Endemic pleural disease associated with exposure to mixed fibrous dust in Turkey.

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.

Lymphocyte function of Michigan dairy farmers exposed to polybrominated biphenyls.

Michigan dairy farm residents ate farm products containing polybrominated biphenyls (PBB's) after the accidential contamination of animal feed with the chemical in that state in 1973. The circulating blood lymphocytes of these residents show significant changes. Abnormalities include decreases in the numbers and percentages of peripheral blood lymphocytes that form rosettes with either sheep erythrocytes alone or with sheep erythrocytes sensitized with antibody and complement, increases in lymphocytes with no detectable surface markers ("null" cells), and altered responses to tests designed to evaluate functional integrity of the cells. There appears to be no consistent correlation between the concentration of PBB's in the plasma and the altered lymphocytes. Studies showed that in Wisconsin dairy farm residents and healthy individuals in the New York area who were not exposed to PBB's there were no such abnormalities.

Central nervous system dysfunction due to lead exposure.

Central nervous system dysfunction was investigated in workers at a secondary lead smelter by means of performance tests. Correlations between test scores and zinc protoporphyrin levels, a biological indicator of lead toxicity, are statistically significant. This correlation should prove to be useful in current efforts to evaluate effects of lead exposure.

Urinary excretion of modified nucleosides in patients with malignant mesothelioma.

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.

Alterations in drug metabolism in workers exposed to polychlorinated biphenyls.

Administration of the polychlorinated biphenyls (PCBs) mixture, Aroclor 1016, to rats elicited a barbiturate type of inducing effect on the hepatic microsomal oxidative enzyme system. Aroclor 1016 caused significant increases in liver cytochrome P-450 content, microsomal protein, and ethylmorphine N-demethylase activity; its effect on benzo(a)pyrene hydroxylase activity was minimal. Unlike the widely studied PCBs mixture, Aroclor 1254, Aroclor 1016 did not induce cytochrome P-448 in liver microsomes. Five workers occupationally exposed to Aroclor 1016 in a capacitor-manufacturing plant showed a significantly lower mean antipyrine half-life (10.8 hr) than the mean half-life of 15.6 hr in non-PCBs-exposed normal subjects. These differences in half-life were accompanied by increased metabolic clearance rates in workers exposed to the PCBs, which strongly suggests that PCBs accelerate the rate of drug metabolism in man. Our studies show that Aroclor 1016 elicits the barbiturate type of inducing effects on drug metabolism in man as well as animals.

Lead intoxication: effects on cytochrome P-450-mediated hepatic oxidations.

Acute administration of lead to rats caused significant decreases in cytochrome P=450, ethylmorphine N-demethylase, and aniline hydroxylase activities and prolonged hexobarbital-induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P-450 levels or in the microsomal oxidative enzymes over a 12-wk period. Eight patients exposed to lead in the process of burning through lead-painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte delta-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of delta-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary delta-aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determined in the 8 subjects prior to and following chelation therapy. In 7 of 8 subjects, chelation therapy shortened the antipyrine half-lives, but the effect was minimal. These studies show that chronic lead exposure results in significant hematopoietic inhibition of the heme biosynthetic pathway without causing significant changes in hepatic cytochrome P-450-associated enzymic activities.

Increased urinary enzyme excretion in workers exposed to nephrotoxic chemicals.

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.

Liver function tests in workers with occupational exposure to polychlorinated biphenyls (PCBs): comparison with yusho and yu-cheng.

The results of liver function tests in a population manufacturing capacitors and transformers are presented. Two clinical field examinations were performed, one in 1976 when PCBs were still used in the manufacturing of the electrical equipment and one at the end of 1979, 2.5 years after discontinuation of PCBs use. A low prevalence of abnormal liver function tests was found and mean values for all tests were within normal laboratory ranges. At the initial examination, weak, but statistically significant correlations were found between log LDH and plasma levels of log HPCB (higher chlorinated congeners of polychlorinated biphenyls) and log TPCB (total polychlorinated biphenyls) among the female workers, while log gamma-GTP correlated significantly only with log HPCB among the male workers. A significant increase to abnormal levels of gamma-GTP was noted at the follow-up examination in both male and female workers, and preliminary results indicate significant correlations between gamma-GTP and serum levels of PCBs among the male workers. These findings are in accordance with previously reported data on populations occupationally exposed to PCBs, but differ from hepatic biochemistry findings in accidental poisonings due to ingestion of cooking oil contaminated with PCBs and related compounds, i.e., polychlorinated dibenzofurans (PCDFs) and polychlorinated quaterphenyls (PCQs). Hence, the importance of considering the related compounds as etiologic factors in PCB poisoning is emphasized.

Ultramorphological sperm characteristics in the risk assessment of health effects after radiation exposure among salvage workers in Chernobyl.

