute renal insufficiency, and respiratory disease were the main causes of hospital admission in the two studies carried out in elderly during short spells of hot weather. The excess of circulatory disease reported by mortality studies, but not by morbidity studies, could be explained by the hypothesis that deaths from circulatory disease occur rapidly in isolated people before they reach a hospital. Since the contrasting patterns of hospital admission and mortality during heat waves could also be due to chance (random variation over time and space in the spectrum of diseases induced by extreme heat), and bias (poor quality of diagnosis on death certificate and other artifacts), it should be confirmed by a concurrent study of mortality and morbidity. Many heat-related diseases may be preventable with adequate warning and an appropriate response to heat emergencies, but preventive efforts are complicated by the short time interval that may elapse between high temperatures and death. Therefore, prevention programs must be based around rapid identification of high-risk conditions and persons. The effectiveness of the intervention measures must be formally evaluated. If cardio- and cerebro-vascular diseases are rapidly fatal health outcomes with a short time interval between exposure to high temperature and death, deaths from circulatory disease might be an useful indicator in evaluating the effectiveness of a heat watch/warning system.

The aim of this study was to confirm the exposure-dependent reduction in lung cancer risk reported for dairy farmers exposed to endotoxin and to evaluate the consequence of leaving dairy farming and taking employment in industry or services, where exposure to microbial agents is lower. Standardized mortality ratios, with 95% confidence intervals, for 2,561 self-employed dairy farmers were estimated, considering the general population of Veneto, Italy, from 1970 to 1998 as the reference. Sixty-two lung cancer cases, whose information was checked against clinical records, were compared with 333 controls in a cohort-nested case-control study. Odds ratios with 95% confidence intervals were estimated by logistic regression analysis. A downward trend of standardized mortality ratios for lung cancer across tertiles of number of dairy cattle on the farm was significant (p0.05) from 1970 to 1984 but not from 1985 to 1998, when most subjects were no longer dairy farmers. Age- and smoking-adjusted odds ratios for lung cancer significantly decreased with increasing number of dairy cattle (p for trend = 0.001) for workers for whomor =15 but not15 years had elapsed from the end of work to the end of follow-up. In conclusion, increased levels of endotoxin (or other associated environmental factors) might be protective against lung cancer; protection diminishes over time after that exposure is removed.

This study reports on longitudinal changes in lung function using spirometry of employees at a beverage processing plant, where exposure information (1995-2001) suggests that the threshold limit value (TLV)-Time Weighted Average (TWA) of 1 ppm was not likely exceeded. Changes over time in lung function (Forced Expiratory Volume of 1st second, FEV1; Forced Vital Capacity, FVC; and FEV1/FVC ratio; all expressed as percent of the predicted) were evaluated by using sparse lung function data obtained from 1993 to 2002 in 43 exposed and 31 unexposed workers. The longitudinal changes were assessed using multiple regression analysis where the dependent variable was the annual change of lung function indices and the independent variables were exposure and smoking habits. With regard to exposure, FVC increased, FEV1 was unchanged, and the FEV1/FVC ratio tended to decrease. The latter difference was not significant when FVC was used as a covariate. The FEV1 is significantly worse in smokers than in non-smokers. These data suggest that no lung function changes occur when the H2O2 levels were compliant to the exposure standard. Our findings support the current TLV-TWA of 1 ppm for H2O2.

