Antiviral effect of high-pressure nasal stimulation.

OBJECTIVE: In a previous study, we reported an increase of nasal nerve growth factor (NGF) in patients treated with high-pressure administration of sterile saline isotonic solution (HPpSIS). Herein we characterized the nasal mucosa in terms of innate immune response and cytokine signature, including antiviral properties. Potential NGF and antiviral benefits of HPpSIS were also discussed. PATIENTS AND METHODS: Twenty (20) patients (11 males, 9 females; age range 30-75 years old) underwent HPpSIS and nasal samples were collected before and after treatment. Nasal scraping was used for morphological (smears and Quick May-Grunwald Giemsa staining, MGG), biochemical (Histamine, Serotonin; ELISA) and molecular (messenger RNA, mRNA) analyses. Amplification of transcripts specific for Toll-like receptor (TLR) 3 (TLR3), TLR7, TLR9, Interleukin-(IL) 18 (IL18), IL13, IL12, eosinophil-derived neurotoxin (EDN), Eosinophil Cationic Protein (ECP), γ Interferon (γIFN), tryptase and serotonin was performed using the 2-step real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR). Clinical and laboratory data were analyzed and compared. RESULTS: The clinical evaluation showed a protective effect of our therapy. Smears showed the presence of leucocytes, eosinophils (EOs) and mast cells (MCs), and increased immunoreactivity for ECP/RNase3 and EDN after HPpSIS. ELISA showed increased levels of Serotonin and EDN associated with unchanged levels of substance P(SP) and histamine. Increased eosinophil-derived neurotoxin eosinophil-derived neurotoxin (EDN) levels were confirmed by in situ fluorescent analysis. HPpSIS induced the upregulation of TLR3, TLR7 and TLR9 transcripts, while no changes were observed for Intercellular Adhesion Molecule 1 (ICAM1), IL18, Interleukin-15 (IL15) and IL12 transcripts nor for Interleukin-6 (IL6) and IL13. No changes were also observed for γIFN and EDN/RNase2 transcripts, while ECP/RNase3 transcripts were significantly upregulated after HPpSIS. Finally, tryptase transcripts were unchanged while serotonin transcripts were significantly increased after HPpSIS. CONCLUSIONS: The clinical and biomolecular changes observed at the nasal mucosa due to HpSS treatment suggest the activation of an innate surveillance, by means of TLR transcription, and a possible anti-viral response due to EDN upregulation. It remains to be verified if NGF, known to be released locally upon HpSIS treatment, might in part be responsible for this local activation.

[Improvement of a sedimentation method for measuring dispersion of fibres from asbestos cement roofs]. / Il metodo deposimetrico per la misura della dispersione di fibre di asbesto dalle coperture in cemento amianto: revisione e perfezionamento.

BACKGROUND: The present article is a follow-up of previous research, in which a sedimentation method was proposed to measure the dispersion of fibre bundles (primary pollution) from asbestos-cement roofs. OBJECTIVES: The aim of this study was to improve and standardize a screening method to evaluate asbestos bundle release from asbestos-containing materials. METHODS: An appropriate instrument (deposimetro) was used to passively sample asbestos on microscope slides by direct sedimentation. The microscopic analysis of samples was improved by the dispersion staining method, combined with the calculation of weight concentrations of asbestos per surface and time unit. The sampling efficiency was improved by introducing a new adhesive treatment of the microscope slides (85% stearyl alcohol, 15% octyldodecan) and a size cut-off restricting the counting method only to fibre bundles with diameters larger than 2 pm. RESULTS: The optimal sampling time was defined as 25-30 days without rain, extending the sampling time established in the previous investigation, and the optimal instrument position was defined at distances of 50 cm (vertical) and 0 cm (horizontal) from the roof edge. The effect of wind direction and velocity on asbestos release was also assessed, showing that wind gusts with a velocity of more than 10 m/s are mostly associated with dispersion peaks. CONCLUSIONS: A simple algorithm was proposed on the basis of field data (n=32) and 5 hazard classes were defined as a function of weight concentrations and asbestos type. The passive sampler is low in cost and is intended for use in large-scale surveys to identifY removal priorities.

