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Finally, after thirty years of research it was possible to examine the dynamics of the frequency of PCs among
Metsovites between 1980 and 2010. As expected, their frequency was found to be decreasing and the age when PCs are first seen was increasing. In regard to mesothelioma, after the first study
141:
was functioning until the early 1990s), but there have been several areas where soil had been used by small populations in the remote past for various domestic uses, as in
Metsovo. In at least two of them there have been small "epidemics" of mesothelioma. The use of this soil has been abandoned for
133:
serpentine zone". It was shaped like a ball, crushed into powder, boiled and applied to the walls. Crushing the ball released more than 200 fibers/ml of air, when the accepted limits for occupational exposure are lower than one fiber/ml. There were minuscule fiber concentrations during the rest of
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in the local dialect) for whitewashing. The material was applied more often on walls around fireplaces, because this kept the walls white, unsoiled from the fire. This whitewash was used by everybody until 1940-1950 and gradually abandoned, so that in 1980 it was used by only 15% of the households
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Having found the most likely cause of PCs and mesotheliomas in
Metsovo and the temporal course of its use, from 1940 to 1950 when it was used by all households until 1980-1985 when it was abandoned, it was possible to project the future course of this epidemic. First, other sources of asbestos
444:
Gogali A, Manda-Stachouli C, Ntzani EE, Matthaiou M, Konstantinidis AK, Zampira I, Koubaniou Ch, Dalavanga Y, Stefanou D, Constantopoulos SH and
Daskalopoulos G. Malignant mesothelioma in Metsovo, Greece, from domestic use of asbestos: 30 years later. Εuropean Respiratory Journal,2012; 39:
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that proved to be malignant mesothelioma. These were only the first of a series of mesotheliomas; seven in five years (1981–1985). This rate is roughly 300-times that expected in a non-asbestos exposed community. The combination of PCs and MM can only be attributed to asbestos exposure.
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in the 1980s, two studies have shown that the incidence of mesothelioma is also dropping. However, the end of this epidemic cannot be predicted safely. Mesotheliomas appear usually 30–50 years after exposure but this can be prolonged, very rarely, to 70 years. Thus, since the use of
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In a field study in
Metsovo and other areas around Ioannina, it was confirmed that PCs were very common among Metsovites, around 50% of adult population, increasing to more than 80% in those above 70; and that they were seen only in Metsovo and three neighbouring villages.
434:
Sakellariou K, Malamou-Mitsi V, Haritou A, Koumpaniou Ch, Stachouli C, Dimoliatis ID, Constantopoulos SH. Malignant pleural mesothelioma from non-occupational asbestos exposure in
Metsovo (North West Greece); slow end of an epidemic? Εuropean Respiratory Journal, 1996; 9:
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Gogali A, Ntzani E, Peristeri S, Tzarouchi L, Manda-Stachouli C, Vadivoulis Th, Dascalopoulos G, Tsampoulas K, Constantopoulos S, and
Dalavanga Y. End of domestic asbestos exposure epidemic in Metsovo; N.W. Greece European Respiratory Society, Annual Congress
71:. However, since the picture was not even remotely similar to calcified pleurisy from previous tuberculosis, they began to investigate the precise frequency of PCs, whether their abnormal incidence was in fact confined to Metsovites, and their true cause.
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Gogali A, Ntzani E, Konstantinidis A, Peristeri S, Tzarouchi L, Manda-Stachouli C, Daskalopoulos G, Constantopoulos SH, Dalavanga YA. Assessment of an isolated environmental and domestic asbestos exposure in
Metsovo NW Greece: evidence of containment
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Constantopoulos SH, Dalavanga YA, Sakellariou K, Goudevenos J, Kotoulas OB. Lymphocytic alveolitis and pleural calcifications in non-occupational asbestos exposure. Protection against neoplasia? American Review of
Respiratory Diseases, 1992; 146:
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Dennis J. Darcey and Tony
Alleman. Occupational and environmental exposure to asbestos. In: Victor L. Roggli, Tim D. Oury and Thomas A. Sporn (Eds). Pathology of asbestos-associated diseases. 2nd edition, Springer Verlag 1992; p.
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Manda-Stachouli C, Dalavanga Y, Dascalopoulos G, Leontaridi Ch, Vassiliou M, Constantopoulos SH. Decreasing prevalence of pleural calcifications among Metsovites with non-occupational asbestos exposure. Chest, 2004; 126:
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Constantopoulos SH, Malamou-Mitsi V, Goudevenos JA, Papathanasiou MP, Pavlidis NA, Papadimitriou CS. High incidence of malignant pleural mesothelioma in neighbouring villages of Northwest Greece. Respiration, 1987; 51:
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Constantopoulos SH. Environmental mesothelioma associated with tremolite asbestos: Lessons from the experiences of Turkey, Greece, Corsica, New Caledonia and Cyprus. Regulatory Toxicology and Pharmacology, 2008; 52:
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Baris ΥΙ, Sahin AA, Ozesmi M, Kerse I, Ozen E, Kolacan B, Altinorrs M, Goktepeli A. An outbreak of pleural mesothelioma and chronic fibrosing pleurisy in the village of Karain/Urug in Anatolia. Thorax 1978; 33:
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IJ, Moutsopoulos HM. Metsovo lung: pleural calcifications and restrictive lung function in north-western Greece; environmental exposure to mineral fiber as etiology. Environmental Research, 1985; 38(2):
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Langer AM, Nolan RP, Constantopoulos SH, Moutsopoulos HM. Association of Metsovo lung and pleural mesothelioma with exposure to tremolite-containing whitewash. Lancet i, 1987; April 25: 965-967
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The possibility of this exposure being occupational seemed very unlikely, as there are no asbestos mines or factories near Metsovo. The nearest such mine (active until 1990) is located near
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Samples of the whitewash were sent to Mount Sinai Hospital, and proved to contain fibers of tremolite asbestos identical to the material previously obtained from the lungs of Metsovites.