We present a pilot study of individuals (liquidators) who were engaged in clean-up operations after the disaster at the nuclear power plant at Chernobyl in Ukraine. In the 10 years since the disaster, adverse health effects among exposed individuals have not been clearly defined. There is widespread fear of damage to the reproductive system, with implications for fertility problems and adverse effects on offspring. Bearing this in mind, methods to evaluate the potential for production of fertile semen have been applied using quantitative ultramorphological (QUM) analysis. QUM analysis examines the organization and integrity of sperm organelles by electron microscopy, using both transmission electron microscopy and scanning electron microscopy. Significant differences were observed between clean-up workers and controls of similar age regarding certain ultramorphological parameters of the sperm head. The results of this pilot study suggest that QUM analysis of human sperm is a feasible approach for evaluating the fertility potential of individuals who were exposed to ionizing radiation from the Chernobyl nuclear power plant accident.

Hemoglobin, serum iron, and zinc protoporphyrin in lead-exposed workers.

In a previous study of secondary lead smelter workers (males), a significant prevalence of low hemoglobin levels (less than 14 g/100 ml) was found; a statistically significant negative correlation between hemoglobin and zinc protoporphyrin was also detected. In the present study serum iron (Fe) levels and total iron binding capacity (TIBC) were included in the investigation of 111 secondary lead smelter workers and 37 nonexposed controls. The distribution and mean values of serum iron and TIBC were found to be in the normal range in the lead exposed workers; there was no significant difference when compared to the control population. There was no significant correlation between blood lead or zinc protoporphyrin and serum iron, TIBC and Fe/TIBC. A statistically significant negative correlation between hemoglobin and blood lead levels was found; the correlation between hemoglobin and zinc protoporphyrin reached a much higher level of significance. The results support the view that anemia (low hemoglobin levels) in lead exposed male workers is related to the heme synthesis inhibiting effects of lead, as reflected by elevated zinc protoporphyrin levels, and is not due to iron deficiency.

Investigation of the health status of Michigan chemical corporation employees.

Clinical findings are reported for a group of 55 employees of the Michigan Chemical Corporation which manufactured FireMaster BP-6 from 1970 to 1974, in addition to a variety of other halogenated fire retardant chemicals. The results are compared with those from a group of male farm residents and consumers from Michigan examined at the same time. An increased prevalence of chest and skin symptoms was observed, compared with farmers. Skin symptoms were more prevalent among former PBB production personnel. Musculosketal symptoms were less prevalent among these workers than among farmers. Serum PBB concentrations are signicantly higher than among farmers. Blood chemistry results were similar for workers and farmers. However, both groups exhibited a significantly higher prevalence of elevated liver function tests (SGOT, SPGT) than a control population of nonexposed farmers. Both farmers and chemical workers showed an association of elevated CEA with serum PBB greater than 10 ppb.

Clinical studies of styrene workers: initial findings.

Styrene monomer is a high volume chemical used chiefly in production of polystyrene. A clinical survey of 493 production workers was undertaken at the oldest and largest monomer production, polymerization, and extrusion facility in the U.S. Relative exposure durations and levels were obtained from occupational histories. Significant differences between the high and low exposure groups were found with regard to history of acute prenarcotic symptoms, acute lower respiratory symptoms, prevalence of FEV 1/FV less than 75 per cent, and elevated GCTP. Other liver function tests, chest x-ray, FVC less than 80 per cent, and hematological parameters showed no distinct pattern. A concomitant mortality study has been mounted and is in progress.

Eosinophilic lung reaction to aluminium and hard metal.

A nonsmoker drill polisher with interstitial lung disease is presented. The environmental exposure was mainly to aluminum oxide, aluminum silicate, and hard metals. Bronchoalveolar lavage revealed high eosinophilia, and transbronchial biopsy specimen disclosed interstitial pneumonia with giant cell infiltrates and peribronchiolar accumulation of macrophages laden with opaque dust. Mineralogic studies done from the tissue revealed a high concentration of exogenous particles that were identified as hard metals and aluminum silicate. These findings are compatible with hard metal pneumoconiosis.

Decrease in vital capacity in PCB-exposed workers in a capacitor manufacturing facility.

Pulmonary function was evaluated in 243 workers exposed to PCB in the manufacture of capacitors. Mean employment was greater than 15 years. Thirty-four of the workers (14%) were found to have a reduced Forced Vital Capacity (FVC less than 80% of Morris' predicted). Of the 34 with reduced FVC, 27 (80%) demonstrated a restrictive pattern of impairment (FEV1/FVC greater than 0.7). Only one of these 27 workers had an abnormal chest roentgenogram (greater than or equal to 1/0 by ILO UC Classification of Radiographs of Pneumoconioses). These findings are of interest in view of recent experimental data indicating the accumulation of PCBs and PCB metabolites in lung tissue (Brandt and Jansson). Restrictive spirometric impairment with no radiographic change is unusual in occupational exposure.

Immunologic dysfunction among PBB-exposed Michigan dairy farmers.