In Italy, occupational diseases are required by law to be listed (however, any occupational diseases not included in the list may be compensated if workers demonstrate causation in court). The list is periodically updated in order to incorporate new findings from medical research. Decree no. 336/94 uses a less inclusive term (chronic obstructive bronchitis) than that used in the earlier decree, no. 482/75 (chronic obstructive pulmonary disease, COPD). Moreover, it includes fewer occupations that involve a risk of developing COPD.In order to find an epidemiological basis that might justify the above changes to Italian law, risk of COPD was investigated in relation to occupation and time, using a case-referent design.The same definition for COPD (clinical history of2 years with shortness of breath and/or winter phlegm and an FEV1 less than 80% of the predicted value, only minimally reversible with bronchodilators and without marked change during the hospital observation period) was used in two case-referent studies. The first study was carried out from 1972 to 1980 (202 cases of COPD and 202 referents matched for age and sex) and the second from 1990 to 1997 (131 cases of COPD and 298 referents, every fourth eligible patient in each calendar year of observation). In both studies cases and referents were classified into 16 occupational categories, and office workers were the reference. All subjects were selected from male patients admitted to the Occupational Health Clinic in Padua. Smoking-adjusted (Mantel-Haenszel analysis, first study), or age-smoking-adjusted (logistic regression analysis, second study) Odds Ratio (OR) and 95% confidence interval (CI) for COPD were estimated in each occupational category and in two main groups: workers employed in occupations at either high or low risk for COPD. The latter OR and the fraction of exposed cases (pc) were used to estimate the population attributable risk (PAR) through: pc(OR-1)/OR.Significantly high risks for COPD in miners and chemical workers were observed in the first period, but not in the second time window. On the other hand, an increased time trend for OR estimates was found in welders, wood carpenters, construction and foundry workers. Among farmers, painters, cotton textile and refractory brick workers, the OR for COPD was significantly above unity in both time periods. PAR was 37% in the first and 52% in the second study.The restrictive definition of occupational COPD, which was introduced by Decree no. 336/94, contrasts with the epidemiological evidence showing that the risk of occupational COPD has increased over time: up to 50% of COPD cases referred to an occupational medicine physician might have an occupational origin.

Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) are not well-established vinyl chloride monomer (VCM)-induced diseases. Our aim was to appraise the role of VCM, alcohol intake, and viral hepatitis infection, and their interactions, in the etiology of HCC and LC. Thirteen cases of HCC and 40 cases of LC were separately compared with 139 referents without chronic liver diseases or cancer in a case-referent study nested in a cohort of 1,658 VCM workers. The odds ratios (ORs) and the 95% confidence intervals (CIs) were estimated by common methods and by fitting models of logistic regression. We used Rothman's synergy index (S) to evaluate interactions. By holding the confounding factors constant at logistic regression analysis, each extra increase of 1,000 ppm times years of VCM cumulative exposure was found to increase the risk of HCC by 71% (OR = 1.71; 95% CI, 1.28-2.44) and the risk of LC by 37% (OR = 1.37; 95% CI, 1.13-1.69). The joint effect of VCM exposure above 2,500 ppm times years and alcohol intake above 60 g/day resulted in ORs of 409 (95% CI, 19.6-8,553) for HCC and 752 (95% CI, 55.3-10,248) for LC; both S indexes suggested a synergistic effect. The joint effect of VCM exposure above 2,500 ppm times years and viral hepatitis infection was 210 (95% CI, 7.13-6,203) for HCC and 80.5 (95% CI, 3.67-1,763) for LC; both S indexes suggested an additive effect. In conclusion, according to our findings, VCM exposure appears to be an independent risk factor for HCC and LC interacting synergistically with alcohol consumption and additively with viral hepatitis infection.

Previous studies have suggested that those in occupations exposed to endotoxin have a reduced rate of lung/respiratory cancer. An initial investigation found a significantly reduced risk of all sites malignant neoplasms in white male crop and livestock farmers, and black male and female crop farmers. This study provides data on lung/respiratory cancers in the same workers. Data were obtained from occupation and industry-coded US death certificates collected from 26 states for the period 1984-1993. Cause, sex, and race specific proportionate mortality ratios (PMRs) were calculated using a National Institute of Occupational Safety and Health computer program. A pooled relative risk (PRR) was obtained by summing up separately and then dividing the sex-race specific observed and expected cases, separately in crop and livestock farmers. Deaths from respiratory cancer were 12,482 and 2,290, and deaths from lung cancer were 12,091 and 2,201. In each sex and race group respiratory and lung cancer PMRs are generally lower than unity. Lung cancer PRR was 0.80 (0.78-0.81) in crop farmers and 0.70 (0.67-0.73) in livestock farmers, a significant difference (p0.0001). Comparison of our findings with those by Nieuwenhuijsen et al. [1999] reporting personal exposure measurements in groups of Californian farmers (endotoxin averaging 132.5 EU/m(3) during livestock farming against 19.9 EU/m(3) during field crop and fruit farming), suggests a decreasing lung cancer risk with increasing endotoxin exposure, and supports a possible dose-response relationship between the two.