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and tremolite, the researchers arranged a meeting with Metsovites where they were told that practically all households in Metsovo were using soil from nearby hills (white soil is
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Baris YI, Saracci R, Simonato L, Skidmore JW, Artvinli M. Malignant mesothelioma and radiological chest abnormalities in two villages in central Turkey. Lancet 1981; 1: 984-987
167:, had to be excluded. Two clinical means of measuring exposure were used for this purpose. Both had been positive in practically all exposed Metsovites during the peak of
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Constantopoulos SH, Saratzis NA, Goudevenos JA, Kontogiannis D, Karantanas A. Katsiotis P. Tremolite white-washing and pleural calcifications . Chest 1987; 92: 709-712
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They had to be over 30, since this is the time needed for PCs to become apparent radiologically. They also had to be below 50, since older individuals born when
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was still used extensively could have been exposed to it, (even if they claimed that they were not using it at home), from the homes of friends and relatives.
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in New York (doctors A. Langer and R. Nolan). Their analysis revealed long thin tremolite asbestos fibers in most biopsies in spite of their minuscule size.
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with extensive PCs in inhabitants of Metsovo. The researchers were told that this was very common to Metsovites and was the result of old tuberculous
107:, a city 150 miles east of Metsovo. Guided by previous research by Izzettin Baris dealing with not-occupational (domestic) exposure of vast areas in
47:(PCs) in almost half the adult population. Both conditions have declined significantly since the whitewash ceased to be used after 1985.
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Constantopoulos SH, Theodoracopoulos P, Dascalopoulos G, Saratzis N, Sideris K. Metsovo lung outside Metsovo. Chest, 1991; 99: 1158-61
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There has never been any commercial use of the soil within the Pindos serpentine zone other than that mentioned (the asbestos mine in
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at least 50–60 years. Outside Greece and Turkey, similar use with similar results has been reported in other areas around the
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stopped between 1980 and 1985, a decreasing incidence of mesothelioma may be expected until 2020-2030 and possibly 2040.
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was the only source of asbestos exposure in Metsovo, as none of the subjects examined had PCs or asbestos fibers.
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The relation to asbestos was identified when, a few months later, two consecutive patients appeared with massive
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Constantopoulos SH, Langer AM, Saratzis N, Nolan RP. Regional findings in Metsovo lung. Lancet ii, 1987; 452-453
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40:
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Constantopoulos S. Metsovo lung. A detective story with a happy ending. PNEUMON Supplement 1, Vol 27, 2014
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Hillerdal G. Malignant mesothelioma 198: review of 4.710 published cases. Br J Dis Chest 1983; 77: 321-328
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300 times that expected in populations not exposed to asbestos. This was accompanied by pleural
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Transbronchial lung biopsies from Metsovites with extensive PCs were then obtained and sent to
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Selikoff IJ, Churg J, Hammond EC. Asbestos exposure and neoplasia. JAMA 1964; 188: 142-146
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the process, while no fibers were detected in the ambient atmosphere of Metsovo.
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was obtained by digging soil from hills 5–10 km from Metsovo within the "
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headed by S.H. Constantopoulos started encountering, almost on a daily basis,
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in northwest Greece. Most of the inhabitants had previously been exposed to a
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179:(BAL). A study of Metsovites between the ages of 30 and 50 confirmed that
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was an epidemic of lung disease resulting from domestic exposure to
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in French) and means something that is not soiled (e.g. by fire).
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Constantopoulos SH, Goudevenos JA, Saratzis NA, Langer AE,
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55:In the early 1980s when the Medical School of
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207:Asbestos is called αμίαντος in Greek (
35:asbestos. This caused an epidemic of
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31:derived from local soils containing
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59:was established, a group of
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51:Locally high rate of PCs
177:bronchoalveolar lavage
37:malignant mesothelioma
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39:(MM) that reached an
93:Mount Sinai Hospital
79:Relation to asbestos
173:computed tomography
476:Asbestos disasters
99:Source of asbestos
23:in the village of
144:Mediterranean Sea
85:pleural effusions
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158:Projected course
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481:Mesothelioma
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65:X-ray images
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17:Metsovo lung
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415:(Submitted)
171:use: chest
465:Categories
232:References
435:1206-1210
380:1565-1570
320:S110-S115
175:(CT) and
41:incidence
33:tremolite
29:whitewash
246:Selikoff
113:erionite
109:Anatolia
69:pleurisy
57:Ioannina
21:asbestos
486:Metsovo
425:617-621
347:181-192
259:266-271
249:319-331
209:amiante
150:in the
25:Metsovo
139:Kozani
131:Pindos
105:Kozani
281:17-33
222:louto
195:Notes
189:louto
181:louto
169:louto
165:louto
127:Louto
117:louto
402:2012
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