In 1973 inadvertent contamination occurred in a special farm feed supplement for lactating cows. Polybrominated biphenyls (PBBs) were used in place of magnesium oxide resulting in serious harm to farm animals, including cattle, chickens, geese, ducks. Farm families, accustomed to eating their own products, were most heavily exposed. To further study the impact of PBBs, 45 adult Michigan farm residents who were originally examined in a clinical field survey were further studied with respect to their immunologic status. For comparison, 46 dairy farm residents in Wisconsin, who had not eaten PBB-contaminated food, were examined, as were 79 healthy subjects in New York City. Abnormalities in the Michigan group included significant decrease in absolute numbers and percentages of T and B-lymphocytes and increased number of lymphocytes with no detectable surface markers ("null cells"). Significant reduction of in vitro immune function was noted in 35--40% of the Michigan farm residents who had eaten food containing PBB. Despite the absence of any apparent numerical reduction, both T and B lymphocyte subpopulations of peripheral blood lymphocytes showed evidence of functional defect. Ten of the 45 Michigan farmers studied showed impaired PHA-induced blastogeneic response, due to the decreased number and percent of T-cells in the PBLs. The decreased immune function detected among the PBB-exposed farm residents tended to affect families as a unit and was independent of exposed individuals' age or sex, speaking against the possibility of genetic predisposition.

Seroprevalence of Kaposi's sarcoma-associated herpesvirus in healthy adults in Israel.

To determine if Kaposi's sarcoma-associated herpesvirus (KSHV) prevalence is correlated with the 9-fold difference in the incidence of classic Kaposi's sarcoma observed among Israeli Jewish populations, we conducted a cross-sectional KSHV seroprevalence survey in a population of 166 HIV-seronegative healthy subjects from the general population (26 women, 140 men). Eight individuals (4.8%) (all men) were seropositive for KSHV; differences between men and women were not statistically significant. If we consider the sensitivity and specificity of the assays, the corrected prevalence would be 6.1% (95% confidence interval 2.0-10.1). We noticed a non-statistically 5.5-fold difference between individuals above and below 40 years of age, but did not find an association with the incidence of classic KS among the Israeli Jewish sub-population, according to their origin. This suggests that KSHV is only necessary, albeit not sufficient, cause of classic Kaposi's sarcoma.

Interstitial pulmonary fibrosis in an automobile body shop worker.

Interstitial pulmonary fibrosis (IPF) is often of uncertain etiology and is therefore named 'idiopathic' pulmonary fibrosis. Some occupational exposures, however, are known to cause interstitial fibrosis, asbestos and silica being well-known examples. We present clinical and pathological findings of a case with IPF and the results of microchemical analysis of inorganic particulate matter in the lung tissue. A very high lung burden of inorganic contaminants was found, including silica and metallic compounds. Emphasis is given to the importance of obtaining detailed occupational histories and conducting microchemical analysis of lung tissue in order to clarify etiological factors in cases with 'idiopathic' pulmonary fibrosis.

Lead poisoning from art restoration and pottery work: unusual exposure source and household risk.

Two cases of lead poisoning following exposures in the arts and crafts environment are presented. The first illustrates the impact of an unusual exposure source experienced by a female art conservator while restoring an antique Peruvian tapestry from the Chancay Period (A.D. 1000-1500). The second demonstrates the extension to the artist's family members of a lead hazard associated with pottery work. Noted were a wide spectrum of clinical and biochemical abnormalities, ranging from severe neurological and gastrointestinal symptoms to subtle alterations in the biosynthetic pathway of heme. Marked elevation of the blood lead level (up to 130 mcg/100 mL) was found in the most severe case of lead poisoning. The cases illustrate the need for industrial hygiene measures in this type of work in order to prevent lead intoxication, both in the adult artist and children in the household. However, in some instances of increased lead absorption in persons with lead-related hobbies, sources other than those associated with arts and crafts should be investigated. This alternative is illustrated by a third case, in which firearms training was the more likely source of excessive exposure. Multiple occupational factors must occasionally be considered in evaluating increased lead absorption.

Malignant mesothelioma in Turkish immigrants residing in Sweden.

Mesothelioma is a rare neoplasm in the general population, but it is strongly associated with previous asbestos exposure. The endemic occurrence of this disease in two villages in central Turkey has raised the question of whether the inhalation of naturally occurring zeolite dust may also be a factor in the development of mesothelioma. During the past few years a large portion of the inhabitants of one of the two villages of concern has immigrated to Sweden. This report presents three cases of malignant pleural mesothelioma and the results of a chest radiographic survey among these immigrants. Mineralogical analysis of lung tissue specimens from two of the cases revealed the presence of both zeolite and asbestos minerals and therefore suggested a synergistic effect involving both types of minerals. The importance of close medical surveillance of this high-risk population is emphasized, as is the possibility that similar cases appear in other countries because of increased migration.