[Active search of work related tumours: preliminary findings]. / La ricerca attiva deli tumori di origine professionale: primi risultati.

UNLABELLED: The OCCAM (Occupational Cancer Monitoring) project enabled the active detection of occupational cancer cases in Lombardy Region. METHODS: OCCAM is based on a record linkage with social security files to obtain occupational histories for all subjects having worked in private firms, since 1974. It provides risks by area, site and job. RESULTS: 271 incident cancer cases obtained by hospital discharge record in the period 2001-2002 where investigate to assess eventually their occupational origin. Approximately 38% where considered to be occupational cancers. CONCLUSIONS: OCCAM provides name of the firms and their economic activity completed by information coming from OCCAM risks ascertainment and deeper knowledge on productive cycle retained by local occupational health services. Thus this system can lead to detection of many cancer cases of occupational origin suitable for compensation and determine strategies for the improvement of the work environment.

[Asbestos risk in the textile industry: braking systems on machinery used until the 1990's]. / Il rischio amianto nel settore tessile: i sistemi frenanti delle macchine di penultima generazione.

BACKGROUND: We recently described asbestos risk in the non-asbestos textile industry as the result of fibre dispersion from ceilings, pipe insulation and machines. OBJECTIVES: The widespread use of brakes with asbestos linings on the machines as well as other functional details were considered for a proper evaluation of their role in producing atmospheric pollution METHODS: All the information was collected on the basis of the personal technical experience of two of the Authors and by direct observation of the machines. RESULTS: All the textile machines (ring spinning, twisting, warping, winding, looms) used until the 1990's were without exception equipped with asbestos-lined mechanical brakes. The heavy action required produced relatively rapid wear of the linings and the dust produced was spread into the atmosphere by the continuous action of the "travelling blowing cleaners" and by the daily cleaning of the machines using compressed air at the end of the shift: violent air blowing undoubtedly caused redispersion of the fine dust from the brakes and also acted as a mechanical grinder on the bundles that sedimented on the machines from the ceilings and pipes, producing more ultrathin respirable fibres. CONCLUSIONS: the contribution of textile machinery to atmospheric pollution by asbestos fibres was significant and due both to the widespread use of brakes with asbestos-containing materials and to the continuous action on the machines of compressed air blowers. Asbestos pollution was certainly high in all the factories so that in the near future still further mesothelioma cases among ex-workers are to be expected.

[Mesothelioma: the aetiological role of ultrathin fibres and repercussions on prevention and medical legal evaluation]. / Mesotelioma: il ruolo delle fibre ultrafini e conseguenti riflessi in campo preventivo e medico legale.

