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1/8. Frequent microsatellite instability in lung cancer from chromate-exposed workers.

    Although chromium has been the most extensively investigated metal with respect to mutagenicity and carcinogenicity, its genetic effects in humans are only partly understood. Our previous study demonstrated that lung cancer from chromate-exposed workers infrequently (20%) displayed p53 gene mutations as well as a particular mutation pattern. In the present study, we examined the replication error (RER) and loss of heterozygosity (LOH) in 38 lung cancers from 28 chromate-exposed workers (chromate lung cancer group) and in 26 lung cancer patients without chromate exposure (non-chromate lung cancer group), using six microsatellite markers containing CA repeats: D3S647 (3p23), D3S966 (3p21.3), D3S1289 (3p21.1), D5S346 (5q21-q22), D9S161 (9p21), and TP53 (17p13.1). The RER phenotype was defined as the presence of microsatellite instability (MSI) at two or more loci. Thirty (78.9%) of 38 tumors in the chromate lung cancer group exhibited RER. In contrast, only four (15.4%) of 26 tumors in the non-chromate lung cancer group exhibited RER. The frequency of RER in the chromate lung cancer group was significantly higher than that in the non-chromate lung cancer group (P < 0.0001). By contrast, the frequency of LOH at 3p, 5q, 9p, and 17p loci in tumors with chromate exposure was not significantly different from that in tumors without chromate exposure. In the chromate lung cancer group, the period of chromate exposure in workers with RER (24.5 /- 6.7 yr) was significantly longer than that in workers without RER (17.0 /- 3.5 yr) (P = 0.0046). In addition, a longer period of chromate exposure was associated with a tendency toward a higher frequency of MSI. This finding suggests that MSI may play a role in chromium-induced carcinogenesis. In addition to our previous study of p53 mutations, the present findings suggest that the carcinogenic mechanism of chromate lung cancer may differ from that of non-chromate lung cancer.
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ranking = 1
keywords = carcinogenesis
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2/8. glioblastoma multiforme occurring in a patient following exposure to polychlorinated biphenyls.

    polychlorinated biphenyls have been shown to be carcinogens in animal studies. Because of lipid solubility and lack of biodegradation, they are known to deposit preferentially in fat and nervous tissue. In this report, we describe a 31-year-old male with prolonged polychlorinated biphenyls exposure who developed glioblastoma multiforme. Fat biopsy documented the presence of markedly elevated PCB levels. A co-worker also developed a malignant astrocytoma. The nature of PCBs and their role in human carcinogenesis are discussed. The possibility of an etiologic link between PCBs and brain tumors should be further investigated.
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ranking = 1
keywords = carcinogenesis
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3/8. pathology of silicon carbide pneumoconiosis.

    silicon carbide is a widely used synthetic abrasive manufactured by heating silica and coke in electric furnaces at 2400 degrees C. Until recently it had been considered a relatively inert dust in humans and animals. However, several roentgenologic surveys had revealed lesions similar to low-grade silicosis. A recent epidemiological study has revealed a 35% incidence of pulmonary problems. tissues from three such workers were available for light microscopy. A mixed pneumoconiosis was found, and lesions can be summarized as follows: (a) abundance of intraalveolar macrophages associated with a mixture of inhaled particles including carbon, silicon, pleomorphic crystals, silicon carbide, and ferruginous bodies showing a thin black central core; (b) nodular fibrosis, generally profuse, containing silica and ferruginous bodies and associated with large amount of carbon pigment; (c) interstitial fibrosis, less prominent than the nodular form; (d) carcinoma in two cases. We believe this pneumoconiosis is sufficiently characteristic to be recognized as a distinct entity. The Stanton hypothesis on fiber properties and carcinogenesis could be applied to silicon carbide dust. At present, it appears that the occupational hazard is limited to the manufacturing process and powdered product used in some industries.
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ranking = 1
keywords = carcinogenesis
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4/8. Areawide chemical contamination. Lessons from case histories.