A meta-analysis of epidemiologic studies for textile industry workers was undertaken in an attempt to evaluate whether the cancer risk varies within the textile industry in relation to the job held or the textile fiber used. We combined studies published up until 1990, when an ad hoc IARC Monograph was issued, and those published after 1990 with the aim of appreciating evidence of reversing trends in cancer risk. Observed and expected cases reported in the original studies were summed up and the totals were divided to obtain a pooled relative risk (PRR) with a 95% confidence interval (CI) estimated with a fixed-effect model. We calculated a chi-square test (x2) of heterogeneity among studies. When PRR and x2 were both significant, PRR and CI were calculated with a random-effect model and the source of heterogeneity was investigated. Lung cancer risk was around 0.4 in the first study on cotton workers published in 1936, around 0.7 in subsequent studies, mostly published in the 1970s and 1980s, and around 1.0 in the last studies published in the 1990s. Papers published in the 1970s and 1980s produced consistent risk estimates for lung cancer risk, which was significantly lower than 1.0 in workers exposed to cotton (PRR 3/4-0.77; CI3/4-0.69-0.86) and wool dust (0.71; 0.50-0.92), as well as in carders and fiber preparers (0.73; 0.54-0.91), weavers (0.71; 0.56-0.85), and spinners and weavers (0.78; 0.66-0.91). Lung cancer PRRs did not significantly deviate from 1.0 in textile workers using synthetic fibers or silk, and in dyers. Increased PRRs were found for sinonasal cancer in workers exposed to cotton dust, and in workers involved in spinning or weaving (4.14; 1.80-6.49). PRR was 1.46 (1.10-1.82) for cancer of the digestive system in textile workers using synthetic fibers or silk, and 1.34 (1.10-1.59) for colorectal cancer in spinners and weavers. The increased bladder cancer PRR in dyers (1.39; 1.07-1.71) is generally attributed to textile dye exposure. In studies published after 1990, there is a general tendency to move toward unity for all the cancer risk estimates, leading to an increasing heterogeneity among studies. Since adjustment for smoking made little difference to the findings, the latter could be attributed to the exposure to textile dusts. The recent findings could be due to a lowering of dust concentration in the workplaces. The reduction of cases of upper respiratory tract cancer parallels with a corresponding increase of lung cancer cases. So, preventive measures have paradoxically increased the lung cancer burden to the textile workers.

Objectives. Diesel exhaust particles (DEPs) containing polycyclic aromatic hydrocarbons stimulate the formation of IgE in humans following single and acute exposure. The aim of the present study was to ascertain whether long-standing occupational exposure to DEPs carries a risk of enhanced serum IgE, and of rhinitis or asthma. Methods. In this cross-sectional study, findings in 76 dockers were compared with those in 63 reference subjects. Among the dockers, drivers and laborers were exposed to diesel emission from forklifts or trucks in the ship-holds, where benzopyrene levels averaged 4.9 ng/m3. Serum IgE levels were measured by the UNICAP method. Atopy, an evident source of high IgE levels, was assessed by the Phadiatop test. The subjects' clinical and occupational histories were collected. Interval variables were analyzed with Student's t- and Levene's F-tests. The odds ratio (OR) with the 95% confidence interval (CI) was obtained by the exact method at univariate and multivariate (logistic regression) analysis. Results. In view of the large difference in serum IgE (P=0.00001) and the prevalence of respiratory diseases (P=0.009) between atopic and non-atopic subjects, we analyzed their data separately. For non-atopic subjects, the risk of presenting high IgE was significantly higher (OR=11.4; CI=1.44–526; P=0.013) and the risk of respiratory disease was significantly lower (OR=0.09; CI=0.00–0.73; P=0.016) in drivers and laborers as a whole than in the reference subjects. None of the ORs was significant among atopic individuals. Conclusions. In non-atopic dockers, long-standing exposure to DEPs at concentrations similar to those in heavily polluted cities increased serum IgE levels but not the incidence of rhinitis or asthma.

