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In this work, a novel calibration approach for minor and trace element quantification in LA-ICP-MS imaging of biological tissues is presented. Droplets of aqueous standard solutions are deposited onto pre-cut pieces of filter paper, allowed to dry, and sputtered with a thin gold layer for use as pseudo-internal standard. Analysis of the standards using LA-ICP-MS is performed using radial line-scans across the filters. In contrast to conventionally used preparation of matrix-matched tissue standards, the dried-droplet approach offers a variety of advantages: The standards are easy to prepare, no characterization of the standards using acid digestion is required, no handling of biological materials is necessary, and the concentration range, as well the number of investigated analytes is almost unlimited. The proposed quantification method has been verified using homogenized tissue standards with known analyte concentrations before being applied to a human malignant mesothelioma biopsy from a patient who had not received any chemotherapeutic treatment. Elemental distribution images were acquired at a lateral resolution of 40 μm per pixel, limits of detection ranging from 0.1 μg g(-1) (Mn, Ni, Cu, Zn) to 13.2 μg g(-1) (K) were reached.

Three malignant pleural mesotheliomas occurred among workers of a small factory that manufactured drying machines for the textile and paper mill industries using asbestos cement (crocidolite, amosite and chrysotile) as insulating panels. The Occupational Medicine Unit of the Local Health Unit of Pistoia, Italy, carried out an intervention programme in the plant in order to 1) assess past asbestos exposure via analysis of the fibre content of samples from drying machines, and of dust samples collected in the factory. Information on the characteristics of occupational exposure was also collected; 2) investigate cancer mortality by means of a mortality study of the employees and, 3) carry out a health intervention programme in workers formally exposed to asbestos in the past.Samples from the drying machines and dust samples collected in the factory were analysed using X-ray diffractometric methods. Information on the characteristics of occupational exposure were collected by interviewing plant workers. Two-hundred and fifty employees who had worked in the factory between 1962 and 2000 were included in the mortality study. Follow-up was performed from 1962 to 2002. Health intervention in workers exposed to asbestos in the past involved general practitioners and occupational physicians (first level medical examinations); pneumologists and radiologists (second level medical examinations) of the local health unit.Asbestos fibres were found both in samples from drying machines and in dust samples collected in the factory. Interviews with workers showed that asbestos exposure varied considerably. The SMR for mesothelioma and lung cancer in 234 male workers were 37.0 (95%CI: 4.47-130.0), and 1.29 (95%CI: 0.26-3.78), respectively, based on mortality rates for Tuscany region. Sixty-two workers underwent first level medical examinations; 57 second level examinations. Chronic obstructive lung disease was found in 3 workers; restrictive lung disease was found in 3 employees, one of whom had pleural plaques.Further investigation is needed in order to identify unknown asbestos exposures in small metal engineering factories.

To examine the range of clinical phenotypes, tumour associations, relevant investigations, response to therapy and outcome in a large series of non-selected patients with paraneoplastic neurological disease (PND) affecting the central nervous system (CNS) in the United Kingdom.Data were obtained on patients either through direct referral or through the British Neurological Surveillance Unit (BNSU) from February 2000 to January 2001. Physicians were asked to supply information about age and sex of patients, presenting neurological syndromes, the basis of the diagnosis of PND, any associated malignancy, and treatment. Case notes were reviewed and follow up data obtained where possible one year after notification.A total of 63 patients (48 females, 15 males) were identified, 48 through the BNSU and 15 through direct referral. Of these 52 were diagnosed as having definite PND, 10 probable PND, and 1 possible PND. The median age of onset of PND was 66 years (range 30-80 years) and only 7 patients (11%) were less than 50 years at presentation. In 53 patients (84%) the PND preceded the diagnosis of cancer. Paraneoplastic sensory neuronopathy, paraneoplastic encephalomyelitis, and paraneoplastic cerebellar degeneration (PCD) were the most common syndromes reported. The benefit of magnetic resonance imaging in the diagnosis of the disease was limited, while fluorodeoxyglucose positron emission tomography was shown to be useful for the detection of an occult malignancy in 10 out of 14 patients. Antineuronal antibodies were positive in 44/57 (77%) of cases. The following tumours were diagnosed: small cell lung cancer (30%), breast cancer (14%), ovarian cancer (8%), non-small cell lung cancer (8%), Hodgkin's lymphoma (6%), other (16%). With the exception of PCD associated with mesothelioma all other tumours diagnosed in these patients had been previously documented as being associated with PND. Only treatment of the tumour was found to be associated with a stable or improved neurological outcome at last follow up (Fisher's exact test = 4.7, p0.03). Median survival time was 43 months (95% CI 28 to 57) from onset of neurological disease as calculated using the Kaplan-Meier survival analysis.PND has a striking female preponderance usually affecting patients in their sixth decade and above. The median survival in our study was 43 months. The majority of patients with PND are not known to have cancer at the time of diagnosis. Our study confirms the importance of diagnosing and treating the underlying tumour.

The paper reports 9 cases of mesothelioma diagnosed by means of histology or cytology that were observed among women resident in the Veneto Region, Northern Italy, whose only activity that could involve exposure to asbestos was as rag sorter. These cases are part of a group of about 260 subjects with mesothelioma whose entire working and residential history has been collected. The women worked as rag sorters between the 1940's and 1960's in textile recycling (8 cases) or (one case) at a paper mill where cotton was used for paper production. The work as rag sorter helps to explain the high proportion of mesotheliomas among women with an occupational exposure to asbestos.

This paper reviews the available literature regarding the work environment in pulp and paper mills and the risk for malignant diseases. An increased risk for lung cancer among pulp and paper mill workers has been reported. Most studies are inconclusive with regard to considerations of etiologic agents. However, maintenance workers seem to be at an increased risk for lung cancer, as well as for malignant mesothelioma, indicating that this occupational group was (is) exposed to asbestos. Workers exposed to chlorine compounds also seem to run an increased risk for lung cancer. An increased risk for malignant lymphomas among pulp mill workers is a constant finding. The increased risk is observed both among sulfite and sulfate workers, indicating a common exposure. Such an exposure could be wood dust, terpenes, or preservatives present in the wood. An increased risk for leukemias has been found in many studies carried out on pulp and paper workers, but the studies do not permit any conclusions about etiologic factors. In some studies an increased risk for stomach cancer has been found. However, the socioeconomic status of the workers is strongly related to stomach cancer, and factors, such as dietary habits, have not been taken into account in any of the reviewed studies. Hence, no further conclusions can be drawn regarding etiologic agents.

Analysis of data obtained by linking the 1960 Swedish Census and the Swedish Cancer Registry has demonstrated an increased risk of pleural mesothelioma among pulp and paper workers. The present study was undertaken with the aim of revealing possible environmental risk factors. The work histories of the 25 cases identified earlier were reviewed. "Certain" or "probable" exposure to asbestos was found among 70% of these workers. The study illustrates how linkage of official registers can be used to identify new risk environments and encourage the establishment of preventive measures.