BACKGROUND: Mesothelioma has until now been considered to be a manifestation, occurring in the pleura and/or peritoneum, of the carcinogenic action of the total burden of inhaled asbestos fibres, in the same way as lung cancer. Because of the pathogenic potential of very low exposure levels, the fact that the onset of the neoplasm always occurs in the parietal pleura, and the absence of any synergism with smoking, which is typical in the case of carcinoma, it was suspected that aetiopathogenetic differences existed but the reasons for such differences still could not be explained. In the past experimental results indicated the oncogenicity of very thin fibres but mesothelioma in practice was not exclusively linked to this specific dimensional size class. OBJECTIVES: The paper proposes to take full advantage of the significant knowledge that must emerged from research carried out in recent years and use this knowledge to reconstruct the mosaic of the aetiopathogenesis of mesothelioma. Due consideration will also be given to the consequent new approach required in the field of medical-legal evaluation of cases and in the field of prevention. RESULTS: The most important knowledge that must today be taken as certain is the fact that mesothelioma is not caused, as is the case for asbestosis, by all the fibres that are inhaled but only by the ultrathin fraction of these fibres, having diameter of 0.2 microm and length of only a few microm. Only fibres of this class of size can cross the pulmonary-pleural barrier and are, therefore, the causal agent of mesothelioma and other benign pleural manifestations (plaques). Moreover the ultrathin fibres that translocate from the lung to the pleura are not distributed casually on the parietal and visceral surfaces but move over the surfaces, to concentrate around the lymphatic reabsorption stomata situated on the parietal pleura. Due to their shape, the fibres cannot easily be absorbed into the stoma via the lymphatic flow and so remain clustered for an indefinite period of time among the mesothelial cells that surround the stoma. The concentration of ultrathin fibres in punctiform areas of the parietal pleura and the extremely long biopersistence of the amphiboles now finally explain how very low exposures can cause mesothelioma in susceptible subjects and why the neoplasm always occurs on the parietal pleura. CONCLUSIONS: In medical-legal assessments of cases of mesothelioma the etiological importance of the ultrathin fraction of fibres means that any assumption of the disease being avoidable must be discarded, at least up to the second half of the 1980s because until then this class of fibres, which today must be considered as the true causal agent of the neoplasm, was not visible under the optical microscope, nor could such fibres be measured or eliminated from the atmosphere of working environments. The filter materials available both for fixed ventilation systems and for individual protective masks were not able to block the ultrathin fibres and were therefore only efficacious for the prevention of asbestosis and probably pulmonary carcinoma. It was only with the use of highly efficient HEPA filters and "absolute" filters towards the end of the 1980s that efficacious protection against all size classes of respirable fibres became possible in industrial plants. Preventive measures in the public hygiene area must also take account of the aetiological role of ultrathin fibres by making full use of electron microscope investigations and by using "absolute" filters for domestic purposes, in ventilation systems and above all in the filter systems of the mechanical devices used in town street cleaning operations.

[Malignant mesothelioma of the pleura in a worker with brief atypical exposure to chrysotile asbestos]. / Mesotelioma maligno della pleura in un lavoratore con breve esposizione atipica ad amianto crisotilo.

BACKGROUND: The appearance of malignant mesothelioma in workers exposed to asbestos dusts even for relatively short periods of time is amply demonstrated in the literature. The workers however were usually exposed to amphiboles in jobs well known as involving exposure, that are characterized by high levels of dusts. OBJECTIVES: To describe a clinical case of pleural mesothelioma that occurred in a patient exposed to chrysotile, in a job (driver) that cannot be directly linked to such high exposure, and which moreover he only did for a few months. METHODS: The clinical history was reconstructed by analyzing the clinical files of the hospital admittances from May 2002 to August 2003, during which the patient underwent radiological examinations (chest x-rays, chest and abdomen TC), cytological examination of the pleural fluid, videothoracoscopic surgery with histological examination (including immunohistochemical coloration) of the tissue taken in biopsy. The job history, as well as any possible non-occupational exposures to asbestos, was examined via a standardised questionnaire, which the patient himself answered, as used in the Lombardy Mesothelioma Register, in operation at the "Clinica del Lavoro" in Milan. RESULTS: Examination of all clinical files confirmed the diagnosis of malignant pleural mesothelioma. Analysis of job history was found appropriate for defining as certain an occupational aetiology due to inhalation of asbestos fibres which occurred for few months as a truck driver in a chrysotile mine.

Olfactory function in workers exposed to moderate airborne cadmium levels.

