Effects of present and past occupational exposures.
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Biomedical subjects
Publications and source records attributed to A Fischbein.
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Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating from breakdown of transfer RNA (tRNA). A high incidence of acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently being observed in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have examined 10 patients with AIDS and 77 male homosexuals without clinical manifestations of AIDS at the time of examination. Elevated levels of modified nucleosides were found in all patients with AIDS. Of further interest was the finding of a high prevalence of abnormal nucleoside levels in the high-risk group, with a trend toward higher levels in those high-risk individuals who had lymphadenomegaly, considered a prodrome of AIDS. These findings indicate that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS thereby increasing the possibility for prevention and early therapy.
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Chloracne was found in 52% of 226 workers in a 1979 cross-sectional survey at a plant where 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) had been manufactured from 1948 to 1969. Mean duration of residual chloracne was 26 years, and in 29 subjects, it had been present for 30 years. A significant increased prevalence of abnormal gamma-glutamyl transpeptidase (GGT) and higher mean GGT were found in those with chloracne, compared to those without. Although mean triglyceride values were higher in those with chloracne, the difference was not statistically significant. Neurological examination showed a statistically significant higher prevalence of abnormal sensory findings in those with chloracne. Increased prevalence of angina and reported myocardial infarction in those with chloracne was not significant when age-adjusted. Increased prevalence of reported sexual dysfunction and decreased libido in those with chloracne compared to those without was statistically significant after age adjustment. No differences were found between those with and without chloracne in serum cholesterol, total urinary porphyrins, or in reproductive outcome.
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Nephrotoxic chemicals are commonly present in the environment, particularly in the workplace. The level of occupational exposure to these chemicals has been so reduced that exposure to these agents now rarely causes clinically evident acute renal disease. A sensitive indicator of renal injury, urinary excretion of N-acetyl-beta-glucosaminidase, was utilized to evaluate persons exposed in the workplace to lead, mercury, or organic solvents, for evidence of renal effects from this exposure. None of the persons had clinically evident renal disease by history, none had hypertension, and all had normal findings on urinalysis. When compared with appropriate control populations, workers exposed to lead, workers exposed to mercury, and two of three groups of workers exposed to organic solvents had significant increases in urinary acetyl glucosaminidase activity. The third group of laboratory workers with low exposure to organic solvents had no increase in urinary acetyl glucosaminidase activity. It is concluded that exposure to environmental nephrotoxins at levels currently considered safe can produce renal effects as manifested by elevations of urinary acetyl glucosaminidase excretion. It is speculated that these renal effects are not always innocuous.
A cross-sectional medical examination of a copper smelter work force included determination of blood lead (Pb-B), zinc protoporphyrin (ZPP), blood cadmium (Cd-B), urinary cadmium (Cd-U), and urinary arsenic (As-U), since it was known that such metal impurities were present in the copper concentrate. A total of 776 copper smelter employees (680 active and 96 retirees and ex-employees) were examined. Another 144 men, never employed in the smelter, but who had worked in copper mines (and sometimes in gold mines) were also examined. Mean Pb-B, ZPP, Cd-B, and As-U were significantly higher in active copper smelter employees than in retirees or miners, indicating exposure and absorption in the copper smelter. Significant correlations between Pb-B and Cd-B, and Cd-U and As-U were present, confirming the common source of absorption. Although there was evidence for an increased lead absorption, this was very moderate, with practically no Pb-B levels in excess of 60 micrograms/dl. A marked effect of smoking on blood cadmium levels was present; nevertheless, for all smoking categories Cd-B levels were significantly higher in active employees, indicating the independent contribution of exposure to cadmium in the smelter. Cd-U did not exceed 10 micrograms/g creatinine, the generally accepted "critical" level for the kidney, but was higher than 2 micrograms/g creatinine, a level very rarely exceeded in the general population, in a sizable proportion of those examined. The highest Cd-U levels were found in retired copper smelter employees; age might have been a contributing factor, besides a longer duration of exposure in the smelter.
Patients with malignant mesothelioma, a neoplasia strongly associated with previous asbestos exposure, excrete in the urine high levels of modified purines, pyrimidines, and their ribosides, breakdown products of transfer RNA. The urinary excretion levels of modified nucleosides were measured in 47 male insulation workers with long term exposure to asbestos and, therefore, at high neoplastic risk. The nucleoside levels of 44 male control subjects were used for comparison. Asbestos-related radiographic changes were found in 70% of the exposed individuals. An increasing severity of radiographic alterations was associated with a greater frequency of elevated nucleoside clusters, especially in m'A, m'I, m'G, and m2(2)G. Duration since onset of exposure was directly related to pseudouridine, m'I, and m2(2)G. Though cigarette smoking contributes to the development of asbestos-related lung cancer, data are presented that support the hypothesis that asbestos exposure is the more important factor related to the elevated values of nucleosides. It was concluded, therefore, that measuring nucleoside levels in populations at high risk of developing certain kinds of cancer may provide a useful diagnostic tool for detecting "preclinical" biochemical changes that may be predictive of future neoplastic manifestations.