    Nine case histories illustrate the mounting problems owing to chemical contamination that often extends beyond the workplace into the community. The effects include not only carcinogenesis and teratogenesis, so much in the public's mind, but also severe neurological and gonadal disabilities immediately after exposure. Recognition of causal relationships is often made by astute clinicians. The experience of the Atomic Bomb Casualty Commission in studying Japanese survivors in Hiroshima and Nagasaki serves as a model for future studies of communities exposed to unusual environmental contamination.
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ranking = 1
keywords = carcinogenesis
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5/8. Chemical carcinogenesis. A soil fumigant, 1,3-dichloropropene, as possible cause of hematologic malignancies.

    Findings from three case reports suggest a causal relationship between exposure to a soil fumigant , 1,3- dichloropropene , and hematologic malignancy. Its chemical relationship to other carcinogens is noted. The purpose of this report is to record this evidence and alert physicians that prior exposure to this chemical of patients initially observed with neoplasms should be noted in the medical history.
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ranking = 4
keywords = carcinogenesis
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6/8. Occupational carcinogenesis: the Louisville experience with vinyl chloride-associated hepatic angiosarcoma.

    Hepatic angiosarcoma in man was first associated with exposure to vinyl chloride in Louisville, kentucky, where it was identified in 10 persons from a single vinyl chloride polymerization plant; clinical manifestations are summarized herein. Following prolonged exposure to vinyl chloride, the onset of this disease is insidious and the clinical picture is that of nonspecific hepatic injury with mildly abnormal biochemical liver test results. carcinoembryonic antigen and alpha fetoprotein are undetectable. Radionuclide and angiographic studies of liver show characteristic but nondiagnostic abnormalities. A definite diagnosis is usually made only by open liver biopsy. Treatment is unsatisfactory but chemotherapy seems to prolong survival. Average survival from diagnosis is about 12 months. Overt liver failure usually occurs only as a preterminal event and was the major cause of death in all of our patients. Preventive measures are now in effect in the plant. This experience illustrates the importance of the clinician in occupationally-related cancer.
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ranking = 4
keywords = carcinogenesis
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7/8. Occupational nasal carcinogenesis among dentists?

    671 dentists were registered in alberta for 1973. In that year two dentists presented at the Cross Cancer Institute with extensive anaplastic squamous cell carcinoma involving the nasal cavity and accessory sinuses, an incidence rate of 298 per 100,000. Owing to the Provincial Cancer Service the registration of malignant disease is virtually complete and during 1973 the total alberta registration of squamous carcinoma of the nasal cavity, accessory sinuses and nasopharynx was 28 cases. Assuming that all 28 cases arose in males over 24 years of age, and knowing that the 1973 alberta population included 412,000 males over the age of 24 years a maximum expected incidence rate of 6.8 per 100,000 would apply to this population group. This paper describes the two dentists referred to above, contrasts the incidence rates previously quoted, discusses the frequency of malignancy among dentists in general and most especially draws attention to the role of inhaled oil droplets produced by high speed air rotor dental drills as a possible occupational carcinogenic hazard in the dental profession. On reviewing the world medical literature no previous report of this hazard has yet been traced. There is no significant risk for dental patients.
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ranking = 4
keywords = carcinogenesis
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8/8. nickel carcinogenesis of the respiratory tract.

    The role of some nickel compounds and other chemical carcinogens in the causation of cancer of the nose and paranasal sinuses must be recognized. Preventive health measures taken by the nickel industry to eliminate the hazard of nickel carcinogenesis have included improved worker hygiene, reduction of refinery dusts and aerosols, and a strict monitoring of employees by regular examination and plasma nickel testing. The treatment of carcinoma limited to the naso-antral wall or ethmoid labyrinth by an en bloc resection is described, as well as the management of cribriform plate CSF leaks sometimes associated with the ethmoid resection. A subcutaneous cheek flap from the lateral rhinotomy is reflected inward against the cribriform plate to control cerebrospinal fluid rhinorrhea.
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ranking = 5
keywords = carcinogenesis
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