OBJECTIVE: The present study investigated the olfactory function in workers exposed to moderate airborne cadmium (Cd) levels, with the purpose of identifying possible early adverse effects of the metal, not demonstrable with the traditional diagnostic methods. METHODS: The exposed group consisted of 33 men employed in cadmium fusion, sintering and alloys lamination. Two reference groups were considered: the first consisted of 39 subjects assigned to manual workings, but not exposed to harmful substances for olfaction (drivers, warehousemen); the second was characterized by 23 subjects exposed to iron and steel welding fumes (iron base alloys), non-specific irritants on the respiratory tract. Olfactory threshold and odor identification ability were separately quantified. Individual occupational exposure was studied by calculating the mean blood and urinary cadmium values (CdB and CdU, respectively) of the five years period during which, for each worker, the highest levels of dose indicators were measured. As indicator of renal tubular damage, urinary beta(2)-microglobulin levels in the same quinquennium were monitored. RESULTS: Mean olfactory threshold scored significantly higher in Cd workers (-5.26 log(10)v/v, P=0.02) than did in controls (welders: -5.78 log(10)v/v; P=0.26 compared to non-exposed -6.37 log(10)v/v). The odor identification test findings for Cd workers were similar to those of the reference groups. Moderate blood and urine cadmium levels (mean CdB 3.7 microg/l; mean CdU 4.4 microg/g creatinine) accompanied threshold impairment. Olfactory threshold weakening was confirmed in the subgroup of Cd workers in which urinary beta(2)-microglobulin never exceeded 300 microg/l (-5.41 log(10)v/v; P=0.045 compared to non-exposed). CONCLUSIONS: These data suggested that possible early toxic effects of the metal can occur at low levels, close to the limits proposed by the American Conference of Governmental Industrial Hygienists (ACGIH), confirming the hypothesis that primary olfactory neuron may represent the early target for cadmium toxic action. The action of the metal seemed to be due to an elective tropism for the olfactory epithelium and not to a non-specific irritant effect on the nasal cavity. The mechanism of this effect did not appear linearly dose-related. These findings underline the importance of olfactory tests to identify the early effects of xenobiotics even at low-exposure levels, and to contribute to verify the adequacy of the current exposure limits.

[The Occupational Medicine Post-Graduate School of Milan]. / La Scuola di Specializzazione in Medicina del Lavoro di Milano.

From its very foundation, post-graduate work for medical doctors has been the main objective of the "Clinica del Lavoro". This completion of the doctor's training has, in the course of the past century, moved in time with the evolution of Occupational Medicine as a science: new developments in the field, the results of experimentation and research carried out in the Clinic, have immediately been passed on to young doctors. The professionals trained in the Clinic have always been considered the very best and have been sought after by the most important medical facilities in the country. Since the beginning of the last century, when Luigi Devoto began to evaluate the infectious, poisonous, and deficiency pathologies connected with the workplace, to the post-war years of rapid growth, when Enrico Vigliani studied and prepared our doctors to deal with dust-related pulmonary diseases, metal-based poisons, and many other problems connected with the transformation of an agricultural society to an industrial society, and up to the present years, which have been characterized by the post-industrial new economy, the "Clinica del Lavoro" has always taught and put into practice the motto of Luigi Devoto: "Occupational medicine is not a part of medicine, but rather a particular way to practice medicine".

[Asbestos risk in the textile industry: final confirmation of data from the Lombardy Mesothelioma Registry]. / Il rischio amianto nel settore tessile: indicazioni dal Registro Mesoteliomi Lombardia e definitiva conferma.

BACKGROUND: Cases of mesothelioma in non-asbestos textile workers have been frequently reported but the identification of asbestos dispersion sources in the workplaces has never been adequately performed. During 3 years of activity of the Mesothelioma Register for Lombardy, 40 cases (10.8% of all cases) were collected in textile workers engaged in all types of productive activities. The hypothesis that a significant asbestos risk for textile workers appeared not negligible. OBJECTIVES: The research was aimed at the identification of asbestos dispersion sources in textile factories. METHODS: Specific information was collected by technicians, maintenance personnel and other experts and direct inspections were carried out in numerous workplaces that had not yet undergone significant changes with respect to the past. Also the industrial machinery utilised in the previous 40-50 years was thoroughly examined. RESULTS: Epidemological evaluation of the recorded cases showed a widespread distribution in the different phases of textile production. Inspections also showed that a large amount of asbestos had been regularly used applied to the ceilings and also to the walls of factories in order to avoid both condensation of steam and reflection of noise. In addition, asbestos had also been widely used to insulate water and steam pipes. The braking systems of most of the machines also had asbestos gaskets, and on several looms some brakes operated continuously in order to keep the warp in constant tension. CONCLUSIONS: Our observations confirmed that since production techniques in the textile industry required working in damp and warm conditions with the noise of the rapidly moving machines, asbestos was very often used because of its absorbent and soundproofing qualities and its resistance to friction. We demonstrated that asbestos was thus widely used in the industry and this certainly produced considerable fibre dispersions in the atmosphere of the workplaces. Asbestos risk must therefore be recognised for all those who have worked in the textile industry in the recent past and, as a result, cases of mesothelioma must be considered occupational diseases.