Background Recent community surveys have reported a risk of chronic obstructive pulmonary disease (COPD) in occupations involving exposure to organic dust and gas/vapour. Aims Our aim was to confirm these results using a case-control design on 131 COPD cases (FEV 1 < 80% of predicted value, minimally reversible with bronchodilators) and 298 controls, selected from registers for patients admitted to our Institute of Occupational Medicine. Methods Surrogates of past exposure were occupation, exposure assigned by a job-exposure matrix, and years spent in a given occupation. The odds ratio (OR) and 95% confidence interval (CI) for COPD were calculated using logistic regression models with office workers as the reference. Results Age-smoking-adjusted ORs (and CIs) were: 15.1 (3.2-71.6) in farmers; 7.2 (1.3-41.1) in cotton workers; 6.4 (1.6-25.5) in welders; 4.7 (1.3-16.4) in painters; 12.1 (1.3 108) in foundry workers; 6.50 (1.14-37.0) in refractory brick workers; and 3.1 (1.0-9.5) in construction workers. In farmers, cotton workers, welders and painters, the adjusted ORs significantly increased (by 6-9%) for each extra year of work, while in other occupations any such increase was of borderline significance. Adjusted ORs were 3.80 (1.21-12.0), 5.83 (1.82-18.6) and 8.86 (2.29-34.3) in workers exposed to high levels of mineral dust, gas/vapour/fume and biological dust, respectively. Consistent risk estimates were obtained for farmers, textile workers, painters and welders. Conclusions Our findings confirm previous epidemiological evidence and are supported by recent observations that cigarette smoke, cotton and organic farm dust contain the same powerful pro-inflammatory agents, and that organic dust and irritant gas induce bronchitis by triggering the same effector molecules as cigarette smoke.

1. The binding of [3H]-imidazenil, an imidazobenzodiazepine carboxamide, to rat cerebellar membranes was characterized at different temperatures. 2. Specific binding was linear with tissue concentrations and reached maximum after 90, 30 and 5 min incubation at 0, 21 and 37 degrees C, respectively. The binding was of high affinity, specific and saturable; non linear regression and Scatchard analysis of the data was compatible with the presence of a single population of receptor sites with Bmax of 0.74 +/- 0.020, 0.90 +/- 0.011 and 1.0 +/- 0.036 pmol mg-1 protein at 0, 21 and 27 degrees C, respectively. Binding affinity decreased with increasing temperature: Kd were 0.29 +/- 0.051 nM (0 degrees C), 1.0 +/- 0.080 nM (21 degrees C) and 2.4 +/- 0.38 nM (37 degrees C). 3. At all tested temperatures, [3H]-imidazenil binding was reversible and the Kd calculated from the dissociation and association rate constants approximated the equilibrium Kd. 4. In the presence of gamma-aminobutyric acid (GABA), Kd increased 4 fold at 0 degrees C, whereas Bmax increased, albeit slightly, at all temperatures. 5. Benzodiazepines (BZDs), imidazopyridines and methyl-beta-carboline-3-carboxylate (beta CCM) were effective inhibitors of [3H]-imidazenil binding. Conversely, GABAA antagonists, barbiturates, picrotoxin and peripheral BZD receptor ligands were devoid of any activity. 6. Comparing [3H]-imidazenil to [3H]-flumazenil binding in various brain areas, similar densities of recognition sites as well as like regional differences in the distribution of binding sites for both radioligands were observed (cortex = striatumcerebellumspinal cord). 7. The present results indicate that [3H]-imidazenil specifically binds to the BZD sites of GABAA receptors. Furthermore, the effects of GABA and temperature differentiate imidazenil from classicalBZDs. It is suggested that the characteristics of imidazenil binding may be relevant to the in vivo pharmacology of the drug.

In the retina, the activation of metabotropic glutamate receptors (mGluRs) reduces the toxic effect of N-methyl-D-aspartate (NMDA). We have induced NMDA-mediated excitotoxicity in the adult rat retina by a single intraocular injection of NMDA. The damage that resulted was estimated by assessing the NMDA-induced loss of retinal choline acetyltransferase (ChAT) activity. The new rigid glutamate analog, dimethyl ester of (+/-)-trans-azetidine-2,4-dicarboxylic acid (t-DMADA), with a putative mGluR-agonistic activity, protected the retina from NMDA-induced loss of ChAT activity. This study demonstrated that t-DMADA can be considered a prototype of new retino-protective agents.

The semisynthetic glycosphingolipid derivative II 3 Neu5-AcGgOse 4 -2-d-erythro-1,3-dihydroxy-2-chloro-acetamide-4- trans -octadacene (LIGA20) attenuated injury induced by the excitotoxic L -dopa metabolite 2,4,5-trihydroxyphenylalanine (TOPA) in cultures of rat cerebellar granule cells when presented simultaneously with TOPA (EC 50 : 9 μM LIGA20). The natural glycosphingolipid ganglioside GM1 up to 200 μM was not neuroprotective as cotreatment, although pretreatment of cells for 2 h was efficacious. This greater potency and speed of LIGA20 action extended to limiting TOPA-induced death of cultured mesencephalic dopaminergic neurons. These data suggest that LIGA20 may have therapeutic potential for the treatment of disorders associated with excitotoxic processes.