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Transfer RNA is the most complex biomacromolecule in both structure and function. The complexity of its structure is caused by a large variety of enzymes which add modifying groups to the four bases after the primary synthesis. The most abundant of these enzymes are the transfer RNA methylases, which add methyl groups at various positions in the macromolecule. These methylating enzymes were found to be, without exception, aberrantly hyperactive in every malignant tumor examined. In turn, every malignant tumor contains a few transfer RNAs that are different in structure from the transfer RNAs in the normal tissue. Again, there is no exception. These are the first qualitatively different biochemical components of every malignant cell, not more or less but different transfer RNAs. The late Alexander Gutman observed that cancer patients excrete in their urine elevated levels of certain methylated bases. From the structure of these bases and our knowledge of their method of synthesis, it became apparent that most of them come from the breakdown of transfer RNA. Their elevation in the urine stems from an extraordinarily high rate of turnover of transfer RNAs in tumor tissue. Highly sophisticated, sensitive methods of analysis were developed for the determination of the modified nucleosides in the urine of cancer patients. When related to the creatinine level of the urine, some of the modified nucleosides and products derived from them were elevated in a large variety of tumors. Perhaps more importantly, it was found that these elevated levels return to normal after effective chemotherapy. Thus, these markers may also be useful in monitoring the effectiveness of therapy. We report here initial studies on the detection of cancer in asbestos workers and possible premalignant conditions in workers with asbestosis.
Pleural mesothelioma, lung cancer, pleural calcification and fibrosis, and interstitial parenchymal fibrosis have been observed among inhabitants of several villages in south-central Turkey. Earlier reports have stated that environmental and lung tissue samples from this area contained the fibrous zeolite mineral erionite, and this mineral has generally been assumed to be the agent responsible for these endemic pathological conditions in the absence of asbestos outcroppings and usage. Several different kinds of asbestos minerals in addition to erionite have now been found in environmental samples taken from the villages where these diseases occur. The lung tissues of mesothelioma patients from these villages contain both fibrous zeolites and asbestos minerals.
A case of lead poisoning in a female art conservator is reported. The patient had experienced excessive lead exposure while restoring an antique Peruvian tapestry from the Chancay period (1000 to 1500 AD) using a powdered pigment (cinnabar), which had been recovered from the same tomb in which the tapestry was found. Over two months, prominent neurological, gastrointestinal, and diffuse muscular symptoms developed. Severe anemia accompanied by basophilic stippling of RBCs led to the diagnosis of lead poisoning, which was confirmed by markedly elevated blood lead levels (up to 130 micrograms/dL) and impairment of heme synthetic enzymes. The severity of the intoxication necessitated chelation therapy. Chemical analysis of the antique powdered pigment showed it to be the source of lead exposure, in that it contained about 1% lead.
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In an attempt to identify health effects associated with low-level lead exposure, 45 cable-manufacturing workers underwent clinical examinations in a cross-sectional study. Thirteen workers were in direct contact with lead-containing stabilizers, while 31 were only indirectly exposed. The directly exposed had a higher prevalence of reported neurological and gastrointestinal symptoms than those with low or insignificant lead exposure. None of the directly exposed had blood lead levels exceeding 60 micrograms per 100 ml. The clinical symptoms correlated with blood lead and zinc protoporphyrin. However, when the data were subjected to hierarchical log-linear modeling, a partial association was found between zinc protoporphyrin and symptoms, but not between blood lead and symptoms. The data suggest that non-specific neurological and gastrointestinal symptoms may occur at relatively low blood lead and zinc protoporphyrin levels, and that measurement of zinc protoporphyrin and exploration of clinical symptoms are valuable components in lead screening programs.
In an effort to assess exposure among workers engaged in capacitors manufacture, PCB concentration was determined in plasma (290) and adipose tissue (61). In general, males had higher concentrations of PCBs than females. The correlation of plasma concentration (1-546 ppb) of the more highly chlorinated PCBs, which had been used in past, with total duration of employment suggested accumulation over time. The gc-ec pattern of these PCB peaks was, in most cases, characteristic of exposure to a PCB mixture with 54% chlorine. The less highly chlorinated PCBs, di-, tri-, and tetrachlorobiphenyls, were the source of current exposure, and were observed in concentrations of 6-2530 ppb in plasma. Higher exposure occurred among persons with direct contact with PCBs in jobs such as capacitor filling. Adipose tissue concentrations, for both the more highly chlorinated PCBs (1-165 ppm) and lower chlorinated PCBs (0.6-414 ppm), were proportional to those in plasma.
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