[Prostate diseases of occupational origin]. / Patologia della prostata ad eziologia professionale.

BACKGROUND: Prostatitis is a poorly defined group of syndromes with multiple causes. Chronic prostatitis may be non-bacterial and due to intrapelvic venous congestion. If the causes persist and adequate treatment is not given, the congestive syndrome may become chronic and interfere with fertility with severe biological damage. OBJECTIVES: Little is known in the field of occupational medicine (as regards clinical and pathogenic aspects) and, on the other hand, little is known by urologists (as far as the aetiological aspects are concerned), the prostatitis-like syndrome due to intrapelvic congestion has been defined in recent studies as non-bacterial prostatitis or prostatodynia, but we prefer to call it "prostatosis". The results of a close cooperation between urologists and occupational physicians are reported. METHODS: Patients with non-bacterial chronic prostatosis were evaluated from the urological and occupational point of view and all the etiological factors of both occupational and non occupational origin were considered. When occupational factors are a conditio sine qua non prostatosis is considered an occupational disease. RESULTS: Two cases of "occupational prostatosis" are described where driving vehicles and a sedentary employment played the most important etiological part. Many other similar cases were observed. CONCLUSIONS: Close cooperation between urologists and occupational physicians makes it possible to complete clinical diagnosis with a careful evaluation of all the factors of both occupational and non-occupational origin and allows the identification of those cases that must be defined as occupational diseases. Prostatosis due to venous congestion deserves the attention of occupational physicians since the distinction between occupational and non-occupational origin must be found both in individual cases and in groups of workers subject to the same factors. Moreover, the present state of knowledge is enough to take preventive measures aimed at reducing the frequency of new cases and avoiding the deterioration of existing cases. It is also possible that some cases of pseudo-cystitis in women might be the result of intrapelvic venous congestion of occupational origin. Anatomical and physiological non-occupational factors as well as certain habits of life style can favor intrapelvic venous congestion, producing conditions of hypersusceptibility to occupational factors and could sometimes cause the disease even in the absence of causes connected to work.

[Presence of asbestos in naval vessels: study of airborne fiber concentrations on Italian railways ferry boats]. / Presenza di amianto sulle navi: studio sulla concentrazione di fibre aerodisperse su navi traghetto delle Ferrovie dello Stato.

Asbestos has been widely used on ships as an insulating material due to its fire-resistant and sound-absorbent properties. It was therefore deemed appropriate to measure the concentrations of airborne asbestos fibres on two ferries in regular service on the Civitavecchia-Golfo Aranci route. Decontamination work had been carried out on these vessels in order to remove, as far as possible, or to confine asbestos. Between 1994 and 1998, the Ultrastructures Laboratory of the Istituto Superiore di Sanità analysed 123 samples via scanning electron microscopy (SEM) with elementary dispersion X spectroscopy (EDXS). The results showed that in 98.4% of the samples concentrations in the air were below 2 fibres/litre, which is the value set by Ministerial Decree of 6/9/94 for buildings to qualify for effective decontamination status. Concentrations above this value, between 2 and 10 fibres/litre, were found in one ferry engine room, where workers were not continuously present since a remote control box was installed there. The results show that there is no environmental dispersion of asbestos fibres in usual navigation conditions; the situation is comparable to that in buildings where asbestos-containing safety materials have been used and that are subject to period checks in accordance with the guidelines included in Ministerial Decree of 6/9/94. Legislation is deemed necessary to make law 257/92 applicable to naval vessels in order to define univocal criteria for risk evaluation, checking, maintenance and custody procedures of asbestos-insulated vessels, and procedures for each job on board involving handling or removal of asbestos-containing material.

[Neoformed multiple hepatic angiomas after exposure to vinyl chloride monomer: report of a case]. / Angiomi epatici multipli neoformati dopo esposizione a cloruro di vinile monomero: descrizione di un caso.

The paper describes the case of a 60 years old man with previous protracted exposure to CVM. After a latency of 20 years, the man developed two hepatic hemangiomas, one characterized by rapid growth (4 cm of diameter in 1 year) and surgically removed. On the basis of the anamnestic data (15 years in a PVC polymerization factory in the reactor vessels department) considering the degree and duration of exposure to CVM, an occupational origin of the hepatic hemangiomas is probable. The ability of CVM to induce sclerosis, necrosis and endothelial hyperplasy in the liver tissue may represent the primum movens of hemangiomas.

[Measurement of airborne asbestos fibers on railroad rolling stock]. / Ricerca di fibre di amianto aerodisperse a bordo di rotabili ferroviari circolanti.

In February 1995 the Italian Railways Health Department set up a special study group in order to assess the effectiveness of the measures adopted against hazards due to the presence of asbestos in rolling stock currently in use on the rail network. The group set up specific procedures for sampling and analysis, on the basis of the criteria fixed for civil buildings in Ministerial Decree of 6/9/94, which was subsequently applied to rolling stock by Ministerial Decree of 26/10/95. In accordance with these procedures the study group carried out environmental studies via test runs programmed by the Railways Technical Departments, on trains made up of different types of vehicles. Insulated, completely or partially deinsulated and originally non-insulated vehicles were studied. Samples were analysed via scanning electron microscopy (SEM) with elementary dispersion X spectroscopy (EDXS) carried out by highly qualified public laboratories (ISPESL--National Institute for Prevention and Work Safety, ARPA--Regional Environmental Protection Agency, CRA--Veneto Region, University Departments). Altogether, from the start of the programme up to September 1998, 1464 samples in 170 test runs on 619 rolling stock vehicles were examined. These involved 83 locomotives, 83 electric rail-cars and 453 carriages. The results showed that in over 99% of the samples the fibre concentrations were below 2 fibres/litre, which is the value fixed by law for buildings and rail vehicles in order to qualify for effective decontamination status. Values exceeding 2 fibres/litre were found in only 4 vehicles, which were withdrawn or blocked for further checks. As a precaution, 18 vehicles where concentrations over 1 but less than 2 fibres/litre were found, were also blocked and their return to service has been postponed for further checks and analyses until the results show concentrations below 1 fibre/litre. Environmental analyses carried out up to the present indicate an overall situation comparable to that usually found in the general environmental without any asbestos dispersion sources. Surveillance and investigations are still under way in order to achieve the aims of the safety programme set up by the Italian Railways to ensure health and environmental protection.

[Sedimentation method for measuring dispersion of fibers from asbestos cement roofs]. / Metodo deposimetrico per la misura della dispersione di fibre dalle coperture in cemento-amianto.

In order to define the need for removal versus conservative interventions regarding asbestos-cement roofs and the possible priorities, visual judgement of the state of deterioration or assessments based on the weight of the superficial friable material that can be removed with adhesives are not sufficient. Since in similar deterioration conditions the dispersion of fibres may vary considerably from case to case, only counting of the dispersed fibres will ensure a correct assessment of the pollution potential of an asbestos-cement weathered surface. The paper describes a simple method for measuring the atmospheric dispersion of fibres based on the well demonstrated fact that primary dispersion from the covering, as from many other sources of asbestos pollution, consists of course bundles that are subject to rapid sedimentation. By means of aluminium boxes containing object-holder slides installed under the edge of the covering for about one month, it is possible, using optical phase-contrast microscopy, to count the fibres that have sedimented and calculate the number of fibres/m2/day. If the method is used with the standardized criteria described, it gives reproducible results, involves low costs and has the advantage of balancing the possible variations in primary dispersion intensity due to changes in the local weather conditions over the relatively long sedimentation sampling period.